Mortality risks associated with empirical antibiotic activity in Escherichia coli bacteraemia: an analysis of electronic health records.
J Antimicrob Chemother
; 77(9): 2536-2545, 2022 08 25.
Article
em En
| MEDLINE
| ID: mdl-35723965
ABSTRACT
BACKGROUND:
Reported bacteraemia outcomes following inactive empirical antibiotics (based on in vitro testing) are conflicting, potentially reflecting heterogeneity in causative species, MIC breakpoints defining resistance/susceptibility, and times to rescue therapy.METHODS:
We investigated adult inpatients with Escherichia coli bacteraemia at Oxford University Hospitals, UK, from 4 February 2014 to 30 June 2021 who were receiving empirical amoxicillin/clavulanate with/without other antibiotics. We used Cox regression to analyse 30â day all-cause mortality by in vitro amoxicillin/clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (>8/2â mg/L), categorical MIC, and a higher resistance breakpoint (>32/2â mg/L), adjusting for other antibiotic activity and confounders including comorbidities, vital signs and blood tests.RESULTS:
A total of 1720 E. coli bacteraemias (1626 patients) were treated with empirical amoxicillin/clavulanate. Thirty-day mortality was 193/1400 (14%) for any active baseline therapy and 52/320 (16%) for inactive baseline therapy (Pâ=â0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive versus active amoxicillin/clavulanate [adjusted HR (aHR)â=â1.27 (95% CI 0.83-1.93); Pâ=â0.28], nor of an association with active aminoglycoside (Pâ=â0.93) or other active antibiotics (Pâ=â0.18). Considering categorical amoxicillin/clavulanate MIC, MICsâ>â32/2â mg/L were associated with mortality [aHRâ=â1.85 versus MICâ=â2/2â mg/L (95% CI 0.99-3.73); Pâ=â0.054]. A higher resistance breakpoint (>32/2â mg/L) was independently associated with higher mortality [aHRâ=â1.82 (95% CI 1.07-3.10); Pâ=â0.027], as were MICsâ>â32/2â mg/L with active empirical aminoglycosides [aHRâ=â2.34 (95% CI 1.40-3.89); Pâ=â0.001], but not MICsâ>â32/2â mg/L with active non-aminoglycoside antibiotic(s) [aHRâ=â0.87 (95% CI 0.40-1.89); Pâ=â0.72].CONCLUSIONS:
We found no evidence that EUCAST-defined amoxicillin/clavulanate resistance was associated with increased mortality, but a higher resistance breakpoint (MICâ>â32/2â mg/L) was. Additional active baseline non-aminoglycoside antibiotics attenuated amoxicillin/clavulanate resistance-associated mortality, but aminoglycosides did not. Granular phenotyping and comparison with clinical outcomes may improve AMR breakpoints.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bacteriemia
/
Infecções por Escherichia coli
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article