Molecular Epidemiology of Extensively Drug-Resistant mcr Encoded Colistin-Resistant Bacterial Strains Co-Expressing Multifarious β-Lactamases

Abstract

Plasmid-mediated colistin resistance (Col-R) conferred by <i>mcr</i> genes endangers the last therapeutic option for multifarious β-lactamase-producing bacteria. The current study aimed to explore the <i>mcr</i> gene molecular epidemiology in extensively drug-resistant (XDR) bacteria. Col-R gram-negative bacterial strains were screened using a minimum inhibitory concentration (MIC) breakpoint ≥4 µg/mL. Resistant isolates were examined for <i>mcr</i> variants, extended-spectrum β-lactamase, AmpC, and carbapenemase genes using polymerase chain reaction (PCR). The MIC breakpoints for <i>mcr</i>-positive strains were determined using broth microdilution and E-test strips. Overall, 19/718 (2.6%) gram-negative rods (GNRs) harboring <i>mcr</i> were identified, particularly in pus (<i>p</i> = 0.01) and tracheal secretions (<i>p</i> = 0.03). Molecular epidemiology data confirmed 18/19 (95%) <i>mcr</i>-1 and 1/19 (5%) <i>mcr</i>-2 genes. Integron detection revealed 15/17 (88%) <i>Int-1</i> and 2/17 (12%) <i>Int-2</i>. Common co-expressing drug-resistant β-lactamase genes included 8/16 (50%) <i>bla</i>_CTM-1, 3/16 (19%) <i>bla</i>_CTM-15, 3/3 (100%) <i>bla</i>_CMY-2, 2/8 (25%) <i>bla</i>_NDM-1, and 2/8 (25%) <i>bla</i>_NDM-5. The MIC₅₀ and MIC₉₀ values (µg/mL) were as follows: <i>Escherichia coli</i>, 12 and 24; <i>Klebsiella pneumoniae</i>, 12 and 32; <i>Acinetobacter baumannii</i>, 8 and 12; and <i>Pseudomonas aeruginosa</i>, 32 and 64, respectively. Treatment of XDR strains has become challenging owing to the co-expression of <i>mcr</i>-1, <i>mcr</i>-2, multifarious β-lactamase genes, and integrons.