Investigation for some Aminoglycosides Modifying Enzymes- Encoding Genes and Co-Resistance to Fluoroquinolones among Klebsiella pneumoniae Isolates from Different Clinical Cases

Abstract

In this study, we investigated the prevalence of aminoglycosides modifying enzymes (AMEs)-encoding genes, including aac(3′)-ΙΙ, ant(3′′)-Ι, aph(3′)-VΙ, and aac(6′)-Ιb-cr and their potential effect on the development of resistance to aminoglycosides and fluoroquinolones in clinical isolates of Klebsiella pneumoniae. According to the phenotypic and biochemical characteristics of 150 clinical samples, 50 (33%) isolates were identified as K. pneumoniae. These isolates were collected from different clinical sources, including urine (15, 30%), blood (12, 24%), sputum (9, 18%), wounds (9, 18%), and burns (5, 10%). The minimum inhibitory concentrations (MICs) assay revealed that the resistance values of isolates were 25 (50%) to gentamicin (≥16µg/ml), 21 (42%) to amikacin (≥64 µg/ml), 15 (30%) to ciprofloxacin (≥4 µg/ml), and 11 (22%) to levofloxacin (≥8 µg/ml). Genotypic detection revealed that aac(3′)-ΙΙ, aac(6′)-Ιb-cr, aph(3′)-VΙ, and ant(3′′)-Ι were found in 47 (94%), 38 (76%), 18 (36%), and 8 (16%) of K. pneumoniae isolates, respectively. The co-resistance pattern for both aminoglycosides and fluoroquinolones was detected in 14 (28%) isolates, of these 10 (71.4%) harbored aac(6′)-Ιb-cr. DNA sequencing for some isolates revealed the presence of point and frameshift mutations in the studied genes. Our study findings suggest that the presence of missense and frameshift mutations may contribute to the elevated resistance to amikacin and gentamicin. The increased prevalence of AMEs-encoding genes among K. pneumoniae isolates could contribute in reducing susceptibility to amikacin and gentamicin. The co-resistance pattern for aminoglycosides and fluoroquinolones was highly associated with the presence of the aac(6′)-Ιb-cr gene.