Effectiveness of amoxicillin and amoxicillin-clavulanate for the treatment of community-acquired pneumonia in adults and children: systematic review and meta-analysis

IntroductionCommunity-acquired pneumonia (CAP) is a key contributor to the global burden of morbidity and mortality, and it drives large volumes of antibiotic use. Despite widespread recommendation to use amoxicillin for treatment, there are concerns of its effectiveness as empirical antibiotics for CAP. The aim of this study is to evaluate existing evidence on the effectiveness of amoxicillin and amoxicillin-clavulanate for CAP in children and adults. MethodsWe systematically searched PubMed, Cochrane Library, Web of Science, and Ovid-MEDLINER with no language restrictions for randomized controlled trials published until July 16, 2024 comparing the effectiveness of amoxicillin or amoxicillin-clavulanate versus other antibiotics or placebo with a primary outcome of clinical resolution or clinical failure. We used a random effects and a fixed effects logistic regression model to estimate the pooled treatment effect size. We performed a network meta-analysis for the indirect comparison between amoxicillin and amoxicillin-clavulanate. ResultsWe extracted data from 44 studies including 45,400 patients. We found no strong evidence of a differential effect on clinical resolution when comparing amoxicillin to other antibiotics (n=15 trials, pooled odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.56-1.38) or amoxicillin-clavulanate to other antibiotics (n=17 trials, OR: 0.89 [95%: 0.76-1.04]). Similarly, no evidence on difference in clinical failure between amoxicillin and other antibiotics (n=8 trials, OR: 1.34 [95%: 0.31, 5.81]) was observed. Sixty-three percent and 23% of amoxicillin and amoxicillin-clavulanate studies, respectively, had low-risk of bias. We found no strong evidence of a differential effect on clinical resolution between adults treated with amoxicillin and amoxicillin-clavulanate (OR: 1.06 [95%: 0.59-1.89]). ConclusionOur study found no strong evidence of any difference in clinical outcomes with amoxicillin compared to amoxicillin-clavulanate or other antibiotics for CAP treatment. However, there are large uncertainties around the pooled estimates. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LICommunity-acquired pneumonia (CAP) is a major cause of hospitalizations and of deaths globally. It is one of the most common causes of childhood hospitalizations in developed countries and the leading cause of death among children in developing countries C_LIO_LIThe World Health Organization (WHO) recommends amoxicillin and amoxicillin-clavulanate as the first and second choice, respectively, of empirical antibiotic treatment for mild to moderate bacterial CAP due to their narrow spectrum of activity and affordability. C_LI What this study addsO_LIWhile clinical trials have been performed to evaluate the effectiveness and efficacy of both antibiotics across different settings, studies directly comparing amoxicillin and amoxicillin-clavulanate are lacking. This study fills the gap through a systematic review to evaluate evidence on effectiveness of amoxicillin and amoxicillin-clavulanate versus other treatments for CAP and an indirect comparison between the two antibiotics. C_LIO_LINo strong evidence of a differential treatment effect when comparing amoxicillin to other antibiotics or amoxicillin-clavulanate to other antibiotics, or of difference in treatment effect between adults treated with amoxicillin and amoxicillin-clavulanate. C_LIO_LIHow this study might affect research, practice or policy C_LIO_LIThis work provides a strong rationale for the WHO recommendation of using amoxicillin as a first-choice empirical antibiotic for CAP in both adults and children. C_LI