In vitro assessment of the antibacterial effects of the combinations of fosfomycin, colistin, trimethoprim and nitrofurantoin against multi-drug-resistant Escherichia coli.

MDR UPEC has become a global health challenge. Our study investigates the pairwise interactions among FOS, COL, NIT and TRI against 29 UPEC strains using the checkerboard method. The synergistic combinations are further evaluated for their bactericidal effects against the most resistant strain (MRS) using the time-kill method. The results showed that 100% of these strains were resistant to TRI and NIT, whereas 75·86% of them were susceptible to FOS and COL. Among all tested strains, only seven strains were highly resistant to all used antibiotics. Remarkably, FOS/COL, COL/NIT and COL/TRI combinations represent the most effective synergistic (fractional inhibitory concentration index <1) combinations against the seven strains at MICs lower than the susceptible breakpoint ranges, followed by FOS/NIT and FOS/TRI, which achieved synergistic interactions against 1/7 and 2/7 of these strains. Importantly, the bactericidal effects (reduction ≥3·0 log10  CFU per ml) were only observed with FOS/COL, COL/NIT and COL/TRI combinations against MRS after 24 h of post-treatment. Our data suggested that FOS/COL, COL/NIT and COL/TRI combinations could be a promising option against MDR UPEC infections. Additionally, FOS/NIT and FOS/TRI probably represent a good option for MDR UPEC with lower MICs.