Efficacy of high doses of intravenous fosfomycin for treatment of urinary tract infection caused by KPC carbapenemase-producing Klebsiella pneumoniae. An observational study.

Abstract

Objectives: To evaluate the efficacy of high-dose intravenous fosfomycin for the treatment of urinary tract infections (UTI) caused by KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). A secondary objective was to evaluate the impact of the results of fosfomycin susceptibility testing on prognosis.

Methods: This is an observational and retrospective study. Patients hospitalized with UTI caused by KPC-Kp receiving treatment with high-dose intravenous fosfomycin were evaluated from December 2012 to June 2018. The primary outcome variable was clinical cure at day 21.

Results: Forty-seven patients were included. The results of commercial microdilution panels showed that KPC-Kp isolates from 14 (29.8%) and 33 (70.2%) patients were non-susceptible and susceptible to fosfomycin, respectively. In 28 available isolates, susceptibility was also determined by the reference agar dilution method. In the global cohort, clinical cure was achieved at day 21 for 33 (70.2%) out of the 47 patients, with no statistical differences found between fosfomycin non-susceptible isolates and fosfomycin susceptible isolates as determined by commercial microdilution (78.6 vs. 66.7%; P = 0.50) or by the reference agar dilution (83.3 vs. 72.7%; P = 1). In the logistic regression analysis, the Pitt index was the only variable related to clinical cure at 21 days. No statistically significant differences were found for the variables associated with fosfomycin susceptibility testing or fosfomycin MIC.

Conclusion: high-dose intravenous fosfomycin can be considered for treatment of hospitalized patients with KPC-Kp UTI in some scenarios. In vitro fosfomycin susceptibility testing for multiresistant KPC-Kp may be of limited clinical value.