Children with fast-breathing pneumonia who were treated with oral amoxicillin had a significantly lower rate of treatment failure compared with children who received a placebo, according to results of a randomized clinical trial published in JAMA Pediatrics. However, by day 4, treatment outcomes were comparable between the two groups.
Amy Sarah Ginsburg, MD, MPH, a senior advisor in international programs at Save the Children U.S.A., and colleagues wrote that pneumonia causes death in approximately 920,000 children aged younger than 5 years around the world. This number, the researchers wrote, underscores the need for more access to care and appropriate antibiotic treatment.
“A 3-day course of twice-daily amoxicillin is recommended by WHO as first-line treatment of nonsevere fast-breathing pneumonia among immune-competent children aged 5 years or younger,” Ginsburg and colleagues wrote. “WHO’s integrated management of childhood illness guidelines identify fast-breathing pneumonia in children with cough or difficult breathing who demonstrate fast breathing without WHO danger signs. However, not all cases of fast breathing are bacterial pneumonia.”
To better understand whether amoxicillin treatment is appropriate in cases of nonsevere fast-breathing pneumonia among HIV-uninfected children in Malawi between the ages of 2 and 59 months, the researchers conducted a double-blind, randomized, clinical noninferiority trial. Ginsburg and colleagues followed-up with the children after 14 days to determine the percentage of children with treatment failure by day 4 and the number of children who had treatment failure or relapse by day 14.
Of the 1,126 children included in the trial, 564 received amoxicillin and 562 received a placebo for 3 days. The average age of these children was 21.3 months.
According to the researchers, treatment failure was identified in 4% of children who took amoxicillin and 7% who took a placebo by day 4, which prompted the data safety monitoring board to stop the study.
Data available for follow-up visits revealed that 10.1% of children who took amoxicillin had treatment failure by day 4 or relapsed by day 14. Slightly more children who took a placebo had treatment failure or relapsed at follow-up (11.8%; RR = 1.16; 95% CI, 0.83%-1.63%).
According to the researchers, the number of nonsevere fast-breathing pneumonia cases that needed amoxicillin treatment for one child to benefit was 33.
“It might be argued that such a large number needed to treat to benefit one child is acceptable relative to the low risks associated with taking antibiotics,” they wrote. “However, it might also be argued that efforts should focus on identifying and providing antibiotics to those children who truly need them to prevent treatment failure or relapse or focus on identifying and providing only supportive care to those children who recover without antibiotics.”
Furthermore, the researchers recommended that follow-up visits on day 4 may be beneficial for low-risk children with fast-breathing pneumonia. They recognized that for many children in settings like sub-Saharan Africa, follow-up cannot be guaranteed, so the use of amoxicillin may be warranted. – by Katherine Bortz
Disclosures: Ginsburg reports receiving grants from the Bill & Melinda Gates Foundation. Please see the study for all other authors’ relevant financial disclosures.