Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: A Propensity Score Adjusted Retrospective Cohort Study

Background: The role of intravenous fosfomycin (iv-FOS) as a part of combination therapy for Gramnegative bacteria bloodstream infections (GNB-BSI) needs to be evaluated in clinical practice, as in vitro data show potential efficacy. Methods: All consecutive patients with a GNB-BSI from 01 January 2021 to 01 April 2023 were included. Primary outcome was 30-day mortality. A Cox regression analysis was used to identify predictors of mortality; an inverse-probability of treatment-weighting (IPTW) analysis was also performed. Results: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57- 78) years, and a median Charlson comorbidity index of 5 (3-7). At GNB-BSI onset, the median SOFA score was 5 (2-7) and 122 patients (34%) presented with septic shock. Pathogens were principally Klebsiella pneumoniae (42%), Escherichia coli (28%) and Pseudomonas aeruginosa (17%); of them, 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and betalactams/beta-lactamases-inhibitors (19%); a combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) g/daily. The use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, P = 0.147). However, on multivariable Cox-regression, combination therapy with iv-FOS resulted in protection for mortality (aHR 0.51, 95% CI 0.28-0.92), but not other combo-therapies (HR 0.69, 95% CI 0.44-1.16). This result was also confirmed with the IPTW-adjusted Cox model (aHR 0.52, 95% CI 0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA > 6, PITT >= 4) and when iv-FOS was initiated within 24 hours of GNB-BSI onset. Conclusions: Fosfomycin in combination therapy for GNB-BSI may have a role in improving survival. These results justify the development of further clinical trials. (c) 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights are reserved, including those for text and data mining, AI training, and similar technologies.