In vitro Activity of Doripenem plus Fosfomycin against Drug-Resistant Clinical Blood Isolates

Abstract

The in vitro activity of doripenem in combination with fosfomycin was evaluated against a wide range of clinical blood isolates. Bacterial isolates of methicillin-resistant Staphylococcus aureus (MRSA; n = 39), Pseudomonas aeruginosa (n = 18), multidrug-resistant Escherichia coli (n = 10), Enterobacter cloacae (n = 3) and Klebsiella pneumoniae (n = 5) were investigated. For synergism testing the checkerboard test was applied and determined by calculation of the fractional inhibitory concentration index. Checkerboard results were verified by time-kill curve tests on selected isolates. Among MRSA, E. coli and K. pneumoniae, 94.9, 80 and 100% of isolates demonstrated synergism, respectively. Selected isolates demonstrated synergism in time-kill curve tests. P. aeruginosa isolates demonstrated no interaction in all isolates. Doripenem plus fosfomycin shows high efficacy with promising results in vitro.

Fosfomycin

“…Against MDR P. aeruginosa, synergy against 50% to 70% of isolates (the Etest was used) was reported with carbapenems (mainly doripenem), while synergy with colistin, tigecycline, or netilmicin was reported for Ͻ15% of strains (59). However, we should note that other published studies reported no synergy against P. aeruginosa between fosfomycin and aminoglycosides or carbapenems using checkerboards and time-kill assays (6,152).…”

“…The available studies showed that synergy between fosfomycin and other antibiotics against K. pneumoniae depends on the underlying enzymes conferring resistance. The fosfomycin-doripenem, fosfomycin-aztreonam, and fosfomycinaztreonam-amdinocillin combinations were highly effective in reducing bacterial populations of drug-resistant K. pneumoniae using checkerboards and time-kill assays (152,153). In ESBLproducing K. pneumoniae strains, synergy with carbapenems (43% to 78%, with imipenem showing the highest rate), colistin (7%), netilmicin (43%), and tigecycline (21%) was reported (59).…”

“…However, antagonism between colistin and fosfomycin against OXA-48-producing K. pneumoniae isolates was reported (checkerboards were used) (156). Regarding E. coli, the data refer to ESBL-producing strains; synergy was reported with carbapenems (by checkerboards, timekill assays, and Etest), aztreonam (by checkerboards and time-kill assays), colistin (by time-kill assay and Etest), netilmicin (by Etest), and tigecycline (by time-kill assays and Etest) (28,59,152,153,157). In addition, synergy was reported with cefoxitin (by time-kill assays) at concentrations equal to the MIC of the isolate but not at higher concentrations (157).…”

Prevalence of Fosfomycin Resistance in Methicillin-Resistant <i>Staphylococcus aureus</i> Isolated from Patients in a University Hospital in China from 2013 to 2015

“…Under such circumstances, fosfomycin has gained attention recently as it has potential synergistic activity with other agents against multidrug-resistant or extensively drug resistant bacteria including MRSA (3,11,12).Several findings have reported that fosfomycin achieves high concentrations in skin and soft tissues (13,14).Since increased CA-MRSA infections have been reported in China, mainly SSTI caused by ST59 MRSA, fosfomycin might become important alternative treatment for SSTI(15).…”

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

“…Fosfomycin combinations have also been evaluated against S. aureus . Cefazolin, doripenem, meropenem, moxifloxacin, and quinupristin/dalfopristin all demonstrated synergy in vitro against both methicillin‐susceptible S. aureus (MSSA) and MRSA . Linezolid in combination with fosfomycin has also repeatedly demonstrated synergy against MSSA and MRSA in both in vitro testing and Galleria mellonella models .…”