The Role of Efflux Pump and Carbapenemase Production in the Development of Multidrug Resistance in Klebsiella Pneumoniae and Acinetobacter Baumannii Strains Isolated from Patients with COVID-19 Infection
Introduction. Patients hospitalized with COVID-19 are often prescribed broad-spectrum antibiotics that can contribute the selection and spread of antibiotic-resistant strains. Purpose. To identify carbapenemase production and the active efflux mechanisms for antibiotics of various classes in multidrug- and extensively drug-resistant Klebsiella pneumoniae and Acinetobacter baumannii strains isolated from patients with COVID-19 infection. Materials and methods. This study included 51 multidrug- and extensively drug-resistant Klebsiella pneumoniae strains and 47 multidrug-resistant strains of Acinetobacter baumannii isolated from patients with COVID-19 infection. The minimum inhibitory concentrations (MICs) for meropenem, imipenem, cefepime, ceftazidime, doxycycline, levofloxacin, tigecycline, rifampicin, chloramphenicol and amikacin were assessed by broth microdilution method for all investigated strains. Moreover, MICs of antibiotics in the presence of efflux pump inhibitor (carbonyl cyanide-chlorophenylhydrazone, CCCP) were determined. For phenotypic detection of metallo-β-lactamase (MBL) production the double-disk EDTA method was performed. Carbapenemase genes were detected by real- time PCR. Results. All of the isolated strains have demonstrated multidrug or extensively drug resistance. All strains of A.baumannii were resistant to carbapenems, levofloxacin, amikacin and were OXA-carbapenemase producers. Susceptibility to carbapenems remained only in 2.0-3.9% of K. pneumoniae strains, to amikacin - in 7.8% of strains. Carbapenemase production was detected in 68.6% of K. pneumoniae strains (NDM - 31.4%, OXA-48 - 23.5%, KPC - 2.0%, co-production of two carbapenemase - 11.8%). Inhibition of efflux pumps made it possible to reduce the MIC values for carbapenems, cephalosporins, levofloxacin, amikacin, tigecycline in 2.1-25.5% of A. baumannii and K. pneumoniae strains. On the other hand, it didn't restore their susceptibility to antibiotics. Conclusion. Resistance to carbapenems and other β-lactams in A.baumannii and K. pneumoniae strains is associated with the production of carbapenemases. The presence of efflux mechanisms in some of the studied strains is an important, but not the only mechanism of antibiotic resistance.