Efficacy of Fosfomycin-Containing Regimens in Treating Severe Infections Caused by KPC-Producing Klebsiella pneumoniae and Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients

Introduction Fosfomycin (FOS) is gaining increasing importance as part of combination therapy for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) and KPC-producing Klebsiella pneumoniae (KPC-Kp) thanks to its in-vitro synergism with several antibiotics, high tissue distribution and good tolerability. We analyzed the effect on 30-day survival of FOS-containing regimens compared to NO-FOS in critically ill patients admitted to intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication of FOS versus NO-FOS group. Materials/methods Monocentric retrospective observational study including SARS-Cov2-negative critically ill patients with KPC-Kp or CRAB infection treated with combination antibiotic therapy with or without FOS for 48h (FOS vs NO-FOS groups). Primary outcome was 30-d mortality, secondary outcomes clinical cure and microbiological eradication. Results Of the 78 patients analyzed, 26 (33.3%) were men, median (IQR) age and Charlson Comorbidity Index (CCI) were 67 years (53-74) and 4 (2-5), respectively. Septic shock was present in 18 patients (23.1%), 37 (47.4%) were CRAB, 41 (52.6%) KPC-Kp. Compared to NO-FOS, patients receiving FOS had higher clinical cure (89.2%vs65.9%, p=0.017), early (<72h) improvement (78.4%vs52.2%, p=0.018), microbiological eradication (87.5%vs62.2%, p=0.027) and lower 7-, 14- and 30-d mortality (0%vs4.6%, p=0.027, 2.7%vs22%, p=0.016, 13.5%vs34.2%, p=0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. At multivariate analysis, receiving FOS was independently associated with survival (HR 0.29, IC95% 0.09-0.93, p=0.038), confirmed after IPTW (HR 0.501 IC95% 0.25-0.98 p=0.042). Conclusions FOS-containing regimens exhibit higher clinical cure, higher microbiological eradication and reduced mortality than NO FOS-containing regimens in critically ill patients with CRAB and KPC-Kp infections.