Efficacy And Safety Of Amoxicillin-Clavulanate Versus Other Broad-Spectrum Antibiotics For Community-Acquired Respiratory Tract Infections: A Systematic Review

Abstract

Background: Community-acquired respiratory tract infections (CA-RTIs) are among the leading causes of global morbidity and antibiotic use.

Despite widespread prescription of amoxicillin-clavulanate, uncertainty persists regarding its comparative efficacy and safety versus other broad-spectrum antibiotics.

Objective: To systematically evaluate clinical outcomes, safety profiles, and resistance implications of amoxicillin-clavulanate compared with alternative broad-spectrum agents in adults and children with CA-RTIs.

Methods: Following PRISMA 2020 guidelines, 11 peer-reviewed studies published between 2000 and 2025 were analyzed, including randomized controlled trials, observational cohorts, and registry data. Studies comparing amoxicillin-clavulanate with fluoroquinolones, macrolides, cephalosporins, co-trimoxazole, or amoxicillin alone were included. Primary outcomes were clinical cure, mortality, and adverse events.

Results: Across studies, amoxicillin-clavulanate demonstrated comparable or superior efficacy to other broad-spectrum antibiotics, with clinical cure rates between 87% and 95% in CAP and AECOPD. Mortality and readmission rates showed no significant difference compared with comparators. Adverse events, primarily gastrointestinal, were slightly higher with amoxicillin-clavulanate. Evidence from large-scale cohorts (Bagge et al., 2021; Wei et al., 2024) and pediatric trials (Gerber et al., 2017; Jehan et al., 2020) supports amoxicillin or amoxicillin-clavulanate as first-line therapies.

Conclusions: Amoxicillin-clavulanate remains an effective and generally safe empirical option for CA-RTIs. Narrow-spectrum alternatives such as amoxicillin alone may be equally effective for mild-to-moderate infections, aligning with antibiotic stewardship principles.