Evaluation of Ceftriaxone-Sulbactam-EDTA Adjuvant Combination against Multidrug Resistant Bacteria in Tertiary Care Hospital, Guntur, Andhra Pradesh, India

Abstract

Introduction: In India, multiple antibiotic resistances are rapidly growing in the bacterial population with a rising threat to public health. To overcome the effect of extended-spectrum beta-lactamases (ESBL), Metallo beta-lactamases (MBL) and carbapenemaseproducing organisms, very few antibiotics are effective; the need of the hour is a new antibiotic or drug combination. Various studies suggested that antibiotic adjuvant therapies can be an alternate approach to curb the rate of drug resistance in microorganisms. A new antibiotic combination of ceftriaxone+ sulbactam+ EDTA (CSE) has recently been proposed to tackle MDR organisms. Aim: To evaluate the in-vitro efficacy of a new antibiotic adjuvant entity CSE, among the Vitek-2 (Biomerieux, France) confirmed Multidrug Resistant (MDR) strains isolated from specimens of Intensive Care Unit (ICU) patients. Materials and Methods: A cross-sectional descriptive study was conducted on a total of 100 consecutive MDR organisms isolated from specimens of ICU admitted patients in NRI general hospital and super specialty care centre in Guntur district, Andhra Pradesh, India. Bacterial growth on the medium was identified using an automated Vitek-2 system using gram negative and gram positive identification card and Antimicrobial Susceptibility Testing (AST) cards. The isolates were identified as ESBL, MBL, AmpCbeta-lactamase, and carbapenemases producing organisms and tested for sensitivity to CSE drug-using Epsilometer (E)-test strips with Minimum Inhibitory Concentrations (MIC) gradient of 0.016-256 µg/mL, and interpreted as sensitive, and resistant based on breakpoints. A descriptive statistical analysis was done by calculating the frequencies of the variables. Results: The more prevalent MDR pathogens were Escherichia coli (36%), Pseudomonas aeruginosa (18%), Klebsiella pneumoniae (15%), and Proteus species (10%). Among Escherichia coli MDR isolates, 16.7% were ESBL+MBL producing and 83.3% were carbapenemase-producing with good susceptibility to CSE 86.7% and 83.3% respectively. Among Pseudomonas aeruginosa 83.3% of ESBL+MBL and carbapenemase-producing organisms were susceptible to CSE. Overall, 88% of MDR strains were sensitive and 12% were resistant to novel CSE combinations among 100 MDR isolates. Conclusion: The novel antibiotic-adjuvant combination CSE is highly effective (88% susceptibility) against ESBL/MBL, AmpC, and carbapenemase-producing MDR bacteria. The enhanced susceptibility may be due to the synergistic effect of all three molecules in the combination.