The effect of inoculum size on the activity of different ratios of Ceftriaxone – Sulbactam [(1:1) vs. (2:1)] against ESBL producing organisms

Abstract

Background and Objective: Antibiotic resistance has become the most importunate health issue and remains a major public health concern worldwide. Production of extended spectrum β-lactamases (ESBL) is one of the major causes of resistance to β-lactam antibiotics. Several in-vitro studies have demonstrated the significant impact of inoculum size on the effectiveness of β-lactam-β-lactamase inhibitor combination. Higher concentration of β-lactamase inhibitor (Sulbactam) will be needed to combat the increased production of ESBLs in infections with high inoculum. The primary objective of the present study is to evaluate Minimum Inhibitory Concentration (MICs) of ESBL producing Enterobacteriaceae, against Ceftriaxone alone and Ceftriaxone with Sulbactam combination (1:1 and 2:1) in presence of normal and higher inoculum of these bacteria. The secondary objective of the study is to demonstrate the in-vitro efficacy of Ceftriaxone-Sulbactam (CS) in presence of higher inoculum of bacteria. Method: ESBL producing strains of Enterobacteriaceae (E. coli, K pneumoniae 30 each) were isolated from patient samples. MIC of Ceftriaxone and Sulbactam alone and in combination (1:1 and 2:1) was determined in presence of both normal (105CFU/ml) and higher inoculum (107CFU/ml) of these bacteria using micro broth dilution method of antimicrobial susceptibility testing. Resultsand Conclusion: The study finds an inoculum effect with Ceftriaxone. After addition of Sulbactam, MIC value for Ceftriaxone was reduced by 4-128 folds and 2-32 folds in ESBL producing strains of E. coli and K. pneumoniae respectively. The findings of the present study demonstrated that CS at 1:1 ratio has better in-vitro activity against ESBL producing strains of E. coli and K. pneumoniae than at a 2:1 ratio in both normal bacterial inoculum and higher bacterial inoculum. This is suggestive of the need for the 1:1 ratio combination of Ceftriaxone-Sulbactam in management of severe infections caused by ESBL producing organisms.