In vitro evaluation of antibiotic synergy for carbapenem-resistant Klebsiella pneumoniae clinical isolates

Background & objectives: The prevalence of severe infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) strains has increased worldwide. With rising resistance to polymyxins, the treatment has become challenging. Given the paucity of novel agents and limited data on combination therapy for CRKP, the present study was performed to test antibiotic combinations, for synergy against clinical isolates of CRKP. Methods: A total of 50 clinical isolates of CRKP were included. Modified carbapenem inactivation method was performed for the detection of carbapenemases. In vitro synergy testing was done for the following combinations: meropenem+colistin, imipenem+tigecycline and polymyxin B+levofloxacin. It was performed with epsilometric test and microdilution checkerboard method. The time kill assay (TKA) was used to confirm the results. The fractional inhibitory concentration was also calculated. Results: All CRKP isolates (100%) were ESBL producers and were completely resistant to amoxicillin-clavulanic acid, cefepime, cefotaxime, ceftazidime and piperacillin-tazobactam. Resistance to ciprofloxacin, amikacin and tetracycline was 96, 88 and 54 per cent, respectively. Overall, 78 (39/50) and 88 per cent (44/50) of the 50 CRKP isolates exhibited synergy by TKA for meropenem-colistin and imipenem-tigecycline, respectively. No synergy was detected for levofloxacin-polymyxin B combination. The best combination among the three was that of imipenem and tigecycline followed by meropenem-colistin. Interpretation & conclusions: Of the three combinations tested, imipenem and tigecycline followed by meropenem-colistin were found to be best. No synergy was detected for levofloxacin-polymyxin B combination.