Pneumonia

Three U.S. airports will begin health screening for travelers from Wuhan, China, because of an outbreak of pneumonia caused by a newly identified coronavirus called 2019-nCoV, according to an announcement from the Centers for Disease Control and Prevention.

CDC/John Hierholzer, MD

Starting today, Jan. 17, 2020, people traveling from Wuhan to New York (JFK), San Francisco (SFO), and Los Angeles (LAX) airports will be screened for symptoms associated with 2019-nCoV, which include fever, cough, and difficulty breathing.

“Based on the information that CDC has today, we believe the current risk for this virus to the general public is low,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during a CDC telebriefing.

To date, 45 cases of 2019-nCoV have been reported in Wuhan, according to the CDC. The Wuhan Municipal Health Commission said 15 patients have been cured and discharged, 5 severe cases are still being treated, and 2 patients have died. Both deaths occurred in older patients, one of whom was aged 69 years and one aged 61 years. One of the patients was known to have underlying health conditions.

Three cases of 2019-nCoV have been confirmed outside of Wuhan, one in Japan and two in Thailand. All three were travelers from Wuhan.

The virus is believed to have originated at Wuhan South China Seafood City, a market that sold seafood, chickens, bats, cats, marmots, and other wild animals. (The market has since been closed and disinfected.) The origin suggests animal-to-human transmission of 2019-nCoV, but it appears that human-to-human transmission can occur as well.

“While most of these infections seem to be happening from animals to people, there is some indication that limited person-to-person spread is happening,” Dr. Messonnier said.

Maridav/Shutterstock

[email protected]

Three U.S. airports will begin health screening for travelers from Wuhan, China, because of an outbreak of pneumonia caused by a newly identified coronavirus called 2019-nCoV, according to an announcement from the Centers for Disease Control and Prevention.

CDC/John Hierholzer, MD

Starting today, Jan. 17, 2020, people traveling from Wuhan to New York (JFK), San Francisco (SFO), and Los Angeles (LAX) airports will be screened for symptoms associated with 2019-nCoV, which include fever, cough, and difficulty breathing.

“Based on the information that CDC has today, we believe the current risk for this virus to the general public is low,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during a CDC telebriefing.

To date, 45 cases of 2019-nCoV have been reported in Wuhan, according to the CDC. The Wuhan Municipal Health Commission said 15 patients have been cured and discharged, 5 severe cases are still being treated, and 2 patients have died. Both deaths occurred in older patients, one of whom was aged 69 years and one aged 61 years. One of the patients was known to have underlying health conditions.

Three cases of 2019-nCoV have been confirmed outside of Wuhan, one in Japan and two in Thailand. All three were travelers from Wuhan.

The virus is believed to have originated at Wuhan South China Seafood City, a market that sold seafood, chickens, bats, cats, marmots, and other wild animals. (The market has since been closed and disinfected.) The origin suggests animal-to-human transmission of 2019-nCoV, but it appears that human-to-human transmission can occur as well.

“While most of these infections seem to be happening from animals to people, there is some indication that limited person-to-person spread is happening,” Dr. Messonnier said.

Maridav/Shutterstock

[email protected]

Three U.S. airports will begin health screening for travelers from Wuhan, China, because of an outbreak of pneumonia caused by a newly identified coronavirus called 2019-nCoV, according to an announcement from the Centers for Disease Control and Prevention.

CDC/John Hierholzer, MD

Starting today, Jan. 17, 2020, people traveling from Wuhan to New York (JFK), San Francisco (SFO), and Los Angeles (LAX) airports will be screened for symptoms associated with 2019-nCoV, which include fever, cough, and difficulty breathing.

“Based on the information that CDC has today, we believe the current risk for this virus to the general public is low,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during a CDC telebriefing.

To date, 45 cases of 2019-nCoV have been reported in Wuhan, according to the CDC. The Wuhan Municipal Health Commission said 15 patients have been cured and discharged, 5 severe cases are still being treated, and 2 patients have died. Both deaths occurred in older patients, one of whom was aged 69 years and one aged 61 years. One of the patients was known to have underlying health conditions.

Three cases of 2019-nCoV have been confirmed outside of Wuhan, one in Japan and two in Thailand. All three were travelers from Wuhan.

The virus is believed to have originated at Wuhan South China Seafood City, a market that sold seafood, chickens, bats, cats, marmots, and other wild animals. (The market has since been closed and disinfected.) The origin suggests animal-to-human transmission of 2019-nCoV, but it appears that human-to-human transmission can occur as well.

“While most of these infections seem to be happening from animals to people, there is some indication that limited person-to-person spread is happening,” Dr. Messonnier said.

Maridav/Shutterstock

[email protected]

The pneumonia outbreak in China traced to a novel coronavirus appears to be contained, although at least two cases have appeared in other countries.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Health authorities in Wuhan, Hubei Province, China, identified the novel coronavirus, 2019-nCoV, responsible for the outbreak of a mysterious pneumonia that resulted in hospitalization of more than 40 patients and one death, according to the Centers for Disease Control and Prevention in a statement on the CDC website.

On Jan. 13, the Thailand’s Ministry of Public Health reported the first imported case of lab-confirmed 2019-nCoV from Wuhan. The Centers for Disease Control and Prevention stated: “The traveler with febrile illness was detected on the same day by thermal surveillance at Suvarnabhumi Airport, Thailand, and was hospitalized the same day. After temperature check and initial assessment, she was transferred to the hospital for further investigations and treatment.”

Samples from this patient tested positive for coronaviruses by reverse transcriptase-polymerase chain reaction. The genomic sequencing analysis was performed by Emerging Infectious Diseases Health Science Center, the Thai Red Cross Society, and the Thai National Institute of Health. The patient is reported to be in stable condition.

The New York Times has reported a case of 2019-nCoV in Japan in a traveler returning from Wuhan. That patient is reported to have recovered and been discharged.

Chinese health authorities transmitted the full genome of “2019 novel coronavirus,” or “2019-nCoV,” to GenBank, the genetic sequence database managed by the National Institutes of Health, and in the Global Initiative on Sharing All Influenza Data portal.

Coronaviruses are a large family of viruses. Most known human coronaviruses only cause mild respiratory disease, such as the common cold. But several coronaviruses have emerged to infect people and cause severe disease, such as has been seen with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The cases in the Wuhan pneumonia outbreak have tested negative for both SARS and MERS.

The outbreak in Wuhan appears to be contained. The World Health Organization reported that the Wuhan health authorities identified and followed 763 close contacts, including health care workers. No additional cases of infection with the novel coronavirus have been identified. The cluster of cases is linked to the Wuhan South China Seafood City market where – in addition to seafood – chickens, bats, marmots, and other animals were sold. That market has been closed since Jan. 1, 2020, for cleaning and disinfection.

The WHO is monitoring the situation closely and is in close contact with Chinese health authorities.

The CDC has issued a Level 1 travel alert and recommended that travelers to Wuhan, a city of over 19 million people, avoid animal and meat markets, avoid contact with sick people, and wash hands often with soap and water. Travelers who have been in Wuhan recently and who experience respiratory symptoms should notify the local health department immediately.

In addition, the CDC recommends that, for symptomatic patients with a history of travel to Wuhan, caution should be exercised in the health care setting. “Ask such patients to don a surgical mask as soon as they are identified. Conduct their evaluation in a private room with the door closed. Personnel entering the room to evaluate the patient should use contact precautions and wear an N95 disposable facepiece respirator. For patients admitted for inpatient care, implement contact and airborne isolation precautions, in addition to standard precautions, until further information becomes available. For additional infection control guidance see: www.cdc.gov/infectioncontrol/guidelines/isolation/index.html.”

[email protected]

The pneumonia outbreak in China traced to a novel coronavirus appears to be contained, although at least two cases have appeared in other countries.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Health authorities in Wuhan, Hubei Province, China, identified the novel coronavirus, 2019-nCoV, responsible for the outbreak of a mysterious pneumonia that resulted in hospitalization of more than 40 patients and one death, according to the Centers for Disease Control and Prevention in a statement on the CDC website.

On Jan. 13, the Thailand’s Ministry of Public Health reported the first imported case of lab-confirmed 2019-nCoV from Wuhan. The Centers for Disease Control and Prevention stated: “The traveler with febrile illness was detected on the same day by thermal surveillance at Suvarnabhumi Airport, Thailand, and was hospitalized the same day. After temperature check and initial assessment, she was transferred to the hospital for further investigations and treatment.”

Samples from this patient tested positive for coronaviruses by reverse transcriptase-polymerase chain reaction. The genomic sequencing analysis was performed by Emerging Infectious Diseases Health Science Center, the Thai Red Cross Society, and the Thai National Institute of Health. The patient is reported to be in stable condition.

The New York Times has reported a case of 2019-nCoV in Japan in a traveler returning from Wuhan. That patient is reported to have recovered and been discharged.

Chinese health authorities transmitted the full genome of “2019 novel coronavirus,” or “2019-nCoV,” to GenBank, the genetic sequence database managed by the National Institutes of Health, and in the Global Initiative on Sharing All Influenza Data portal.

Coronaviruses are a large family of viruses. Most known human coronaviruses only cause mild respiratory disease, such as the common cold. But several coronaviruses have emerged to infect people and cause severe disease, such as has been seen with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The cases in the Wuhan pneumonia outbreak have tested negative for both SARS and MERS.

The outbreak in Wuhan appears to be contained. The World Health Organization reported that the Wuhan health authorities identified and followed 763 close contacts, including health care workers. No additional cases of infection with the novel coronavirus have been identified. The cluster of cases is linked to the Wuhan South China Seafood City market where – in addition to seafood – chickens, bats, marmots, and other animals were sold. That market has been closed since Jan. 1, 2020, for cleaning and disinfection.

The WHO is monitoring the situation closely and is in close contact with Chinese health authorities.

The CDC has issued a Level 1 travel alert and recommended that travelers to Wuhan, a city of over 19 million people, avoid animal and meat markets, avoid contact with sick people, and wash hands often with soap and water. Travelers who have been in Wuhan recently and who experience respiratory symptoms should notify the local health department immediately.

In addition, the CDC recommends that, for symptomatic patients with a history of travel to Wuhan, caution should be exercised in the health care setting. “Ask such patients to don a surgical mask as soon as they are identified. Conduct their evaluation in a private room with the door closed. Personnel entering the room to evaluate the patient should use contact precautions and wear an N95 disposable facepiece respirator. For patients admitted for inpatient care, implement contact and airborne isolation precautions, in addition to standard precautions, until further information becomes available. For additional infection control guidance see: www.cdc.gov/infectioncontrol/guidelines/isolation/index.html.”

[email protected]

The pneumonia outbreak in China traced to a novel coronavirus appears to be contained, although at least two cases have appeared in other countries.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Health authorities in Wuhan, Hubei Province, China, identified the novel coronavirus, 2019-nCoV, responsible for the outbreak of a mysterious pneumonia that resulted in hospitalization of more than 40 patients and one death, according to the Centers for Disease Control and Prevention in a statement on the CDC website.

On Jan. 13, the Thailand’s Ministry of Public Health reported the first imported case of lab-confirmed 2019-nCoV from Wuhan. The Centers for Disease Control and Prevention stated: “The traveler with febrile illness was detected on the same day by thermal surveillance at Suvarnabhumi Airport, Thailand, and was hospitalized the same day. After temperature check and initial assessment, she was transferred to the hospital for further investigations and treatment.”

Samples from this patient tested positive for coronaviruses by reverse transcriptase-polymerase chain reaction. The genomic sequencing analysis was performed by Emerging Infectious Diseases Health Science Center, the Thai Red Cross Society, and the Thai National Institute of Health. The patient is reported to be in stable condition.

The New York Times has reported a case of 2019-nCoV in Japan in a traveler returning from Wuhan. That patient is reported to have recovered and been discharged.

Chinese health authorities transmitted the full genome of “2019 novel coronavirus,” or “2019-nCoV,” to GenBank, the genetic sequence database managed by the National Institutes of Health, and in the Global Initiative on Sharing All Influenza Data portal.

Coronaviruses are a large family of viruses. Most known human coronaviruses only cause mild respiratory disease, such as the common cold. But several coronaviruses have emerged to infect people and cause severe disease, such as has been seen with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The cases in the Wuhan pneumonia outbreak have tested negative for both SARS and MERS.

The outbreak in Wuhan appears to be contained. The World Health Organization reported that the Wuhan health authorities identified and followed 763 close contacts, including health care workers. No additional cases of infection with the novel coronavirus have been identified. The cluster of cases is linked to the Wuhan South China Seafood City market where – in addition to seafood – chickens, bats, marmots, and other animals were sold. That market has been closed since Jan. 1, 2020, for cleaning and disinfection.

The WHO is monitoring the situation closely and is in close contact with Chinese health authorities.

The CDC has issued a Level 1 travel alert and recommended that travelers to Wuhan, a city of over 19 million people, avoid animal and meat markets, avoid contact with sick people, and wash hands often with soap and water. Travelers who have been in Wuhan recently and who experience respiratory symptoms should notify the local health department immediately.

In addition, the CDC recommends that, for symptomatic patients with a history of travel to Wuhan, caution should be exercised in the health care setting. “Ask such patients to don a surgical mask as soon as they are identified. Conduct their evaluation in a private room with the door closed. Personnel entering the room to evaluate the patient should use contact precautions and wear an N95 disposable facepiece respirator. For patients admitted for inpatient care, implement contact and airborne isolation precautions, in addition to standard precautions, until further information becomes available. For additional infection control guidance see: www.cdc.gov/infectioncontrol/guidelines/isolation/index.html.”

[email protected]

An outbreak of pneumonia of unknown etiology has occurred in Wuhan, China, according to a statement from the Centers for Disease Control and Prevention.

As of Jan. 5, 2020, 59 cases of the disease have been reported by the Wuhan Municipal Health Commission. The cluster of cases is linked to the Wuhan South China Seafood City market where – in addition to seafood – chickens, bats, marmots, and other animals were sold. That market has been closed since Jan. 1, 2020, for cleaning and disinfection.

Wuhan health authorities are closely monitoring over 150 contacts for symptoms. Laboratory results have been negative for influenza, avian influenza, adenovirus, and the viruses that caused SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). So far, there are no reports of person-to-person transmission or health care worker infection of this pneumonia.

The World Health Organization reported that, as of Dec. 31, 2019, about one-quarter of patients were severely ill with the pneumonia and the rest were stable. Symptoms reported include fever, difficulty breathing, and chest radiographs showing invasive lesions in both lungs. All patients are being treated in isolation and efforts to identify the pathogen are ongoing.

[email protected]

An outbreak of pneumonia of unknown etiology has occurred in Wuhan, China, according to a statement from the Centers for Disease Control and Prevention.

As of Jan. 5, 2020, 59 cases of the disease have been reported by the Wuhan Municipal Health Commission. The cluster of cases is linked to the Wuhan South China Seafood City market where – in addition to seafood – chickens, bats, marmots, and other animals were sold. That market has been closed since Jan. 1, 2020, for cleaning and disinfection.

Wuhan health authorities are closely monitoring over 150 contacts for symptoms. Laboratory results have been negative for influenza, avian influenza, adenovirus, and the viruses that caused SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). So far, there are no reports of person-to-person transmission or health care worker infection of this pneumonia.

The World Health Organization reported that, as of Dec. 31, 2019, about one-quarter of patients were severely ill with the pneumonia and the rest were stable. Symptoms reported include fever, difficulty breathing, and chest radiographs showing invasive lesions in both lungs. All patients are being treated in isolation and efforts to identify the pathogen are ongoing.

[email protected]

An outbreak of pneumonia of unknown etiology has occurred in Wuhan, China, according to a statement from the Centers for Disease Control and Prevention.

As of Jan. 5, 2020, 59 cases of the disease have been reported by the Wuhan Municipal Health Commission. The cluster of cases is linked to the Wuhan South China Seafood City market where – in addition to seafood – chickens, bats, marmots, and other animals were sold. That market has been closed since Jan. 1, 2020, for cleaning and disinfection.

Wuhan health authorities are closely monitoring over 150 contacts for symptoms. Laboratory results have been negative for influenza, avian influenza, adenovirus, and the viruses that caused SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). So far, there are no reports of person-to-person transmission or health care worker infection of this pneumonia.

The World Health Organization reported that, as of Dec. 31, 2019, about one-quarter of patients were severely ill with the pneumonia and the rest were stable. Symptoms reported include fever, difficulty breathing, and chest radiographs showing invasive lesions in both lungs. All patients are being treated in isolation and efforts to identify the pathogen are ongoing.

[email protected]

Even on-time pneumococcal vaccines don’t completely protect children with asthma from developing invasive pneumococcal disease, a meta-analysis has determined.

Despite receiving pneumococcal valent 7, 10, or 13, children with asthma were still almost twice as likely to develop the disease as were children without asthma, Jose A. Castro-Rodriguez, MD, PhD, and colleagues reported in Pediatrics (2020 Jan. doi: 10.1542/peds.2019-1200). None of the studies included rates for those who received the pneumococcal polysaccharide vaccine (PPSV23).

“For the first time, this meta-analysis reveals 90% increased odds of invasive pneumococcal disease (IPD) among [vaccinated] children with asthma,” said Dr. Castro-Rodriguez, of Pontificia Universidad Católica de Chile, Santiago, and colleagues. “If confirmed, these findings will bear clinical and public health importance,” they noted, because guidelines now recommend PPSV23 after age 2 in children with asthma only if they’re treated with prolonged high-dose oral corticosteroids.

However, because the analysis comprised only four studies, the authors cautioned that the results aren’t enough to justify changes to practice recommendations.

Asthma treatment with inhaled corticosteroids (ICS) may be driving the increased risk, Dr. Castro-Rodriguez and his coauthors suggested. ICS deposition in the oropharynx could boost oropharyngeal candidiasis risk by weakening the mucosal immune response, the researchers noted. And that same process may be at work with Streptococcus pneumoniae.

A prior study found that children with asthma who received ICS for at least 1 month were almost four times more likely to have oropharyngeal colonization by S. pneumoniae as were those who didn’t get the drugs. Thus, a higher carrier rate of S. pneumoniae in the oropharynx, along with asthma’s impaired airway clearance, might increase the risk of pneumococcal diseases, the investigators explained.

Dr. Castro-Rodriguez and colleagues analyzed four studies with more than 4,000 cases and controls, and about 26 million person-years of follow-up.

Rates and risks of IPD in the four studies were as follows:

• Among those with IPD, 27% had asthma, with 18% of those without, an adjusted odds ratio (aOR) of 1.8.
• In a European of patients who received at least 3 doses of PCV7, IPD rates per 100,000 person-years for 5-year-olds were 11.6 for children with asthma and 7.3 for those without. For 5- to 17-year-olds with and without asthma, the rates were 2.3 and 1.6, respectively.
• In 2001, a Korean found an aOR of 2.08 for IPD in children with asthma, compared with those without. In 2010, the aOR was 3.26. No vaccine types were reported in the study.
• of IPD were 3.7 per 100,000 person-years for children with asthma, compared with 2.5 for healthy controls – an adjusted relative risk of 1.5.

The pooled estimate of the four studies revealed an aOR of 1.9 for IPD among children with asthma, compared with those without, Dr. Castro-Rodriguez and his team concluded.

None of the studies reported hospital admissions, mortality, length of hospital stay, intensive care admission, invasive respiratory support, or additional medication use.

One, however, did find asthma severity was significantly associated with increasing IPD treatment costs per 100,000 person-years: $72,581 for healthy controls, compared with $100,020 for children with mild asthma, $172,002 for moderate asthma, and $638,452 for severe asthma.

In addition, treating all-cause pneumonia was more expensive in children with asthma. For all-cause pneumonia, the researchers found that estimated costs per 100,000 person-years for mild, moderate, and severe asthma were $7.5 million, $14.6 million, and $46.8 million, respectively, compared with $1.7 million for healthy controls.

The authors had no relevant financial disclosures.

[email protected]

SOURCE: Castro-Rodriguez J et al. Pediatrics. 2020 Jan. doi: 10.1542/peds.2019-1200.

Even on-time pneumococcal vaccines don’t completely protect children with asthma from developing invasive pneumococcal disease, a meta-analysis has determined.

Despite receiving pneumococcal valent 7, 10, or 13, children with asthma were still almost twice as likely to develop the disease as were children without asthma, Jose A. Castro-Rodriguez, MD, PhD, and colleagues reported in Pediatrics (2020 Jan. doi: 10.1542/peds.2019-1200). None of the studies included rates for those who received the pneumococcal polysaccharide vaccine (PPSV23).

“For the first time, this meta-analysis reveals 90% increased odds of invasive pneumococcal disease (IPD) among [vaccinated] children with asthma,” said Dr. Castro-Rodriguez, of Pontificia Universidad Católica de Chile, Santiago, and colleagues. “If confirmed, these findings will bear clinical and public health importance,” they noted, because guidelines now recommend PPSV23 after age 2 in children with asthma only if they’re treated with prolonged high-dose oral corticosteroids.

However, because the analysis comprised only four studies, the authors cautioned that the results aren’t enough to justify changes to practice recommendations.

Asthma treatment with inhaled corticosteroids (ICS) may be driving the increased risk, Dr. Castro-Rodriguez and his coauthors suggested. ICS deposition in the oropharynx could boost oropharyngeal candidiasis risk by weakening the mucosal immune response, the researchers noted. And that same process may be at work with Streptococcus pneumoniae.

A prior study found that children with asthma who received ICS for at least 1 month were almost four times more likely to have oropharyngeal colonization by S. pneumoniae as were those who didn’t get the drugs. Thus, a higher carrier rate of S. pneumoniae in the oropharynx, along with asthma’s impaired airway clearance, might increase the risk of pneumococcal diseases, the investigators explained.

Dr. Castro-Rodriguez and colleagues analyzed four studies with more than 4,000 cases and controls, and about 26 million person-years of follow-up.

Rates and risks of IPD in the four studies were as follows:

• Among those with IPD, 27% had asthma, with 18% of those without, an adjusted odds ratio (aOR) of 1.8.
• In a European of patients who received at least 3 doses of PCV7, IPD rates per 100,000 person-years for 5-year-olds were 11.6 for children with asthma and 7.3 for those without. For 5- to 17-year-olds with and without asthma, the rates were 2.3 and 1.6, respectively.
• In 2001, a Korean found an aOR of 2.08 for IPD in children with asthma, compared with those without. In 2010, the aOR was 3.26. No vaccine types were reported in the study.
• of IPD were 3.7 per 100,000 person-years for children with asthma, compared with 2.5 for healthy controls – an adjusted relative risk of 1.5.

The pooled estimate of the four studies revealed an aOR of 1.9 for IPD among children with asthma, compared with those without, Dr. Castro-Rodriguez and his team concluded.

None of the studies reported hospital admissions, mortality, length of hospital stay, intensive care admission, invasive respiratory support, or additional medication use.

One, however, did find asthma severity was significantly associated with increasing IPD treatment costs per 100,000 person-years: $72,581 for healthy controls, compared with $100,020 for children with mild asthma, $172,002 for moderate asthma, and $638,452 for severe asthma.

In addition, treating all-cause pneumonia was more expensive in children with asthma. For all-cause pneumonia, the researchers found that estimated costs per 100,000 person-years for mild, moderate, and severe asthma were $7.5 million, $14.6 million, and $46.8 million, respectively, compared with $1.7 million for healthy controls.

The authors had no relevant financial disclosures.

[email protected]

SOURCE: Castro-Rodriguez J et al. Pediatrics. 2020 Jan. doi: 10.1542/peds.2019-1200.

Even on-time pneumococcal vaccines don’t completely protect children with asthma from developing invasive pneumococcal disease, a meta-analysis has determined.

Despite receiving pneumococcal valent 7, 10, or 13, children with asthma were still almost twice as likely to develop the disease as were children without asthma, Jose A. Castro-Rodriguez, MD, PhD, and colleagues reported in Pediatrics (2020 Jan. doi: 10.1542/peds.2019-1200). None of the studies included rates for those who received the pneumococcal polysaccharide vaccine (PPSV23).

“For the first time, this meta-analysis reveals 90% increased odds of invasive pneumococcal disease (IPD) among [vaccinated] children with asthma,” said Dr. Castro-Rodriguez, of Pontificia Universidad Católica de Chile, Santiago, and colleagues. “If confirmed, these findings will bear clinical and public health importance,” they noted, because guidelines now recommend PPSV23 after age 2 in children with asthma only if they’re treated with prolonged high-dose oral corticosteroids.

However, because the analysis comprised only four studies, the authors cautioned that the results aren’t enough to justify changes to practice recommendations.

Asthma treatment with inhaled corticosteroids (ICS) may be driving the increased risk, Dr. Castro-Rodriguez and his coauthors suggested. ICS deposition in the oropharynx could boost oropharyngeal candidiasis risk by weakening the mucosal immune response, the researchers noted. And that same process may be at work with Streptococcus pneumoniae.

A prior study found that children with asthma who received ICS for at least 1 month were almost four times more likely to have oropharyngeal colonization by S. pneumoniae as were those who didn’t get the drugs. Thus, a higher carrier rate of S. pneumoniae in the oropharynx, along with asthma’s impaired airway clearance, might increase the risk of pneumococcal diseases, the investigators explained.

Dr. Castro-Rodriguez and colleagues analyzed four studies with more than 4,000 cases and controls, and about 26 million person-years of follow-up.

Rates and risks of IPD in the four studies were as follows:

• Among those with IPD, 27% had asthma, with 18% of those without, an adjusted odds ratio (aOR) of 1.8.
• In a European of patients who received at least 3 doses of PCV7, IPD rates per 100,000 person-years for 5-year-olds were 11.6 for children with asthma and 7.3 for those without. For 5- to 17-year-olds with and without asthma, the rates were 2.3 and 1.6, respectively.
• In 2001, a Korean found an aOR of 2.08 for IPD in children with asthma, compared with those without. In 2010, the aOR was 3.26. No vaccine types were reported in the study.
• of IPD were 3.7 per 100,000 person-years for children with asthma, compared with 2.5 for healthy controls – an adjusted relative risk of 1.5.

The pooled estimate of the four studies revealed an aOR of 1.9 for IPD among children with asthma, compared with those without, Dr. Castro-Rodriguez and his team concluded.

None of the studies reported hospital admissions, mortality, length of hospital stay, intensive care admission, invasive respiratory support, or additional medication use.

One, however, did find asthma severity was significantly associated with increasing IPD treatment costs per 100,000 person-years: $72,581 for healthy controls, compared with $100,020 for children with mild asthma, $172,002 for moderate asthma, and $638,452 for severe asthma.

In addition, treating all-cause pneumonia was more expensive in children with asthma. For all-cause pneumonia, the researchers found that estimated costs per 100,000 person-years for mild, moderate, and severe asthma were $7.5 million, $14.6 million, and $46.8 million, respectively, compared with $1.7 million for healthy controls.

The authors had no relevant financial disclosures.

[email protected]

SOURCE: Castro-Rodriguez J et al. Pediatrics. 2020 Jan. doi: 10.1542/peds.2019-1200.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).

The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
 

Pathogens

Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.

Defining severe community-acquired pneumonia

The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.

Major criteria are:

• Septic shock requiring vasopressors.
• Respiratory failure requiring mechanical ventilation.

Minor criteria are:

• Respiratory rate greater than or equal to 30 breaths/min.
• Ratio of arterial O₂ partial pressure to fractional inspired O₂ less than or equal to 250.
• Multilobar infiltrates.
• Confusion/disorientation.
• Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
• Leukopenia (white blood cell count less than 4,000 cells/mcL).
• Thrombocytopenia (platelet count less than 100,000 mcL)
• Hypothermia (core temperature less than 36º C).
• Hypotension requiring aggressive fluid resuscitation.

Management and diagnostic testing

Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.

For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.

Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
 

Empiric antibiotic therapy

Healthy adults without comorbidities should be treated with monotherapy of either:

• Amoxicillin 1 g three times daily.
• OR doxycycline 100 mg twice daily.
• OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.

Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:

• Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
• OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).

Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:

• Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
• OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).

If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.

Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):

• Beta-lactam and macrolide.
• OR fluoroquinolone and beta-lactam.

It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.

Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
 

The bottom line

CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.

For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.

 

Reference

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.

Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).

The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
 

Pathogens

Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.

Defining severe community-acquired pneumonia

The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.

Major criteria are:

• Septic shock requiring vasopressors.
• Respiratory failure requiring mechanical ventilation.

Minor criteria are:

• Respiratory rate greater than or equal to 30 breaths/min.
• Ratio of arterial O₂ partial pressure to fractional inspired O₂ less than or equal to 250.
• Multilobar infiltrates.
• Confusion/disorientation.
• Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
• Leukopenia (white blood cell count less than 4,000 cells/mcL).
• Thrombocytopenia (platelet count less than 100,000 mcL)
• Hypothermia (core temperature less than 36º C).
• Hypotension requiring aggressive fluid resuscitation.

Management and diagnostic testing

Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.

For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.

Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
 

Empiric antibiotic therapy

Healthy adults without comorbidities should be treated with monotherapy of either:

• Amoxicillin 1 g three times daily.
• OR doxycycline 100 mg twice daily.
• OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.

Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:

• Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
• OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).

Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:

• Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
• OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).

If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.

Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):

• Beta-lactam and macrolide.
• OR fluoroquinolone and beta-lactam.

It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.

Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
 

The bottom line

CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.

For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.

 

Reference

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.

Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).

The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
 

Pathogens

Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.

Defining severe community-acquired pneumonia

The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.

Major criteria are:

• Septic shock requiring vasopressors.
• Respiratory failure requiring mechanical ventilation.

Minor criteria are:

• Respiratory rate greater than or equal to 30 breaths/min.
• Ratio of arterial O₂ partial pressure to fractional inspired O₂ less than or equal to 250.
• Multilobar infiltrates.
• Confusion/disorientation.
• Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
• Leukopenia (white blood cell count less than 4,000 cells/mcL).
• Thrombocytopenia (platelet count less than 100,000 mcL)
• Hypothermia (core temperature less than 36º C).
• Hypotension requiring aggressive fluid resuscitation.

Management and diagnostic testing

Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.

For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.

Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
 

Empiric antibiotic therapy

Healthy adults without comorbidities should be treated with monotherapy of either:

• Amoxicillin 1 g three times daily.
• OR doxycycline 100 mg twice daily.
• OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.

Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:

• Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
• OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).

Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:

• Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
• OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).

If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.

Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):

• Beta-lactam and macrolide.
• OR fluoroquinolone and beta-lactam.

It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.

Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
 

The bottom line

CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.

For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.

 

Reference

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.

Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.

Andrew D. Bowser/MDedge News

Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.

Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.

“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.

The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.

In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.

Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.

The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.

The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.  

Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.

“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.

The authors reported having no disclosures related to this research.

This article was updated 10/23/2019.

SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.

NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.

Andrew D. Bowser/MDedge News

Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.

Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.

“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.

The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.

In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.

Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.

The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.

The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.  

Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.

“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.

The authors reported having no disclosures related to this research.

This article was updated 10/23/2019.

SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.

NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.

Andrew D. Bowser/MDedge News

Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.

Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.

“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.

The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.

In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.

Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.

The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.

The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.  

Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.

“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.

The authors reported having no disclosures related to this research.

This article was updated 10/23/2019.

SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.

Recurrent invasive pneumococcal disease in children could be a signal of underlying primary immunodeficiency, according to a systematic review published in JAMA Pediatrics.

Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.

They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.

Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.

One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).

Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.

The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.

Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.

In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.

Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”

In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.

“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.

No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.

SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.

Recurrent invasive pneumococcal disease in children could be a signal of underlying primary immunodeficiency, according to a systematic review published in JAMA Pediatrics.

Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.

They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.

Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.

One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).

Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.

The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.

Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.

In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.

Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”

In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.

“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.

No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.

SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.

Recurrent invasive pneumococcal disease in children could be a signal of underlying primary immunodeficiency, according to a systematic review published in JAMA Pediatrics.

Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.

They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.

Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.

One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).

Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.

The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.

Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.

In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.

Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”

In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.

“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.

No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.

SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.

Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.

Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.

Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).

Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).

The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.

However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.

The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.

SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.

Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.

Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.

Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).

Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).

The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.

However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.

The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.

SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.

Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.

Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.

Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).

Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).

The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.

However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.

The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.

SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]