Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem

In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria. We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to β-lactams and colistin, treated with 16 g of fosfomycin daily for 10–14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS. Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time–kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued. Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.