Abstract
Background: Cefazolin is in vitro active against wild isolates of Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP), but clinical evidence supporting the contemporary susceptibility breakpoint issued by the Clinical and Laboratory Standards Institute (CLSI) are limited. Methods: Between 2010 and 2015, adults with monomicrobial community-onset EKP bacteremia with definitive cefazolin treatment (DCT) at two hospitals were analyzed. Cefazolin minimum inhibitory concentrations (MICs) were correlated with clinical outcomes, including primary (treatment failure of DCT) and secondary (30-day mortality after bacteremia onset, recurrent bacteremia, and mortality within 90 days after the end of DCT) outcomes. Results: Overall, 466 bacteremic episodes, including 340 (76.2%) episodes due to E. coli, 90 (20.2%) Klebsiella species, and 16 (3.6%) P. mirabilis isolates, were analyzed. The mean age of these patients was 67.8 years and female-predominated (68.4%). A crude 15- and 30-day mortality rate was 0.7% and 2.2%, respectively, and 11.2% experienced treatment failure of DCT. A significant linear-by-linear association of cefazolin MICs, with the rate of treatment failure, 30-day crude mortality, recurrent bacteremia or 90-day mortality after the DCT was present (all γ = 1.00, p = 0.01). After adjustment, the significant impact of cefazolin MIC breakpoint on treatment failure and 30-day crude mortality was most evident in 2 mg/L (>2 mg/L vs. ≤2 mg/L; adjusted hazard ratio, 3.69 and 4.79; p < 0.001 and 0.02, respectively). Conclusion: For stabilized patients with community-onset EKP bacteremia after appropriate empirical antimicrobial therapy, cefazolin might be recommended as a definitive therapy for cefazolin-susceptible EKP bacteremia, based on the contemporary CLSI breakpoint.
Highlights
Cefazolin, a parental first-generation cephalosporin, is bactericidal against Staphylococcus aureus, streptococci, Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) [1]
As previously described [4,19], antimicrobial therapy was considered to be appropriate when the following two criteria were fulfilled: (i) the route and dosage of antimicrobial administration were as recommended in the Sanford Guide [20]; and (ii) causative pathogens exhibited in vitro susceptibility to the administrated drugs according to the contemporary Clinical and Laboratory Standards Institute (CLSI) breakpoint [12]
In the Kaplan–Meier curves analyzed by the Cox proportional hazard model, with adjustment for two independent determinants, the impact of cefazolin minimum inhibitory concentrations (MICs) on 30-day crude morality was most evident in the MIC breakpoint of 2 mg/L (AHR, 4.79; p = 0.02; Figure 3B)
Summary
A parental first-generation cephalosporin, is bactericidal against Staphylococcus aureus, streptococci, Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) [1]. To provide the rationale of the MIC breakpoint revision, we analyzed clinical characteristics and outcomes of adults with EKP bacteremia definitively treated by cefazolin treatment. Cefazolin is in vitro active against wild isolates of Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP), but clinical evidence supporting the contemporary susceptibility breakpoint issued by the Clinical and Laboratory Standards Institute (CLSI) are limited. Cefazolin minimum inhibitory concentrations (MICs) were correlated with clinical outcomes, including primary (treatment failure of DCT) and secondary (30-day mortality after bacteremia onset, recurrent bacteremia, and mortality within 90 days after the end of DCT) outcomes. A significant linear-by-linear association of cefazolin MICs, with the rate of treatment failure, 30-day crude mortality, recurrent bacteremia or 90-day mortality after the DCT was present (all γ = 1.00, p = 0.01). Conclusion: For stabilized patients with community-onset EKP bacteremia after appropriate empirical antimicrobial therapy, cefazolin might be recommended as a definitive therapy for cefazolin-susceptible EKP bacteremia, based on the contemporary CLSI breakpoint
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