Interactions of polymyxin B in combination with aztreonam, minocycline, meropenem and rifampicin against Escherichia coli producing NDM and OXA-48-group carbapenemases.

Antimicrobial Agents and Chemotherapy
A OlssonThomas Tängdén

Abstract

Objectives. Carbapenemase-producing Enterobacterales pose an increasing medical threat. Combination therapy is often used for severe infections; however, there is little evidence supporting the optimal selection of drugs. This study aimed to determine the in vitro effects of polymyxin B combinations against carbapenemase-producing Escherichia coli. Methods. The interactions of polymyxin B in combination with aztreonam, meropenem, minocycline or rifampicin against 20 clinical isolates of NDM and OXA-48-group-producing E. coli were evaluated using time-lapse microscopy. 24-h samples were spotted on plates with and without 4 x MIC polymyxin B for viable counts. Whole-genome sequencing was applied to identify resistance genes and mutations. Finally, potential associations between combination effects and bacterial genotypes were assessed using Fisher's exact test. Results. Synergistic and bactericidal effects were observed with polymyxin B and minocycline against 11/20 strains and with polymyxin B and rifampicin against 9/20 strains. The combinations of polymyxin B and aztreonam or meropenem showed synergy against 2/20 strains. Negligible resistance development against polymyxin B was detected. Synergy with polymyxin B and minocycli...Continue Reading

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