The evidence is in: Less is more when it comes to treating uncomplicated community-acquired pneumonia (CAP) in young children. Five days of antibiotic therapy resulted in a superior clinical response compared to 10 days of treatment and had the added benefit of a lower risk of inducing antibiotic resistance, according to the randomized, controlled SCOUT-CAP trial.
“Several studies have shown shorter antibiotic courses to be non-inferior to the standard treatment strategy but in our study, we show that a shortened 5-day course of therapy was superior to standard therapy because the short course achieved similar outcomes with fewer days of antibiotics,” Derek Williams, MD, MPH, Vanderbilt University Medical Center, Nashville, Tennessee, told Medscape Medical News in an email.
“These data are immediately applicable to frontline clinicians and we hope this study will shift the paradigm towards more judicious treatment approaches for childhood pneumonia, resulting in care that is safer and more effective,” he added.
The study was published online January 18 in JAMA Pediatrics.
Uncomplicated CAP
The study enrolled children aged 6 months to 71 months diagnosed with uncomplicated CAP who demonstrated early clinical improvement in response to 5 days of antibiotic treatment. Participants were prescribed either amoxicillin, amoxicillin and clavulanate, or cefdinir according to standard of care and were randomized on day 6 to another 5 days of their initially prescribed antibiotic course or to placebo.
“Those assessed on day 6 were eligible only if they had not yet received a dose of antibiotic therapy on that day,” the authors write. The primary endpoint was end-of-treatment response, adjusted for the duration of antibiotic risk as assessed by RADAR. As the authors explain, RADAR is a composite endpoint that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects (AEs) in an ordinal desirability of outcome ranking, or DOOR.
“There were no differences between strategies in the DOOR or in its individual components,” Williams and colleagues point out. A total of 380 children took part in the study. The mean age of participants was 35.7 months, and half were male.
Over 90% of children randomized to active therapy were prescribed amoxicillin. “Fewer than 10% of children in either strategy had an inadequate clinical response,” the authors report.
However, the 5-day antibiotic strategy had a 69% (95% CI, 63% – 75%) probability of children achieving a more desirable RADAR outcome compared with the standard, 10-day course, as assessed either on days 6 to 10 at outcome assessment visit one (OAV1) or at OAV2 on days 19 to 25.
There were also no significant differences between the two groups in the percentage of participants with persistent symptoms at either assessment point, they note. At assessment visit one, 40% of children assigned to the short-course strategy and 37% of children assigned to the 10-day strategy reported an antibiotic-related AE, most of which were mild.
Resistome Analysis
Some 171 children were included in a resistome analysis in which throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The total number of resistance genes per prokaryotic cell (RGPC) was significantly lower in children treated with antibiotics for 5 days compared with children who were treated for 10 days.
Specifically, the median number of total RGPC was 1.17 (95% CI, 0.35 – 2.43) for the short-course strategy and 1.33 (95% CI, 0.46 – 11.08) for the standard-course strategy (P = .01). Similarly, the median number of β-lactamase RGPC was 0.55 (0.18 – 1.24) for the short-course strategy and 0.60 (0.21 – 2.45) for the standard-course strategy (P = .03).
“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors observe. For example, reducing treatment from 10 to 5 days for outpatient CAP could reduce the number of days spent on antibiotics by up to 7.5 million days in the US each year.
“If we can safely reduce antibiotic exposure, we can minimize antibiotic side effects while also helping to slow antibiotic resistance,” Williams pointed out.
Fewer days of having to give their child repeated doses of antibiotics is also more convenient for families, he added.
Asked to comment on the study, David Greenberg, MD, professor of pediatrics and infectious diseases, Ben Gurion University of the Negev, Israel, explained that the length of antibiotic therapy as recommended by various guidelines is more or less arbitrary, some infections being excepted.
“There have been no studies evaluating the recommendation for a 100-day treatment course, and it’s kind of a joke because if you look at the treatment of just about any infection, it’s either for 7 days or 14 days or even 20 days because it’s easy to calculate, it’s not that anybody proved that treatment of whatever infection it is should last this long,” he told Medscape Medical News.
Moreover, adherence to a shorter antibiotic course is much better than it is to a longer course. If, for example, physicians tell a mother to take two bottles of antibiotics for a treatment course of 10 days, she’ll finish the first bottle which is good for 5 days and, because the child is fine, “she forgets about the second bottle,” Greenberg said.
In one of the first studies to compare a short vs long course of antibiotic therapy in uncomplicated CAP in young children (https://pubmed.ncbi.nlm.nih.gov/23989106/), Greenberg and colleagues initially compared a 3-day course of high-dose amoxicillin to a 10-day course of the same treatment, but the 3-day course was associated with an unacceptable failure rate. (At the time, the World Health Organization was recommending a 3-day course of antibiotics for the treatment of uncomplicated CAP in children.)
They stopped the study and then initiated a second study in which they compared a 5-day course of the same antibiotic to a 10-day course and found the 5-day course was comparable to the 10-day course in terms of clinical cure rates. As a result of his study, Greenberg has long since prescribed a 5-day course of antibiotics for his own patients.
“Five days is good,” he affirmed. “And if patients start a 10-day course of an antibiotic for, say, a urinary tract infection and a subsequent culture comes back negative, they don’t have to finish the antibiotics either.” Greenberg said.
Williams said he has no financial ties to industry. Greenberg said he has served as a consultant for Pfizer, Merck, Johnson & Johnson, and AstraZeneca. He is also a founder of the company Beyond Air.
JAMA Pediatr. Published online January 18, 2022. Abstract
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