Short-Course vs Long-Course Antibiotic Therapy for Children With Nonsevere Community-Acquired Pneumonia: A Systematic Review and Meta-analysis

Abstract

Importance: Short-course antibiotic therapy could enhance adherence and reduce adverse drug effects and costs. However, based on sparse evidence, most guidelines recommend a longer course of antibiotics for nonsevere childhood community-acquired pneumonia (CAP).

Objective: To determine whether a shorter course of antibiotics was noninferior to a longer course for childhood nonsevere CAP.

Data sources: MEDLINE, Embase, Web of Science, the Cochrane Library, and 3 Chinese databases from inception to March 31, 2022, as well as clinical trial registries and Google.com.

Study selection: Randomized clinical trials comparing a shorter- vs longer-course therapy using the same oral antibiotic for children with nonsevere CAP were included.

Data extraction and synthesis: Random-effects models were used to pool the data, which were analyzed from April 15, 2022, to May 15, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence.

Main outcomes and measures: Treatment failure, defined by persistence of pneumonia or the new appearance of any general danger signs of CAP (eg, lethargy, unconsciousness, seizures, or inability to drink), elevated temperature (>38 °C) after completion of treatment, change of antibiotic, hospitalization, death, missing more than 3 study drug doses, loss to follow-up, or withdrawal of informed consent.

Results: Nine randomized clinical trials including 11 143 participants were included in this meta-analysis. A total of 98% of the participants were aged 2 to 59 months, and 58% were male. Eight studies with 10 662 patients reported treatment failure. Treatment failure occurred in 12.8% vs 12.6% of participants randomized to a shorter vs a longer course of antibiotics. High-quality evidence showed that a shorter course of oral antibiotic was noninferior to a longer course with respect to treatment failure for children with nonsevere CAP (risk ratio, 1.01; 95% CI, 0.92-1.11; risk difference, 0.00; 95% CI, -0.01 to 0.01; I2 = 0%). A 3-day course of antibiotic treatment was noninferior to a 5-day course for the outcome of treatment failure (risk ratio, 1.01; 95% CI, 0.91-1.12; I2 = 0%), and a 5-day course was noninferior to a 10-day course (risk ratio, 0.87; 95% CI, 0.50-1.53; I2 = 0%). A shorter course of antibiotics was associated with fewer reports of gastroenteritis (risk ratio, 0.79; 95% CI, 0.66-0.95) and lower caregiver absenteeism (incident rate ratio, 0.74; 95% CI, 0.65-0.84).

Conclusions and relevance: Results of this meta-analysis suggest that a shorter course of antibiotics was noninferior to a longer course in children aged 2 to 59 months with nonsevere CAP. Clinicians should consider prescribing a shorter course of antibiotics for the management of pediatric nonsevere CAP.

Figure 1.. Study Flow Diagram

CAP indicates community-acquired pneumonia; CBM, China Biology Medicine; CNKI, China National Knowledge Infrastructure; and RCT, randomized clinical trial.

Figure 2.. Results for the Outcome of Treatment Failure

CAP-IT indicates Community-Acquired Pneumonia: a randomized controlled trial; ISCAP, INDIACLEN Short Course Amoxicillin Pneumonia Study Group; MASCOT, Multicentre Amoxycillin Short Course Therapy; RR, risk ratio; SAFER, Short-Course Antimicrobial Therapy for Pediatric Respiratory Infections; and SCOUT-CAP, Short-Course Outpatient Therapy of Community Acquired Pneumonia. ^aThree days vs 10 days. ^bFive days vs 10 days.

Figure 3.. Results for the Outcome of Relapse

ISCAP indicates INDIACLEN Short Course Amoxicillin Pneumonia Study Group; MASCOT, Multicentre Amoxycillin Short Course Therapy; RR, risk ratio; and SAFER, Short-Course Antimicrobial Therapy for Pediatric Respiratory Infections.