Characterization of phylogroups of Klebsiella pneumoniae ( K. quasipneumoniae and K. variicola ) harbouring bla OXA-232, with special reference to ceftazidime/avibactam/aztreonam synergy and their genetic profile

Abstract Background Klebsiella pneumoniae is a ‘critical priority’ pathogen responsible for several infections. The emerging evidence of carbapenem resistance in the phylogroups of K. pneumoniae (KpI), namely K. quasipneumoniae (KpII) and K. variicola (KpIII), has drawn attention. Objectives Given the paucity of data, this study was conducted to characterize phylogroups harbouring blaOXA-232 with special reference to ceftazidime/avibactam/aztreonam (CAZ/AVI/ATM) synergy. Methods This cross-sectional study was performed on 150 previously characterized K. pneumoniae isolates (KpI, KpII, KpIII). Susceptibility against meropenem, ceftazidime/avibactam, aztreonam, polymyxin B, colistin and cefiderocol was determined using broth microdilution. CAZ/AVI/ATM synergy was assessed using gradient diffusion and disc diffusion methods and confirmed by time–kill assay. Detection of blaOXA-232 and class A, B and D carbapenemase genes was performed by PCR. Clonality of the ceftazidime/avibactam-resistant isolates was studied by ERIC-PCR. Susceptibility was compared with the genetic profile by chi-squared and Fisher’s exact tests. Results Seventy-two isolates (48%) carried blaOXA-232 of which 87.5% were carbapenem resistant; susceptibility to cefiderocol, colistin and polymyxin B was 80.95% (51), 82.5% (52) and 84.12% (53), respectively. Difference in cefiderocol resistance (P = 0.03) and colistin susceptibility (P = 0.03) was significant among phylogroups. CAZ/AVI/ATM synergy was observed in 92.3% (24) of the ceftazidime/avibactam-resistant isolates, with blaOXA-232 alone in 12 (50%), and blaOXA-232 in combination with blaNDM ± blaOXA-48 or other MBLs in 12 (50%). Multiple clones were detected. Conclusions Synergy to the CAZ/AVI/ATM combination in the blaOXA-232-positive, ceftazidime/avibactam-resistant, carbapenem-resistant K. pneumoniae phylogroups was noted (92.3%). Cefiderocol and polymyxins were other therapeutic options.