Shorter antibiotic regimen enough in kids with pneumonia?

Children with non-severe community-acquired pneumonia (CAP) may benefit from a 5-day antibiotic regimen compared with the current standard regimen of 10 days, according to results of the US-based SCOUT-CAP trial.

“In this … trial [of] children with outpatient CAP demonstrating early clinical improvement, a 5-day antibiotic strategy was superior to a 10-day strategy,” said the authors.

The multicentre, double-blind trial involved 380 healthy children aged 6–71 months (mean age 35.7 months, 51 percent male, 62 percent White) with non-severe CAP who demonstrated early clinical improvement. All children received an outpatient regimen comprising 5 days of oral β-lactam* antibiotic therapy. On day 6, they were randomized 1:1 to continue the same antibiotic therapy for another 5 days (standard course) or receive placebo for 5 days (short course). Throat swabs were collected in a subgroup of participants at the second outcome assessment visit (OAV 2; between days 19 and 25) to quantify antibiotic resistance genes (ARGs) in oropharyngeal flora.

Ninety-one percent of patients received amoxicillin monotherapy, while five and four percent received amoxicillin-clavulanate and cefdinir, respectively.

Inadequate clinical response at the first OAV (OAV 1; day 6–10) and second OAV did not differ between the short- and standard-course groups (OAV 1: 1 percent vs <1 percent; OAV 2: 1 percent vs 2 percent). [JAMA Pediatr 2021;doi:10.1001/jamapediatrics.2021.5547]

There were no deaths, hospitalizations, or surgeries for persistent or worsening pneumonia.

The number of patients with persistent symptoms also did not significantly differ between the short- and standard-course groups at OAV 1 (7 percent vs 8 percent) and OAV 2 (6 percent in each group).

The number of patients reporting antibiotic-associated adverse effects (AEs) also did not significantly differ between the short- and standard-course groups at OAV 1 (40 percent vs 37 percent) and OAV 2 (51 percent vs 48 percent). At OAV 1, 11 percent of each group experienced a moderate to severe AE; the proportion was 19 percent of each group at OAV 2.

The probability of a more desirable ordinal desirability of outcome ranking (DOOR) for the short-course regimen was 0.48 at both OAV 1 and OAV 2, indicating no difference between the short- and standard-course groups. The short-course regimen had a 69 percent probability of a more desirable RADAR** outcome compared with the standard-course regimen.

Among the 171 children who were assessed for ARGs, there was a significantly lower number of ARGs per prokaryotic cell (RGPC) in the short-course compared with the standard-course regimen (median 1.17 vs 1.33; p=0.01 for total RGPC and median 0.55 vs 0.60; p=0.03 for β-lactamase RGPC).

“Our results suggest that a small reduction (5 days) in exposure to β-lactam therapy is associated with fewer ARGs in the respiratory microbiota,” the authors said. However, they cautioned that the duration of this reduction in ARGs remains uncertain.

Why a shorter regimen?

“It’s critical that we minimize the use of unnecessary antibiotics, both to eliminate the risk of antibiotic side effects and to slow the progression of antimicrobial resistance, a global public health threat,” said first author Assistant Professor Derek Williams, Chief, Division of Pediatric Hospital Medicine at Monroe Carell Jr. Children’s Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, Tennessee, US.

“[In this study,] the shortened approach achieved similar clinical response, resolution of symptoms, and antibiotic-associated AEs with fewer days of antibiotic therapy,” the authors noted, highlighting that guidelines that recommend longer regimens for uncomplicated CAP need to be re-examined.

“These data may be immediately applied by clinicians, and we hope this study will help shift the paradigm for childhood pneumonia toward more judicious treatment approaches, resulting in care that is safer and more effective,” Williams said.

Despite the positive findings, the authors cautioned that it is quite likely that some of the patients did not have bacterial pneumonia, and recommended further research incorporating viral testing and biomarkers. The results also may not apply to children with underlying conditions, severe pneumonia, or without early improvement.

*amoxicillin, amoxicillin and clavulanate (80–100 mg/kg/day [maximum 2,000 mg/day] for both) or cefdinir (12–16 mg/kg/day [maximum 600 mg/day])

**End-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite of clinical response, symptom resolution, and antibiotic-associated adverse effects in an ordinal DOOR