High-Dose Cefepime May Be Effective Treatment for Enterobacterales Bacteremia

High-dose cefepime and carbapenem therapy for the treatment of bacteremia caused by Enterobacterales organisms with moderate to increased risk for clinically significant AmpC production are associated with a similar risk of 30-day mortality, according to study results published in Open Forum Infectious Diseases.

Researchers conducted a retrospective cohort study between January 2015 and March 2022 to evaluate adult patients hospitalized with Enterobacter cloacae, Klebsiella aerogenes, and Citrobacter freundii bacteremia between January 2015 and March 2022. Included patients were receiving either high-dose cefepime or carbapenem therapy (meropenem or ertapenem). The primary outcome was the risk of mortality within 30 days of index blood culture collection. The researchers determined propensity scores via multivariable logistic regression to estimate the probability of receiving cefepime or carbapenem as definitive therapy. Cox regression models were used to compare the risk of 30-day mortality between the treatment groups, with adjustments via inverse probability of treatment weighting and time-varying covariates. 

Among 315 patients who met inclusion criteria, 169 were in the cefepime group and 146 were in the carbapenem group. The median patient age was 63 (IQR, 53-74.5) years, 55.2% were men, and 59% were admitted to an intensive care unit at least once during hospitalization. There were 23.1% and 21.9% immunocompromised patients in the cefepime and carbapenems groups, respectively. Immunocompromised patients included those who received chemotherapy or radiation within the previous 30 days, those who were positive for HIV infection with a CD4⁺ count of more than 200 cells/mm³, and those who reported chronic steroid use.

In both unadjusted and adjusted analyses, the risk of 30-day mortality did not significantly differ between patients in the cefepime and carbapenem groups (adjusted hazards ratio [aHR], 1.45; 95% CI, 0.79-2.14). Results were similar when analysis of patients in the cefepime group was restricted to those with susceptible dose-dependent isolates (aHR, 1.19; 95% CI, 0.52-1.77). 

Independent predictors of increased 30-day mortality risk included a Pitt bacteremia score above 4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 0.52-1.77), and the presence of ceftriaxone-resistance AmpC-E isolates (aHR, 1.32; 95% CI, 1.03-1.59). Of note, receipt of a prolonged β-lactam infusion was associated with decreased 30-day mortality risk (aHR, 0.67; 95% CI, 0.40-0.89).

Limitations of this study include the lack of AmpC-E isolate genotyping and potential selection bias due to the lack of random treatment allocation. 

“[H]igh dose cefepime may be a reasonable option for bacteremia caused by AmpC-E with moderate to high risk of clinically significant AmpC β-lactamase production,” the researchers concluded.