Ceftriaxone-Sulbactam-EDTA (CSE) is the first cephalosporin-β-lactamase inhibitor combination with an Antibiotic Resistance Breaker – Disodium Edetate, recently evaluated in a Phase-3 clinical trial for treatment of adults with complicated urinary tract infections (NCT03477422). The addition of Sulbactam and EDTA expands the spectrum of activity of Ceftriaxone to include extended-spectrum-β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing bacteria. This study evaluated the in vitro activity of CSE against 3150 isolates (716 (22.73%) E. coli; 435 (13.81%) K. pneumoniae; 1075 (34.13%) A. baumannii; 924 (29.33%) P. aeruginosa) collected from 22 hospitals in India during 2013-16.
3150 non-duplicate gram-negative clinical isolates were collected, and susceptibility testing was conducted using reference broth microdilution method for CSE and comparators. CLSI defined phenotypic methods were used for ESBL and MBL detection, and thereafter, all isolates were further characterized genotypically using single PCRs and a panel of primers for detection of most beta-lactamase enzymes, including blaTEM, blaSHV, blaCTX-M, blaAmpC, blaOXA, blaKPC, blaVIM, blaNDM, and blaIMP.
Of the 3150 isolates, 2717 (86.25%) were β-lactamase producers, of which, 851 (31.32%) tested positive for ESBL, 1591 (58.56%) tested positive for MBL, while 275 (10.12%) tested positive for both ESBL and MBL production during phenotypic evaluation. Once the genotype data were available, isolates were re-characterized as per the functional classification of β-lactamases into four distinct categories, including ESBL, AmpC, Carbapenemase and MBL. An astonishing 1866 (59.23%) isolates harbored at least one MBL gene, of which, the prevalence was the highest in A. baumannii (78.6%), followed by K. pneumoniae (63%), P. aeruginosa (46.6%) and E. coli (44.1%). A summary of the results of susceptibility testing is shown in Figures 1, 2 and 3.
CSE showed a high overall susceptibility in ESBL- and MBL- producing bacteria and could provide a useful alternative to carbapenems and colistin in clinical settings.
Venus Medicine Research Centre:
M. Chaudhary, VENUS MEDICINE RESEARCH CENTRE: Board Member and Shareholder , Salary .
N. S. Patil, None
M. A. Mir, VENUS MEDICINE RESEARCH CENTRE: Employee , Salary .
S. Chaudhary, Venus Medicine Research Centre: Employee and Shareholder , Salary .
P. Mandale, Venus Medicine Research Centre: Employee , Salary .