Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem. (29th October 2018)

• Record Type: Journal Article
• Authors: Perdigão Neto, Lauro Vieira; Oliveira, Maura S; Martins, Roberta Cristina Ruedas; Marchi, Ana Paula; Gaudereto, Juliana Januário; da Costa, Lucianna Auxi Teixeira Josino; de Lima, Lia Fernandes Alves; Takeda, Christianne Fernandes Valente; Costa, Silvia F; Levin, Anna S
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 74:Number 1(2019)
• Page Start: 177
• Page End: 181
• Publication Date: 2018-10-29
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dky406
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: 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. Methods: 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. Results: 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. Conclusions: 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.