Detection of resistance genes and evaluation of synergistic effects of antibiotic combinations in colistin-resistant Klebsiella pneumoniae clinical isolates

Abstract

OBJECTIVE

Rising antimicrobial resistance in Klebsiella pneumoniae is major public health issue, linked to high morbidity, and mortality. This study aims to identify resistance genes in Klebsiella pneumoniae strains from a university hospital in Istanbul, and to determine effects of combining several commonly used antibiotics.

BACKGROUND

Excessive antibiotic use has increased prevalence of antibiotic resistance in Klebsiella pneumoniae isolates severely limiting treatment options for clinicians.

METHODS

Twenty-one consecutive resistant Klebsiella pneumoniae isolates from various samples from Hospitals of Bezmialem Vakıf University were analyzed. Identifications and susceptibilities were done using commercial methods (VITEK MS, VITEK®2, bioMérieux). Colistin resistance was assessed by microdilution test and resistance genes (blaKPC, blaOXA48, blaNDM) were detected via PCR using specific primers. Checkerboard testing was used to determine colistin(C), meropenem(M), gentamycin(G), trimethoprim/sulphamethoxazole(B), ceftazidime/avibactam(S), and tigecycline(T) susceptibilities singly or in combinations.

RESULTS

All strains were blaOXA48 positive whereas 19% blaNDM positive, and 4.7% blaKPC positive. Preliminary data showed synergism in significant number of isolates particularly in C+S, C+M, and C+T combinations, though not uniformly. Also, significant amount of additive effect and indifferent interactions, where antibiotics did not interact with each other, were noticed in different isolate-antibiotic combinations. It should be underlined that these data are preliminary, and clearer picture may be obtained by increasing number of samples.

CONCLUSIONS

While detection of blaOXA-48 in all strains is expected, detection of blaKPC in 4.7% and blaNDM in 19% of strains is concerning. Significant interactions were noted with some antibiotic combinations and further testing with large number of isolates is suggested.