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

Background

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 non–FOS-containing regimens in critically ill patients admitted to the intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication in the FOS vs. the NO-FOS group.

Methods

This was a 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 ≥48 h (FOS vs. NO-FOS groups, respectively). The primary outcome was 30-day mortality; secondary outcomes were clinical cure and microbiological eradication.

Results

Of the 78 patients analyzed, 26 (33.3%) were men, with a median (IQR) age and Charlson Comorbidity Index (CCI) of 67 years (53–74) and 4 (2–5), respectively. Septic shock was present in 18 patients (23.1%); 37 (47.4%) were receiving FOS, 41 (52.6%) were not receiving FOS; CRAB and KPC-Kp were isolated in 44 (56.4%) and 34 (43.6%) of patients, respectivley. Compared to NO-FOS, patients receiving FOS had a higher clinical cure (89.2% vs. 65.9%, P = 0.017), early (<72 h) improvement (78.4% vs. 52.2%, P = 0.018), microbiological eradication (87.5% vs 62.2%, P = 0.027), and lower 7-, 14- and 30-day mortality (0% vs. 4.6%, P =0.027; 2.7% vs 22%, P = 0.016; and 13.5% vs. 34.2%, P = 0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. On multivariable analysis, receiving FOS was independently associated with survival (hazard ratio = 0.29, 95% CI = 0.09-0.93, P = 0.038), confirmed after IPTW (HR = 0.501 95% CI = 0.25-0.98 P = 0.042).

Conclusions

FOS-containing regimens exhibited a higher clinical cure, higher microbiological eradication and reduced mortality compared with regimens not containing FOS in critically ill patients with CRAB and KPC-Kp infections.