Infectious Diseases

It’s a typically busy Friday and the doctor is running 20 minutes behind schedule. He enters the next exam room and the sight of the patient makes him forget the apology he had prepared.

C5Media/Getty Images

The 10 month old looks miserable. Red eyes. Snot dripping from his nose. A red rash that extends from his face and involves most of the chest, arms, and upper thighs.

“When did this start?” he asks the mother as he searches for a surgical mask in the cabinet next to the exam table.

“Two days after we returned from our vacation in France,” the worried young woman replies. “Do you think it could be measles?”

Between Jan. 1 and Aug. 8, 2019, 1,182 cases of measles had been confirmed in the United States. That’s more than three times the number of cases reported in all of 2018, and the highest number of cases reported in a single year in more than a quarter century. While 75% of the cases this year have been linked to outbreaks in New York, individuals from 30 states have been affected.

Given the widespread nature of the outbreak, it makes sense for every ambulatory office to have a plan for managing exposures to infectious diseases including measles. With measles in particular, time is limited to deliver effective postexposure prophylaxis and prevent the spread of measles in the community, making it difficult to develop a plan on the fly.

Schedule strategically. You don’t want a patient with measles hanging out in your waiting room. According to the American Academy of Pediatrics, measures to prevent the transmission of contagious infectious agents in ambulatory facilities begin at the time the visit is scheduled. When there is measles transmission in the community, consider using a standardized script when scheduling patients that includes questions about fever, rash, other symptoms typical for measles, and possible exposures. Some offices will have procedures in place that can be adapted to care for patients with suspected measles. When a patient presents for suspected chicken pox, do you advise them to come at the end of the day to minimize exposures? Enter through a side door? Perform a car visit?

Triage promptly. Mask patients with fever and rash, move to a private room, and close the door.

Once measles is suspected, only health care personnel who are immune to measles should enter the exam room. According to the Centers for Disease Control and Prevention, presumptive evidence of measles immunity in health care providers is written documentation of vaccination with two doses of live measles or MMR vaccine administered at least 28 days apart, laboratory evidence of immunity (that is, positive measles IgG), laboratory confirmation of disease, or birth before 1957.

Even though health care providers born before 1957 are presumed to have had the disease at some point and have traditionally been considered immune, the CDC suggests that health care facilities consider giving these individuals two doses of MMR vaccine unless they have prior laboratory confirmation of disease immunity. Do you know who in your office is immune or would you need to scramble if you had an exposure?

When measles is suspected, health care personnel should wear an N-95 if they have been fit tested and the appropriate mask is available. Practically, most ambulatory offices do not stock N-95 masks and the next best choice is a regular surgical mask.

Order the recommended tests to confirm the diagnosis, but do not wait for the results to confirm the diagnosis. The CDC recommends testing serum for IgM antibodies and sending a throat or nasopharyngeal swab to look for the virus by polymerase chain reaction testing. Measles virus also is shed in the urine so collecting a urine specimen for testing may increase the chances of finding the virus. Depending on where you practice, the tests may take 3 days or more to result. Contact your local health department as soon as you consider a measles diagnosis.

Discharge patients home or transferred to a higher level of care if this is necessary as quickly as possible. Fortunately, most patients with measles do not require hospitalization. Do not send patients to the hospital simply for the purpose of laboratory testing if this can be accomplished quickly in your office or for evaluation by other providers. This just creates the potential for more exposures. If a patient does require higher-level care, provider-to-provider communication about the suspected diagnosis and the need for airborne isolation should take place.

Keep the door closed. Once a patient with suspected measles is discharged from a regular exam room, the door should remain closed, and it should not be used for at least 1 hour. Remember that infectious virus can remain in the air for 1-2 hours after a patient leaves an area. The same is true for the waiting room.

Develop the exposure list. In general, patients and family members who were in the waiting room at the same time as the index patient and up to 1-2 hours after the index patient left are considered exposed. Measles is highly contagious and 9 out of 10 susceptible people who are exposed will develop disease. How many infants aged less than 1 year might be in your waiting room at any given time? How many immunocompromised patients or family members? Public health authorities can help determine who needs prophylaxis.

Don’t get anxious and start testing everyone for measles, especially patients who lack typical signs and symptoms or exposures. Ordering a test in a patient who has a low likelihood of measles is more likely to result in a false-positive test than a true-positive test. False-positive measles IgM tests can be seen with some viral infections, including parvovirus and Epstein-Barr. Some rheumatologic disorders also can contribute to false-positive tests.

Review your office procedure for vaccine counseling. The 10 month old with measles in the opening vignette should have been given an MMR vaccine before travel. The vaccine is recommended for infants aged 6-11 months who are traveling outside the United States, but it doesn’t count toward the vaccine series. Reimmunize young travelers at 12-15 months and again at 4-6 years. The CDC has developed a toolkit that contains resources for taking to parents about vaccines. It is available at https://www.cdc.gov/measles/toolkit/healthcare-providers.html.

It’s a typically busy Friday and the doctor is running 20 minutes behind schedule. He enters the next exam room and the sight of the patient makes him forget the apology he had prepared.

C5Media/Getty Images

The 10 month old looks miserable. Red eyes. Snot dripping from his nose. A red rash that extends from his face and involves most of the chest, arms, and upper thighs.

“When did this start?” he asks the mother as he searches for a surgical mask in the cabinet next to the exam table.

“Two days after we returned from our vacation in France,” the worried young woman replies. “Do you think it could be measles?”

Between Jan. 1 and Aug. 8, 2019, 1,182 cases of measles had been confirmed in the United States. That’s more than three times the number of cases reported in all of 2018, and the highest number of cases reported in a single year in more than a quarter century. While 75% of the cases this year have been linked to outbreaks in New York, individuals from 30 states have been affected.

Given the widespread nature of the outbreak, it makes sense for every ambulatory office to have a plan for managing exposures to infectious diseases including measles. With measles in particular, time is limited to deliver effective postexposure prophylaxis and prevent the spread of measles in the community, making it difficult to develop a plan on the fly.

Schedule strategically. You don’t want a patient with measles hanging out in your waiting room. According to the American Academy of Pediatrics, measures to prevent the transmission of contagious infectious agents in ambulatory facilities begin at the time the visit is scheduled. When there is measles transmission in the community, consider using a standardized script when scheduling patients that includes questions about fever, rash, other symptoms typical for measles, and possible exposures. Some offices will have procedures in place that can be adapted to care for patients with suspected measles. When a patient presents for suspected chicken pox, do you advise them to come at the end of the day to minimize exposures? Enter through a side door? Perform a car visit?

Triage promptly. Mask patients with fever and rash, move to a private room, and close the door.

Once measles is suspected, only health care personnel who are immune to measles should enter the exam room. According to the Centers for Disease Control and Prevention, presumptive evidence of measles immunity in health care providers is written documentation of vaccination with two doses of live measles or MMR vaccine administered at least 28 days apart, laboratory evidence of immunity (that is, positive measles IgG), laboratory confirmation of disease, or birth before 1957.

Even though health care providers born before 1957 are presumed to have had the disease at some point and have traditionally been considered immune, the CDC suggests that health care facilities consider giving these individuals two doses of MMR vaccine unless they have prior laboratory confirmation of disease immunity. Do you know who in your office is immune or would you need to scramble if you had an exposure?

When measles is suspected, health care personnel should wear an N-95 if they have been fit tested and the appropriate mask is available. Practically, most ambulatory offices do not stock N-95 masks and the next best choice is a regular surgical mask.

Order the recommended tests to confirm the diagnosis, but do not wait for the results to confirm the diagnosis. The CDC recommends testing serum for IgM antibodies and sending a throat or nasopharyngeal swab to look for the virus by polymerase chain reaction testing. Measles virus also is shed in the urine so collecting a urine specimen for testing may increase the chances of finding the virus. Depending on where you practice, the tests may take 3 days or more to result. Contact your local health department as soon as you consider a measles diagnosis.

Discharge patients home or transferred to a higher level of care if this is necessary as quickly as possible. Fortunately, most patients with measles do not require hospitalization. Do not send patients to the hospital simply for the purpose of laboratory testing if this can be accomplished quickly in your office or for evaluation by other providers. This just creates the potential for more exposures. If a patient does require higher-level care, provider-to-provider communication about the suspected diagnosis and the need for airborne isolation should take place.

Keep the door closed. Once a patient with suspected measles is discharged from a regular exam room, the door should remain closed, and it should not be used for at least 1 hour. Remember that infectious virus can remain in the air for 1-2 hours after a patient leaves an area. The same is true for the waiting room.

Develop the exposure list. In general, patients and family members who were in the waiting room at the same time as the index patient and up to 1-2 hours after the index patient left are considered exposed. Measles is highly contagious and 9 out of 10 susceptible people who are exposed will develop disease. How many infants aged less than 1 year might be in your waiting room at any given time? How many immunocompromised patients or family members? Public health authorities can help determine who needs prophylaxis.

Don’t get anxious and start testing everyone for measles, especially patients who lack typical signs and symptoms or exposures. Ordering a test in a patient who has a low likelihood of measles is more likely to result in a false-positive test than a true-positive test. False-positive measles IgM tests can be seen with some viral infections, including parvovirus and Epstein-Barr. Some rheumatologic disorders also can contribute to false-positive tests.

Review your office procedure for vaccine counseling. The 10 month old with measles in the opening vignette should have been given an MMR vaccine before travel. The vaccine is recommended for infants aged 6-11 months who are traveling outside the United States, but it doesn’t count toward the vaccine series. Reimmunize young travelers at 12-15 months and again at 4-6 years. The CDC has developed a toolkit that contains resources for taking to parents about vaccines. It is available at https://www.cdc.gov/measles/toolkit/healthcare-providers.html.

It’s a typically busy Friday and the doctor is running 20 minutes behind schedule. He enters the next exam room and the sight of the patient makes him forget the apology he had prepared.

C5Media/Getty Images

The 10 month old looks miserable. Red eyes. Snot dripping from his nose. A red rash that extends from his face and involves most of the chest, arms, and upper thighs.

“When did this start?” he asks the mother as he searches for a surgical mask in the cabinet next to the exam table.

“Two days after we returned from our vacation in France,” the worried young woman replies. “Do you think it could be measles?”

Between Jan. 1 and Aug. 8, 2019, 1,182 cases of measles had been confirmed in the United States. That’s more than three times the number of cases reported in all of 2018, and the highest number of cases reported in a single year in more than a quarter century. While 75% of the cases this year have been linked to outbreaks in New York, individuals from 30 states have been affected.

Given the widespread nature of the outbreak, it makes sense for every ambulatory office to have a plan for managing exposures to infectious diseases including measles. With measles in particular, time is limited to deliver effective postexposure prophylaxis and prevent the spread of measles in the community, making it difficult to develop a plan on the fly.

Schedule strategically. You don’t want a patient with measles hanging out in your waiting room. According to the American Academy of Pediatrics, measures to prevent the transmission of contagious infectious agents in ambulatory facilities begin at the time the visit is scheduled. When there is measles transmission in the community, consider using a standardized script when scheduling patients that includes questions about fever, rash, other symptoms typical for measles, and possible exposures. Some offices will have procedures in place that can be adapted to care for patients with suspected measles. When a patient presents for suspected chicken pox, do you advise them to come at the end of the day to minimize exposures? Enter through a side door? Perform a car visit?

Triage promptly. Mask patients with fever and rash, move to a private room, and close the door.

Once measles is suspected, only health care personnel who are immune to measles should enter the exam room. According to the Centers for Disease Control and Prevention, presumptive evidence of measles immunity in health care providers is written documentation of vaccination with two doses of live measles or MMR vaccine administered at least 28 days apart, laboratory evidence of immunity (that is, positive measles IgG), laboratory confirmation of disease, or birth before 1957.

Even though health care providers born before 1957 are presumed to have had the disease at some point and have traditionally been considered immune, the CDC suggests that health care facilities consider giving these individuals two doses of MMR vaccine unless they have prior laboratory confirmation of disease immunity. Do you know who in your office is immune or would you need to scramble if you had an exposure?

When measles is suspected, health care personnel should wear an N-95 if they have been fit tested and the appropriate mask is available. Practically, most ambulatory offices do not stock N-95 masks and the next best choice is a regular surgical mask.

Order the recommended tests to confirm the diagnosis, but do not wait for the results to confirm the diagnosis. The CDC recommends testing serum for IgM antibodies and sending a throat or nasopharyngeal swab to look for the virus by polymerase chain reaction testing. Measles virus also is shed in the urine so collecting a urine specimen for testing may increase the chances of finding the virus. Depending on where you practice, the tests may take 3 days or more to result. Contact your local health department as soon as you consider a measles diagnosis.

Discharge patients home or transferred to a higher level of care if this is necessary as quickly as possible. Fortunately, most patients with measles do not require hospitalization. Do not send patients to the hospital simply for the purpose of laboratory testing if this can be accomplished quickly in your office or for evaluation by other providers. This just creates the potential for more exposures. If a patient does require higher-level care, provider-to-provider communication about the suspected diagnosis and the need for airborne isolation should take place.

Keep the door closed. Once a patient with suspected measles is discharged from a regular exam room, the door should remain closed, and it should not be used for at least 1 hour. Remember that infectious virus can remain in the air for 1-2 hours after a patient leaves an area. The same is true for the waiting room.

Develop the exposure list. In general, patients and family members who were in the waiting room at the same time as the index patient and up to 1-2 hours after the index patient left are considered exposed. Measles is highly contagious and 9 out of 10 susceptible people who are exposed will develop disease. How many infants aged less than 1 year might be in your waiting room at any given time? How many immunocompromised patients or family members? Public health authorities can help determine who needs prophylaxis.

Don’t get anxious and start testing everyone for measles, especially patients who lack typical signs and symptoms or exposures. Ordering a test in a patient who has a low likelihood of measles is more likely to result in a false-positive test than a true-positive test. False-positive measles IgM tests can be seen with some viral infections, including parvovirus and Epstein-Barr. Some rheumatologic disorders also can contribute to false-positive tests.

Review your office procedure for vaccine counseling. The 10 month old with measles in the opening vignette should have been given an MMR vaccine before travel. The vaccine is recommended for infants aged 6-11 months who are traveling outside the United States, but it doesn’t count toward the vaccine series. Reimmunize young travelers at 12-15 months and again at 4-6 years. The CDC has developed a toolkit that contains resources for taking to parents about vaccines. It is available at https://www.cdc.gov/measles/toolkit/healthcare-providers.html.

LJUBLJANA, SLOVENIA – A prospective international surveillance study has provided new insights into the surprisingly substantial clinical burden of viral meningitis caused by enteroviruses and human parechoviruses in young infants, Seilesh Kadambari, MBBS, PhD, said in his ESPID Young Investigator Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.

This comprehensive study captured all cases of laboratory-confirmed enterovirus (EV) and human parechovirus (HPeV) meningitis in infants less than 90 days old seen by pediatricians in the United Kingdom and Ireland during a 13-month period starting in July 2014, a time free of outbreaks. Dr. Kadambari, a pediatrician at the University of Oxford (England), was first author of the study. It was for this project, as well as his earlier studies shedding light on congenital viral infections, that he received the Young Investigator honor.

Among the key findings of the U.K./Ireland surveillance study: The incidence of EV/HPeV meningitis was more than twice that of bacterial meningitis in the same age group and more than fivefold higher than that of group B streptococcal meningitis, the No. 1 cause of bacterial meningitis in early infancy. Moreover, more than one-half of infants with EV/HPeV meningitis had low levels of inflammatory markers and no cerebrospinal fluid pleocytosis, which underscores the importance of routinely testing the cerebrospinal fluid for viral causes of meningitis in such patients using modern molecular tools such as multiplex polymerase chain reaction, according to Dr. Kadambari.

“Also, not a single one of the patients with EV/HPeV meningitis had a secondary bacterial infection – and that has important implications for management of our antibiotic stewardship programs,” he observed.

The study (Arch Dis Child. 2019 Jun;104(6):552-7) identified 668 cases of EV meningitis and 35 of HPeV meningitis, for an incidence of 0.79 and 0.04 per 1,000 live births, respectively. The most common clinical presentations were those generally seen in meningitis: fever, irritability, and reduced feeding. Circulatory shock was present in 43% of the infants with HPeV and 27% of the infants with EV infections.

Of infants with EV meningitis, 11% required admission to an intensive care unit, as did 23% of those with HPeV meningitis. Two babies with EV meningitis died and four others had continued neurologic complications at 12 months of follow-up. In contrast, all infants with HPeV survived without long-term sequelae.

Reassuringly, none of the 189 infants who underwent formal hearing testing had sensorineural hearing loss.

The surveillance study data have played an influential role in evidence-based guidelines for EV diagnosis and characterization published by the European Society of Clinical Virology (J Clin Virol. 2018 Apr;101:11-7).

An earlier study led by Dr. Kadambari documented a hefty sevenfold increase in the rate of laboratory-confirmed viral meningo-encephalitis in England and Wales during 2004-2013 across all age groups (J Infect. 2014 Oct;69[4]:326-32).

He attributed this increase to improved diagnosis of viral forms of meningitis through greater use of polymerase chain reaction. The study, based upon National Health Service hospital records, showed that more than 90% of all cases of viral meningo-encephalitis in infants less than 90 days old were caused by EV, a finding that prompted the subsequent prospective U.K./Ireland surveillance study.

Dr. Kadambari closed by noting the past decade had seen a greatly improved ability to diagnose congenital viral infections, but those improvements are not good enough.

“In the decade ahead, we hope to improve the management of this poorly understood group of infections,” the pediatrician promised.

Planned efforts include a cost-effectiveness analysis of a cytomegalovirus vaccine, an ESPID-funded research project aimed at identifying which EV/HPeV strains are most responsible for outbreaks and isolated severe disease, and gaining insight into the host-immunity factors associated with a proclivity to develop EV/HPeV meningitis in early infancy.

Dr. Kadambari reported having no financial conflicts regarding his studies, which was funded largely by Public Health England and university grants.

[email protected]

SOURCE: Kadambari S et al. Arch Dis Child. 2019;104:552-7.

LJUBLJANA, SLOVENIA – A prospective international surveillance study has provided new insights into the surprisingly substantial clinical burden of viral meningitis caused by enteroviruses and human parechoviruses in young infants, Seilesh Kadambari, MBBS, PhD, said in his ESPID Young Investigator Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.

This comprehensive study captured all cases of laboratory-confirmed enterovirus (EV) and human parechovirus (HPeV) meningitis in infants less than 90 days old seen by pediatricians in the United Kingdom and Ireland during a 13-month period starting in July 2014, a time free of outbreaks. Dr. Kadambari, a pediatrician at the University of Oxford (England), was first author of the study. It was for this project, as well as his earlier studies shedding light on congenital viral infections, that he received the Young Investigator honor.

Among the key findings of the U.K./Ireland surveillance study: The incidence of EV/HPeV meningitis was more than twice that of bacterial meningitis in the same age group and more than fivefold higher than that of group B streptococcal meningitis, the No. 1 cause of bacterial meningitis in early infancy. Moreover, more than one-half of infants with EV/HPeV meningitis had low levels of inflammatory markers and no cerebrospinal fluid pleocytosis, which underscores the importance of routinely testing the cerebrospinal fluid for viral causes of meningitis in such patients using modern molecular tools such as multiplex polymerase chain reaction, according to Dr. Kadambari.

“Also, not a single one of the patients with EV/HPeV meningitis had a secondary bacterial infection – and that has important implications for management of our antibiotic stewardship programs,” he observed.

The study (Arch Dis Child. 2019 Jun;104(6):552-7) identified 668 cases of EV meningitis and 35 of HPeV meningitis, for an incidence of 0.79 and 0.04 per 1,000 live births, respectively. The most common clinical presentations were those generally seen in meningitis: fever, irritability, and reduced feeding. Circulatory shock was present in 43% of the infants with HPeV and 27% of the infants with EV infections.

Of infants with EV meningitis, 11% required admission to an intensive care unit, as did 23% of those with HPeV meningitis. Two babies with EV meningitis died and four others had continued neurologic complications at 12 months of follow-up. In contrast, all infants with HPeV survived without long-term sequelae.

Reassuringly, none of the 189 infants who underwent formal hearing testing had sensorineural hearing loss.

The surveillance study data have played an influential role in evidence-based guidelines for EV diagnosis and characterization published by the European Society of Clinical Virology (J Clin Virol. 2018 Apr;101:11-7).

An earlier study led by Dr. Kadambari documented a hefty sevenfold increase in the rate of laboratory-confirmed viral meningo-encephalitis in England and Wales during 2004-2013 across all age groups (J Infect. 2014 Oct;69[4]:326-32).

He attributed this increase to improved diagnosis of viral forms of meningitis through greater use of polymerase chain reaction. The study, based upon National Health Service hospital records, showed that more than 90% of all cases of viral meningo-encephalitis in infants less than 90 days old were caused by EV, a finding that prompted the subsequent prospective U.K./Ireland surveillance study.

Dr. Kadambari closed by noting the past decade had seen a greatly improved ability to diagnose congenital viral infections, but those improvements are not good enough.

“In the decade ahead, we hope to improve the management of this poorly understood group of infections,” the pediatrician promised.

Planned efforts include a cost-effectiveness analysis of a cytomegalovirus vaccine, an ESPID-funded research project aimed at identifying which EV/HPeV strains are most responsible for outbreaks and isolated severe disease, and gaining insight into the host-immunity factors associated with a proclivity to develop EV/HPeV meningitis in early infancy.

Dr. Kadambari reported having no financial conflicts regarding his studies, which was funded largely by Public Health England and university grants.

[email protected]

SOURCE: Kadambari S et al. Arch Dis Child. 2019;104:552-7.

LJUBLJANA, SLOVENIA – A prospective international surveillance study has provided new insights into the surprisingly substantial clinical burden of viral meningitis caused by enteroviruses and human parechoviruses in young infants, Seilesh Kadambari, MBBS, PhD, said in his ESPID Young Investigator Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.

This comprehensive study captured all cases of laboratory-confirmed enterovirus (EV) and human parechovirus (HPeV) meningitis in infants less than 90 days old seen by pediatricians in the United Kingdom and Ireland during a 13-month period starting in July 2014, a time free of outbreaks. Dr. Kadambari, a pediatrician at the University of Oxford (England), was first author of the study. It was for this project, as well as his earlier studies shedding light on congenital viral infections, that he received the Young Investigator honor.

Among the key findings of the U.K./Ireland surveillance study: The incidence of EV/HPeV meningitis was more than twice that of bacterial meningitis in the same age group and more than fivefold higher than that of group B streptococcal meningitis, the No. 1 cause of bacterial meningitis in early infancy. Moreover, more than one-half of infants with EV/HPeV meningitis had low levels of inflammatory markers and no cerebrospinal fluid pleocytosis, which underscores the importance of routinely testing the cerebrospinal fluid for viral causes of meningitis in such patients using modern molecular tools such as multiplex polymerase chain reaction, according to Dr. Kadambari.

“Also, not a single one of the patients with EV/HPeV meningitis had a secondary bacterial infection – and that has important implications for management of our antibiotic stewardship programs,” he observed.

The study (Arch Dis Child. 2019 Jun;104(6):552-7) identified 668 cases of EV meningitis and 35 of HPeV meningitis, for an incidence of 0.79 and 0.04 per 1,000 live births, respectively. The most common clinical presentations were those generally seen in meningitis: fever, irritability, and reduced feeding. Circulatory shock was present in 43% of the infants with HPeV and 27% of the infants with EV infections.

Of infants with EV meningitis, 11% required admission to an intensive care unit, as did 23% of those with HPeV meningitis. Two babies with EV meningitis died and four others had continued neurologic complications at 12 months of follow-up. In contrast, all infants with HPeV survived without long-term sequelae.

Reassuringly, none of the 189 infants who underwent formal hearing testing had sensorineural hearing loss.

The surveillance study data have played an influential role in evidence-based guidelines for EV diagnosis and characterization published by the European Society of Clinical Virology (J Clin Virol. 2018 Apr;101:11-7).

An earlier study led by Dr. Kadambari documented a hefty sevenfold increase in the rate of laboratory-confirmed viral meningo-encephalitis in England and Wales during 2004-2013 across all age groups (J Infect. 2014 Oct;69[4]:326-32).

He attributed this increase to improved diagnosis of viral forms of meningitis through greater use of polymerase chain reaction. The study, based upon National Health Service hospital records, showed that more than 90% of all cases of viral meningo-encephalitis in infants less than 90 days old were caused by EV, a finding that prompted the subsequent prospective U.K./Ireland surveillance study.

Dr. Kadambari closed by noting the past decade had seen a greatly improved ability to diagnose congenital viral infections, but those improvements are not good enough.

“In the decade ahead, we hope to improve the management of this poorly understood group of infections,” the pediatrician promised.

Planned efforts include a cost-effectiveness analysis of a cytomegalovirus vaccine, an ESPID-funded research project aimed at identifying which EV/HPeV strains are most responsible for outbreaks and isolated severe disease, and gaining insight into the host-immunity factors associated with a proclivity to develop EV/HPeV meningitis in early infancy.

Dr. Kadambari reported having no financial conflicts regarding his studies, which was funded largely by Public Health England and university grants.

[email protected]

SOURCE: Kadambari S et al. Arch Dis Child. 2019;104:552-7.

The Centers for Disease Control and Prevention has updated its recommendation for serologic detection of Lyme disease, according to CDC investigators.

At the 1994 Second National Conference on Serologic Diagnosis of Lyme Disease, several groups and organizations convened, recommending a two-test methodology for Lyme disease detection. First, an enzyme immunoassay (EIA) or immunofluorescence assay should be used, followed by a western immunoblot assay for specimens yielding positive or equivocal results. The guideline advised that all future tests should be evaluated against a challenge panel, and that new assays should only move forward if their specificity, sensitivity, and precision equaled or surpassed the performance of tests used in the recommended two-test procedure.

On July 29, 2019, the Food and Drug Administration approved several Lyme disease serologic assays with new indications for use based on a modified two-test methodology, with a second EIA replacing the western immunoblot assay.

“Clearance by FDA of the new Lyme disease assays indicates that test performance has been evaluated and is ‘substantially equivalent to or better than’ a legally marketed predicate test,” the CDC investigators noted (MMWR Morb Mortal Wkly Rep. 2019 Aug 15;68(32):703).

The recommendation advises that FDA-cleared “serologic assays that utilize EIA rather than western immunoblot assay in a two-test format are acceptable alternatives for the laboratory diagnosis of Lyme disease.”

[email protected]

The Centers for Disease Control and Prevention has updated its recommendation for serologic detection of Lyme disease, according to CDC investigators.

At the 1994 Second National Conference on Serologic Diagnosis of Lyme Disease, several groups and organizations convened, recommending a two-test methodology for Lyme disease detection. First, an enzyme immunoassay (EIA) or immunofluorescence assay should be used, followed by a western immunoblot assay for specimens yielding positive or equivocal results. The guideline advised that all future tests should be evaluated against a challenge panel, and that new assays should only move forward if their specificity, sensitivity, and precision equaled or surpassed the performance of tests used in the recommended two-test procedure.

On July 29, 2019, the Food and Drug Administration approved several Lyme disease serologic assays with new indications for use based on a modified two-test methodology, with a second EIA replacing the western immunoblot assay.

“Clearance by FDA of the new Lyme disease assays indicates that test performance has been evaluated and is ‘substantially equivalent to or better than’ a legally marketed predicate test,” the CDC investigators noted (MMWR Morb Mortal Wkly Rep. 2019 Aug 15;68(32):703).

The recommendation advises that FDA-cleared “serologic assays that utilize EIA rather than western immunoblot assay in a two-test format are acceptable alternatives for the laboratory diagnosis of Lyme disease.”

[email protected]

The Centers for Disease Control and Prevention has updated its recommendation for serologic detection of Lyme disease, according to CDC investigators.

At the 1994 Second National Conference on Serologic Diagnosis of Lyme Disease, several groups and organizations convened, recommending a two-test methodology for Lyme disease detection. First, an enzyme immunoassay (EIA) or immunofluorescence assay should be used, followed by a western immunoblot assay for specimens yielding positive or equivocal results. The guideline advised that all future tests should be evaluated against a challenge panel, and that new assays should only move forward if their specificity, sensitivity, and precision equaled or surpassed the performance of tests used in the recommended two-test procedure.

On July 29, 2019, the Food and Drug Administration approved several Lyme disease serologic assays with new indications for use based on a modified two-test methodology, with a second EIA replacing the western immunoblot assay.

“Clearance by FDA of the new Lyme disease assays indicates that test performance has been evaluated and is ‘substantially equivalent to or better than’ a legally marketed predicate test,” the CDC investigators noted (MMWR Morb Mortal Wkly Rep. 2019 Aug 15;68(32):703).

The recommendation advises that FDA-cleared “serologic assays that utilize EIA rather than western immunoblot assay in a two-test format are acceptable alternatives for the laboratory diagnosis of Lyme disease.”

[email protected]

SEATTLE – Levine Children’s Hospital, in Charlotte, N.C., dropped its central line–associated bloodstream infection rate from 1.13 per 1,000 line days to 0.67 in just a few months, with a mix of common sense steps and public accountability.

M. Alexander Otto/MDedge News

Levine Children’s was at about the 50th percentile for CLABSIs, compared with other children’s hospitals, but dropped to the 10th percentile after the changes. There were 21 CLABSIs in 2017, but only 12 in 2018. The hospital went 6 straight months without a CLABSI after the changes were made. The efforts saved about $300,000 and 63 patient days.

“We really had great success,” said Kayla S. Koch, MD, a pediatric hospitalist at Levine Children’s, who presented the findings at Pediatric Hospital Medicine.

Hospital units had been working to reduce CLABSIs, but they were each doing their own thing. “Many of our units were already dabbling, so we just sort of brought them together. We standardized the process and got everyone on the same page,” said copresenter Ketan P. Nadkarni, MD, also a pediatric hospitalist at Levine Children’s.

It wasn’t hard to get buy-in. “I don’t think the units were aware that everyone was doing it differently,” and were on board once the problem was explained. Also, using the same approach throughout the hospital made it easier for nurses and physicians moving between units, he said.

Each morning, the nurse supervisor and patient nurse would partner up at the bedside to check that central venous lines were set up correctly. They examined the alcohol disinfectant caps to make sure they were clean; determined that children were getting chlorhexidine gluconate baths; checked the dressings for bleeding and soiling; noted in the electronic medical record why the patient had a central line; and discussed with hospitalists if it were still needed. Problems were addressed immediately.

These quality processes were all tracked on wall racks placed in plain sight on each unit, including the neonatal and pediatric ICUs. Each central line patient had a card that listed what needed to be done, with a green stripe on one side and a red stripe on the other. If everything was done right, the green side faced out; if even one thing was done wrong, the red side was displayed, for all to see. It brought accountability to the process, the presenters said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The wall rack also had the central line audit schedule, plus diagrams that showed every failed item, the reason for it, and the unit’s compliance rate. Anyone walking by could see at a glance how the unit was doing that day and overall.

The number of dressing options was reduced from 10 to 2, a SorbaView SHIELD and a Tegaderm-like dressing, which made it easier to standardize the efforts. A protocol also was put in place to reinforce oozing dressings, instead of automatically changing them. “We were doing too many changes,” Dr. Koch said.

Compliance with the bundle was almost 90%. Staff “really got into it, and it was great to see,” she said.

The “initial success was almost unexpected, and so dramatic.” The goal now is to sustain the improvements, and roll them out to radiology and other places were central lines are placed, Dr. Nadkarni said.

There was no external funding, and the investigators had no disclosures.

[email protected]

SEATTLE – Levine Children’s Hospital, in Charlotte, N.C., dropped its central line–associated bloodstream infection rate from 1.13 per 1,000 line days to 0.67 in just a few months, with a mix of common sense steps and public accountability.

M. Alexander Otto/MDedge News

Levine Children’s was at about the 50th percentile for CLABSIs, compared with other children’s hospitals, but dropped to the 10th percentile after the changes. There were 21 CLABSIs in 2017, but only 12 in 2018. The hospital went 6 straight months without a CLABSI after the changes were made. The efforts saved about $300,000 and 63 patient days.

“We really had great success,” said Kayla S. Koch, MD, a pediatric hospitalist at Levine Children’s, who presented the findings at Pediatric Hospital Medicine.

Hospital units had been working to reduce CLABSIs, but they were each doing their own thing. “Many of our units were already dabbling, so we just sort of brought them together. We standardized the process and got everyone on the same page,” said copresenter Ketan P. Nadkarni, MD, also a pediatric hospitalist at Levine Children’s.

It wasn’t hard to get buy-in. “I don’t think the units were aware that everyone was doing it differently,” and were on board once the problem was explained. Also, using the same approach throughout the hospital made it easier for nurses and physicians moving between units, he said.

Each morning, the nurse supervisor and patient nurse would partner up at the bedside to check that central venous lines were set up correctly. They examined the alcohol disinfectant caps to make sure they were clean; determined that children were getting chlorhexidine gluconate baths; checked the dressings for bleeding and soiling; noted in the electronic medical record why the patient had a central line; and discussed with hospitalists if it were still needed. Problems were addressed immediately.

These quality processes were all tracked on wall racks placed in plain sight on each unit, including the neonatal and pediatric ICUs. Each central line patient had a card that listed what needed to be done, with a green stripe on one side and a red stripe on the other. If everything was done right, the green side faced out; if even one thing was done wrong, the red side was displayed, for all to see. It brought accountability to the process, the presenters said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The wall rack also had the central line audit schedule, plus diagrams that showed every failed item, the reason for it, and the unit’s compliance rate. Anyone walking by could see at a glance how the unit was doing that day and overall.

The number of dressing options was reduced from 10 to 2, a SorbaView SHIELD and a Tegaderm-like dressing, which made it easier to standardize the efforts. A protocol also was put in place to reinforce oozing dressings, instead of automatically changing them. “We were doing too many changes,” Dr. Koch said.

Compliance with the bundle was almost 90%. Staff “really got into it, and it was great to see,” she said.

The “initial success was almost unexpected, and so dramatic.” The goal now is to sustain the improvements, and roll them out to radiology and other places were central lines are placed, Dr. Nadkarni said.

There was no external funding, and the investigators had no disclosures.

[email protected]

SEATTLE – Levine Children’s Hospital, in Charlotte, N.C., dropped its central line–associated bloodstream infection rate from 1.13 per 1,000 line days to 0.67 in just a few months, with a mix of common sense steps and public accountability.

M. Alexander Otto/MDedge News

Levine Children’s was at about the 50th percentile for CLABSIs, compared with other children’s hospitals, but dropped to the 10th percentile after the changes. There were 21 CLABSIs in 2017, but only 12 in 2018. The hospital went 6 straight months without a CLABSI after the changes were made. The efforts saved about $300,000 and 63 patient days.

“We really had great success,” said Kayla S. Koch, MD, a pediatric hospitalist at Levine Children’s, who presented the findings at Pediatric Hospital Medicine.

Hospital units had been working to reduce CLABSIs, but they were each doing their own thing. “Many of our units were already dabbling, so we just sort of brought them together. We standardized the process and got everyone on the same page,” said copresenter Ketan P. Nadkarni, MD, also a pediatric hospitalist at Levine Children’s.

It wasn’t hard to get buy-in. “I don’t think the units were aware that everyone was doing it differently,” and were on board once the problem was explained. Also, using the same approach throughout the hospital made it easier for nurses and physicians moving between units, he said.

Each morning, the nurse supervisor and patient nurse would partner up at the bedside to check that central venous lines were set up correctly. They examined the alcohol disinfectant caps to make sure they were clean; determined that children were getting chlorhexidine gluconate baths; checked the dressings for bleeding and soiling; noted in the electronic medical record why the patient had a central line; and discussed with hospitalists if it were still needed. Problems were addressed immediately.

These quality processes were all tracked on wall racks placed in plain sight on each unit, including the neonatal and pediatric ICUs. Each central line patient had a card that listed what needed to be done, with a green stripe on one side and a red stripe on the other. If everything was done right, the green side faced out; if even one thing was done wrong, the red side was displayed, for all to see. It brought accountability to the process, the presenters said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The wall rack also had the central line audit schedule, plus diagrams that showed every failed item, the reason for it, and the unit’s compliance rate. Anyone walking by could see at a glance how the unit was doing that day and overall.

The number of dressing options was reduced from 10 to 2, a SorbaView SHIELD and a Tegaderm-like dressing, which made it easier to standardize the efforts. A protocol also was put in place to reinforce oozing dressings, instead of automatically changing them. “We were doing too many changes,” Dr. Koch said.

Compliance with the bundle was almost 90%. Staff “really got into it, and it was great to see,” she said.

The “initial success was almost unexpected, and so dramatic.” The goal now is to sustain the improvements, and roll them out to radiology and other places were central lines are placed, Dr. Nadkarni said.

There was no external funding, and the investigators had no disclosures.

[email protected]

The U.S. Food and Drug Administration granted special approval to a new drug combo intended for the treatment of “a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug-resistant pulmonary” tuberculosis, according to an FDA news release.

The effectiveness of the combination treatment of pretomanid tablets with bedaquiline and linezolid was shown in a clinical study of patients with extensively drug-resistant, treatment-intolerant, or nonresponsive multidrug-resistant pulmonary tuberculosis of the lungs. Of 107 infected patients who were evaluated 6 months after the end of therapy, 95 (89%) were deemed successes, which significantly exceeded the historical success rates for treatment of extensively drug-resistant TB, the FDA reported. The trial is sponsored by the Global Alliance for TB Drug Development.

The most common adverse effects reported included peripheral neuropathy, anemia, nausea, vomiting, headache, increased liver enzymes, dyspepsia, rash, visual impairment, low blood sugar, and diarrhea, according to the release.

“Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs,” stated FDA Principal Deputy Commissioner Amy Abernethy, MD, PhD, in the release. She also explained that the approval marked the second time a drug was approved under the “Limited Population Pathway for Antibacterial and Antifungal Drugs, a pathway advanced by Congress to spur development of drugs targeting infections that lack effective therapies.”

In 2016, the World Health Organization reported that there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB, according to the release, demonstrating the need for new therapeutics.
 

[email protected]

SOURCE: U.S. Food and Drug Administration. Aug. 14, 2019. News release.

The U.S. Food and Drug Administration granted special approval to a new drug combo intended for the treatment of “a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug-resistant pulmonary” tuberculosis, according to an FDA news release.

The effectiveness of the combination treatment of pretomanid tablets with bedaquiline and linezolid was shown in a clinical study of patients with extensively drug-resistant, treatment-intolerant, or nonresponsive multidrug-resistant pulmonary tuberculosis of the lungs. Of 107 infected patients who were evaluated 6 months after the end of therapy, 95 (89%) were deemed successes, which significantly exceeded the historical success rates for treatment of extensively drug-resistant TB, the FDA reported. The trial is sponsored by the Global Alliance for TB Drug Development.

The most common adverse effects reported included peripheral neuropathy, anemia, nausea, vomiting, headache, increased liver enzymes, dyspepsia, rash, visual impairment, low blood sugar, and diarrhea, according to the release.

“Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs,” stated FDA Principal Deputy Commissioner Amy Abernethy, MD, PhD, in the release. She also explained that the approval marked the second time a drug was approved under the “Limited Population Pathway for Antibacterial and Antifungal Drugs, a pathway advanced by Congress to spur development of drugs targeting infections that lack effective therapies.”

In 2016, the World Health Organization reported that there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB, according to the release, demonstrating the need for new therapeutics.
 

[email protected]

SOURCE: U.S. Food and Drug Administration. Aug. 14, 2019. News release.

The U.S. Food and Drug Administration granted special approval to a new drug combo intended for the treatment of “a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug-resistant pulmonary” tuberculosis, according to an FDA news release.

The effectiveness of the combination treatment of pretomanid tablets with bedaquiline and linezolid was shown in a clinical study of patients with extensively drug-resistant, treatment-intolerant, or nonresponsive multidrug-resistant pulmonary tuberculosis of the lungs. Of 107 infected patients who were evaluated 6 months after the end of therapy, 95 (89%) were deemed successes, which significantly exceeded the historical success rates for treatment of extensively drug-resistant TB, the FDA reported. The trial is sponsored by the Global Alliance for TB Drug Development.

The most common adverse effects reported included peripheral neuropathy, anemia, nausea, vomiting, headache, increased liver enzymes, dyspepsia, rash, visual impairment, low blood sugar, and diarrhea, according to the release.

“Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs,” stated FDA Principal Deputy Commissioner Amy Abernethy, MD, PhD, in the release. She also explained that the approval marked the second time a drug was approved under the “Limited Population Pathway for Antibacterial and Antifungal Drugs, a pathway advanced by Congress to spur development of drugs targeting infections that lack effective therapies.”

In 2016, the World Health Organization reported that there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB, according to the release, demonstrating the need for new therapeutics.
 

[email protected]

SOURCE: U.S. Food and Drug Administration. Aug. 14, 2019. News release.

High levels of enterovirus (EV) peptides were found in the cerebrospinal fluid (CSF) and serum samples of individuals with acute flaccid myelitis (AFM) that were not present in a variety of control individuals, according to the results of a small study of patients with and without AFM published online in mBio.

CDC

In 2018, CSF samples from AFM patients were investigated by viral-capture high-throughput sequencing. These CSF and serum samples, as well as those from multiple controls, were tested for antibodies to human EVs using peptide microarrays, according to Nischay Mishra, PhD, of Columbia University, New York, and colleagues.

Although EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case, antibodies to EV peptides were present in 11 of 14 AFM patients (79%), which was a significantly higher rate than in control groups, including non-AFM patients (1 of 5, or 20%), children with Kawasaki disease (0 of 10), and adults with non-AFM CNS diseases (2 of 11, 18%), according to the authors.

In addition, 6 of 14 (43%) CSF samples and 8 of 11 (73%) serum samples from AFM patients were immunoreactive to an EV-D68–specific peptide, whereas samples from the three control groups were not immunoreactive in either CSF or sera. Previous studies have suggested that infection with EV-D68 and EV-A71 may contribute to AFM.

“There have been 570 confirmed cases since CDC began tracking AFM in August 2014. AFM outbreaks were reported to the CDC in 2014, 2016, and 2018. AFM affects the spinal cord and is characterized by the sudden onset of muscle weakness in one or more limbs. Spikes in AFM cases, primarily in children, have coincided in time and location with outbreaks of EV-D68 and a related enterovirus, EV-A71,” according to an NIH media advisory discussing the article.

In particular, as the study authors point out, a potential link to EV-D68 has also been based on the presence of viral RNA in some respiratory and stool specimens and the observation that EV-D68 infection can result in spinal cord infection.

“While other etiologies of AFM continue to be investigated, our study provides further evidence that EV infection may be a factor in AFM. In the absence of direct detection of a pathogen, antibody evidence of pathogen exposure within the CNS can be an important indicator of the underlying cause of disease,” Dr. Mishra and his colleagues added.

“These initial results may provide avenues to further explore how exposure to EV may contribute to AFM as well as the development of diagnostic tools and treatments,” the researchers concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no competing financial interests.

[email protected]

SOURCE: Mishra N et al. mBio. 2019 Aug;10(4):e01903-19.

High levels of enterovirus (EV) peptides were found in the cerebrospinal fluid (CSF) and serum samples of individuals with acute flaccid myelitis (AFM) that were not present in a variety of control individuals, according to the results of a small study of patients with and without AFM published online in mBio.

CDC

In 2018, CSF samples from AFM patients were investigated by viral-capture high-throughput sequencing. These CSF and serum samples, as well as those from multiple controls, were tested for antibodies to human EVs using peptide microarrays, according to Nischay Mishra, PhD, of Columbia University, New York, and colleagues.

Although EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case, antibodies to EV peptides were present in 11 of 14 AFM patients (79%), which was a significantly higher rate than in control groups, including non-AFM patients (1 of 5, or 20%), children with Kawasaki disease (0 of 10), and adults with non-AFM CNS diseases (2 of 11, 18%), according to the authors.

In addition, 6 of 14 (43%) CSF samples and 8 of 11 (73%) serum samples from AFM patients were immunoreactive to an EV-D68–specific peptide, whereas samples from the three control groups were not immunoreactive in either CSF or sera. Previous studies have suggested that infection with EV-D68 and EV-A71 may contribute to AFM.

“There have been 570 confirmed cases since CDC began tracking AFM in August 2014. AFM outbreaks were reported to the CDC in 2014, 2016, and 2018. AFM affects the spinal cord and is characterized by the sudden onset of muscle weakness in one or more limbs. Spikes in AFM cases, primarily in children, have coincided in time and location with outbreaks of EV-D68 and a related enterovirus, EV-A71,” according to an NIH media advisory discussing the article.

In particular, as the study authors point out, a potential link to EV-D68 has also been based on the presence of viral RNA in some respiratory and stool specimens and the observation that EV-D68 infection can result in spinal cord infection.

“While other etiologies of AFM continue to be investigated, our study provides further evidence that EV infection may be a factor in AFM. In the absence of direct detection of a pathogen, antibody evidence of pathogen exposure within the CNS can be an important indicator of the underlying cause of disease,” Dr. Mishra and his colleagues added.

“These initial results may provide avenues to further explore how exposure to EV may contribute to AFM as well as the development of diagnostic tools and treatments,” the researchers concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no competing financial interests.

[email protected]

SOURCE: Mishra N et al. mBio. 2019 Aug;10(4):e01903-19.

High levels of enterovirus (EV) peptides were found in the cerebrospinal fluid (CSF) and serum samples of individuals with acute flaccid myelitis (AFM) that were not present in a variety of control individuals, according to the results of a small study of patients with and without AFM published online in mBio.

CDC

In 2018, CSF samples from AFM patients were investigated by viral-capture high-throughput sequencing. These CSF and serum samples, as well as those from multiple controls, were tested for antibodies to human EVs using peptide microarrays, according to Nischay Mishra, PhD, of Columbia University, New York, and colleagues.

Although EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case, antibodies to EV peptides were present in 11 of 14 AFM patients (79%), which was a significantly higher rate than in control groups, including non-AFM patients (1 of 5, or 20%), children with Kawasaki disease (0 of 10), and adults with non-AFM CNS diseases (2 of 11, 18%), according to the authors.

In addition, 6 of 14 (43%) CSF samples and 8 of 11 (73%) serum samples from AFM patients were immunoreactive to an EV-D68–specific peptide, whereas samples from the three control groups were not immunoreactive in either CSF or sera. Previous studies have suggested that infection with EV-D68 and EV-A71 may contribute to AFM.

“There have been 570 confirmed cases since CDC began tracking AFM in August 2014. AFM outbreaks were reported to the CDC in 2014, 2016, and 2018. AFM affects the spinal cord and is characterized by the sudden onset of muscle weakness in one or more limbs. Spikes in AFM cases, primarily in children, have coincided in time and location with outbreaks of EV-D68 and a related enterovirus, EV-A71,” according to an NIH media advisory discussing the article.

In particular, as the study authors point out, a potential link to EV-D68 has also been based on the presence of viral RNA in some respiratory and stool specimens and the observation that EV-D68 infection can result in spinal cord infection.

“While other etiologies of AFM continue to be investigated, our study provides further evidence that EV infection may be a factor in AFM. In the absence of direct detection of a pathogen, antibody evidence of pathogen exposure within the CNS can be an important indicator of the underlying cause of disease,” Dr. Mishra and his colleagues added.

“These initial results may provide avenues to further explore how exposure to EV may contribute to AFM as well as the development of diagnostic tools and treatments,” the researchers concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no competing financial interests.

[email protected]

SOURCE: Mishra N et al. mBio. 2019 Aug;10(4):e01903-19.

Cardiac biomarkers were used to predict the likelihood of cardiovascular events at day 1 and day 30 in patients with community-acquired pneumonia, in a recently conducted study.

Thomas Northcut/Thinkstock

These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.

“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”

Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.

Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.

With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.

After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO₂/FiO₂) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.

Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.

This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
 

SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.

Cardiac biomarkers were used to predict the likelihood of cardiovascular events at day 1 and day 30 in patients with community-acquired pneumonia, in a recently conducted study.

Thomas Northcut/Thinkstock

These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.

“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”

Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.

Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.

With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.

After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO₂/FiO₂) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.

Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.

This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
 

SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.

Cardiac biomarkers were used to predict the likelihood of cardiovascular events at day 1 and day 30 in patients with community-acquired pneumonia, in a recently conducted study.

Thomas Northcut/Thinkstock

These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.

“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”

Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.

Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.

With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.

After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO₂/FiO₂) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.

Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.

This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
 

SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.

LJUBLJANA, SLOVENIA – A new age-adjusted quick Sequential Organ Failure Assessment (qSOFA) score designed for use in children presenting to the ED with fever showed good predictive value for admission to critical care within the next 48 hours, Aakash Khanijau, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“In the needle-in-a-haystack scenario that’s seen in pediatric emergency departments, our novel, age-adjusted qSOFA score could potentially improve the rapid identification and treatment of children with suspected sepsis presenting to the ED,” said Dr. Khanijau of the University of Liverpool (England).

He presented an exceptionally large retrospective validation study of the score’s performance in 12,393 children (median age, 2.5 years) who presented to EDs with fever, of whom 1,521 were admitted for suspected sepsis. Of the hospitalized children, 145 were admitted to critical care within the first 48 hours.

The pediatric qSOFA score had 72% sensitivity and 85% specificity for critical care admission within 48 hours, with a positive predictive value of 5.4% and, more importantly, a whopping negative predictive value of 99.6%.

“That very high negative predictive value underlines the powerful discriminatory nature of our tool in the emergency department setting,” Dr. Khanijau observed, adding that the score’s area under the receiver operating characteristic curve was 0.81, which is considered a good predictive value.

The impetus for developing an age-adjusted pediatric qSOFA score stems from the fact that the original qSOFA score was designed for rapid assessment of adults with suspected sepsis and isn’t applicable in children. Other existing scores, including SIRS (the Systemic Inflammatory Response Syndrome criteria), the full SOFA, and PELOD-2 (the Pediatric Logistic Organ Dysfunction score), take longer to determine than the adapted qSOFA in a setting where speed is of the essence, he explained.

The original qSOFA components are altered mentation, systolic blood pressure, and respiratory rate. The novel score developed by Dr. Khanijau and coworkers swaps out systolic BP in favor of capillary refill time and age-adjusted heart rate using the thresholds previously established in a landmark study from the Children’s Hospital of Philadelphia (Pediatrics. 2013 Apr;131[4]:e1150-7.)

“Our reasoning here is that arterial hypertension is known to be a much later sign of circulatory compromise in children and may provide less discriminatory value than signs such as delayed capillary refill time and tachycardia early in presentation in the emergency department,” according to Dr. Khanijau.


The novel scoring system features four criteria. One point each is given for a capillary refill time of 3 seconds or longer; anything less than “Alert” on the Alert, Responds to Voice, Respond to Pain, and Unresponsive scale; a heart rate above the 99th percentile on the age-adjusted curves; and a respiratory rate above the age-adjusted 99th percentile. Thus, scores can range from 0 to 4. In the validation study, a score of 2 or more spelled a 890% increased likelihood of being admitted to a critical care setting within 48 hours. It was also associated with a 100-fold increased likelihood of death during the hospitalization, which occurred in 10 children.

Asked how the new predictive score could change clinical management, Dr. Khanijau replied, “I think the key thing it does here is it identifies the children at risk of requiring critical care and should therefore motivate us in the children achieving that threshold to promptly investigate thoroughly for suspected sepsis using the more comprehensive tools, like the full SOFA.”

He reported having no financial conflicts of interest regarding his study.

[email protected]

SOURCE: Khanijau A et al. ESPID 2019, Abstract.

LJUBLJANA, SLOVENIA – A new age-adjusted quick Sequential Organ Failure Assessment (qSOFA) score designed for use in children presenting to the ED with fever showed good predictive value for admission to critical care within the next 48 hours, Aakash Khanijau, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“In the needle-in-a-haystack scenario that’s seen in pediatric emergency departments, our novel, age-adjusted qSOFA score could potentially improve the rapid identification and treatment of children with suspected sepsis presenting to the ED,” said Dr. Khanijau of the University of Liverpool (England).

He presented an exceptionally large retrospective validation study of the score’s performance in 12,393 children (median age, 2.5 years) who presented to EDs with fever, of whom 1,521 were admitted for suspected sepsis. Of the hospitalized children, 145 were admitted to critical care within the first 48 hours.

The pediatric qSOFA score had 72% sensitivity and 85% specificity for critical care admission within 48 hours, with a positive predictive value of 5.4% and, more importantly, a whopping negative predictive value of 99.6%.

“That very high negative predictive value underlines the powerful discriminatory nature of our tool in the emergency department setting,” Dr. Khanijau observed, adding that the score’s area under the receiver operating characteristic curve was 0.81, which is considered a good predictive value.

The impetus for developing an age-adjusted pediatric qSOFA score stems from the fact that the original qSOFA score was designed for rapid assessment of adults with suspected sepsis and isn’t applicable in children. Other existing scores, including SIRS (the Systemic Inflammatory Response Syndrome criteria), the full SOFA, and PELOD-2 (the Pediatric Logistic Organ Dysfunction score), take longer to determine than the adapted qSOFA in a setting where speed is of the essence, he explained.

The original qSOFA components are altered mentation, systolic blood pressure, and respiratory rate. The novel score developed by Dr. Khanijau and coworkers swaps out systolic BP in favor of capillary refill time and age-adjusted heart rate using the thresholds previously established in a landmark study from the Children’s Hospital of Philadelphia (Pediatrics. 2013 Apr;131[4]:e1150-7.)

“Our reasoning here is that arterial hypertension is known to be a much later sign of circulatory compromise in children and may provide less discriminatory value than signs such as delayed capillary refill time and tachycardia early in presentation in the emergency department,” according to Dr. Khanijau.


The novel scoring system features four criteria. One point each is given for a capillary refill time of 3 seconds or longer; anything less than “Alert” on the Alert, Responds to Voice, Respond to Pain, and Unresponsive scale; a heart rate above the 99th percentile on the age-adjusted curves; and a respiratory rate above the age-adjusted 99th percentile. Thus, scores can range from 0 to 4. In the validation study, a score of 2 or more spelled a 890% increased likelihood of being admitted to a critical care setting within 48 hours. It was also associated with a 100-fold increased likelihood of death during the hospitalization, which occurred in 10 children.

Asked how the new predictive score could change clinical management, Dr. Khanijau replied, “I think the key thing it does here is it identifies the children at risk of requiring critical care and should therefore motivate us in the children achieving that threshold to promptly investigate thoroughly for suspected sepsis using the more comprehensive tools, like the full SOFA.”

He reported having no financial conflicts of interest regarding his study.

[email protected]

SOURCE: Khanijau A et al. ESPID 2019, Abstract.

LJUBLJANA, SLOVENIA – A new age-adjusted quick Sequential Organ Failure Assessment (qSOFA) score designed for use in children presenting to the ED with fever showed good predictive value for admission to critical care within the next 48 hours, Aakash Khanijau, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“In the needle-in-a-haystack scenario that’s seen in pediatric emergency departments, our novel, age-adjusted qSOFA score could potentially improve the rapid identification and treatment of children with suspected sepsis presenting to the ED,” said Dr. Khanijau of the University of Liverpool (England).

He presented an exceptionally large retrospective validation study of the score’s performance in 12,393 children (median age, 2.5 years) who presented to EDs with fever, of whom 1,521 were admitted for suspected sepsis. Of the hospitalized children, 145 were admitted to critical care within the first 48 hours.

The pediatric qSOFA score had 72% sensitivity and 85% specificity for critical care admission within 48 hours, with a positive predictive value of 5.4% and, more importantly, a whopping negative predictive value of 99.6%.

“That very high negative predictive value underlines the powerful discriminatory nature of our tool in the emergency department setting,” Dr. Khanijau observed, adding that the score’s area under the receiver operating characteristic curve was 0.81, which is considered a good predictive value.

The impetus for developing an age-adjusted pediatric qSOFA score stems from the fact that the original qSOFA score was designed for rapid assessment of adults with suspected sepsis and isn’t applicable in children. Other existing scores, including SIRS (the Systemic Inflammatory Response Syndrome criteria), the full SOFA, and PELOD-2 (the Pediatric Logistic Organ Dysfunction score), take longer to determine than the adapted qSOFA in a setting where speed is of the essence, he explained.

The original qSOFA components are altered mentation, systolic blood pressure, and respiratory rate. The novel score developed by Dr. Khanijau and coworkers swaps out systolic BP in favor of capillary refill time and age-adjusted heart rate using the thresholds previously established in a landmark study from the Children’s Hospital of Philadelphia (Pediatrics. 2013 Apr;131[4]:e1150-7.)

“Our reasoning here is that arterial hypertension is known to be a much later sign of circulatory compromise in children and may provide less discriminatory value than signs such as delayed capillary refill time and tachycardia early in presentation in the emergency department,” according to Dr. Khanijau.


The novel scoring system features four criteria. One point each is given for a capillary refill time of 3 seconds or longer; anything less than “Alert” on the Alert, Responds to Voice, Respond to Pain, and Unresponsive scale; a heart rate above the 99th percentile on the age-adjusted curves; and a respiratory rate above the age-adjusted 99th percentile. Thus, scores can range from 0 to 4. In the validation study, a score of 2 or more spelled a 890% increased likelihood of being admitted to a critical care setting within 48 hours. It was also associated with a 100-fold increased likelihood of death during the hospitalization, which occurred in 10 children.

Asked how the new predictive score could change clinical management, Dr. Khanijau replied, “I think the key thing it does here is it identifies the children at risk of requiring critical care and should therefore motivate us in the children achieving that threshold to promptly investigate thoroughly for suspected sepsis using the more comprehensive tools, like the full SOFA.”

He reported having no financial conflicts of interest regarding his study.

[email protected]

SOURCE: Khanijau A et al. ESPID 2019, Abstract.

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.

gl0ck/Thinkstock

Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.

The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.

As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.

The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.

“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.

The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).

[email protected]

An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.

gl0ck/Thinkstock

Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.

The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.

As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.

The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.

“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.

The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).

[email protected]

An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.

gl0ck/Thinkstock

Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.

The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.

As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.

The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.

“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.

The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).

[email protected]