Amikacin treatment in patients with Enterobacterales bacteraemia: impact of MIC on mortality
Iris Zohar1,2, Debby Ben David2,3, Orna Schwartz4
1Infectious Disease Unit, Edith Wolfson Medical Center, Holon, Israel.
Background:
Recently, breakpoints of Enterobacterales to amikacin were changed from MIC ≤ 16 mg/L to MIC ≤ 4 mg/L based mainly on laboratory data with little supporting clinical evidence. Our aim was to investigate the relation between MIC of Enterobacterales to amikacin and mortality among patients with Enterobacterales bacteraemia from a urinary tract source treated with amikacin.
Patients And Methods:
This retrospective, single-centre study included patients with Enterobacterales urinary source bacteraemia treated with amikacin, with Low (MIC ≤ 4 mg/L) and High (MIC 8 or 16 mg/L) MICs. A cohort of patients treated with ertapenem was used to assess if amikacin MIC is a marker of severity independent of antimicrobial treatment. The primary outcome was 30-day mortality. Multivariate logistic regression analysis was done to assess risk factors for mortality.
Results:
We included 85 patients, 46 (54.1%) were male, and mean age was 79.0 years (SD 11.7). Sixty-one patients (71.8%) had Low MIC and 24 (28.2%) had High MIC. Thirty-day mortality was 8.2% and 29.2% in the Low and High MIC groups, respectively (P = 0.031). Risk factors for 30-day mortality were age, infection by Enterobacterales other than Escherichia coli and high amikacin MIC. In a cohort of 88 patients treated with ertapenem, amikacin MIC was not associated with 30-day mortality.
Conclusions:
We demonstrated a relation between higher amikacin MIC levels (8 and 16 mg/L) and increased 30-day mortality in patients treated with amikacin for bacteraemia secondary to a urinary source. These findings support the new CLSI breakpoint change of Enterobacterales to amikacin.
Insights
Higher amikacin minimum inhibitory concentrations (MICs) in Enterobacterales urinary tract infections correlate with increased patient mortality. This finding supports updated clinical breakpoints for amikacin susceptibility testing.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Pharmacology
Background:
- Updated clinical breakpoints for amikacin in Enterobacterales are based on laboratory data, lacking robust clinical evidence.
- The clinical significance of amikacin minimum inhibitory concentrations (MICs) for Enterobacterales bacteraemia requires investigation.
Purpose of the Study:
- To examine the relationship between amikacin MICs in Enterobacterales and 30-day mortality in patients with urinary tract bacteraemia treated with amikacin.
- To determine if amikacin MIC is an independent marker of severity in Enterobacterales bacteraemia.
Main Methods:
- Retrospective, single-centre study of patients with Enterobacterales urinary source bacteraemia treated with amikacin.
- Patients categorized into Low (MIC ≤ 4 mg/L) and High (MIC 8 or 16 mg/L) amikacin MIC groups.
- Multivariate logistic regression analysis to identify mortality risk factors; comparison with ertapenem-treated cohort.
Main Results:
- Higher amikacin MIC (8-16 mg/L) was associated with significantly increased 30-day mortality (29.2% vs 8.2%, P=0.031).
- Independent risk factors for mortality included advanced age, non-E. coli Enterobacterales, and high amikacin MIC.
- Amikacin MIC did not correlate with mortality in a separate cohort treated with ertapenem.
Conclusions:
- Elevated amikacin MICs (8-16 mg/L) are linked to higher 30-day mortality in patients with urinary source Enterobacterales bacteraemia receiving amikacin.
- These clinical findings support the recent revision of CLSI breakpoints for amikacin against Enterobacterales.
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