Beschreibung:
<jats:title>Abstract</jats:title>
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<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>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 30 day all-cause mortality by in vitro amoxicillin/clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (&gt;8/2 mg/L), categorical MIC, and a higher resistance breakpoint (&gt;32/2 mg/L), adjusting for other antibiotic activity and confounders including comorbidities, vital signs and blood tests.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>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 (P = 0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive versus active amoxicillin/clavulanate [adjusted HR (aHR) = 1.27 (95% CI 0.83–1.93); P = 0.28], nor of an association with active aminoglycoside (P = 0.93) or other active antibiotics (P = 0.18). Considering categorical amoxicillin/clavulanate MIC, MICs &gt; 32/2 mg/L were associated with mortality [aHR = 1.85 versus MIC = 2/2 mg/L (95% CI 0.99–3.73); P = 0.054]. A higher resistance breakpoint (&gt;32/2 mg/L) was independently associated with higher mortality [aHR = 1.82 (95% CI 1.07–3.10); P = 0.027], as were MICs &gt; 32/2 mg/L with active empirical aminoglycosides [aHR = 2.34 (95% CI 1.40–3.89); P = 0.001], but not MICs &gt; 32/2 mg/L with active non-aminoglycoside antibiotic(s) [aHR = 0.87 (95% CI 0.40–1.89); P = 0.72].</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>We found no evidence that EUCAST-defined amoxicillin/clavulanate resistance was associated with increased mortality, but a higher resistance breakpoint (MIC &gt; 32/2 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.</jats:p>
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