Efficacy of fosfomycin-containing regimens in treating severe infections caused by KPC-producing klebsiella pneumoniae and carbapenem-resistant acinetobacter baumannii in critically ill patients

• Published in: International journal of antimicrobial agents 2024-12, Vol.64 (6), p.107365, Article 107365
• Main Authors: Oliva, A., Curtolo, A., Falletta, A., Sacco, F., Lancellotti, F., Carnevalini, M., Ceccarelli, G., Roma, G., Bufi, M., Magni, G., Raponi, G.M., Venditti, M., Mastroianni, C.M.
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii - drug effects; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Acinetobacter Infections - mortality; Aged; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacterial Proteins - genetics; beta-Lactamases - metabolism; Carbapenem-resistant A. baumannii; Carbapenems - pharmacology; Carbapenems - therapeutic use; Combination regimens; CRAB; Critical Illness; Critically ill; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Fosfomycin - pharmacology; Fosfomycin - therapeutic use; Humans; Intensive care unit; Intensive Care Units; Klebsiella Infections - drug therapy; Klebsiella Infections - microbiology; Klebsiella Infections - mortality; Klebsiella pneumoniae - drug effects; KPC-Kp; KPC-producing K. pneumoniae; Male; Middle Aged; Retrospective Studies; Treatment Outcome
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2024.107365

•Fosfomycin (FOS) is increasingly used as part of combination therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) and KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, although clinical evidence of a real benefit of a FOS-containing combination for treatment of CRAB and KPC-Kp is still scant.•The clinical efficacy of FOS-containing regimens was compared to therapeutic regimens without FOS (NO-FOS) in critically ill patients with CRAB and KPC-Kp infections.•Receiving a FOS-containing regimen was associated with a lower 7-, 14- and 30-day mortality than those in the NO-FOS group, especially in the KPC-Kp group.•Patients who received FOS had a higher rate of clinical cure, early improvement, and microbiological eradication than those without FOS, especially in patients with KPC-Kp infections.•FOS was well tolerated, with an adverse event rate similar to that associated with regimens without FOS. 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. 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. 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 (