Results of a gold-standard study published November 2 in JAMA hold promise for reducing the length of antibiotic courses for pediatric patients with pneumonia.
Julia Bielicki, PhD, of St George’s University of London, London, United Kingdom, the lead researcher of the CAP-IT trial, told Medscape Medical News, “The most important thing is that we really managed to involve patients who are quite typical of children being diagnosed with and treated for community-acquired pneumonia in the hospital setting.” Concerned about promoting antibiotic resistance, researchers there and elsewhere are trying to reduce the length of antibiotic courses.
In CAP-IT, 814 children who were initially hospitalized for pneumonia or were treated in an emergency department were randomly assigned in a 1:1 ratio to receive oral amoxicillin at either a lower dose (35–50 mg/kg/d) or a higher dose (70–90 mg/kg/d) and to receive either a shorter course (3 days) or a longer course (7 days) of antibiotics. “Dosing in children is a tricky beast,” Bielicki said; for the administration of antibiotic suspensions, it is easier to round the dosing to the nearest mL, she said.
The Infectious Diseases Society of America (IDSA) and the Pediatric Infectious Diseases Society have recommended against the routine use of chest x-rays (CXRs) for children who are outpatients with suspected pneumonia. Despite that recommendation, CXRs were obtained in >80% of cases in a study of 30 US emergency departments. Bielicki said the use of CXRs is “a very contentious issue.” In the United Kingdom, the diagnosis of CAP is based on the clinical exam, per recommendations of the British Thoracic Society. Because of this, she noted, “our findings are generalizable to the population of children being managed with pneumonia in the UK and similar other settings.”
The endpoint for comparison was antibiotic re-treatment within 28 days, and the results were quite striking. Antibiotic re-treatment was needed in 12.6% of those who received lower doses and in 12.4% of those who received higher doses. Similarly, re-treatment was needed in 12.5% of the 3-day group vs 12.5% in the 7-day group. Both differences were far below the 8% noninferiority margin. (The IDSA has used a noninferiority margin of 10% in its trials.)
Symptom resolution was a secondary outcome and was not significantly different between the groups.
At baseline, 42% of the children were colonized by Streptococcus pneumoniae. In 17% of those cases, S pneumoniae was nonsusceptible to penicillin. (Nonsusceptiblility to penicillin was defined as a minimum inhibitory concentration [MIC] to penicillin of >0.1 μg/mL.) No penicillin-resistant pneumococci were identified (MIC to penicillin ≥2.0 μg/mL) at any time during the study.
The most common adverse events in all the children were diarrhea (44%), rash (24%), and thrush (7%). There was no significant difference in these symptoms between the treatment groups. More children on the 3-day course completed the entire treatment regimen.
Nick Bennett, MBBChir, PhD, medical director of infectious diseases, ICON, who was not involved in the study, told Medscape Medical News via email, “The study seemed well designed and thoughtfully executed.” He added, “The study population is the most important factor in considering amoxicillin dose and duration — about 95% were vaccinated, and UK schedules include Prevnar 13, [which] targets serotypes known to have higher rates of invasive disease and antibiotic resistance.” So “knowing that high-risk strains are unlikely” enabled the researchers “to consider lower-dose and shorter-duration oral amoxicillin.”
Bennett was critical of one point — that children with severe CAP were excluded from this study. Severe CAP typically means that cases are associated with sepsis, complicated disease, or care at the intensive care unit level. He noted that, per the IDSA’s pediatric CAP guidelines, “twice daily dosing would not be optimal in the setting of higher-MIC strains.”
Bennett believes the results are “applicable to fully vaccinated younger children in areas with no significant resistant pneumococcus being treated for mild to moderate CAP.” He did concur that the benefits of the shorter course include fewer side effects and “a reduced risk of further antibiotic resistance developing.”
Bielicki concluded, “The big headline is that it’s possible to reduce antibiotic exposure for children with community-acquired pneumonia,” and this will be particularly important for the treatment of children in low- and middle-income countries.
Bielicki received grants from the National Institute of Health Research during the conduct of the study. Her spouse was senior corporate counsel at Novartis International AG until June 2020 and owns stock and stock options. Bennett has disclosed no relevant financial relationships.
JAMA. 2021;326:1713-1724. Abstract
Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.