Evaluation of Ceftriaxone-Sulbactam-EDTA against Carbapenem-resistant Enterobacterales and non-fermenters: correlating in vitro susceptibility with molecular detection of carbapenemase genes by Xpert Carba-R.

Abstract

Carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a major therapeutic challenge because of the increasing prevalence of multidrug resistance and carbapenemase production. Although Ceftriaxone-Sulbactam-Disodium EDTA (CSE) has demonstrated encouraging in vitro activity against multidrug-resistant Gram-negative pathogens, evidence regarding its activity against carbapenem-resistant isolates and its relationship with carbapenemase genotype remains limited. This study thus evaluated the in vitro activity of CSE against CR-GNB and correlated the relationship between phenotypic susceptibility and carbapenemase genotype. A total of 208 non-duplicate carbapenem-resistant clinical isolates comprising Enterobacterales and non-fermenting Gram-negative bacilli were recovered from patients admitted to a tertiary care centre. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disk diffusion method, and carbapenemase genes (blaNDM, blaKPC, blaOXA-48, blaIMP and blaVIM) were detected using the Xpert® Carba-R assay. Overall, CSE demonstrated 65.9% susceptibility, with a combined susceptible-intermediate rate of 88.5%. Acinetobacter baumannii exhibited the highest susceptibility (85.5%), whereas Pseudomonas aeruginosa showed the lowest susceptibility (23.8%). Carbapenemase genes were detected in 72.6% of isolates, with blaNDM (60.6%) and blaOXA-48 (42.8%) predominating; co-harbouring of blaNDM and blaOXA-48 was the most frequent genotypic profile (31.3%). Multivariable logistic regression demonstrated that isolates harbouring blaOXA-48 alone (adjusted odds ratio [aOR] 5.11; p = 0.008) and blaNDM + blaOXA-48 (aOR 3.24; p = 0.004) were independently associated with CSE susceptibility. CSE demonstrated substantial in vitro activity against CR-GNB despite extensive multidrug resistance. Integration of rapid molecular carbapenemase detection with phenotypic susceptibility testing may improve interpretation of antimicrobial susceptibility and support evidence-based therapeutic decision-making for carbapenem-resistant Gram-negative infections.