No evidence of difference in mortality with amoxicillin versus co-amoxiclav for hospital treatment of community-acquired pneumonia

Jia Wei; Aashna Uppal; Christy Nganjimi; Hermione Warr; Yasin Ibrahim; Qingze Gu; Hang Yuan; Najib M Rahman; Nicola Jones; A Sarah Walker; David W Eyre

doi:10.1016/j.jinf.2024.106161

No evidence of difference in mortality with amoxicillin versus co-amoxiclav for hospital treatment of community-acquired pneumonia

J Infect. 2024 Apr 23;88(6):106161. doi: 10.1016/j.jinf.2024.106161. Online ahead of print.

Authors

Affiliations

¹ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
² Department of Engineering Science, University of Oxford, Oxford, UK.
³ Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁴ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford, UK; The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
⁵ Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.
⁶ Nuffield Department of Medicine, University of Oxford, Oxford, UK; The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; The National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Oxford, UK.
⁷ Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK; The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK; The National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Oxford, UK. Electronic address: david.eyre@bdi.ox.ac.uk.

PMID: 38663754
DOI: 10.1016/j.jinf.2024.106161

Abstract

Objectives: Current guidelines recommend broad-spectrum antibiotics for high-severity community-acquired pneumonia (CAP), potentially contributing to antimicrobial resistance (AMR). We aim to compare outcomes in CAP patients treated with amoxicillin (narrow-spectrum) versus co-amoxiclav (broad-spectrum), to understand if narrow-spectrum antibiotics could be used more widely.

Methods: We analysed electronic health records from adults (≥16 y) admitted to hospital with a primary diagnosis of pneumonia between 01-January-2016 and 30-September-2023 in Oxfordshire, United Kingdom. Patients receiving baseline ([-12 h,+24 h] from admission) amoxicillin or co-amoxiclav were included. The association between 30-day all-cause mortality and baseline antibiotic was examined using propensity score (PS) matching and inverse probability treatment weighting (IPTW) to address confounding by baseline characteristics and disease severity. Subgroup analyses by disease severity and sensitivity analyses with missing covariates imputed were also conducted.

Results: Among 16,072 admissions with a primary diagnosis of pneumonia, 9685 received either baseline amoxicillin or co-amoxiclav. There was no evidence of a difference in 30-day mortality between patients receiving initial co-amoxiclav vs. amoxicillin (PS matching: marginal odds ratio 0.97 [0.76-1.27], p = 0.61; IPTW: 1.02 [0.78-1.33], p = 0.87). Results remained similar across stratified analyses of mild, moderate, and severe pneumonia. Results were also similar with missing data imputed. There was also no evidence of an association between 30-day mortality and use of additional macrolides or additional doxycycline.

Conclusions: There was no evidence of co-amoxiclav being advantageous over amoxicillin for treatment of CAP in 30-day mortality at a population-level, regardless of disease severity. Wider use of narrow-spectrum empirical treatment of moderate/severe CAP should be considered to curb potential for AMR.

Keywords: 30-day mortality; Amoxicillin; Antimicrobial resistance; Co-amoxiclav; Community-acquired pneumonia.