Methods: MICs were conducted on baseline and post-treatment isolates recovered during treatment period. MICs were determined using CLSI reference methods and MIC changes from baseline were further assessed. Bacterial DNA was extracted by the alkaline lysis method. β-lactamase (BL) genes were amplified in single PCRs using a panel of primers for detection of most beta-lactamase enzymes, including extended-spectrum beta-lactamases (ESBLs) (blaTEM, blaSHV, blaCTX-M), metallo-beta-lactamases (MBLs) (blaVIM, blaNDM, blaIMP), carbapenemases (blaOXA, blaKPC) and Class C cephalosporinases (blaAmpC).
Results: 9/143 [2/74 (2.7%) in CSE; 7/69 (10.1%) in MR (meropenem)] patients had a microbiological failure at the TOC visit. Of these 9 patients (all E. coli), a variation in the post-treatment genotypic profile was noted for 4 patients (44.4%) in the MR group and 2 of these patients also reported a ≥4-fold increase in post-treatment MIC. Both patients harbored 4 distinct BL genes (blaTEM + blaSHV + blaCTX-M + blaAmpC) at baseline, and had acquired two additional genes (blaOXA, blaKPC), both carbapenemases, as a result of treatment failure (after 6 days and 8 days of IV therapy respectively) with MR. In the first case, MIC increased 16-fold (1 µg/mL to 16 µg/mL for MR and 2 µg/mL to 32 µg/mL for CSE), while in the second case, MIC increased 8-fold (1 µg/mL to 8 µg/mL) for MR and 32-fold (1 µg/mL to 32 µg/mL) for CSE. No such increase in MIC or acquisition of resistant genes was noted in patients that failed therapy with CSE.
Conclusion: These findings highlight the need for an effective choice of empirical therapy as failed treatments could lead to selection for resistant genes, rendering once susceptible drug non-susceptible.
M. A. Mir,
VENUS MEDICINE RESEARCH CENTRE:
M. Chaudhary, VENUS MEDICINE RESEARCH CENTRE: Board Member and Shareholder , Salary .
A. Pyasi, Venus Medicine Research Centre: Employee , Salary .
N. S. Patil, None
R. Girotra, Venus Medicine Research Centre: Employee , Salary .
S. Narang, None
N. Fatima, None