Dissemination of integrons and carbapenemase-encoding genes among multidrug resistant Proteus mirabilis isolated from urinary tract infections in Egypt
摘要
Proteus mirabilis (P. mirabilis) is an opportunistic pathogen responsible for various community-acquired and nosocomial infections, particularly urinary tract infections (UTIs). Rising resistance to broad-spectrum antibiotics, including carbapenems, is narrowing treatment options and poses a major public health concern. This study aimed to investigate the antimicrobial susceptibility patterns of P. mirabilis isolates obtained from UTI patients. Then, to assess the molecular determinants of carbapenem-resistant isolates with a focus on the role of integrons in resistance gene dissemination.
MethodsA total of 101 P. mirabilis isolates were recovered from 600 urine samples collected from both inpatients and outpatients at Minia University Hospitals, Egypt. The disc diffusion method was utilized for phenotypic identification and to determine the antimicrobial susceptibility profiles of carbapenem-resistant isolates. Subsequently, conventional PCR was performed to screen for eleven carbapenemase-encoding genes, AmpC β-lactamase genes, and integrons.
ResultsAmong the 101 isolates, 57 (56.4%) were resistant to imipenem, with the majority recovered from inpatients (80.7%) and catheterized patients (56.1%). Carbapenem-resistant isolates exhibited significantly higher resistance rates to ceftazidime (87.7% vs. 27.3%), aztreonam (50.9% vs. 18.2%), and gentamicin (15.8% vs. 0%) compared to carbapenem-sensitive isolates (p < 0.05). Multidrug resistance (MDR) was identified in 93% of the imipenem-resistant isolates. Molecular analysis revealed a predominance of class B metallo-β-lactamases, with, blaVIM−1 (78.9%) and blaNDM (24.6%) being the most common. Additionally, class A and class D carbapenemase genes were detected, although at comparatively lower frequencies. Out of 101 isolates, 39 (38.6%) were identified as ESBL producers, of which 13 (33%) were positive for either the blaTEM or blaSHV gene. AmpC β-lactamase gene (blaFOX) was identified in 7.9% of isolates. Integrons were widespread, with intI1 present in 91.2% and intI2 in 47.4% of resistant isolates. Notably, co-carriage of three or more carbapenemase genes was observed in 64.9% of resistant isolates, all of which exhibited MDR phenotypes.
ConclusionCarbapenem resistance in P. mirabilis is highly prevalent and strongly linked to MDR, integron carriage. This reflects the ongoing evolution of antibiotic resistance and the key function of integrons in spreading resistance genes. The detection of isolates carrying several carbapenemase genes simultaneously is particularly worrisome. These findings highlight the importance of implementing antimicrobial stewardship alongside ongoing molecular surveillance to effectively track and control the spread of resistant strains.