Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.

Gram-negative bacteria are common causes of urinary tract infections (UTIs). Such pathogens can acquire genes encoding multiple mechanisms of antimicrobial resistance, including carbapenem resistance. The aim of this study was to detect the carbapenemase-producing ability of some Gram-negative bacterial isolates from urine specimens of patients suffering from complicated UTIs at two vital tertiary care hospitals in Cairo, Egypt; to determine the prevalence of carbapenemase genes among plasmid-bearing isolates; and explore the possibility of horizontal gene transfer to other bacterial species. The collected isolates were subjected to antimicrobial susceptibility testing, phenotypic analysis of carbapenemase production, and molecular detection of plasmid-borne carbapenemase genes, then the extracted plasmids were transformed into competent E. coli DH5α. A total of 256 Gram-negative bacterial clinical isolates were collected, 65 (25.4%) isolates showed carbapenem resistance of which 36 (55.4%) were carbapenemase-producers, and of these 31 (47.7%) harbored plasmids. The extracted plasmids were used as templates for PCR amplification of blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP carbapenemase genes. The blaOXA-48 gene was detected in 24 (77.4%) of the tested isolates while blaVIM gene was detected in 8 (25.8%), both blaKPC and blaNDM genes were co-present in 1 (3.2%) isolate. Plasmids carrying the blaOXA-48 gene from 4 K. pneumoniae clinical isolates were successfully transformed into competent E. coli DH5α. The transformants were carbapenemase-producers and acquired resistance to some of the tested antimicrobial agents as compared to untransformed E. coli DH5α. The study concluded that the rate of carbapenem resistance among Gram-negative bacterial uropathogens in Cairo, Egypt is relatively high and can be transferred horizontally to other bacterial host(s).

Multidrug-resistant (MDR) uropathogens have become a public health threat, especially in developing countries. Carbapenems are a class of antimicrobial agents often reserved for infections caused by MDR microorganisms. The aim of this study was to determine the prevalence and genotypic basis of plasmid-mediated carbapenem resistance among MDR uropathogens from one of the major clinical settings in Cairo, Egypt. A total of 150 bacterial isolates from patients suffering from urinary tract infections were collected from the Microbiology lab of El-Demerdash Hospital, Cairo, Egypt. All isolates were identified using standard methods. Antimicrobial susceptibility testing was carried out by Kirby Bauer's disk diffusion method following the CLSI guidelines. Plasmids were extracted from MDR uropathogens that also showed carbapenem resistance to be used as templates for PCR amplification. The resulting amplicons were subjected to DNA sequencing. The extracted plasmids were also transformed into Escherichia coli DH5α to compare the phenotypic resistance of the transformants with that of the clinical isolates from which the plasmids were extracted. Of the 150 collected isolates, 116 (77.3%) were Gram-negative, 51 of which (44%) were MDR. Carbapenem resistance was observed in 16/51 (31.4%) of the MDR isolates, 12 of which harbored plasmids. The blaOXA gene was detected in the plasmids of only 9 MDR carbapenem-resistant isolates. From this study, it can be concluded that Gram-negative uropathogens show high rates of multidrug-resistance. The prevalence of MDR uropathogens that are also carbapenem-resistant has increased greatly over the past few years, and this resistance can be easily acquired by horizontal transfer.

Background: The emergence of multidrug-resistant (MDR) uropathogens has become a public health threat and current knowledge of the genotypic basis of bacterial resistance is essential for selecting appropriate treatment options. Objectives: To determine the prevalence of antimicrobial resistance among MDR uropathogens and to elucidate the molecular bases of plasmid-mediated resistance. Methods: Bacterial isolates were recovered from urine specimens of 150 out-patients with signs and symptoms of urinary tract infections (UTIs) at El-Demerdash Hospital, Cairo, Egypt. Standard methods were used for identification, antimicrobial suscep- tibility testing was performed according to CLSI guidelines. Results: Among the recovered isolates, 22.7% and 77.3% were Gram-positive, and negative, respectively. Of which; 43.3% were MDR with 60% harboring plasmids. Extended spectrum β-lactamase (ESBL) genes blaCTX-M, blaSHV, and blaTEM were detected on plasmids of 89.7%, 41%, and 84.6% of the tested isolates, respectively. The aminoglycoside resistance gene aac6’-Ib/aac-6’-Ib- cr was found on plasmids of 92.3% of the tested isolates followed by qnrS (92.3%), qnrB (46.2%), and qnrA (7.7%). The most prevalent quinolone efflux pump gene was oqxB (38.5%), followed by oqxA (20.5%), then qepA (10.3%). Conclusion: High levels of resistance to nitrofurans, β-lactam/β-lactamase inhibitor, cephalosporins, aminoglycosides, and fluoroquinolones were detected, and their use as empirical treatment for UTIs has become questionable. Keywords: ESBLs; qnR; plasmid-mediated; uropathgens; antibacterial resistance.

Background The dissemination of carbapenem resistance via carbapenemases, such as the metallo-β-lactamase NDM, among Enterobacterales poses a public health threat. The aim of this study was to characterize a plasmid carrying the blaNDM-1 gene, which was extracted from a clinical Klebsiella pneumoniae uropathogen from an Egyptian patient suffering from a urinary tract infection. Methods and results The recovered plasmid was transformed into competent E. coli DH5α which acquired phenotypic resistance to cefoxitin, ceftazidime, and ampicillin/sulbactam, and intermediate sensitivity to ceftriaxone and imipenem (a carbapenem). Whole plasmid sequencing was performed on the extracted plasmid using the DNBSEQ™ platform. The obtained forward and reverse reads were assembled into contigs using the PRINSEQ and PLACNETw web tools. The obtained contigs were uploaded to PlasmidFinder and ResFinder for in silico plasmid typing and detection of antimicrobial resistance genes, respectively. The final consensus sequence was obtained using the Staden Package software. The plasmid (pNDMKP37, NCBI accession OK623716.1) was typed as an IncX3 plasmid with a size of 46,160 bp and harbored the antibiotic resistance genes blaNDM-1, bleMBL, and aph(3’)-VI. The plasmid also carried mobile genetic elements involved in the dissemination of antimicrobial resistance including insertion sequences IS30, IS630, and IS26. Conclusions This is Egypt’s first report of a transmissible plasmid co-harboring blaNDM-1 and aph(3’)-VI genes. Moreover, the respective plasmid is of great medical concern as it has caused the horizontal transmission of multidrug-resistant phenotypes to the transformant. Therefore, new guidelines should be implemented for the rational use of broad-spectrum antibiotics, particularly carbapenems.