Abstract

Objective: Current study was undertaken to find microbiological cut off for CSE1034 against bacteria which are resistant or susceptible to ceftriaxone, based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Methods: In the current investigations, 843 clinical isolates of Enterobacteriaceae isolated from patients of one of the largest tertiary care centre of North India were analyzed. Breakpoint of CSE1034 was determined using the methods reported earlier with pharmacokinetic and pharmacodynamic correlation. Results: Out of 843 isolates of Enterobacteriaceae, 663 isolates were ceftriaxone resistant and remaining 180 isolates were ceftriaxone susceptible. The MIC cut off for CSE1034 against ceftriaxone resistant Enterobacteriaceae was ≤8 µg/ml. The MIC cut off of ceftriaxone susceptible was ≤1 µg/ml. Similarly, the AST cut off for CSE1034 against ceftriaxone susceptible Enterobacteriaceae was ≥21 mm in accordance with EUCAST. The AST cut off for CSE1034 against ceftriaxone resistant Enterobacteriaceae was ≥23 mm. Conclusions: In conclusion, based on PK/PD analysis, the MIC cut off for CSE1034 against ceftriaxone resistant Enterobacteriaceae was ≤8 µg/ml (susceptible), 16–32 µg/ml (intermediate) and ≥64 µg/ml (resistant). Considering the MIC intersection point of regression line for AST calculation, the cut off CSE1034 against ceftriaxone resistant Enterobacteriaceae was ≥23 mm (susceptible), 20–22 mm (intermediate) and ≤19 mm (resistant), respectively. CSE1034 seems to be a better alternative than ceftriaxone alone for combating ESBL and MBL producing resistant pathogens which synergistically provides clinically relevant concentration at higher susceptible MIC values as observed through PK-PD findings and current study.