Comparison of Antimicrobial Activity between Ceftriaxone-Sulbactam-Disodium EDTA and Ceftazidime-Avibactam against Carbapenemase Producing Enterobacterales Isolates from a Tertiary Care Hospital: An In-vitro Study

Introduction: The spread of Multidrug-Resistant (MDR) organisms worldwide poses a significant public health challenge, particularly in the South Asian region, including India. Infections caused by Metallo-β-Lactamase (MBL) producing Enterobacterales are a notable concern. The rising incidence of MBL-producing isolates underscores the urgent need for innovative therapeutic strategies and effective antimicrobial combinations to address these threats. Combination treatments such as Ceftriaxone Sulbactam-disodium Ethylenediamine Tetraacetate (EDTA) (CSE) and Ceftazidime-Avibactam (CZA) have emerged as promising alternatives to conventional antibiotics. Aim: To compare the in-vitro efficacy of two antibiotic combinations, namely CSE and CZA, against Carbapenemaseproducing Enterobacterales isolates. Materials and Methods: An in-vitro study was conducted over a period of six months from June 2024 to November 2024 at the Department of Microbiology, SRM Medical College Hospital, Chengalpattu, Tamil Nadu, India. A total of 141 Enterobacterales isolates that were resistant to either Imipenem or Meropenem, obtained from various clinical samples, were included. Phenotypic differentiation was performed using the EDTAmodified Carbapenem Inactivation Method (eCIM) method in conjunction with the modified Carbapenem Inactivation Method (mCIM) method. Further in-vitro susceptibility testing was conducted using the Kirby-Bauer disk diffusion method to compare the two antibiotic combinations, namely CSE and CZA. Demographic parameters including age, gender, sample type, ward and organism-wise distribution were assessed throughout the course of this study. Data analysis was performed using percentage susceptibility and frequency distribution. The p-value was determined using Fisher’s exact test, with a p-value<0.05 regarded as statistically significant. Results: Among 141 Carbapenem-Resistant Enterobacterales (CRE) isolates, 39 (27.66%) were phenotypically identified as Carbapenemase producers using the mCIM-eCIM method. Antimicrobial susceptibility testing of these isolates, performed using the Kirby-Bauer disk diffusion method, revealed that all 39 (100%) Carbapenemase-producing isolates were susceptible to CSE. In contrast, only 9 (23%) serine carbapenemase-producing isolates were susceptible to CZA, while 30 (77%) MBL-producing isolates demonstrated resistance. Conclusion: In this study, CSE emerged as a potent antibacterial agent against MBL-producing isolates. Therefore, it is strongly recommended to include CSE in the routine susceptibility panel and consider its use as a carbapenem and colistin-sparing drug against carbapenemase producers, especially MBL-producing Enterobacterales isolates.