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Hypermucoviscous K pneumoniae Shows Reduced Drug Resistance

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TOPLINE:

Hypermucoviscous Klebsiella pneumoniae (hmKp) strains demonstrate a significantly lower prevalence of extended-spectrum beta-lactamase (ESBL) production and slightly lower carbapenem resistance than non-hmKp strains, according to a recent meta-analysis of 2049 clinical isolates.

METHODOLOGY:

  • Researchers conducted a meta-analysis to assess the prevalence of ESBL-producing strains and carbapenem-resistant strains among the hmKp and non-hmKp clinical isolates.
  • They included 15 studies published between 2014 and 2023, with 2049 clinical isolates of K pneumoniae identified using a string test to distinguish hypermucoviscous from non-hypermucoviscous strains.
  • These studies spanned across four continents: Asia, Africa, Europe, and North America.
  • The primary outcome was the prevalence of ESBL-producing and carbapenem-resistant strains, determined through antimicrobial susceptibility testing.

TAKEAWAY:

  • The hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains than non-hmKp strains (pooled odds ratio [OR], 0.26; P = .003).
  • Similarly, hmKp strains were associated with a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR, 0.63; P = .038).

IN PRACTICE:

“Therapeutic options for CRKP [carbapenem-resistant K pneumoniae] infections are extremely limited due to the scarcity of effective antibacterial drugs. Therefore, it is crucial to consider the risks posed by CRKP strains when administering treatment to patients with hmKp infections and a history of the aforementioned risk factors,” the authors wrote.

SOURCE:

The study was led by Hiroki Namikawa, Department of Medical Education and General Practice, Graduate School of Medicine, Osaka Metropolitan University, Japan. It was published online on December 16, 2024, in Emerging Microbes & Infections.

LIMITATIONS:

Only three databases (PubMed, Scopus, and Cochrane Library) were searched for identifying studies, potentially missing relevant studies from other sources. Furthermore, only articles published in English were included, which may have restricted the scope of analysis. Additionally, geographical distribution was predominantly limited to Asia, limiting the global applicability of the results.

DISCLOSURES:

No funding sources were mentioned, and no conflicts of interest were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE:

Hypermucoviscous Klebsiella pneumoniae (hmKp) strains demonstrate a significantly lower prevalence of extended-spectrum beta-lactamase (ESBL) production and slightly lower carbapenem resistance than non-hmKp strains, according to a recent meta-analysis of 2049 clinical isolates.

METHODOLOGY:

  • Researchers conducted a meta-analysis to assess the prevalence of ESBL-producing strains and carbapenem-resistant strains among the hmKp and non-hmKp clinical isolates.
  • They included 15 studies published between 2014 and 2023, with 2049 clinical isolates of K pneumoniae identified using a string test to distinguish hypermucoviscous from non-hypermucoviscous strains.
  • These studies spanned across four continents: Asia, Africa, Europe, and North America.
  • The primary outcome was the prevalence of ESBL-producing and carbapenem-resistant strains, determined through antimicrobial susceptibility testing.

TAKEAWAY:

  • The hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains than non-hmKp strains (pooled odds ratio [OR], 0.26; P = .003).
  • Similarly, hmKp strains were associated with a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR, 0.63; P = .038).

IN PRACTICE:

“Therapeutic options for CRKP [carbapenem-resistant K pneumoniae] infections are extremely limited due to the scarcity of effective antibacterial drugs. Therefore, it is crucial to consider the risks posed by CRKP strains when administering treatment to patients with hmKp infections and a history of the aforementioned risk factors,” the authors wrote.

SOURCE:

The study was led by Hiroki Namikawa, Department of Medical Education and General Practice, Graduate School of Medicine, Osaka Metropolitan University, Japan. It was published online on December 16, 2024, in Emerging Microbes & Infections.

LIMITATIONS:

Only three databases (PubMed, Scopus, and Cochrane Library) were searched for identifying studies, potentially missing relevant studies from other sources. Furthermore, only articles published in English were included, which may have restricted the scope of analysis. Additionally, geographical distribution was predominantly limited to Asia, limiting the global applicability of the results.

DISCLOSURES:

No funding sources were mentioned, and no conflicts of interest were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Hypermucoviscous Klebsiella pneumoniae (hmKp) strains demonstrate a significantly lower prevalence of extended-spectrum beta-lactamase (ESBL) production and slightly lower carbapenem resistance than non-hmKp strains, according to a recent meta-analysis of 2049 clinical isolates.

METHODOLOGY:

  • Researchers conducted a meta-analysis to assess the prevalence of ESBL-producing strains and carbapenem-resistant strains among the hmKp and non-hmKp clinical isolates.
  • They included 15 studies published between 2014 and 2023, with 2049 clinical isolates of K pneumoniae identified using a string test to distinguish hypermucoviscous from non-hypermucoviscous strains.
  • These studies spanned across four continents: Asia, Africa, Europe, and North America.
  • The primary outcome was the prevalence of ESBL-producing and carbapenem-resistant strains, determined through antimicrobial susceptibility testing.

TAKEAWAY:

  • The hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains than non-hmKp strains (pooled odds ratio [OR], 0.26; P = .003).
  • Similarly, hmKp strains were associated with a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR, 0.63; P = .038).

IN PRACTICE:

“Therapeutic options for CRKP [carbapenem-resistant K pneumoniae] infections are extremely limited due to the scarcity of effective antibacterial drugs. Therefore, it is crucial to consider the risks posed by CRKP strains when administering treatment to patients with hmKp infections and a history of the aforementioned risk factors,” the authors wrote.

SOURCE:

The study was led by Hiroki Namikawa, Department of Medical Education and General Practice, Graduate School of Medicine, Osaka Metropolitan University, Japan. It was published online on December 16, 2024, in Emerging Microbes & Infections.

LIMITATIONS:

Only three databases (PubMed, Scopus, and Cochrane Library) were searched for identifying studies, potentially missing relevant studies from other sources. Furthermore, only articles published in English were included, which may have restricted the scope of analysis. Additionally, geographical distribution was predominantly limited to Asia, limiting the global applicability of the results.

DISCLOSURES:

No funding sources were mentioned, and no conflicts of interest were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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What to Know About Sexually Transmitted Ringworm

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Mon, 12/16/2024 - 13:39

Ringworm (also known as tinea, jock itch, or athlete’s foot) is a common infection caused by dermatophyte fungi, known to affect skin, hair, or nails. It causes skin infections that are typically mild and are often treated with topical antifungals.

However, in recent years, newly emerging dermatophyte strains have been causing more severe and harder-to-treat ringworm. Notably, one emerging strain, Trichophyton mentagrophytes genotype VII(TMVII), is associated with sexual contact. In recent years, TMVII infections linked to sexual contact have been reported among men who have sex with men in Europe and in travelers returning from Southeast Asia. The first US case of TMVII was reported in June 2024, after which public health authorities were alerted to additional cases; all were associated with recent sexual contact. Other dermatophyte species have also been reported to cause ringworm transmitted through sexual contact. 

Here are some key points to know about sexually transmitted ringworm. 

Tell me more about sexually transmitted ringworm: What is causing it?

Skin-to-skin contact is a common mode of ringworm transmission. In recent years, transmission of ringworm via intimate or sexual contact has been increasingly recognized. However, clinicians may not immediately consider ringworm when evaluating genital, facial, or perianal lesions. Infections with sexually transmitted TMVII commonly cause lesions on anatomical sites that may be exposed during intimate or sexual contact, such as the face, genitals, and perianal region. Sexual transmission of TMVII has been reported in Europe, predominantly among men who have sex with men, for several years. Other dermatophyte strains have been reported in association with sexual contact, including the emerging strain Trichophyton indotineae. However, sexual transmission is not the main mode of transmission for T indotineae and other dermatophyte strains. 

When should clinicians suspect a potential case of sexually transmitted ringworm?

Providers should consider sexually transmitted ringworm when seeing ringworm in locations associated with intimate contact (for example, a rash on or around the genitals, perianal area, or mouth). 

The typical appearance of ringworm is a raised, ring-like, erythematous rash with a scaly border that grows over time. The rash may appear pink, brown, or gray on different types of skin. Patients may note itching and flaking of the rash. In areas with hair such as the beard area, ringworm can present as pustules and be associated with hair loss.

Emerging ringworm infections can present in atypical or more severe ways, including a highly inflammatory (painful, scarring, or otherwise severe) rash, a rash affecting a large area or multiple sites, nodules, and pustules. 

Sexually transmitted ringworm may be considered based on sexual history and recent sexual contact with someone with known TMVII. Recent history of travel to a region with reported sexually transmitted ringworm may increase suspicion of TMVII. In patients with a travel history to South Asia, T indotineae should be considered, especially if the rash does not improve with oral terbinafine

How can testing help guide the diagnosis of sexually transmitted ringworm infection?

When evaluating a rash that may represent ringworm, providers should use a confirmatory test such as potassium hydroxide (KOH) preparation when possible. KOH prep can confirm the presence of a fungus that causes ringworm, but it does not identify the species or type of ringworm. Testing such as fungal culture and molecular testing can help identify specific types of ringworm, but these tests are not often performed and may take a long time to yield results.

Routine fungal cultures cannot identify TMVII and T indotineae; these tests may identify the genus Trichophyton, but only advanced molecular testing, which is available at selected US laboratories, can identify TMVII and T indotineae

We recommend confirmatory testing because ringworm can easily be misdiagnosed as skin conditions such as psoriasis or eczema. The use of topical steroids can worsen a ringworm infection, so clinicians should be cautious about treating a rash with topical steroids if the etiology is unclear. Treatment should not be delayed if testing is not available. 

Clinicians who suspect a case of TMVII infection or infection with another emerging type of severe or antifungal-resistant ringworm can contact the Centers for Disease Control and Prevention (CDC) at [email protected]. More details on how clinicians can pursue testing to identify emerging strains of ringworm can be found on the American Academy of Dermatology (AAD) emerging diseases task force website. 

How should clinicians treat and manage sexually transmitted ringworm? 

If TMVII infection is suspected, providers can consider starting empirical treatment with oral terbinafine. Although data are limited, experience from case series suggests that TMVII may require oral antifungal treatment because it can cause severe skin infections and often does not improve with topical antifungals. Clinicians should advise patients that they may need prolonged treatment courses until the rash resolves, with possible need for treatment courses of 6-8 weeks or longer. 

Any diagnosis of a sexually transmitted infection is an opportunity to engage patients in comprehensive sexual health services. Patients with suspected sexually transmitted ringworm should be evaluated for HIV and other sexually transmitted infections, including syphilischlamydia, and gonorrhea; clinicians should discuss and facilitate access to other preventive services, such as HIV pre-exposure prophylaxis if the patient is HIV negative and at risk for HIV. Patients should also notify their partner(s) about the diagnosis. 

Is sexually transmitted ringworm a public health concern? 

It is important to know that very few cases of TMVII have been reported in the United States thus far. CDC continues to monitor emerging dermatophyte strains because these types of ringworm can cause more severe or difficult-to-treat infections. Clinicians should be aware of the potential severity of sexually transmitted ringworm infections and of how diagnosis and treatment of these infections may differ from typical management of ringworm.

So far, TMVII, the dermatophyte strain most associated with spread through sexual contact, has not been documented to have antifungal resistance. More rarely, sexually transmitted ringworm may be caused by other emerging dermatophyte strains that are antifungal resistant, such as T indotineaeItraconazole is the recommended first-line treatment for T indotineae infections. 

How can clinicians counsel patients with sexually transmitted ringworm?

Ringworm can spread with skin-to-skin contact, so patients should avoid such contact with others while they have a rash. They should also avoid sharing personal items (such as razors or towels) and clothing, and launder their clothing, towels, and bedding in a high heat cycle. 

People can reduce their risk of getting all types of ringworm infection by keeping their skin clean and dry, changing their socks and underwear daily, and wearing sandals in public locker rooms and other public spaces. People should avoid skin-to-skin contact with anyone with ringworm or an unexplained rash. Before having sex, people can check in with their partners and be aware of unexplained rashes on their partners’ bodies.

Where can clinicians go to learn more about sexually transmitted and other emerging types of ringworm?

CDC has partnered with the AAD to create set of online resources for clinicians for diagnosing and managing emerging dermatophyte infections. Clinicians who suspect or confirm antimicrobial resistant ringworm infection are also encouraged to submit cases to the AAD’s Emerging Diseases Registry. Clinicians wanting further guidance on how to manage suspected or confirmed ringworm infection with an emerging dermatophyte strain can also contact the CDC at [email protected]. Useful information on emerging dermatophyte infections for providers and patients is also available on CDC’s website.

Relevant Reading

Zucker J et al. MMWR Morb Mortal Wkly Rep. 2024;73:985-988.Spivack S et al. Emerg Infect Dis. 2024;30:807-809.Jabet A et al. Emerg Infect Dis. 2023;29:1411-1414.

A version of this article appeared on Medscape.com. 

Dr Anand is Epidemic Intelligence Service Officer, Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia. Dr Gold is Medical Officer, Mycotic Diseases Branch, Centers for Disease Control and Prevention. Dr Quilter is Medical Officer, Division of STD Prevention, Centers for Disease Control and Prevention. None reported any relevant conflicts of interest. 

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Ringworm (also known as tinea, jock itch, or athlete’s foot) is a common infection caused by dermatophyte fungi, known to affect skin, hair, or nails. It causes skin infections that are typically mild and are often treated with topical antifungals.

However, in recent years, newly emerging dermatophyte strains have been causing more severe and harder-to-treat ringworm. Notably, one emerging strain, Trichophyton mentagrophytes genotype VII(TMVII), is associated with sexual contact. In recent years, TMVII infections linked to sexual contact have been reported among men who have sex with men in Europe and in travelers returning from Southeast Asia. The first US case of TMVII was reported in June 2024, after which public health authorities were alerted to additional cases; all were associated with recent sexual contact. Other dermatophyte species have also been reported to cause ringworm transmitted through sexual contact. 

Here are some key points to know about sexually transmitted ringworm. 

Tell me more about sexually transmitted ringworm: What is causing it?

Skin-to-skin contact is a common mode of ringworm transmission. In recent years, transmission of ringworm via intimate or sexual contact has been increasingly recognized. However, clinicians may not immediately consider ringworm when evaluating genital, facial, or perianal lesions. Infections with sexually transmitted TMVII commonly cause lesions on anatomical sites that may be exposed during intimate or sexual contact, such as the face, genitals, and perianal region. Sexual transmission of TMVII has been reported in Europe, predominantly among men who have sex with men, for several years. Other dermatophyte strains have been reported in association with sexual contact, including the emerging strain Trichophyton indotineae. However, sexual transmission is not the main mode of transmission for T indotineae and other dermatophyte strains. 

When should clinicians suspect a potential case of sexually transmitted ringworm?

Providers should consider sexually transmitted ringworm when seeing ringworm in locations associated with intimate contact (for example, a rash on or around the genitals, perianal area, or mouth). 

The typical appearance of ringworm is a raised, ring-like, erythematous rash with a scaly border that grows over time. The rash may appear pink, brown, or gray on different types of skin. Patients may note itching and flaking of the rash. In areas with hair such as the beard area, ringworm can present as pustules and be associated with hair loss.

Emerging ringworm infections can present in atypical or more severe ways, including a highly inflammatory (painful, scarring, or otherwise severe) rash, a rash affecting a large area or multiple sites, nodules, and pustules. 

Sexually transmitted ringworm may be considered based on sexual history and recent sexual contact with someone with known TMVII. Recent history of travel to a region with reported sexually transmitted ringworm may increase suspicion of TMVII. In patients with a travel history to South Asia, T indotineae should be considered, especially if the rash does not improve with oral terbinafine

How can testing help guide the diagnosis of sexually transmitted ringworm infection?

When evaluating a rash that may represent ringworm, providers should use a confirmatory test such as potassium hydroxide (KOH) preparation when possible. KOH prep can confirm the presence of a fungus that causes ringworm, but it does not identify the species or type of ringworm. Testing such as fungal culture and molecular testing can help identify specific types of ringworm, but these tests are not often performed and may take a long time to yield results.

Routine fungal cultures cannot identify TMVII and T indotineae; these tests may identify the genus Trichophyton, but only advanced molecular testing, which is available at selected US laboratories, can identify TMVII and T indotineae

We recommend confirmatory testing because ringworm can easily be misdiagnosed as skin conditions such as psoriasis or eczema. The use of topical steroids can worsen a ringworm infection, so clinicians should be cautious about treating a rash with topical steroids if the etiology is unclear. Treatment should not be delayed if testing is not available. 

Clinicians who suspect a case of TMVII infection or infection with another emerging type of severe or antifungal-resistant ringworm can contact the Centers for Disease Control and Prevention (CDC) at [email protected]. More details on how clinicians can pursue testing to identify emerging strains of ringworm can be found on the American Academy of Dermatology (AAD) emerging diseases task force website. 

How should clinicians treat and manage sexually transmitted ringworm? 

If TMVII infection is suspected, providers can consider starting empirical treatment with oral terbinafine. Although data are limited, experience from case series suggests that TMVII may require oral antifungal treatment because it can cause severe skin infections and often does not improve with topical antifungals. Clinicians should advise patients that they may need prolonged treatment courses until the rash resolves, with possible need for treatment courses of 6-8 weeks or longer. 

Any diagnosis of a sexually transmitted infection is an opportunity to engage patients in comprehensive sexual health services. Patients with suspected sexually transmitted ringworm should be evaluated for HIV and other sexually transmitted infections, including syphilischlamydia, and gonorrhea; clinicians should discuss and facilitate access to other preventive services, such as HIV pre-exposure prophylaxis if the patient is HIV negative and at risk for HIV. Patients should also notify their partner(s) about the diagnosis. 

Is sexually transmitted ringworm a public health concern? 

It is important to know that very few cases of TMVII have been reported in the United States thus far. CDC continues to monitor emerging dermatophyte strains because these types of ringworm can cause more severe or difficult-to-treat infections. Clinicians should be aware of the potential severity of sexually transmitted ringworm infections and of how diagnosis and treatment of these infections may differ from typical management of ringworm.

So far, TMVII, the dermatophyte strain most associated with spread through sexual contact, has not been documented to have antifungal resistance. More rarely, sexually transmitted ringworm may be caused by other emerging dermatophyte strains that are antifungal resistant, such as T indotineaeItraconazole is the recommended first-line treatment for T indotineae infections. 

How can clinicians counsel patients with sexually transmitted ringworm?

Ringworm can spread with skin-to-skin contact, so patients should avoid such contact with others while they have a rash. They should also avoid sharing personal items (such as razors or towels) and clothing, and launder their clothing, towels, and bedding in a high heat cycle. 

People can reduce their risk of getting all types of ringworm infection by keeping their skin clean and dry, changing their socks and underwear daily, and wearing sandals in public locker rooms and other public spaces. People should avoid skin-to-skin contact with anyone with ringworm or an unexplained rash. Before having sex, people can check in with their partners and be aware of unexplained rashes on their partners’ bodies.

Where can clinicians go to learn more about sexually transmitted and other emerging types of ringworm?

CDC has partnered with the AAD to create set of online resources for clinicians for diagnosing and managing emerging dermatophyte infections. Clinicians who suspect or confirm antimicrobial resistant ringworm infection are also encouraged to submit cases to the AAD’s Emerging Diseases Registry. Clinicians wanting further guidance on how to manage suspected or confirmed ringworm infection with an emerging dermatophyte strain can also contact the CDC at [email protected]. Useful information on emerging dermatophyte infections for providers and patients is also available on CDC’s website.

Relevant Reading

Zucker J et al. MMWR Morb Mortal Wkly Rep. 2024;73:985-988.Spivack S et al. Emerg Infect Dis. 2024;30:807-809.Jabet A et al. Emerg Infect Dis. 2023;29:1411-1414.

A version of this article appeared on Medscape.com. 

Dr Anand is Epidemic Intelligence Service Officer, Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia. Dr Gold is Medical Officer, Mycotic Diseases Branch, Centers for Disease Control and Prevention. Dr Quilter is Medical Officer, Division of STD Prevention, Centers for Disease Control and Prevention. None reported any relevant conflicts of interest. 

Ringworm (also known as tinea, jock itch, or athlete’s foot) is a common infection caused by dermatophyte fungi, known to affect skin, hair, or nails. It causes skin infections that are typically mild and are often treated with topical antifungals.

However, in recent years, newly emerging dermatophyte strains have been causing more severe and harder-to-treat ringworm. Notably, one emerging strain, Trichophyton mentagrophytes genotype VII(TMVII), is associated with sexual contact. In recent years, TMVII infections linked to sexual contact have been reported among men who have sex with men in Europe and in travelers returning from Southeast Asia. The first US case of TMVII was reported in June 2024, after which public health authorities were alerted to additional cases; all were associated with recent sexual contact. Other dermatophyte species have also been reported to cause ringworm transmitted through sexual contact. 

Here are some key points to know about sexually transmitted ringworm. 

Tell me more about sexually transmitted ringworm: What is causing it?

Skin-to-skin contact is a common mode of ringworm transmission. In recent years, transmission of ringworm via intimate or sexual contact has been increasingly recognized. However, clinicians may not immediately consider ringworm when evaluating genital, facial, or perianal lesions. Infections with sexually transmitted TMVII commonly cause lesions on anatomical sites that may be exposed during intimate or sexual contact, such as the face, genitals, and perianal region. Sexual transmission of TMVII has been reported in Europe, predominantly among men who have sex with men, for several years. Other dermatophyte strains have been reported in association with sexual contact, including the emerging strain Trichophyton indotineae. However, sexual transmission is not the main mode of transmission for T indotineae and other dermatophyte strains. 

When should clinicians suspect a potential case of sexually transmitted ringworm?

Providers should consider sexually transmitted ringworm when seeing ringworm in locations associated with intimate contact (for example, a rash on or around the genitals, perianal area, or mouth). 

The typical appearance of ringworm is a raised, ring-like, erythematous rash with a scaly border that grows over time. The rash may appear pink, brown, or gray on different types of skin. Patients may note itching and flaking of the rash. In areas with hair such as the beard area, ringworm can present as pustules and be associated with hair loss.

Emerging ringworm infections can present in atypical or more severe ways, including a highly inflammatory (painful, scarring, or otherwise severe) rash, a rash affecting a large area or multiple sites, nodules, and pustules. 

Sexually transmitted ringworm may be considered based on sexual history and recent sexual contact with someone with known TMVII. Recent history of travel to a region with reported sexually transmitted ringworm may increase suspicion of TMVII. In patients with a travel history to South Asia, T indotineae should be considered, especially if the rash does not improve with oral terbinafine

How can testing help guide the diagnosis of sexually transmitted ringworm infection?

When evaluating a rash that may represent ringworm, providers should use a confirmatory test such as potassium hydroxide (KOH) preparation when possible. KOH prep can confirm the presence of a fungus that causes ringworm, but it does not identify the species or type of ringworm. Testing such as fungal culture and molecular testing can help identify specific types of ringworm, but these tests are not often performed and may take a long time to yield results.

Routine fungal cultures cannot identify TMVII and T indotineae; these tests may identify the genus Trichophyton, but only advanced molecular testing, which is available at selected US laboratories, can identify TMVII and T indotineae

We recommend confirmatory testing because ringworm can easily be misdiagnosed as skin conditions such as psoriasis or eczema. The use of topical steroids can worsen a ringworm infection, so clinicians should be cautious about treating a rash with topical steroids if the etiology is unclear. Treatment should not be delayed if testing is not available. 

Clinicians who suspect a case of TMVII infection or infection with another emerging type of severe or antifungal-resistant ringworm can contact the Centers for Disease Control and Prevention (CDC) at [email protected]. More details on how clinicians can pursue testing to identify emerging strains of ringworm can be found on the American Academy of Dermatology (AAD) emerging diseases task force website. 

How should clinicians treat and manage sexually transmitted ringworm? 

If TMVII infection is suspected, providers can consider starting empirical treatment with oral terbinafine. Although data are limited, experience from case series suggests that TMVII may require oral antifungal treatment because it can cause severe skin infections and often does not improve with topical antifungals. Clinicians should advise patients that they may need prolonged treatment courses until the rash resolves, with possible need for treatment courses of 6-8 weeks or longer. 

Any diagnosis of a sexually transmitted infection is an opportunity to engage patients in comprehensive sexual health services. Patients with suspected sexually transmitted ringworm should be evaluated for HIV and other sexually transmitted infections, including syphilischlamydia, and gonorrhea; clinicians should discuss and facilitate access to other preventive services, such as HIV pre-exposure prophylaxis if the patient is HIV negative and at risk for HIV. Patients should also notify their partner(s) about the diagnosis. 

Is sexually transmitted ringworm a public health concern? 

It is important to know that very few cases of TMVII have been reported in the United States thus far. CDC continues to monitor emerging dermatophyte strains because these types of ringworm can cause more severe or difficult-to-treat infections. Clinicians should be aware of the potential severity of sexually transmitted ringworm infections and of how diagnosis and treatment of these infections may differ from typical management of ringworm.

So far, TMVII, the dermatophyte strain most associated with spread through sexual contact, has not been documented to have antifungal resistance. More rarely, sexually transmitted ringworm may be caused by other emerging dermatophyte strains that are antifungal resistant, such as T indotineaeItraconazole is the recommended first-line treatment for T indotineae infections. 

How can clinicians counsel patients with sexually transmitted ringworm?

Ringworm can spread with skin-to-skin contact, so patients should avoid such contact with others while they have a rash. They should also avoid sharing personal items (such as razors or towels) and clothing, and launder their clothing, towels, and bedding in a high heat cycle. 

People can reduce their risk of getting all types of ringworm infection by keeping their skin clean and dry, changing their socks and underwear daily, and wearing sandals in public locker rooms and other public spaces. People should avoid skin-to-skin contact with anyone with ringworm or an unexplained rash. Before having sex, people can check in with their partners and be aware of unexplained rashes on their partners’ bodies.

Where can clinicians go to learn more about sexually transmitted and other emerging types of ringworm?

CDC has partnered with the AAD to create set of online resources for clinicians for diagnosing and managing emerging dermatophyte infections. Clinicians who suspect or confirm antimicrobial resistant ringworm infection are also encouraged to submit cases to the AAD’s Emerging Diseases Registry. Clinicians wanting further guidance on how to manage suspected or confirmed ringworm infection with an emerging dermatophyte strain can also contact the CDC at [email protected]. Useful information on emerging dermatophyte infections for providers and patients is also available on CDC’s website.

Relevant Reading

Zucker J et al. MMWR Morb Mortal Wkly Rep. 2024;73:985-988.Spivack S et al. Emerg Infect Dis. 2024;30:807-809.Jabet A et al. Emerg Infect Dis. 2023;29:1411-1414.

A version of this article appeared on Medscape.com. 

Dr Anand is Epidemic Intelligence Service Officer, Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia. Dr Gold is Medical Officer, Mycotic Diseases Branch, Centers for Disease Control and Prevention. Dr Quilter is Medical Officer, Division of STD Prevention, Centers for Disease Control and Prevention. None reported any relevant conflicts of interest. 

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New Hope for Antimicrobial Peptides?

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The story of antimicrobial peptides (AMPs), particularly in tackling antibiotic resistance, has been one of false dawns and unfulfilled promises. But perhaps a new generation of “smarter” compounds could see them find a wider role in clinical practice, said experts.

AMPs may be small molecules, consisting of short chains of amino acids, but these naturally occurring compounds have an important function: They are the “frontline defense” against invasive bacteria, said Henrik Franzyk, MSc Engineering, associate professor in the Department of Drug Design and Pharmacology at the University of Copenhagen in Denmark.

 

Multifunction Line of Defense

AMPs are cationic, meaning they are positively charged. “The reason why nature has maintained these molecules is that all the microbes out there have a negative surface charge,” explained Hans-Georg Sahl, PhD, emeritus professor of pharmaceutical microbiology at the University of Bonn in Germany.

While AMPs are also hydrophobic, they are often amphipathic, with both hydrophobic and hydrophilic regions that allow them to target cell membranes and cause them to rupture similarly to how detergent acts. 

“Thus, the content of a cell gets released, and it destroys the pathogen,” explained Paulina Szymczak, a PhD candidate in the Institute of AI for Health at Helmholtz Munich, Neuherberg, Germany.

“There are variations of that theme,” said Eefjan Breukink, PhD, professor of microbial membranes and antibiotics at Utrecht University in the Netherlands. “And then it depends on the sequence of the particular peptide,” as some can cross the cell membrane and damage the bacterium internally.

Szymczak explained that AMPs can, in this way, target the cell DNA, as both the membrane and the DNA are negatively charged. “That’s also what makes them so powerful because they don’t have just one mechanism of action, as opposed to conventional antibiotics.” 

 

Indiscriminate Killers

But they also have another crucial function. They activate the innate immune system via so-called resident immune cells that are “sitting in the tissues and waiting for bacteria to turn up,” explained Franzyk.

“The problem with antibodies is that they typically need to replicate,” he continued, which takes between 4 and 7 days — a timeline that is much better suited to tackling a viral infection. Bacteria, on the other hand, have a replication cycle of just 30 minutes.

Another big problem is that AMPs kill cells indiscriminately, including our own.

“But the human body is clever in that it only produces these antimicrobial peptides where the bacteria are, so they are not circulating in the blood,” said Franzyk. If a small part of tissue becomes infected, the innate immune cells start producing AMPs, which may kill the bacteria, or call on other immune cells to help.

As part of this process, “they will also kill part of our own tissue, but that’s the price we have to pay,” he said.

 

Local Applications

It is this aspect that has, so far, limited the use of AMPs in clinical practice, certainly as a replacement for conventional antibiotics limited by bacterial resistance. The trials conducted so far have been, by and large, negative, which has dampened enthusiasm and led to the perception that the risk they pose is too great for large-scale investment.

AMPs “are not made for what we need from antibiotics in the first place,” explained Sahl. “That is, a nice, easy distribution in the body, going into abscesses” and throughout the tissues.

He continued that AMPs are “more about controlling the flora in our bodies,” and they are “really not made for being used systemically.” 

Szymczak and colleagues are now working on designing active peptides with a strong antibacterial profile but limited toxicity for systematic use.

However, the “downside with these peptides is that they are not orally available, so you can’t take a pill,” Breukink said, but instead they need to be administered intravenously.

There are, nevertheless, some antibiotics in clinical use that have the same molecular features as AMPs. These include colistin, a last-resort treatment for multidrug-resistant gram-negative bacteria, and daptomycin, which is used in the treatment of systemic infections caused by gram-positive species.

Szymczak added that there have been successes in using AMPs in a more targeted way, such as using a topical cream. Another potentially promising avenue is lung infections, which are being studied in mouse models.

 

Less Prone to Resistance

Crucially, AMPs are markedly less prone to bacterial resistance than conventional antibiotics, partly because of their typical target: the cell membrane.

“Biologically and evolutionarily, it is a very costly operation to rebuild the membrane and change its charge,” Szymczak explained. “It’s quite hard for bacteria to learn this because it’s not a single protein that you have to mutate but the whole membrane.”

This is seen in the laboratory, where it takes around five generations, or passages, for bacteria to develop resistance when grown in the presence of antibiotics, but up to 40 passages when cultured with an AMP.

The limits of the ability of AMPs to withstand the development of bacterial resistance have been tested in the real world.

Colistin has been used widely in Asia as a growth promoter, especially in pig farming. Franzyk explained that farmers have used enormous quantities of this AMP-based antibiotic, which has indeed led to the development of resistance, including contamination of meat for human consumption, leading to resistance spreading to other parts of the world.

“The bad thing about this is it’s not something each individual bacteria needs to acquire,” he said. Because resistance is stored on small, cyclic DNA called plasmids, it “can be transferred from one bacterial species to another.”

 

Novel Avenues

Franzyk suggested that AMPs could nevertheless be used in combination with, or to modify, existing antibiotics to revitalize those for which there is already bacterial resistance, or to allow antibiotics that ordinarily target only gram-positive bacteria to also treat gram-negative infections, for example.

Szymczak and her colleagues are using artificial intelligence to design novel AMP candidates. Instead of manually going through compounds and checking their activity profiles in the lab, those steps are carried out computationally “so that, in the end, you synthesize as few candidates as possible” and can proceed to a mouse model “as fast as possible.”

She personally is looking at the issue of strain-specific activity to design a compound that would target, for example, only multidrug-resistant strains. “What we can do now is something that will target everything, so a kind of last resort peptide. But we are trying to make them smarter in their targets.”

Szymczak also pointed out that cancer cells are “negatively charged, similarly to bacterial cells, as opposed to mammalian cells, which are neutral.”

“So in theory, maybe we could design something that will target cancer cells but not our host cells, and that would be extremely exciting.” However, she underlined that, first, they are trying to tackle antimicrobial resistance before looking at other spaces.

Finally, Breukink is screening for small antibacterial compounds in fungi that are around half the size of a normal peptide and more hydrophobic, meaning there is a much greater chance of them being orally available.

But “you first have to test, of course,” he said, as “if you don’t have specific targets, then you will get problems with toxicity, or other issues that you do not foresee.” 

No funding was declared. No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

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The story of antimicrobial peptides (AMPs), particularly in tackling antibiotic resistance, has been one of false dawns and unfulfilled promises. But perhaps a new generation of “smarter” compounds could see them find a wider role in clinical practice, said experts.

AMPs may be small molecules, consisting of short chains of amino acids, but these naturally occurring compounds have an important function: They are the “frontline defense” against invasive bacteria, said Henrik Franzyk, MSc Engineering, associate professor in the Department of Drug Design and Pharmacology at the University of Copenhagen in Denmark.

 

Multifunction Line of Defense

AMPs are cationic, meaning they are positively charged. “The reason why nature has maintained these molecules is that all the microbes out there have a negative surface charge,” explained Hans-Georg Sahl, PhD, emeritus professor of pharmaceutical microbiology at the University of Bonn in Germany.

While AMPs are also hydrophobic, they are often amphipathic, with both hydrophobic and hydrophilic regions that allow them to target cell membranes and cause them to rupture similarly to how detergent acts. 

“Thus, the content of a cell gets released, and it destroys the pathogen,” explained Paulina Szymczak, a PhD candidate in the Institute of AI for Health at Helmholtz Munich, Neuherberg, Germany.

“There are variations of that theme,” said Eefjan Breukink, PhD, professor of microbial membranes and antibiotics at Utrecht University in the Netherlands. “And then it depends on the sequence of the particular peptide,” as some can cross the cell membrane and damage the bacterium internally.

Szymczak explained that AMPs can, in this way, target the cell DNA, as both the membrane and the DNA are negatively charged. “That’s also what makes them so powerful because they don’t have just one mechanism of action, as opposed to conventional antibiotics.” 

 

Indiscriminate Killers

But they also have another crucial function. They activate the innate immune system via so-called resident immune cells that are “sitting in the tissues and waiting for bacteria to turn up,” explained Franzyk.

“The problem with antibodies is that they typically need to replicate,” he continued, which takes between 4 and 7 days — a timeline that is much better suited to tackling a viral infection. Bacteria, on the other hand, have a replication cycle of just 30 minutes.

Another big problem is that AMPs kill cells indiscriminately, including our own.

“But the human body is clever in that it only produces these antimicrobial peptides where the bacteria are, so they are not circulating in the blood,” said Franzyk. If a small part of tissue becomes infected, the innate immune cells start producing AMPs, which may kill the bacteria, or call on other immune cells to help.

As part of this process, “they will also kill part of our own tissue, but that’s the price we have to pay,” he said.

 

Local Applications

It is this aspect that has, so far, limited the use of AMPs in clinical practice, certainly as a replacement for conventional antibiotics limited by bacterial resistance. The trials conducted so far have been, by and large, negative, which has dampened enthusiasm and led to the perception that the risk they pose is too great for large-scale investment.

AMPs “are not made for what we need from antibiotics in the first place,” explained Sahl. “That is, a nice, easy distribution in the body, going into abscesses” and throughout the tissues.

He continued that AMPs are “more about controlling the flora in our bodies,” and they are “really not made for being used systemically.” 

Szymczak and colleagues are now working on designing active peptides with a strong antibacterial profile but limited toxicity for systematic use.

However, the “downside with these peptides is that they are not orally available, so you can’t take a pill,” Breukink said, but instead they need to be administered intravenously.

There are, nevertheless, some antibiotics in clinical use that have the same molecular features as AMPs. These include colistin, a last-resort treatment for multidrug-resistant gram-negative bacteria, and daptomycin, which is used in the treatment of systemic infections caused by gram-positive species.

Szymczak added that there have been successes in using AMPs in a more targeted way, such as using a topical cream. Another potentially promising avenue is lung infections, which are being studied in mouse models.

 

Less Prone to Resistance

Crucially, AMPs are markedly less prone to bacterial resistance than conventional antibiotics, partly because of their typical target: the cell membrane.

“Biologically and evolutionarily, it is a very costly operation to rebuild the membrane and change its charge,” Szymczak explained. “It’s quite hard for bacteria to learn this because it’s not a single protein that you have to mutate but the whole membrane.”

This is seen in the laboratory, where it takes around five generations, or passages, for bacteria to develop resistance when grown in the presence of antibiotics, but up to 40 passages when cultured with an AMP.

The limits of the ability of AMPs to withstand the development of bacterial resistance have been tested in the real world.

Colistin has been used widely in Asia as a growth promoter, especially in pig farming. Franzyk explained that farmers have used enormous quantities of this AMP-based antibiotic, which has indeed led to the development of resistance, including contamination of meat for human consumption, leading to resistance spreading to other parts of the world.

“The bad thing about this is it’s not something each individual bacteria needs to acquire,” he said. Because resistance is stored on small, cyclic DNA called plasmids, it “can be transferred from one bacterial species to another.”

 

Novel Avenues

Franzyk suggested that AMPs could nevertheless be used in combination with, or to modify, existing antibiotics to revitalize those for which there is already bacterial resistance, or to allow antibiotics that ordinarily target only gram-positive bacteria to also treat gram-negative infections, for example.

Szymczak and her colleagues are using artificial intelligence to design novel AMP candidates. Instead of manually going through compounds and checking their activity profiles in the lab, those steps are carried out computationally “so that, in the end, you synthesize as few candidates as possible” and can proceed to a mouse model “as fast as possible.”

She personally is looking at the issue of strain-specific activity to design a compound that would target, for example, only multidrug-resistant strains. “What we can do now is something that will target everything, so a kind of last resort peptide. But we are trying to make them smarter in their targets.”

Szymczak also pointed out that cancer cells are “negatively charged, similarly to bacterial cells, as opposed to mammalian cells, which are neutral.”

“So in theory, maybe we could design something that will target cancer cells but not our host cells, and that would be extremely exciting.” However, she underlined that, first, they are trying to tackle antimicrobial resistance before looking at other spaces.

Finally, Breukink is screening for small antibacterial compounds in fungi that are around half the size of a normal peptide and more hydrophobic, meaning there is a much greater chance of them being orally available.

But “you first have to test, of course,” he said, as “if you don’t have specific targets, then you will get problems with toxicity, or other issues that you do not foresee.” 

No funding was declared. No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

The story of antimicrobial peptides (AMPs), particularly in tackling antibiotic resistance, has been one of false dawns and unfulfilled promises. But perhaps a new generation of “smarter” compounds could see them find a wider role in clinical practice, said experts.

AMPs may be small molecules, consisting of short chains of amino acids, but these naturally occurring compounds have an important function: They are the “frontline defense” against invasive bacteria, said Henrik Franzyk, MSc Engineering, associate professor in the Department of Drug Design and Pharmacology at the University of Copenhagen in Denmark.

 

Multifunction Line of Defense

AMPs are cationic, meaning they are positively charged. “The reason why nature has maintained these molecules is that all the microbes out there have a negative surface charge,” explained Hans-Georg Sahl, PhD, emeritus professor of pharmaceutical microbiology at the University of Bonn in Germany.

While AMPs are also hydrophobic, they are often amphipathic, with both hydrophobic and hydrophilic regions that allow them to target cell membranes and cause them to rupture similarly to how detergent acts. 

“Thus, the content of a cell gets released, and it destroys the pathogen,” explained Paulina Szymczak, a PhD candidate in the Institute of AI for Health at Helmholtz Munich, Neuherberg, Germany.

“There are variations of that theme,” said Eefjan Breukink, PhD, professor of microbial membranes and antibiotics at Utrecht University in the Netherlands. “And then it depends on the sequence of the particular peptide,” as some can cross the cell membrane and damage the bacterium internally.

Szymczak explained that AMPs can, in this way, target the cell DNA, as both the membrane and the DNA are negatively charged. “That’s also what makes them so powerful because they don’t have just one mechanism of action, as opposed to conventional antibiotics.” 

 

Indiscriminate Killers

But they also have another crucial function. They activate the innate immune system via so-called resident immune cells that are “sitting in the tissues and waiting for bacteria to turn up,” explained Franzyk.

“The problem with antibodies is that they typically need to replicate,” he continued, which takes between 4 and 7 days — a timeline that is much better suited to tackling a viral infection. Bacteria, on the other hand, have a replication cycle of just 30 minutes.

Another big problem is that AMPs kill cells indiscriminately, including our own.

“But the human body is clever in that it only produces these antimicrobial peptides where the bacteria are, so they are not circulating in the blood,” said Franzyk. If a small part of tissue becomes infected, the innate immune cells start producing AMPs, which may kill the bacteria, or call on other immune cells to help.

As part of this process, “they will also kill part of our own tissue, but that’s the price we have to pay,” he said.

 

Local Applications

It is this aspect that has, so far, limited the use of AMPs in clinical practice, certainly as a replacement for conventional antibiotics limited by bacterial resistance. The trials conducted so far have been, by and large, negative, which has dampened enthusiasm and led to the perception that the risk they pose is too great for large-scale investment.

AMPs “are not made for what we need from antibiotics in the first place,” explained Sahl. “That is, a nice, easy distribution in the body, going into abscesses” and throughout the tissues.

He continued that AMPs are “more about controlling the flora in our bodies,” and they are “really not made for being used systemically.” 

Szymczak and colleagues are now working on designing active peptides with a strong antibacterial profile but limited toxicity for systematic use.

However, the “downside with these peptides is that they are not orally available, so you can’t take a pill,” Breukink said, but instead they need to be administered intravenously.

There are, nevertheless, some antibiotics in clinical use that have the same molecular features as AMPs. These include colistin, a last-resort treatment for multidrug-resistant gram-negative bacteria, and daptomycin, which is used in the treatment of systemic infections caused by gram-positive species.

Szymczak added that there have been successes in using AMPs in a more targeted way, such as using a topical cream. Another potentially promising avenue is lung infections, which are being studied in mouse models.

 

Less Prone to Resistance

Crucially, AMPs are markedly less prone to bacterial resistance than conventional antibiotics, partly because of their typical target: the cell membrane.

“Biologically and evolutionarily, it is a very costly operation to rebuild the membrane and change its charge,” Szymczak explained. “It’s quite hard for bacteria to learn this because it’s not a single protein that you have to mutate but the whole membrane.”

This is seen in the laboratory, where it takes around five generations, or passages, for bacteria to develop resistance when grown in the presence of antibiotics, but up to 40 passages when cultured with an AMP.

The limits of the ability of AMPs to withstand the development of bacterial resistance have been tested in the real world.

Colistin has been used widely in Asia as a growth promoter, especially in pig farming. Franzyk explained that farmers have used enormous quantities of this AMP-based antibiotic, which has indeed led to the development of resistance, including contamination of meat for human consumption, leading to resistance spreading to other parts of the world.

“The bad thing about this is it’s not something each individual bacteria needs to acquire,” he said. Because resistance is stored on small, cyclic DNA called plasmids, it “can be transferred from one bacterial species to another.”

 

Novel Avenues

Franzyk suggested that AMPs could nevertheless be used in combination with, or to modify, existing antibiotics to revitalize those for which there is already bacterial resistance, or to allow antibiotics that ordinarily target only gram-positive bacteria to also treat gram-negative infections, for example.

Szymczak and her colleagues are using artificial intelligence to design novel AMP candidates. Instead of manually going through compounds and checking their activity profiles in the lab, those steps are carried out computationally “so that, in the end, you synthesize as few candidates as possible” and can proceed to a mouse model “as fast as possible.”

She personally is looking at the issue of strain-specific activity to design a compound that would target, for example, only multidrug-resistant strains. “What we can do now is something that will target everything, so a kind of last resort peptide. But we are trying to make them smarter in their targets.”

Szymczak also pointed out that cancer cells are “negatively charged, similarly to bacterial cells, as opposed to mammalian cells, which are neutral.”

“So in theory, maybe we could design something that will target cancer cells but not our host cells, and that would be extremely exciting.” However, she underlined that, first, they are trying to tackle antimicrobial resistance before looking at other spaces.

Finally, Breukink is screening for small antibacterial compounds in fungi that are around half the size of a normal peptide and more hydrophobic, meaning there is a much greater chance of them being orally available.

But “you first have to test, of course,” he said, as “if you don’t have specific targets, then you will get problems with toxicity, or other issues that you do not foresee.” 

No funding was declared. No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

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The Multipronged Problem of Candida auris

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The Multipronged Problem of Candida auris

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

  • Overnight international hospitalization
  • Recent stay in a long-term acute care facility
  • Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

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Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

  • Overnight international hospitalization
  • Recent stay in a long-term acute care facility
  • Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

  • Overnight international hospitalization
  • Recent stay in a long-term acute care facility
  • Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

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AMR Could Surpass Cancer as Leading Cause of Death by 2050

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Antimicrobial resistance (AMR) is globally recognized as one of the greatest health threats of the 21st century, responsible for 1.27 million deaths annually. “According to the WHO, if no measures are taken promptly, AMR could lead to more deaths than cancer by 2050,” Arnaud Marchant, MD, PhD, director of the European Plotkin Institute for Vaccinology at Université libre de Bruxelles (EPIV-ULB), Anderlecht, Belgium, said in an interview with MediQuality, part of the Medscape Professional Network. “This is a huge problem, and vaccination could be part of the solution.”

EPIV-ULB marked the start of the World AMR Awareness Week (November 18-24) with an event highlighting the critical role of vaccination to counter the rise for resistant pathogens. During the event, MediQuality interviewed Marchant, along with several other experts in the field.

 

Antibiotics Losing Effectiveness

Marc Van Ranst, PhD, virologist at Rega Institute KU Leuven in Leuven, Belgium, echoed Marchant’s concerns. He noted that “an increasing number of bacteria are becoming resistant to more antibiotics.” “While antibiotics were once miracle drugs, they have now stopped — or almost stopped — working against certain bacteria. Although we are discovering more effective therapies, bacterial infections are increasingly likely to worsen due to AMR.”

Van Ranst issued a stark warning: “If this trend continues, it is entirely reasonable to predict that in 25 years, some antibiotics will become useless, certain bacterial infections will be much harder to treat, and deaths will outnumber those caused by cancer. It’s worth noting, however, that as cancer treatments improve, cancer-related deaths are expected to decline, further highlighting the growing burden of AMR-related fatalities.”

 

Viruses, Vaccines, and Resistance

Van Ranst emphasized that while AMR primarily involves bacteria, viral infections and vaccination against them also play a role in addressing the issue. “When vaccines prevent illness, they reduce the need for unnecessary antibiotic use. In the past, antibiotics were frequently prescribed for respiratory infections — typically caused by viruses — leading to misuse and heightened resistance. By preventing viral infections through vaccines, we reduce inappropriate antibiotic prescriptions and, subsequently, AMR.”

 

Strategic Areas of Focus

To maximize the impact of vaccination in combating AMR, Belgium must prioritize several strategic areas, according to EPIV-ULB. “Expanding vaccination coverage for recommended vaccines is crucial to effectively preventing the spread of resistant pathogens,” said Marchant.

“Innovation and development of new vaccines are also essential, including targeted research into vaccines for infections that are currently unavoidable through other means. Enhancing epidemiological surveillance through national data collection and analysis will further clarify the impact of vaccines on AMR and inform policy decisions.”

EPIV-ULB underscored the importance of educating the public and healthcare professionals. “Public awareness is essential to addressing vaccine hesitancy by providing clear information on the importance of prevention,” Marchant explained. “Healthcare professional training must also improve, encouraging preventive practices and judicious antibiotic use. Furthermore, additional research is necessary to fill data gaps and develop predictive models that can guide vaccine development in the future.”

 

Role of Vaccination

According to EPIV-ULB, Belgium needs a strengthened national strategy to address AMR effectively. “Complementary solutions are increasingly important as antimicrobials lose efficacy and treatments become more complex,” Marchant said. “Vaccination offers a proactive and effective preventive solution, directly and indirectly reducing the spread of resistant pathogens.”

Vaccines combat AMR through various mechanisms. “They prevent diseases such as pneumococcal pneumonia and meningitis, reducing the need for antibiotics to treat these infections,” Marchant explained. “Additionally, vaccination lowers inappropriate antibiotic use by preventing viral infections, reducing the risk of overprescribing antibiotics in cases where they are unnecessary. Lastly, herd immunity from vaccination slows the circulation of resistant pathogens, limiting their spread.”

Van Ranst urged healthcare professionals to prioritize vaccinating at-risk populations as identified by Belgium’s Superior Health Council. These include the elderly with underlying conditions and pregnant women, especially for influenza vaccines. University Hospitals Leuven in Belgium, also conducts annual vaccination campaigns for its staff, combining flu and COVID vaccines to increase uptake.

 

A Global Challenge

Marc Noppen, MD, PhD, director of University Hospital Brussels, Belgium, emphasized the complexity of AMR as a global issue. “The problem isn’t solely due to human antibiotic use; it also stems from veterinary medicine, plant breeding, and animal husbandry. This is a multifactorial, worldwide issue that requires public awareness. Improved vaccination strategies are one way to address AMR, particularly in this post-COVID era of heightened skepticism toward vaccines,” he explained.

Marie-Lise Verschelden from Pfizer highlighted the need for cooperation across the healthcare sector. “Belgium is fortunate to have a fantastic ecosystem of academics, clinicians, and industry experts. Collaboration, including government involvement, is critical to advancing our efforts. At Pfizer, we continue to develop new vaccines and technologies, and the COVID crisis has reinforced the critical role of vaccination in combating AMR. Through our vaccine portfolio and ongoing developments, we are well-positioned to contribute significantly to this global challenge.”

Elisabeth Van Damme from GSK reiterated that AMR is a global issue requiring joint efforts. “Existing vaccines are underutilized. Vaccination protects against certain infectious diseases, reducing the need for antibiotics. Antibiotics, in turn, are sometimes prescribed incorrectly, especially for viral infections they cannot treat. At GSK, we are already developing new vaccines to meet future needs.”

Vaccination remains a cornerstone in the fight against AMR. As pathogens grow increasingly resistant to antibiotics, coordinated efforts and innovative vaccine development are essential to mitigating this global health crisis.

 

This story was translated and adapted from MediQuality using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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Antimicrobial resistance (AMR) is globally recognized as one of the greatest health threats of the 21st century, responsible for 1.27 million deaths annually. “According to the WHO, if no measures are taken promptly, AMR could lead to more deaths than cancer by 2050,” Arnaud Marchant, MD, PhD, director of the European Plotkin Institute for Vaccinology at Université libre de Bruxelles (EPIV-ULB), Anderlecht, Belgium, said in an interview with MediQuality, part of the Medscape Professional Network. “This is a huge problem, and vaccination could be part of the solution.”

EPIV-ULB marked the start of the World AMR Awareness Week (November 18-24) with an event highlighting the critical role of vaccination to counter the rise for resistant pathogens. During the event, MediQuality interviewed Marchant, along with several other experts in the field.

 

Antibiotics Losing Effectiveness

Marc Van Ranst, PhD, virologist at Rega Institute KU Leuven in Leuven, Belgium, echoed Marchant’s concerns. He noted that “an increasing number of bacteria are becoming resistant to more antibiotics.” “While antibiotics were once miracle drugs, they have now stopped — or almost stopped — working against certain bacteria. Although we are discovering more effective therapies, bacterial infections are increasingly likely to worsen due to AMR.”

Van Ranst issued a stark warning: “If this trend continues, it is entirely reasonable to predict that in 25 years, some antibiotics will become useless, certain bacterial infections will be much harder to treat, and deaths will outnumber those caused by cancer. It’s worth noting, however, that as cancer treatments improve, cancer-related deaths are expected to decline, further highlighting the growing burden of AMR-related fatalities.”

 

Viruses, Vaccines, and Resistance

Van Ranst emphasized that while AMR primarily involves bacteria, viral infections and vaccination against them also play a role in addressing the issue. “When vaccines prevent illness, they reduce the need for unnecessary antibiotic use. In the past, antibiotics were frequently prescribed for respiratory infections — typically caused by viruses — leading to misuse and heightened resistance. By preventing viral infections through vaccines, we reduce inappropriate antibiotic prescriptions and, subsequently, AMR.”

 

Strategic Areas of Focus

To maximize the impact of vaccination in combating AMR, Belgium must prioritize several strategic areas, according to EPIV-ULB. “Expanding vaccination coverage for recommended vaccines is crucial to effectively preventing the spread of resistant pathogens,” said Marchant.

“Innovation and development of new vaccines are also essential, including targeted research into vaccines for infections that are currently unavoidable through other means. Enhancing epidemiological surveillance through national data collection and analysis will further clarify the impact of vaccines on AMR and inform policy decisions.”

EPIV-ULB underscored the importance of educating the public and healthcare professionals. “Public awareness is essential to addressing vaccine hesitancy by providing clear information on the importance of prevention,” Marchant explained. “Healthcare professional training must also improve, encouraging preventive practices and judicious antibiotic use. Furthermore, additional research is necessary to fill data gaps and develop predictive models that can guide vaccine development in the future.”

 

Role of Vaccination

According to EPIV-ULB, Belgium needs a strengthened national strategy to address AMR effectively. “Complementary solutions are increasingly important as antimicrobials lose efficacy and treatments become more complex,” Marchant said. “Vaccination offers a proactive and effective preventive solution, directly and indirectly reducing the spread of resistant pathogens.”

Vaccines combat AMR through various mechanisms. “They prevent diseases such as pneumococcal pneumonia and meningitis, reducing the need for antibiotics to treat these infections,” Marchant explained. “Additionally, vaccination lowers inappropriate antibiotic use by preventing viral infections, reducing the risk of overprescribing antibiotics in cases where they are unnecessary. Lastly, herd immunity from vaccination slows the circulation of resistant pathogens, limiting their spread.”

Van Ranst urged healthcare professionals to prioritize vaccinating at-risk populations as identified by Belgium’s Superior Health Council. These include the elderly with underlying conditions and pregnant women, especially for influenza vaccines. University Hospitals Leuven in Belgium, also conducts annual vaccination campaigns for its staff, combining flu and COVID vaccines to increase uptake.

 

A Global Challenge

Marc Noppen, MD, PhD, director of University Hospital Brussels, Belgium, emphasized the complexity of AMR as a global issue. “The problem isn’t solely due to human antibiotic use; it also stems from veterinary medicine, plant breeding, and animal husbandry. This is a multifactorial, worldwide issue that requires public awareness. Improved vaccination strategies are one way to address AMR, particularly in this post-COVID era of heightened skepticism toward vaccines,” he explained.

Marie-Lise Verschelden from Pfizer highlighted the need for cooperation across the healthcare sector. “Belgium is fortunate to have a fantastic ecosystem of academics, clinicians, and industry experts. Collaboration, including government involvement, is critical to advancing our efforts. At Pfizer, we continue to develop new vaccines and technologies, and the COVID crisis has reinforced the critical role of vaccination in combating AMR. Through our vaccine portfolio and ongoing developments, we are well-positioned to contribute significantly to this global challenge.”

Elisabeth Van Damme from GSK reiterated that AMR is a global issue requiring joint efforts. “Existing vaccines are underutilized. Vaccination protects against certain infectious diseases, reducing the need for antibiotics. Antibiotics, in turn, are sometimes prescribed incorrectly, especially for viral infections they cannot treat. At GSK, we are already developing new vaccines to meet future needs.”

Vaccination remains a cornerstone in the fight against AMR. As pathogens grow increasingly resistant to antibiotics, coordinated efforts and innovative vaccine development are essential to mitigating this global health crisis.

 

This story was translated and adapted from MediQuality using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Antimicrobial resistance (AMR) is globally recognized as one of the greatest health threats of the 21st century, responsible for 1.27 million deaths annually. “According to the WHO, if no measures are taken promptly, AMR could lead to more deaths than cancer by 2050,” Arnaud Marchant, MD, PhD, director of the European Plotkin Institute for Vaccinology at Université libre de Bruxelles (EPIV-ULB), Anderlecht, Belgium, said in an interview with MediQuality, part of the Medscape Professional Network. “This is a huge problem, and vaccination could be part of the solution.”

EPIV-ULB marked the start of the World AMR Awareness Week (November 18-24) with an event highlighting the critical role of vaccination to counter the rise for resistant pathogens. During the event, MediQuality interviewed Marchant, along with several other experts in the field.

 

Antibiotics Losing Effectiveness

Marc Van Ranst, PhD, virologist at Rega Institute KU Leuven in Leuven, Belgium, echoed Marchant’s concerns. He noted that “an increasing number of bacteria are becoming resistant to more antibiotics.” “While antibiotics were once miracle drugs, they have now stopped — or almost stopped — working against certain bacteria. Although we are discovering more effective therapies, bacterial infections are increasingly likely to worsen due to AMR.”

Van Ranst issued a stark warning: “If this trend continues, it is entirely reasonable to predict that in 25 years, some antibiotics will become useless, certain bacterial infections will be much harder to treat, and deaths will outnumber those caused by cancer. It’s worth noting, however, that as cancer treatments improve, cancer-related deaths are expected to decline, further highlighting the growing burden of AMR-related fatalities.”

 

Viruses, Vaccines, and Resistance

Van Ranst emphasized that while AMR primarily involves bacteria, viral infections and vaccination against them also play a role in addressing the issue. “When vaccines prevent illness, they reduce the need for unnecessary antibiotic use. In the past, antibiotics were frequently prescribed for respiratory infections — typically caused by viruses — leading to misuse and heightened resistance. By preventing viral infections through vaccines, we reduce inappropriate antibiotic prescriptions and, subsequently, AMR.”

 

Strategic Areas of Focus

To maximize the impact of vaccination in combating AMR, Belgium must prioritize several strategic areas, according to EPIV-ULB. “Expanding vaccination coverage for recommended vaccines is crucial to effectively preventing the spread of resistant pathogens,” said Marchant.

“Innovation and development of new vaccines are also essential, including targeted research into vaccines for infections that are currently unavoidable through other means. Enhancing epidemiological surveillance through national data collection and analysis will further clarify the impact of vaccines on AMR and inform policy decisions.”

EPIV-ULB underscored the importance of educating the public and healthcare professionals. “Public awareness is essential to addressing vaccine hesitancy by providing clear information on the importance of prevention,” Marchant explained. “Healthcare professional training must also improve, encouraging preventive practices and judicious antibiotic use. Furthermore, additional research is necessary to fill data gaps and develop predictive models that can guide vaccine development in the future.”

 

Role of Vaccination

According to EPIV-ULB, Belgium needs a strengthened national strategy to address AMR effectively. “Complementary solutions are increasingly important as antimicrobials lose efficacy and treatments become more complex,” Marchant said. “Vaccination offers a proactive and effective preventive solution, directly and indirectly reducing the spread of resistant pathogens.”

Vaccines combat AMR through various mechanisms. “They prevent diseases such as pneumococcal pneumonia and meningitis, reducing the need for antibiotics to treat these infections,” Marchant explained. “Additionally, vaccination lowers inappropriate antibiotic use by preventing viral infections, reducing the risk of overprescribing antibiotics in cases where they are unnecessary. Lastly, herd immunity from vaccination slows the circulation of resistant pathogens, limiting their spread.”

Van Ranst urged healthcare professionals to prioritize vaccinating at-risk populations as identified by Belgium’s Superior Health Council. These include the elderly with underlying conditions and pregnant women, especially for influenza vaccines. University Hospitals Leuven in Belgium, also conducts annual vaccination campaigns for its staff, combining flu and COVID vaccines to increase uptake.

 

A Global Challenge

Marc Noppen, MD, PhD, director of University Hospital Brussels, Belgium, emphasized the complexity of AMR as a global issue. “The problem isn’t solely due to human antibiotic use; it also stems from veterinary medicine, plant breeding, and animal husbandry. This is a multifactorial, worldwide issue that requires public awareness. Improved vaccination strategies are one way to address AMR, particularly in this post-COVID era of heightened skepticism toward vaccines,” he explained.

Marie-Lise Verschelden from Pfizer highlighted the need for cooperation across the healthcare sector. “Belgium is fortunate to have a fantastic ecosystem of academics, clinicians, and industry experts. Collaboration, including government involvement, is critical to advancing our efforts. At Pfizer, we continue to develop new vaccines and technologies, and the COVID crisis has reinforced the critical role of vaccination in combating AMR. Through our vaccine portfolio and ongoing developments, we are well-positioned to contribute significantly to this global challenge.”

Elisabeth Van Damme from GSK reiterated that AMR is a global issue requiring joint efforts. “Existing vaccines are underutilized. Vaccination protects against certain infectious diseases, reducing the need for antibiotics. Antibiotics, in turn, are sometimes prescribed incorrectly, especially for viral infections they cannot treat. At GSK, we are already developing new vaccines to meet future needs.”

Vaccination remains a cornerstone in the fight against AMR. As pathogens grow increasingly resistant to antibiotics, coordinated efforts and innovative vaccine development are essential to mitigating this global health crisis.

 

This story was translated and adapted from MediQuality using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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New Strategy Led to Modest Decline in Antibiotic Misuse

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TOPLINE:

Multifaceted antimicrobial stewardship interventions show varying effectiveness and modest reductions in unnecessary antibiotic prescriptions, particularly in general practice. 

METHODOLOGY:

  • Researchers conducted this study to assess the impact of an intervention on antibiotic prescribing and dispensing for common infections.
  • Healthcare professionals from general practice, out-of-hours services, nursing homes, and community pharmacies in France, Greece, Lithuania, Poland, and Spain registered their interactions with patients related to antibiotic prescribing and dispensing both prior to and following the intervention.
  • Overall, 407 healthcare professionals participated in the first registration, of whom 345 undertook the intervention and participated in the second registration; they documented 10,744 infections during the initial registration and 10,132 cases during the second period.
  • The 5-hour intervention included evaluating and discussing feedback on the outcomes of the initial registration, improving communication skills, and offering communication tools.
  • The impact of this intervention was calculated from potential unnecessary antibiotic prescriptions, non–first-line antibiotic choices, and percentage of good and wrong safety advice given for each prescription.

TAKEAWAY:

  • General practice clinicians showed a significant overall reduction in unnecessary antibiotic prescriptions from 72.2% during the first registration to 65.2% after the intervention (P < .001), with variations across countries ranging from a 19.9% reduction in Lithuania to a 1.3% increase in Greece.
  • Out-of-hours services showed a minimal change in unnecessary antibiotic prescribing from 52.5% to 52.1%, whereas nursing homes showed a slight increase from 56.1% to 58.6%.
  • Community pharmacies showed significant improvements, with the provision of correct advice increasing by 17% (P < .001) and safety checks improving from 47% to 55.3% in 1 year (P < .001).
  • However, the choice of non–first-line antibiotics significantly increased by 29.2% in the second registration period (P < .001).

IN PRACTICE:

“These findings highlight the need for alternative and tailored approaches in antimicrobial stewardship programs in long-term care facilities, with a greater focus on nurses. This includes implementing hygiene measures and empowering nurses to improve the diagnosis of suspected infections, such as urinary tract infections, while debunking prevalent myths and providing clear-cut information for better management of these common infections,” the authors wrote.

SOURCE:

The study was led by Ana García-Sangenís, of Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina, Barcelona, Spain, and was published online on November 12, 2024, in Family Practice.

LIMITATIONS:

The study lacked a control group, which limited the ability to attribute changes solely to the intervention. The voluntary participation of healthcare professionals might have introduced selection bias, as participants might have had a greater interest in quality improvement programs than the general population of healthcare providers. Clinical outcomes were not evaluated, which may have created ambiguity regarding whether complication rates or clinical failures varied between the groups.

DISCLOSURES:

This study received funding from the European Union’s Third Health Programme. One author reported receiving fees from pharmaceutical companies and acting as a member of the board of Steno Diabetes Center, Odense, Denmark.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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TOPLINE:

Multifaceted antimicrobial stewardship interventions show varying effectiveness and modest reductions in unnecessary antibiotic prescriptions, particularly in general practice. 

METHODOLOGY:

  • Researchers conducted this study to assess the impact of an intervention on antibiotic prescribing and dispensing for common infections.
  • Healthcare professionals from general practice, out-of-hours services, nursing homes, and community pharmacies in France, Greece, Lithuania, Poland, and Spain registered their interactions with patients related to antibiotic prescribing and dispensing both prior to and following the intervention.
  • Overall, 407 healthcare professionals participated in the first registration, of whom 345 undertook the intervention and participated in the second registration; they documented 10,744 infections during the initial registration and 10,132 cases during the second period.
  • The 5-hour intervention included evaluating and discussing feedback on the outcomes of the initial registration, improving communication skills, and offering communication tools.
  • The impact of this intervention was calculated from potential unnecessary antibiotic prescriptions, non–first-line antibiotic choices, and percentage of good and wrong safety advice given for each prescription.

TAKEAWAY:

  • General practice clinicians showed a significant overall reduction in unnecessary antibiotic prescriptions from 72.2% during the first registration to 65.2% after the intervention (P < .001), with variations across countries ranging from a 19.9% reduction in Lithuania to a 1.3% increase in Greece.
  • Out-of-hours services showed a minimal change in unnecessary antibiotic prescribing from 52.5% to 52.1%, whereas nursing homes showed a slight increase from 56.1% to 58.6%.
  • Community pharmacies showed significant improvements, with the provision of correct advice increasing by 17% (P < .001) and safety checks improving from 47% to 55.3% in 1 year (P < .001).
  • However, the choice of non–first-line antibiotics significantly increased by 29.2% in the second registration period (P < .001).

IN PRACTICE:

“These findings highlight the need for alternative and tailored approaches in antimicrobial stewardship programs in long-term care facilities, with a greater focus on nurses. This includes implementing hygiene measures and empowering nurses to improve the diagnosis of suspected infections, such as urinary tract infections, while debunking prevalent myths and providing clear-cut information for better management of these common infections,” the authors wrote.

SOURCE:

The study was led by Ana García-Sangenís, of Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina, Barcelona, Spain, and was published online on November 12, 2024, in Family Practice.

LIMITATIONS:

The study lacked a control group, which limited the ability to attribute changes solely to the intervention. The voluntary participation of healthcare professionals might have introduced selection bias, as participants might have had a greater interest in quality improvement programs than the general population of healthcare providers. Clinical outcomes were not evaluated, which may have created ambiguity regarding whether complication rates or clinical failures varied between the groups.

DISCLOSURES:

This study received funding from the European Union’s Third Health Programme. One author reported receiving fees from pharmaceutical companies and acting as a member of the board of Steno Diabetes Center, Odense, Denmark.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Multifaceted antimicrobial stewardship interventions show varying effectiveness and modest reductions in unnecessary antibiotic prescriptions, particularly in general practice. 

METHODOLOGY:

  • Researchers conducted this study to assess the impact of an intervention on antibiotic prescribing and dispensing for common infections.
  • Healthcare professionals from general practice, out-of-hours services, nursing homes, and community pharmacies in France, Greece, Lithuania, Poland, and Spain registered their interactions with patients related to antibiotic prescribing and dispensing both prior to and following the intervention.
  • Overall, 407 healthcare professionals participated in the first registration, of whom 345 undertook the intervention and participated in the second registration; they documented 10,744 infections during the initial registration and 10,132 cases during the second period.
  • The 5-hour intervention included evaluating and discussing feedback on the outcomes of the initial registration, improving communication skills, and offering communication tools.
  • The impact of this intervention was calculated from potential unnecessary antibiotic prescriptions, non–first-line antibiotic choices, and percentage of good and wrong safety advice given for each prescription.

TAKEAWAY:

  • General practice clinicians showed a significant overall reduction in unnecessary antibiotic prescriptions from 72.2% during the first registration to 65.2% after the intervention (P < .001), with variations across countries ranging from a 19.9% reduction in Lithuania to a 1.3% increase in Greece.
  • Out-of-hours services showed a minimal change in unnecessary antibiotic prescribing from 52.5% to 52.1%, whereas nursing homes showed a slight increase from 56.1% to 58.6%.
  • Community pharmacies showed significant improvements, with the provision of correct advice increasing by 17% (P < .001) and safety checks improving from 47% to 55.3% in 1 year (P < .001).
  • However, the choice of non–first-line antibiotics significantly increased by 29.2% in the second registration period (P < .001).

IN PRACTICE:

“These findings highlight the need for alternative and tailored approaches in antimicrobial stewardship programs in long-term care facilities, with a greater focus on nurses. This includes implementing hygiene measures and empowering nurses to improve the diagnosis of suspected infections, such as urinary tract infections, while debunking prevalent myths and providing clear-cut information for better management of these common infections,” the authors wrote.

SOURCE:

The study was led by Ana García-Sangenís, of Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina, Barcelona, Spain, and was published online on November 12, 2024, in Family Practice.

LIMITATIONS:

The study lacked a control group, which limited the ability to attribute changes solely to the intervention. The voluntary participation of healthcare professionals might have introduced selection bias, as participants might have had a greater interest in quality improvement programs than the general population of healthcare providers. Clinical outcomes were not evaluated, which may have created ambiguity regarding whether complication rates or clinical failures varied between the groups.

DISCLOSURES:

This study received funding from the European Union’s Third Health Programme. One author reported receiving fees from pharmaceutical companies and acting as a member of the board of Steno Diabetes Center, Odense, Denmark.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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Does Antibiotic Use During Influenza Infection Worsen Lung Immunity?

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TOPLINE:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

  • Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycinampicillin, and metronidazole) starting 7 days before influenza infection.
  • The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
  • Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
  • Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

  • Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
  • The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
  • The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
  • In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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TOPLINE:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

  • Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycinampicillin, and metronidazole) starting 7 days before influenza infection.
  • The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
  • Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
  • Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

  • Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
  • The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
  • The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
  • In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

  • Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycinampicillin, and metronidazole) starting 7 days before influenza infection.
  • The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
  • Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
  • Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

  • Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
  • The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
  • The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
  • In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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New mRNA Vaccine May Shield Against C difficile Infections

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New mRNA Vaccine May Shield Against C difficile Infections

A group of researchers from the University of Pennsylvania, Philadelphia, has developed a messenger RNA (mRNA) vaccine, delivered via lipid nanoparticles (LNPs) — the same type as the COVID-19 vaccine produced by Moderna and Pfizer — targeting Clostridioides difficile (formerly Clostridium difficile). According to the authors, the results of their preclinical studypublished in Science, demonstrated this technology as a promising platform for C difficile vaccine development and could be the starting point for curbing intestinal infections that, in their most severe forms (pseudomembranous colitistoxic megacolon), can be fatal.

An Increasingly Pressing Issue

C difficile is the leading cause of infectious diarrhea acquired in healthcare settings. In recent years, community-acquired C difficile infections have also become more frequent. The increase in infections has been attributed to the emergence of highly virulent and antibiotic-resistant strains.

2019 study reported a global incidence of C difficile infections at 2.2 per 1000 hospital admissions per year and 3.5 per 10,000 patient-days per year.
 

The Vaccine Candidate

Vaccine candidates tested so far have used toxoids or recombinant proteins targeting the combined repetitive oligopeptide (CROP) or receptor-binding domain (RBD) of the two primary C difficile toxins, TcdA and TcdB. The US researchers are now exploring the mRNA-LNP vaccine approach to target multiple antigens simultaneously. They developed a bivalent vaccine (including the CROP and RBD domains of both toxins) and a trivalent vaccine (with an additional virulence factor, the metalloprotease Pro-Pro endopeptidase-1).

Mice vaccinated with the bivalent and trivalent vaccines produced immunoglobulin G antibody titers two to four times higher than those elicited by recombinant protein with an adjuvant. The vaccination stimulated the proliferation of follicular T helper cells and the antigen-specific response of B lymphocytes, laying the foundation for a strong and long-lasting humoral response. The vaccines were also immunogenic in hamsters.

Vaccinated mice not only survived a toxin dose five times higher than the 100% lethal dose but also demonstrated the vaccine’s protective effect through serum transfer; unvaccinated mice given serum from vaccinated mice survived the lethal challenge. More importantly, when exposed to a lethal dose of the bacterium itself, all vaccinated mice survived.

To demonstrate the vaccine’s efficacy in patients with a history of C difficile infection and high recurrence risk — ideal candidates for vaccination — the researchers vaccinated mice that had previously survived a sublethal infection. Six months after the initial infection and vaccination, these mice remained protected against mortality when reexposed to the bacterium.

Additionally, a quadrivalent vaccine that included an immunogen targeting C difficile spores — key agents in transmission — also proved effective. Low levels of bacteria and toxins in the feces of mice vaccinated in this way suggested that spore vaccination could limit initial colonization.

In tests with nonhuman primates, two doses of the vaccines targeting either the vegetative form or the spores elicited strong immune responses against bacterial toxins and virulence factors. Human trials may indeed be on the horizon.
 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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A group of researchers from the University of Pennsylvania, Philadelphia, has developed a messenger RNA (mRNA) vaccine, delivered via lipid nanoparticles (LNPs) — the same type as the COVID-19 vaccine produced by Moderna and Pfizer — targeting Clostridioides difficile (formerly Clostridium difficile). According to the authors, the results of their preclinical studypublished in Science, demonstrated this technology as a promising platform for C difficile vaccine development and could be the starting point for curbing intestinal infections that, in their most severe forms (pseudomembranous colitistoxic megacolon), can be fatal.

An Increasingly Pressing Issue

C difficile is the leading cause of infectious diarrhea acquired in healthcare settings. In recent years, community-acquired C difficile infections have also become more frequent. The increase in infections has been attributed to the emergence of highly virulent and antibiotic-resistant strains.

2019 study reported a global incidence of C difficile infections at 2.2 per 1000 hospital admissions per year and 3.5 per 10,000 patient-days per year.
 

The Vaccine Candidate

Vaccine candidates tested so far have used toxoids or recombinant proteins targeting the combined repetitive oligopeptide (CROP) or receptor-binding domain (RBD) of the two primary C difficile toxins, TcdA and TcdB. The US researchers are now exploring the mRNA-LNP vaccine approach to target multiple antigens simultaneously. They developed a bivalent vaccine (including the CROP and RBD domains of both toxins) and a trivalent vaccine (with an additional virulence factor, the metalloprotease Pro-Pro endopeptidase-1).

Mice vaccinated with the bivalent and trivalent vaccines produced immunoglobulin G antibody titers two to four times higher than those elicited by recombinant protein with an adjuvant. The vaccination stimulated the proliferation of follicular T helper cells and the antigen-specific response of B lymphocytes, laying the foundation for a strong and long-lasting humoral response. The vaccines were also immunogenic in hamsters.

Vaccinated mice not only survived a toxin dose five times higher than the 100% lethal dose but also demonstrated the vaccine’s protective effect through serum transfer; unvaccinated mice given serum from vaccinated mice survived the lethal challenge. More importantly, when exposed to a lethal dose of the bacterium itself, all vaccinated mice survived.

To demonstrate the vaccine’s efficacy in patients with a history of C difficile infection and high recurrence risk — ideal candidates for vaccination — the researchers vaccinated mice that had previously survived a sublethal infection. Six months after the initial infection and vaccination, these mice remained protected against mortality when reexposed to the bacterium.

Additionally, a quadrivalent vaccine that included an immunogen targeting C difficile spores — key agents in transmission — also proved effective. Low levels of bacteria and toxins in the feces of mice vaccinated in this way suggested that spore vaccination could limit initial colonization.

In tests with nonhuman primates, two doses of the vaccines targeting either the vegetative form or the spores elicited strong immune responses against bacterial toxins and virulence factors. Human trials may indeed be on the horizon.
 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A group of researchers from the University of Pennsylvania, Philadelphia, has developed a messenger RNA (mRNA) vaccine, delivered via lipid nanoparticles (LNPs) — the same type as the COVID-19 vaccine produced by Moderna and Pfizer — targeting Clostridioides difficile (formerly Clostridium difficile). According to the authors, the results of their preclinical studypublished in Science, demonstrated this technology as a promising platform for C difficile vaccine development and could be the starting point for curbing intestinal infections that, in their most severe forms (pseudomembranous colitistoxic megacolon), can be fatal.

An Increasingly Pressing Issue

C difficile is the leading cause of infectious diarrhea acquired in healthcare settings. In recent years, community-acquired C difficile infections have also become more frequent. The increase in infections has been attributed to the emergence of highly virulent and antibiotic-resistant strains.

2019 study reported a global incidence of C difficile infections at 2.2 per 1000 hospital admissions per year and 3.5 per 10,000 patient-days per year.
 

The Vaccine Candidate

Vaccine candidates tested so far have used toxoids or recombinant proteins targeting the combined repetitive oligopeptide (CROP) or receptor-binding domain (RBD) of the two primary C difficile toxins, TcdA and TcdB. The US researchers are now exploring the mRNA-LNP vaccine approach to target multiple antigens simultaneously. They developed a bivalent vaccine (including the CROP and RBD domains of both toxins) and a trivalent vaccine (with an additional virulence factor, the metalloprotease Pro-Pro endopeptidase-1).

Mice vaccinated with the bivalent and trivalent vaccines produced immunoglobulin G antibody titers two to four times higher than those elicited by recombinant protein with an adjuvant. The vaccination stimulated the proliferation of follicular T helper cells and the antigen-specific response of B lymphocytes, laying the foundation for a strong and long-lasting humoral response. The vaccines were also immunogenic in hamsters.

Vaccinated mice not only survived a toxin dose five times higher than the 100% lethal dose but also demonstrated the vaccine’s protective effect through serum transfer; unvaccinated mice given serum from vaccinated mice survived the lethal challenge. More importantly, when exposed to a lethal dose of the bacterium itself, all vaccinated mice survived.

To demonstrate the vaccine’s efficacy in patients with a history of C difficile infection and high recurrence risk — ideal candidates for vaccination — the researchers vaccinated mice that had previously survived a sublethal infection. Six months after the initial infection and vaccination, these mice remained protected against mortality when reexposed to the bacterium.

Additionally, a quadrivalent vaccine that included an immunogen targeting C difficile spores — key agents in transmission — also proved effective. Low levels of bacteria and toxins in the feces of mice vaccinated in this way suggested that spore vaccination could limit initial colonization.

In tests with nonhuman primates, two doses of the vaccines targeting either the vegetative form or the spores elicited strong immune responses against bacterial toxins and virulence factors. Human trials may indeed be on the horizon.
 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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Could a Virus Reverse Antibiotic Resistance?

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Peering through his microscope in 1910, Franco-Canadian microbiologist Félix d’Hérelle noticed some “clear spots” in his bacterial cultures, an anomaly that turned out to be viruses preying on the bacteria. Years later, Mr. d’Hérelle would come to use these viruses, which he called bacteriophages, to treat patients plagued with dysentery after World War I.

In the decades that followed, Mr. d’Hérelle and others used this phage therapy to treat bubonic plague and other bacterial infections until the technique fell into disuse after the widespread adoption of antibiotics in the 1940s.

But now, with bacteria evolving resistance to more and more antibiotics, phage therapy is drawing a second look from researchers — sometimes with a novel twist. Instead of simply using the phages to kill bacteria directly, the new strategy aims to catch the bacteria in an evolutionary dilemma — one in which they cannot evade phages and antibiotics simultaneously.

This plan, which uses something called “phage steering,” has shown promising results in initial tests, but the scope of its usefulness remains to be proven.

There’s certainly need to find new ways to respond to bacterial infections. More than 70% of hospital-acquired bacterial infections in the United States are resistant to at least one type of antibiotic. And some pathogens, such as AcinetobacterPseudomonas, Escherichia coli, and Klebsiella — classified by the World Health Organization as some of the biggest threats to human health — are resistant to multiple antibiotics. In 2019, antibacterial resistance was linked to 4.95 million deaths globally, heightening the call for more effective treatment options.

One of the ways that bacteria can evolve resistance to antibiotics is by using structures in their membranes that are designed to move unwanted molecules out of the cell. By modifying these “efflux pumps” to recognize the antibiotic, bacteria can eliminate the drug before it poisons them.

As it turns out, some phages appear to use these same efflux pumps to invade the bacterial cell. The phage presumably attaches its tail to the outer portion of the pump protein, like a key slipping into a lock, and then injects its genetic material into the cell. This lucky coincidence led Paul Turner, PhD, an evolutionary biologist at Yale University, New Haven, Connecticut, to suggest that treating a patient with phages and antibiotics simultaneously could trap bacteria in a no-win situation: If they evolve to modify their efflux pumps so the phage can’t bind, the pumps will no longer expel antibiotics, and the bacteria will lose their resistance. But if they retain their antibiotic resistance, the phages will kill them, as Dr. Turner and colleagues explained in the 2023 Annual Review of Virology.

The result, in other words, is a two-pronged attack, said Michael Hochberg, PhD, an evolutionary biologist at the French National Centre for Scientific Research who studies how to prevent the evolution of bacterial resistance. “It’s kind of like a crisscross effect.” The same principle can target other bacterial molecules that play a dual role in resistance to viruses and antibiotics.

Turner tested this hypothesis on multidrug-resistant Pseudomonas aeruginosa, which causes dangerous infections, especially in healthcare settings. This bacterium has four efflux pumps involved in antibiotic resistance, and Dr. Turner predicted that if he could find a phage that used one of the pumps as a way into the cell, the bacterium would be forced to slam the door on the phage by mutating the receptor — thereby impeding its ability to pump out antibiotics.

Sampling from the environment, Dr. Turner’s team collected 42 phage strains that infect P aeruginosa. Out of all the phages, one, OMKO1, bound to an efflux pump, making it the perfect candidate for the experiment.

The researchers then cultured antibiotic-resistant P aeruginosa together with OMKO1, hoping this would force the bacterium to modify its efflux pump to resist the phage. They exposed these phage-resistant bacteria, as well as their normal, phage-sensitive counterparts, to four antibiotics the bacteria had been resistant to: tetracycline, erythromycin, ciprofloxacin, and ceftazidime.

As the theory predicted, the bacteria that had evolved resistance to the phage were more sensitive to the antibiotics than those that had not been exposed to the phage. This suggests that the bacteria had, indeed, been forced to lose their antibiotic resistance through their need to fight off the phage.

Other researchers have also shown that phage steering can resensitize bacteria to common antibiotics they’d become resistant to. One study, by an international research team, showed that a phage called Phab24 can be used to restore sensitivity to the antibiotic colistin in Acinetobacter baumannii, which causes life-threatening diseases.

In a second study, researchers at Monash University in Australia sampled infectious bacteria from patients. They found that several phages, including strains known as phi-FG02 and phi-CO01, were already present in some of the samples, and that A baumannii bacteria exposed to the phages had inactivated a gene that helps create the microbe’s important outer layer, or capsule. This layer serves as the entry point for the phages, but it also helps the bacterium to form biofilms that keep out antibiotics — so removing the layer rendered A baumannii susceptible to several antibiotics that it was previously resistant to.

In a third study, researchers from the University of Liverpool discovered that, when a P aeruginosa strain that was resistant to all antibiotics was exposed to phages, the bacterium became sensitive to two antibiotics that were otherwise considered ineffective against P aeruginosa.

Dr. Turner’s team has used phage steering in dozens of cases of personalized therapy in clinical settings, said Benjamin Chan, PhD, a microbiologist at Yale University who works with Dr. Turner. The results, many still unpublished, have been promising so far. Nonrespiratory infections are relatively easy to clear off, and lung infections, which the phage steering approach wouldn’t be expected to eradicate completely, often show some improvement.

“I would say that we have been quite successful in using phage steering to treat difficult-to-manage infections, reducing antimicrobial resistance in many cases,” he said. But he notes that it is sometimes difficult to determine whether phage steering really was responsible for the cures.
 

Devil in the details

Phage therapy may not work for all antibiotic-resistant bacteria, said molecular biologist Graham Hatfull, PhD, of the University of Pittsburgh in Pennsylvania. That’s because phages are very host specific, and for most phages, no one knows what target they bind to on the bacterial cell surface. For phage steering to work against antibiotic resistance, the phage has to bind to a molecule that’s involved in that resistance — and it’s not clear how often that fortuitous coincidence occurs.

Jason Gill, PhD, who studies bacteriophage biology at Texas A&M University, College Station, said that it is not easy to predict if a phage will induce antibiotic sensitivity. So you always have to hunt for the right virus each time.

Dr. Gill knows from experience how complicated the approach can get. He was part of a team of researchers and doctors who used phages to treat a patient with a multidrug-resistant A baumannii infection. Less than 4 days after the team administered phages intravenously and through the skin, the patient woke up from a coma and became responsive to the previously ineffective antibiotic minocycline — a striking success.

But when Dr. Gill tried a similar experiment in cell cultures, he got a different result. The A baumannii developed resistance to the phages, but they also maintained their resistance to minocycline. “There’s not a complete mechanistic understanding,” said Dr. Gill. “The linkage between phage resistance and antibiotic sensitivity probably varies by bacterial strain, phage and antibiotic.” That means phage steering may not always work.

Dr. Turner, for his part, pointed out another potential problem: That phages could work too well. If phage therapy kills large amounts of bacteria and deposits their remains in the bloodstream quickly, for example, this could trigger septic shock in patients. Scientists do not yet know how to address this problem.

Another concern is that doctors have less precise control over phages than antibiotics. “Phages can mutate, they can adapt, they have a genome,” said Dr. Hochberg. Safety concerns, he notes, are one factor inhibiting the routine use of phage therapy in countries like the United States, restricting it to case-by-case applications such as Dr. Turner and Dr. Chan’s.

Phage therapy may have been too high-tech for the 1940s, and even today, scientists grapple with how to use it. What we need now, said Dr. Turner, are rigorous experiments that will teach us how to make it work.

This article originally appeared in Knowable Magazine on September 09, 2024. Knowable Magazine is an independent journalistic endeavor from Annual Reviews, a nonprofit publisher dedicated to synthesizing and integrating knowledge for the progress of science and the benefit of society. Sign up for Knowable Magazine’s newsletter. A version of this article appeared on Medscape.com.

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Peering through his microscope in 1910, Franco-Canadian microbiologist Félix d’Hérelle noticed some “clear spots” in his bacterial cultures, an anomaly that turned out to be viruses preying on the bacteria. Years later, Mr. d’Hérelle would come to use these viruses, which he called bacteriophages, to treat patients plagued with dysentery after World War I.

In the decades that followed, Mr. d’Hérelle and others used this phage therapy to treat bubonic plague and other bacterial infections until the technique fell into disuse after the widespread adoption of antibiotics in the 1940s.

But now, with bacteria evolving resistance to more and more antibiotics, phage therapy is drawing a second look from researchers — sometimes with a novel twist. Instead of simply using the phages to kill bacteria directly, the new strategy aims to catch the bacteria in an evolutionary dilemma — one in which they cannot evade phages and antibiotics simultaneously.

This plan, which uses something called “phage steering,” has shown promising results in initial tests, but the scope of its usefulness remains to be proven.

There’s certainly need to find new ways to respond to bacterial infections. More than 70% of hospital-acquired bacterial infections in the United States are resistant to at least one type of antibiotic. And some pathogens, such as AcinetobacterPseudomonas, Escherichia coli, and Klebsiella — classified by the World Health Organization as some of the biggest threats to human health — are resistant to multiple antibiotics. In 2019, antibacterial resistance was linked to 4.95 million deaths globally, heightening the call for more effective treatment options.

One of the ways that bacteria can evolve resistance to antibiotics is by using structures in their membranes that are designed to move unwanted molecules out of the cell. By modifying these “efflux pumps” to recognize the antibiotic, bacteria can eliminate the drug before it poisons them.

As it turns out, some phages appear to use these same efflux pumps to invade the bacterial cell. The phage presumably attaches its tail to the outer portion of the pump protein, like a key slipping into a lock, and then injects its genetic material into the cell. This lucky coincidence led Paul Turner, PhD, an evolutionary biologist at Yale University, New Haven, Connecticut, to suggest that treating a patient with phages and antibiotics simultaneously could trap bacteria in a no-win situation: If they evolve to modify their efflux pumps so the phage can’t bind, the pumps will no longer expel antibiotics, and the bacteria will lose their resistance. But if they retain their antibiotic resistance, the phages will kill them, as Dr. Turner and colleagues explained in the 2023 Annual Review of Virology.

The result, in other words, is a two-pronged attack, said Michael Hochberg, PhD, an evolutionary biologist at the French National Centre for Scientific Research who studies how to prevent the evolution of bacterial resistance. “It’s kind of like a crisscross effect.” The same principle can target other bacterial molecules that play a dual role in resistance to viruses and antibiotics.

Turner tested this hypothesis on multidrug-resistant Pseudomonas aeruginosa, which causes dangerous infections, especially in healthcare settings. This bacterium has four efflux pumps involved in antibiotic resistance, and Dr. Turner predicted that if he could find a phage that used one of the pumps as a way into the cell, the bacterium would be forced to slam the door on the phage by mutating the receptor — thereby impeding its ability to pump out antibiotics.

Sampling from the environment, Dr. Turner’s team collected 42 phage strains that infect P aeruginosa. Out of all the phages, one, OMKO1, bound to an efflux pump, making it the perfect candidate for the experiment.

The researchers then cultured antibiotic-resistant P aeruginosa together with OMKO1, hoping this would force the bacterium to modify its efflux pump to resist the phage. They exposed these phage-resistant bacteria, as well as their normal, phage-sensitive counterparts, to four antibiotics the bacteria had been resistant to: tetracycline, erythromycin, ciprofloxacin, and ceftazidime.

As the theory predicted, the bacteria that had evolved resistance to the phage were more sensitive to the antibiotics than those that had not been exposed to the phage. This suggests that the bacteria had, indeed, been forced to lose their antibiotic resistance through their need to fight off the phage.

Other researchers have also shown that phage steering can resensitize bacteria to common antibiotics they’d become resistant to. One study, by an international research team, showed that a phage called Phab24 can be used to restore sensitivity to the antibiotic colistin in Acinetobacter baumannii, which causes life-threatening diseases.

In a second study, researchers at Monash University in Australia sampled infectious bacteria from patients. They found that several phages, including strains known as phi-FG02 and phi-CO01, were already present in some of the samples, and that A baumannii bacteria exposed to the phages had inactivated a gene that helps create the microbe’s important outer layer, or capsule. This layer serves as the entry point for the phages, but it also helps the bacterium to form biofilms that keep out antibiotics — so removing the layer rendered A baumannii susceptible to several antibiotics that it was previously resistant to.

In a third study, researchers from the University of Liverpool discovered that, when a P aeruginosa strain that was resistant to all antibiotics was exposed to phages, the bacterium became sensitive to two antibiotics that were otherwise considered ineffective against P aeruginosa.

Dr. Turner’s team has used phage steering in dozens of cases of personalized therapy in clinical settings, said Benjamin Chan, PhD, a microbiologist at Yale University who works with Dr. Turner. The results, many still unpublished, have been promising so far. Nonrespiratory infections are relatively easy to clear off, and lung infections, which the phage steering approach wouldn’t be expected to eradicate completely, often show some improvement.

“I would say that we have been quite successful in using phage steering to treat difficult-to-manage infections, reducing antimicrobial resistance in many cases,” he said. But he notes that it is sometimes difficult to determine whether phage steering really was responsible for the cures.
 

Devil in the details

Phage therapy may not work for all antibiotic-resistant bacteria, said molecular biologist Graham Hatfull, PhD, of the University of Pittsburgh in Pennsylvania. That’s because phages are very host specific, and for most phages, no one knows what target they bind to on the bacterial cell surface. For phage steering to work against antibiotic resistance, the phage has to bind to a molecule that’s involved in that resistance — and it’s not clear how often that fortuitous coincidence occurs.

Jason Gill, PhD, who studies bacteriophage biology at Texas A&M University, College Station, said that it is not easy to predict if a phage will induce antibiotic sensitivity. So you always have to hunt for the right virus each time.

Dr. Gill knows from experience how complicated the approach can get. He was part of a team of researchers and doctors who used phages to treat a patient with a multidrug-resistant A baumannii infection. Less than 4 days after the team administered phages intravenously and through the skin, the patient woke up from a coma and became responsive to the previously ineffective antibiotic minocycline — a striking success.

But when Dr. Gill tried a similar experiment in cell cultures, he got a different result. The A baumannii developed resistance to the phages, but they also maintained their resistance to minocycline. “There’s not a complete mechanistic understanding,” said Dr. Gill. “The linkage between phage resistance and antibiotic sensitivity probably varies by bacterial strain, phage and antibiotic.” That means phage steering may not always work.

Dr. Turner, for his part, pointed out another potential problem: That phages could work too well. If phage therapy kills large amounts of bacteria and deposits their remains in the bloodstream quickly, for example, this could trigger septic shock in patients. Scientists do not yet know how to address this problem.

Another concern is that doctors have less precise control over phages than antibiotics. “Phages can mutate, they can adapt, they have a genome,” said Dr. Hochberg. Safety concerns, he notes, are one factor inhibiting the routine use of phage therapy in countries like the United States, restricting it to case-by-case applications such as Dr. Turner and Dr. Chan’s.

Phage therapy may have been too high-tech for the 1940s, and even today, scientists grapple with how to use it. What we need now, said Dr. Turner, are rigorous experiments that will teach us how to make it work.

This article originally appeared in Knowable Magazine on September 09, 2024. Knowable Magazine is an independent journalistic endeavor from Annual Reviews, a nonprofit publisher dedicated to synthesizing and integrating knowledge for the progress of science and the benefit of society. Sign up for Knowable Magazine’s newsletter. A version of this article appeared on Medscape.com.

 

Peering through his microscope in 1910, Franco-Canadian microbiologist Félix d’Hérelle noticed some “clear spots” in his bacterial cultures, an anomaly that turned out to be viruses preying on the bacteria. Years later, Mr. d’Hérelle would come to use these viruses, which he called bacteriophages, to treat patients plagued with dysentery after World War I.

In the decades that followed, Mr. d’Hérelle and others used this phage therapy to treat bubonic plague and other bacterial infections until the technique fell into disuse after the widespread adoption of antibiotics in the 1940s.

But now, with bacteria evolving resistance to more and more antibiotics, phage therapy is drawing a second look from researchers — sometimes with a novel twist. Instead of simply using the phages to kill bacteria directly, the new strategy aims to catch the bacteria in an evolutionary dilemma — one in which they cannot evade phages and antibiotics simultaneously.

This plan, which uses something called “phage steering,” has shown promising results in initial tests, but the scope of its usefulness remains to be proven.

There’s certainly need to find new ways to respond to bacterial infections. More than 70% of hospital-acquired bacterial infections in the United States are resistant to at least one type of antibiotic. And some pathogens, such as AcinetobacterPseudomonas, Escherichia coli, and Klebsiella — classified by the World Health Organization as some of the biggest threats to human health — are resistant to multiple antibiotics. In 2019, antibacterial resistance was linked to 4.95 million deaths globally, heightening the call for more effective treatment options.

One of the ways that bacteria can evolve resistance to antibiotics is by using structures in their membranes that are designed to move unwanted molecules out of the cell. By modifying these “efflux pumps” to recognize the antibiotic, bacteria can eliminate the drug before it poisons them.

As it turns out, some phages appear to use these same efflux pumps to invade the bacterial cell. The phage presumably attaches its tail to the outer portion of the pump protein, like a key slipping into a lock, and then injects its genetic material into the cell. This lucky coincidence led Paul Turner, PhD, an evolutionary biologist at Yale University, New Haven, Connecticut, to suggest that treating a patient with phages and antibiotics simultaneously could trap bacteria in a no-win situation: If they evolve to modify their efflux pumps so the phage can’t bind, the pumps will no longer expel antibiotics, and the bacteria will lose their resistance. But if they retain their antibiotic resistance, the phages will kill them, as Dr. Turner and colleagues explained in the 2023 Annual Review of Virology.

The result, in other words, is a two-pronged attack, said Michael Hochberg, PhD, an evolutionary biologist at the French National Centre for Scientific Research who studies how to prevent the evolution of bacterial resistance. “It’s kind of like a crisscross effect.” The same principle can target other bacterial molecules that play a dual role in resistance to viruses and antibiotics.

Turner tested this hypothesis on multidrug-resistant Pseudomonas aeruginosa, which causes dangerous infections, especially in healthcare settings. This bacterium has four efflux pumps involved in antibiotic resistance, and Dr. Turner predicted that if he could find a phage that used one of the pumps as a way into the cell, the bacterium would be forced to slam the door on the phage by mutating the receptor — thereby impeding its ability to pump out antibiotics.

Sampling from the environment, Dr. Turner’s team collected 42 phage strains that infect P aeruginosa. Out of all the phages, one, OMKO1, bound to an efflux pump, making it the perfect candidate for the experiment.

The researchers then cultured antibiotic-resistant P aeruginosa together with OMKO1, hoping this would force the bacterium to modify its efflux pump to resist the phage. They exposed these phage-resistant bacteria, as well as their normal, phage-sensitive counterparts, to four antibiotics the bacteria had been resistant to: tetracycline, erythromycin, ciprofloxacin, and ceftazidime.

As the theory predicted, the bacteria that had evolved resistance to the phage were more sensitive to the antibiotics than those that had not been exposed to the phage. This suggests that the bacteria had, indeed, been forced to lose their antibiotic resistance through their need to fight off the phage.

Other researchers have also shown that phage steering can resensitize bacteria to common antibiotics they’d become resistant to. One study, by an international research team, showed that a phage called Phab24 can be used to restore sensitivity to the antibiotic colistin in Acinetobacter baumannii, which causes life-threatening diseases.

In a second study, researchers at Monash University in Australia sampled infectious bacteria from patients. They found that several phages, including strains known as phi-FG02 and phi-CO01, were already present in some of the samples, and that A baumannii bacteria exposed to the phages had inactivated a gene that helps create the microbe’s important outer layer, or capsule. This layer serves as the entry point for the phages, but it also helps the bacterium to form biofilms that keep out antibiotics — so removing the layer rendered A baumannii susceptible to several antibiotics that it was previously resistant to.

In a third study, researchers from the University of Liverpool discovered that, when a P aeruginosa strain that was resistant to all antibiotics was exposed to phages, the bacterium became sensitive to two antibiotics that were otherwise considered ineffective against P aeruginosa.

Dr. Turner’s team has used phage steering in dozens of cases of personalized therapy in clinical settings, said Benjamin Chan, PhD, a microbiologist at Yale University who works with Dr. Turner. The results, many still unpublished, have been promising so far. Nonrespiratory infections are relatively easy to clear off, and lung infections, which the phage steering approach wouldn’t be expected to eradicate completely, often show some improvement.

“I would say that we have been quite successful in using phage steering to treat difficult-to-manage infections, reducing antimicrobial resistance in many cases,” he said. But he notes that it is sometimes difficult to determine whether phage steering really was responsible for the cures.
 

Devil in the details

Phage therapy may not work for all antibiotic-resistant bacteria, said molecular biologist Graham Hatfull, PhD, of the University of Pittsburgh in Pennsylvania. That’s because phages are very host specific, and for most phages, no one knows what target they bind to on the bacterial cell surface. For phage steering to work against antibiotic resistance, the phage has to bind to a molecule that’s involved in that resistance — and it’s not clear how often that fortuitous coincidence occurs.

Jason Gill, PhD, who studies bacteriophage biology at Texas A&M University, College Station, said that it is not easy to predict if a phage will induce antibiotic sensitivity. So you always have to hunt for the right virus each time.

Dr. Gill knows from experience how complicated the approach can get. He was part of a team of researchers and doctors who used phages to treat a patient with a multidrug-resistant A baumannii infection. Less than 4 days after the team administered phages intravenously and through the skin, the patient woke up from a coma and became responsive to the previously ineffective antibiotic minocycline — a striking success.

But when Dr. Gill tried a similar experiment in cell cultures, he got a different result. The A baumannii developed resistance to the phages, but they also maintained their resistance to minocycline. “There’s not a complete mechanistic understanding,” said Dr. Gill. “The linkage between phage resistance and antibiotic sensitivity probably varies by bacterial strain, phage and antibiotic.” That means phage steering may not always work.

Dr. Turner, for his part, pointed out another potential problem: That phages could work too well. If phage therapy kills large amounts of bacteria and deposits their remains in the bloodstream quickly, for example, this could trigger septic shock in patients. Scientists do not yet know how to address this problem.

Another concern is that doctors have less precise control over phages than antibiotics. “Phages can mutate, they can adapt, they have a genome,” said Dr. Hochberg. Safety concerns, he notes, are one factor inhibiting the routine use of phage therapy in countries like the United States, restricting it to case-by-case applications such as Dr. Turner and Dr. Chan’s.

Phage therapy may have been too high-tech for the 1940s, and even today, scientists grapple with how to use it. What we need now, said Dr. Turner, are rigorous experiments that will teach us how to make it work.

This article originally appeared in Knowable Magazine on September 09, 2024. Knowable Magazine is an independent journalistic endeavor from Annual Reviews, a nonprofit publisher dedicated to synthesizing and integrating knowledge for the progress of science and the benefit of society. Sign up for Knowable Magazine’s newsletter. A version of this article appeared on Medscape.com.

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The Battle Against Recurrent UTIs in Welsh Women

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Changed
Tue, 09/03/2024 - 05:00

 

TOPLINE:

The prevalence of recurrent urinary tract infections (rUTIs) and the use of antibiotics for prevention are substantial among women in Wales, particularly among those over the age of 57 years. A high level of resistance to two recommended antibiotics was observed, suggesting that more frequent urine cultures could better guide antibiotic selection for treatment and prophylaxis.

METHODOLOGY:

  • The researchers conducted a retrospective cross-sectional study using a large databank of patients in Wales to describe the characteristics and urine profiles of women with rUTIs between 2010 and 2022.
  • They created two cohorts: One with 92,213 women (median age, 60 years) who experienced rUTIs, defined as two or more acute episodes within 6 months or three or more acute episodes within 12 months.
  • Another cohort comprised of 26,862 women (median age, 71 years) were prescribed prophylactic antibiotics, which was defined as receiving three or more consecutive prescriptions of the same UTI-specific antibiotic (trimethoprim, nitrofurantoin, or cefalexin), with intervals of 21-56 days between prescriptions.
  • Urine culture results in the 12 months before a rUTI diagnosis and 18 months before prophylactic antibiotic initiation and all urine culture results within 7 days of an acute UTI were analyzed to assess antibiotic resistance patterns.

TAKEAWAY:

  • Overall, 6% of women had rUTIs, 1.7% of which were prescribed prophylactic antibiotics with proportions increasing sharply after age 57.
  • Nearly half of the women (49%) who were prescribed a prophylactic antibiotic qualified as having rUTIs in the 18 months before initiation.
  • This study showed that 80.8% of women with rUTIs had a urine culture result documented in the 12 months preceding the diagnosis.
  • More than half (64%) of the women taking prophylactic antibiotics had a urine culture result documented before starting treatment, and 18% of those prescribed trimethoprim had resistance to the antibiotic.

IN PRACTICE:

“More frequent urine cultures in the workup of rUTI diagnosis and prophylactic antibiotic initiation could better inform antibiotic choice,” the authors wrote.

SOURCE:

The study was led by Leigh Sanyaolu, BSc (Hons), MRCS, MRCGP, PGDip, a general practitioner from the Division of Population Medicine and PRIME Centre Wales at Cardiff University in Cardiff, and was published online in the British Journal of General Practice.

LIMITATIONS:

The study’s reliance on electronic health records may have led to coding errors and missing data. The diagnosis of UTIs may have been difficult in older women with increased frailty as they can have fewer specific symptoms and asymptomatic bacteriuria, which can be misdiagnosed as a UTI.

DISCLOSURES:

This work was supported by Health and Care Research Wales. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE:

The prevalence of recurrent urinary tract infections (rUTIs) and the use of antibiotics for prevention are substantial among women in Wales, particularly among those over the age of 57 years. A high level of resistance to two recommended antibiotics was observed, suggesting that more frequent urine cultures could better guide antibiotic selection for treatment and prophylaxis.

METHODOLOGY:

  • The researchers conducted a retrospective cross-sectional study using a large databank of patients in Wales to describe the characteristics and urine profiles of women with rUTIs between 2010 and 2022.
  • They created two cohorts: One with 92,213 women (median age, 60 years) who experienced rUTIs, defined as two or more acute episodes within 6 months or three or more acute episodes within 12 months.
  • Another cohort comprised of 26,862 women (median age, 71 years) were prescribed prophylactic antibiotics, which was defined as receiving three or more consecutive prescriptions of the same UTI-specific antibiotic (trimethoprim, nitrofurantoin, or cefalexin), with intervals of 21-56 days between prescriptions.
  • Urine culture results in the 12 months before a rUTI diagnosis and 18 months before prophylactic antibiotic initiation and all urine culture results within 7 days of an acute UTI were analyzed to assess antibiotic resistance patterns.

TAKEAWAY:

  • Overall, 6% of women had rUTIs, 1.7% of which were prescribed prophylactic antibiotics with proportions increasing sharply after age 57.
  • Nearly half of the women (49%) who were prescribed a prophylactic antibiotic qualified as having rUTIs in the 18 months before initiation.
  • This study showed that 80.8% of women with rUTIs had a urine culture result documented in the 12 months preceding the diagnosis.
  • More than half (64%) of the women taking prophylactic antibiotics had a urine culture result documented before starting treatment, and 18% of those prescribed trimethoprim had resistance to the antibiotic.

IN PRACTICE:

“More frequent urine cultures in the workup of rUTI diagnosis and prophylactic antibiotic initiation could better inform antibiotic choice,” the authors wrote.

SOURCE:

The study was led by Leigh Sanyaolu, BSc (Hons), MRCS, MRCGP, PGDip, a general practitioner from the Division of Population Medicine and PRIME Centre Wales at Cardiff University in Cardiff, and was published online in the British Journal of General Practice.

LIMITATIONS:

The study’s reliance on electronic health records may have led to coding errors and missing data. The diagnosis of UTIs may have been difficult in older women with increased frailty as they can have fewer specific symptoms and asymptomatic bacteriuria, which can be misdiagnosed as a UTI.

DISCLOSURES:

This work was supported by Health and Care Research Wales. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

 

TOPLINE:

The prevalence of recurrent urinary tract infections (rUTIs) and the use of antibiotics for prevention are substantial among women in Wales, particularly among those over the age of 57 years. A high level of resistance to two recommended antibiotics was observed, suggesting that more frequent urine cultures could better guide antibiotic selection for treatment and prophylaxis.

METHODOLOGY:

  • The researchers conducted a retrospective cross-sectional study using a large databank of patients in Wales to describe the characteristics and urine profiles of women with rUTIs between 2010 and 2022.
  • They created two cohorts: One with 92,213 women (median age, 60 years) who experienced rUTIs, defined as two or more acute episodes within 6 months or three or more acute episodes within 12 months.
  • Another cohort comprised of 26,862 women (median age, 71 years) were prescribed prophylactic antibiotics, which was defined as receiving three or more consecutive prescriptions of the same UTI-specific antibiotic (trimethoprim, nitrofurantoin, or cefalexin), with intervals of 21-56 days between prescriptions.
  • Urine culture results in the 12 months before a rUTI diagnosis and 18 months before prophylactic antibiotic initiation and all urine culture results within 7 days of an acute UTI were analyzed to assess antibiotic resistance patterns.

TAKEAWAY:

  • Overall, 6% of women had rUTIs, 1.7% of which were prescribed prophylactic antibiotics with proportions increasing sharply after age 57.
  • Nearly half of the women (49%) who were prescribed a prophylactic antibiotic qualified as having rUTIs in the 18 months before initiation.
  • This study showed that 80.8% of women with rUTIs had a urine culture result documented in the 12 months preceding the diagnosis.
  • More than half (64%) of the women taking prophylactic antibiotics had a urine culture result documented before starting treatment, and 18% of those prescribed trimethoprim had resistance to the antibiotic.

IN PRACTICE:

“More frequent urine cultures in the workup of rUTI diagnosis and prophylactic antibiotic initiation could better inform antibiotic choice,” the authors wrote.

SOURCE:

The study was led by Leigh Sanyaolu, BSc (Hons), MRCS, MRCGP, PGDip, a general practitioner from the Division of Population Medicine and PRIME Centre Wales at Cardiff University in Cardiff, and was published online in the British Journal of General Practice.

LIMITATIONS:

The study’s reliance on electronic health records may have led to coding errors and missing data. The diagnosis of UTIs may have been difficult in older women with increased frailty as they can have fewer specific symptoms and asymptomatic bacteriuria, which can be misdiagnosed as a UTI.

DISCLOSURES:

This work was supported by Health and Care Research Wales. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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