Phenotypic–Genotypic Concordance and Antibiotic Combination Synergy in Multidrug-Resistant Klebsiella pneumoniae: A Comparative Analysis of Clinical Isolates

Abstract

Background: Managing hospital infections caused by multidrug-resistant Klebsiella pneumoniae is challenging. Molecular resistance markers do not always predict phenotypic results. The aim of this study was to compare phenotypic and genotypic results of antimicrobial resistance and assess the preliminary in vitro activity of antimicrobial combinations. This single center laboratory study included 100 Enterobacteriaceae, 50 of which were K. pneumoniae. The isolates were tested for antimicrobial susceptibility to 13 antibiotics. Extended spectrum beta-lactamase (ESBL) and carbapenemase activity were tested. Five resistance genes were PCR amplified and 10 checkerboard assays were performed on neonatal isolates. Paired concordance was evaluated with Cohen’s kappa and exact McNemar’s test. Results: The 50 K. pneumoniae isolates were multidrug-resistant, and nine were extensively drug-resistant. ESBL activity was seen in 35 (70%) of the isolates, and 36 (72%) had CTX-M. Other genes identified were blaNDM-1 (24, 48%), blaKPC (11, 22%). ESBL and blaCTX-M concordance was 70% (kappa = 0.272). Blu Carba NP and blaNDM-1/blaKPC concordance was 62% (kappa = 0.317). MMV675968 combined with either colistin or meropenem yielded a FICI of 0.50. The solithromycin combination yielded a FICI of 0.75. Paired concordance was limited, and two of the combinations evaluated met the assay-specific synergy criteria. Molecular tests should not replace phenotypic tests. Results of checkerboard tests should be validated by other methods.