Adverse events during intravenous fosfomycin therapy in a real-life scenario. Risk factors and the potential role of therapeutic drug monitoring

• DOI: 10.1186/s12879-024-09541-4
• Publication Date: 2024-06-28T08:02:37Z
• Authors: Simona Biscarini; Davide Mangioni; Chiara Bobbio; Ludovica Mela; Laura Alagna; Sara Baldelli; Francesco Blasi; Ciro Canetta; Ferruccio Ceriotti; Andrea Gori; Giacomo Grasselli; Bianca Mariani; Antonio Muscatello; Dario Cattaneo; Alessandra Bandera
• Keywords: Fosfomycin; Medical microbiology; Pharmacotherapy; Adverse drug reaction

Abstract Background Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) real-life setting. Patients and methods Retrospective study of patients receiving for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated graded CTCAE ≥ II were considered. Demographic clinical risk factors IVFOF-related analysed with simple multivariable regression models. The determination TDM was made a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) plasma samples. performance (trough levels (Cmin) intermittent infusion, steady state (Css) continuous infusion) predicting ≤ 5 days after its assessment evaluated. Results Two hundred twenty-four included. At initiation, 81/224 (36.2%) ICU 35/224 (15.7%) had septic shock. most frequent infection site the low respiratory tract (124/224, 55.4%). Ninety-five (42.4%) experienced 1AEs, median time 4.0 (2.0–7.0) initiation. Hypernatremia AE (53/224, 23.7%). Therapy discontinuation due occurred 38/224 (17.0%). setting, infections shock resulted (RR adjusted 1.59 (95%CI:1.09–2.31), 1.46 (95%CI:1.03–2.07) 1.73 (95%CI:1.27–2.37), respectively), while daily dose did not. Of 68 undergone TDM, values predicted overall hypernatremia AUROC 0.65 (95%CI:0.44–0.86) 0.91 (95%CI:0.79-1.0) respectively Cmin, 0.67 (95%CI:0.39–0.95) 0.76 (95%CI:0.52-1.0) Css. Conclusions We provided real world data IVFOF-based regimens AEs. deserves further research as it represent valid tool predict Key points Real intravenous bacterial over 40% (therapy 17%) related baseline severity but not dose. showed promising results