Efficacy of Novel Combinations of Antibiotics against Multidrug-Resistant—New Delhi Metallo-Beta-Lactamase-Producing Strains of <i>Enterobacterales</i>

Abstract

The emergence of multidrug-resistance (MDR)—New Delhi metallo-beta-lactamase (NDM)-producing microorganisms—has become a serious concern for treating such infections. Therefore, we investigated the effective antimicrobial combinations against multidrug-resistant New Delhi metallo-beta-lactamase-producing strains of Enterobacterales. The tests were carried out using the 2D(two-dimensional) checkerboard method. Of 7 antimicrobials, i.e., doripenem (DRP), streptomycin (STR), cefoxitin (FOX), imipenem (IPM), cefotaxime (CTX), meropenem (MER), and gentamicin (GEN), 19 different combinations were used, and out of them, three combinations showed synergistic effects against 31 highly drug-resistant strains carrying blaNDM and other associated resistance markers. Changes in the minimum inhibitory concentration (MIC) values were interpreted using the test fractional inhibitory concentration index (FIC Index). The FIC Index values of these combinations were found in the range of 0.1562 to 0.5, which shows synergy, whereas no synergism was observed in the remaining antimicrobial combinations. We conclude that these antibiotic combinations can be analyzed in in vivo and pharmacological studies to establish an effective therapeutic approach.

Keywords

• antimicrobial resistance
• antibiotics synergy
• carbapenemase
• NDM-beta-lactamase