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

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Journal Article
Authors/contributors
Title
No evidence of difference in mortality with amoxicillin versus co-amoxiclav for hospital treatment of community-acquired pneumonia
Abstract
Objectives: Current guidelines recommend broad-spectrum antibiotics for high-severity community-ac­ quired 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-spec­ trum), 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.
Publication
Journal of Infection
Date
06/2024
Volume
88
Issue
6
Pages
106161
Journal Abbr
Journal of Infection
DOI
10.1016/j.jinf.2024.106161
URL
https://linkinghub.elsevier.com/retrieve/pii/S0163445324000951
Accessed
1/30/26, 3:46 PM
ISSN
01634453
Language
en
Library Catalog
DOI.org (Crossref)
Notes

Most clinically treated cases do not have the causative pathogen identified

Summary

EHR data from a large UK teaching hospital where they compared Amoxicillin vs Co-Amoxiclav

7 Years worth of data 16 + 2016-2023

Used ICD diagnosis Codes to define Pneumonia (ICDJ13-18)

ICD codes only when patient admitted to hospital, excluded covid, linked micro and radiology data used to assess the performance of coding data

Used Antibiotics

-12 ->24 hours

Main exposure

Amoxicillin ant baseline vs Coamoxiclav

Other exposures

Binary exposure

Whether they received Clari/Azithro/ery or gent

Exclusion

No amox or co amoxicalv ,

A mixture of both

Other antibiotics eg QUinolones, Pip taz however was 4.05% of episodes as first line

Covariates

Age, Sex , Ethnicity, IMD percentline, Admission specialty and admission hour of the day, admission day of the week, calendar time, hospital admission in the year (binary), LOS in alst year, Charlson co-mobidity score, hopsital frailty risk score, recent UTI, immunsuppression, autoimmune diseases, admission vital signs (-24/+24), laboratory tests , CURB 65 , PSI PORt and smart COP

Frailty defined by codes rather than clinically

Statistical Methods

In observational/EHR studies multiple factors influence treatment choice, e.g. patient comorbidities or CAP severity, leading to treat ments given for more severe diseases potentially being associated with worse outcomes. Therefore, to estimate the effect of baseline amoxicillin vs. co-amoxiclav on 30-day all-cause mortality following CAP, we used two causal methods designed to account for this.

Provided all factors influencing treatment assignment are modelled, they can produce estimates of treatm ent effects comparable to es timates from experimental trials.

Compared this witha  multivariable regression model, to emulate a target trial to provide a causal estimate of the effect of initiating antibiotics with coamoxiclac vs amoxillin

Propensity matching and Inverser Probability treatment weighting (If everyone received Amox vs If everyone received co amox)

Results

9685 admissions with pneumonia meeting critera. -> 61% Blood culture

3.1% were blood culture positive with a pneumonia associated organis,

<0.1% have mycoplasma detected

2/1113= legionella psoitive

BC

194 (2.0% strep pneumo) 98% susceptible to penicillin

40 Staph Aureus

K Pneumoniae 29 (0.3%)

Pseud 23 0.2%

H Influneza 10 (0.1%)

9038(93.3% ) had > 1 chet c ray

7082 evidence of pneumonia on xray

2841(29.3%), received amoxicillin, 57% oral , 664 IV and 546 oral and IV ; 5.0

Amoxicillin (55.3%) received baseline coamox 6.8 days

PH in gas more likely to get coamox and lactate,age, males, specialty and 11-15

No difference between mortality

26% of BC positive pneumonias would not have responded to amox

Citation
Wei, J., Uppal, A., Nganjimi, C., Warr, H., Ibrahim, Y., Gu, Q., Yuan, H., Rahman, N. M., Jones, N., Walker, A. S., & Eyre, D. W. (2024). No evidence of difference in mortality with amoxicillin versus co-amoxiclav for hospital treatment of community-acquired pneumonia. Journal of Infection, 88(6), 106161. https://doi.org/10.1016/j.jinf.2024.106161
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