Genotypic to Phenotypic Resistance Discrepancies Identified Involving β-Lactamase Genes, bla KPC, bla IMP, bla NDM-1, and bla VIM in Uropathogenic Klebsiella pneumoniae

Umme Laila Urmi; Shamsun Nahar; Masud Rana; Fahmida Sultana; Nusrat Jahan; Billal Hossain; Mohammed Shah Alam; Abu Syed Md Mosaddek; Judy McKimm; Nor Azlina A Rahman; Salequl Islam; Mainul Haque

doi:10.2147/IDR.S262493

Genotypic to Phenotypic Resistance Discrepancies Identified Involving β-Lactamase Genes, bla KPC, bla IMP, bla NDM-1, and bla VIM in Uropathogenic Klebsiella pneumoniae

Infect Drug Resist. 2020 Aug 18:13:2863-2875. doi: 10.2147/IDR.S262493. eCollection 2020.

Authors

Affiliations

¹ Department of Microbiology, Jahangirnagar University, Dhaka 1342, Bangladesh.
² Department of Microbiology, Gono Bishwabidyalay, Savar, Dhaka 1342, Bangladesh.
³ Department of Pharmacology, Uttara Adhunik Medical College, Uttara, Dhaka, Bangladesh.
⁴ Medical Education, Strategic Educational Development, Leadership for the Health Professions, Swansea University Medical School, Swansea University, Swansea, Wales SA2 8PP, UK.
⁵ Department of Physical Rehabilitation Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan 25200, Malaysia.
⁶ Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur 57000, Malaysia.

Abstract

Introduction: Klebsiella pneumoniae carbapenemase (KPC) belongs to the Group-A β-lactamases that incorporate serine at their active site and hydrolyze various penicillins, cephalosporins, and carbapenems. Metallo-beta-lactamases (MBLs) are group-B enzymes that contain one or two essential zinc ions in the active sites and hydrolyze almost all clinically available β-lactam antibiotics. Klebsiella pneumoniae remains the pathogen with the most antimicrobial resistance to KPC and MBLs.

Methods: This research investigated the blaKPC, and MBL genes, namely, blaIMP, blaVIM, and blaNDM-1 and their phenotypic resistance to K. pneumoniae isolated from urinary tract infections (UTI) in Bangladesh. Isolated UTI K. pneumoniae were identified by API-20E and 16s rDNA gene analysis. Their phenotypic antimicrobial resistance was examined by the Kirby-Bauer disc diffusion method, followed by minimal inhibitory concentration (MIC) determination. blaKPC, blaIMP, blaNDM-1, and blaVIM genes were evaluated by polymerase chain reactions (PCR) and confirmed by sequencing.

Results: Fifty-eight K. pneumoniae were identified from 142 acute UTI cases. Their phenotypic resistance to amoxycillin-clavulanic acid, cephalexin, cefuroxime, ceftriaxone, and imipenem were 98.3%, 100%, 96.5%, 91.4%, 75.1%, respectively. Over half (31/58) of the isolates contained either blaKPC or one of the MBL genes. Individual prevalence of blaKPC, blaIMP, blaNDM-1, and blaVIM were 15.5% (9), 10.3% (6), 22.4% (13), and 19% (11), respectively. Of these, eight isolates (25.8%, 8/31) were found to have two genes in four different combinations. The co-existence of the ESBL genes generated more resistance than each one individually. Some isolates appeared phenotypically susceptible to imipenem in the presence of blaKPC, blaIMP, blaVIM, and blaNDM-1 genes, singly or in combination.

Conclusion: The discrepancy of genotype and phenotype resistance has significant consequences for clinical bacteriology, precision in diagnosis, the prudent selection of antimicrobials, and rational prescribing. Heterogeneous phenotypes of antimicrobial susceptibility testing should be taken seriously to avoid inappropriate diagnostic and therapeutic decisions.

Keywords: Bangladesh; Klebsiella pneumoniae; blaIMP; blaKPC; blaNDM-1; blaVIM; co-resistance; heteroresistance; urinary tract infections.

Grants and funding

SI received research funding from the Grants for Advanced Research in Education (GARE), the Ministry of Education, Bangladesh (LS201685). The grant provided support for study design, data collection, and laboratory investigation, but not manuscript publication. This study was further supported by a research grant from the World Academy of Sciences (TWAS) awarded to Dr. Shamsun Nahar (Award ID: RG/BIO/AS_I–FR3240297771). The latter grant has provided support for laboratory investigation and manuscript processing and publication. The authors would like to thank the Award bodies and study participants for their active support.