Emergence of fosfomycin resistance among isolates of multidrug-resistant Enterobacter species at a tertiary care hospital in Dhaka, Bangladesh

Abstract

Background: The emergence of multidrug-resistant Enterobacter species as a worrying resistant pathogen seriously threatened human health. The rising rate of resistance to commonly used antibiotics limit the choice hence it is urgent to evaluate the antimicrobial activity of older drug like Fosfomycin. Objective: The study aimed to seek the frequency of fosfomycin resistance in the clinical isolates of Enterobacter species and to detect the fosfomycin resistance gene along with antibiotic resistance pattern. Methods: This cross-sectional study was conducted in the Department of Microbiology of a tertiary care hospital in Bangladesh from July 2018 to June 2019. Enterobacter spp. was isolated from a total of 350 samples by a standard microbiological method. Antibiotic susceptibility was performed by the disk diffusion technique. Antibiotic susceptibility and minimum inhibitory concentration (MIC) of fosfomycin were determined by the agar dilution method. Fosfomycin resistance gene fosA, fosA3, fosA4, fosA5, fosB, fosB2, fosC, fosC2 and fosX among fosfomycin‑resistant Enterobacter spp detected by polymerase chain reaction (PCR) using specific primer. Sequencing of fosA and fosA₅ was performed by capillary method, and the nucleotide sequence of fosA₅ has been deposited to GenBank. Results: Out of 28 Enterobacter spp. 7 (25%) fosfomycin resistant Enterobacter spp. were detected by agar dilution method. Out of 7 fosfomycin-resistant strains, 4 (57.14%) were isolated from urine samples. Fifteen (53.57%) isolates of Enterobacter spp. were multidrug-resistant detected by disc diffusion technique. All of the fosfomycin-resistant isolates were MDR. A significant rise in the MIC was found between 256µg/ml- ≥4096 µg/ml to fosfomycin. PCR revealed that 100% of fosfomycin resistant isolates are positive for fosA, 71.43% and 28.57% were positive for fosA₅ and fosB₂ respectively. Sequencing of fosA₅ gene established the FosA family fosfomycin resistance glutathione transferase gene. Conclusion: The results of this study showed a high proportion of fosfomycin resistance among multidrug-resistant Enterobacter spp. irrespective of fosfomycin usage in Bangladesh. FosA family fosfomycin resistance glutathione transferase gene emerging in Bangladesh. Bangladesh Medical Res Counc Bull 2022; 48(3): 203-210