Current clinical use of intravenous fosfomycin in ICU patients in two European countries

C Putensen, B Ellger, S G Sakka, A Weyland, K Schmidt, M Zoller, N Weiler, D Kindgen-Milles, U Jaschinski, J Weile, S Lindau, M Kieninger, A Faltlhauser, N Jung, P Teschendorf, M Adamzik, M Gründling, T Wahlers, H Gerlach, F-A Litty, C Putensen, B Ellger, S G Sakka, A Weyland, K Schmidt, M Zoller, N Weiler, D Kindgen-Milles, U Jaschinski, J Weile, S Lindau, M Kieninger, A Faltlhauser, N Jung, P Teschendorf, M Adamzik, M Gründling, T Wahlers, H Gerlach, F-A Litty

Abstract

Purpose: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions.

Methods: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575).

Results: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy.

Conclusion: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Keywords: Gram-negative; Gram-positive; Intensive care; Intravenous fosfomycin; Multidrug resistance; Non-interventional study.

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