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

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.

Oral and Intravenous Fosfomycin for the Treatment of Complicated Urinary Tract Infections

“…However, we believe that, in Canada, the majority of IV fosfomycin use will be in combination therapy with other antimicrobials [14]. In fact, extensive case reports, case series, cohort descriptive studies, and clinical trials have described the use of fosfomycin in combination with other antimicrobial agents in central nervous system infections, respiratory infections, complicated urinary tract infections, infectious endocarditis and septicemia, osteomyelitis, and soft tissue infections [14,15]. In these studies, clinical resolution of infections involving fosfomycin treatment occurred in ∼80% of treated patients.…”

“…In these studies, clinical resolution of infections involving fosfomycin treatment occurred in ∼80% of treated patients. Intravenous fosfomycin used in combination with a variety of antimicrobials (e.g., β-lactams, carbapenems, glycopeptides, fluoroquinolones, and colistin) has demonstrated additive and frequently synergistic activity in vitro [14,15].…”

Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

“…The most common adverse events reported with the IV fosfomycin formulation are hypokalemia 1090 PHARMACOTHERAPY Volume 39, Number 11, 2019 and hypernatremia. 5 In a retrospective study that spanned more than 5.5 years in France and enrolled 72 patients who received fosfomycin 4 g IV every 8 hours, the most common adverse event was hypokalemia (26%), occurring on average at 4 days on therapy. 106 The mechanism is likely due to increased urinary potassium excretion in the distal tubules.…”

“…Despite its discovery 50 years ago and subsequent widespread use in Europe and Asia, fosfomycin currently retains acceptable activity against most clinically relevant MDR bacteria . A recent prospective observational study conducted in patients in 20 intensive care units in Germany and Austria indicated that fosfomycin continues to be used in combination with other antibiotics for the treatment of severe MDR infections in critically ill patients with reasonable clinical success . Its bactericidal mechanism, broad spectrum of activity, availability in both intravenous (IV) and oral formulations, and well‐tolerated safety profile make fosfomycin an attractive consideration for MDR infection treatment …”

“…4 A recent prospective observational study conducted in patients in 20 intensive care units in Germany and Austria indicated that fosfomycin continues to be used in combination with other antibiotics for the treatment of severe MDR infections in critically ill patients with reasonable clinical success. 5 Its bactericidal mechanism, broad spectrum of activity, availability in both intravenous (IV) and oral formulations, and welltolerated safety profile make fosfomycin an attractive consideration for MDR infection treatment. 6,7 In the United States, fosfomycin tromethamine (Monurol; Zambon Switzerland Ltd, Cadempino, Switzerland) is the oral dosage form approved for uncomplicated urinary tract infections (UTIs) caused by susceptible Escherichia coli and Enterococcus faecalis in adult women.…”