Antibacterial Potential of <i>Azadirachta indica</i> against ESBL and Carbapenemase-producing Multidrug-resistant UPEC

Background: The increasing prevalence of antibiotic-resistant Escherichia coli strains presents significant challenges in the treatment of Urinary Tract Infections (UTIs), especially in resource-limited settings. Nearly 50% of E. coli isolates are ESBL producers and exhibit resistance to commonly used antibiotics. Genetic analysis has identified a high occurrence of resistance genes such as CTX-M-15 and NDM, which confer resistance even to last-line antibiotics. Aim: To evaluate the antibacterial efficacy of A. against genetically confirmed ESBL- and carbapenemase-producing uropathogenic E. coli, i.e. UPEC strains isolated from UTI patients. Methods: A total of 273 UPEC strains were isolated from symptomatic UTI patients (146 females and 127 males). Phenotypic and molecular identification of ESBL and carbapenemase production was conducted using CLSI 2022 guidelines, with PCR used to detect CTX-M and NDM resistance genes. The antibacterial potential of A. indica extract was assessed using the Kirby-Bauer disc diffusion method and compared with the standard antibiotic Gentamicin. Results: Among the 273 UPEC isolates, 70% were Multidrug-Resistant (MDR), with 82 isolates producing ESBL and 62 producing carbapenemase. The A. indica extract demonstrated significant antibacterial activity, with zones of inhibition averaging 20.18 ± 0.89 mm against ESBL-producing strains and 20.91 ± 1.3 mm against carbapenemase-producing strains—comparable to Gentamicin at 100% concentration. Resistance was more prevalent among hospitalised patients than outpatients. Conclusion: The study highlights the high prevalence of MDR UPEC strains and underscores the urgent need for effective alternatives to conventional antibiotics. The significant antibacterial activity of A. indica against ESBL- and carbapenemase-producing UPEC suggests its potential use as an adjunct or alternative therapy in UTI management. Incorporating plant-based treatments such as A. indica could provide a sustainable, cost-effective strategy to combat antibiotic-resistant infections, particularly in resource-constrained environments. Major Findings: Azadirachta indica extract under study showed promising antibacterial activity against both ESBLand carbapenemase-producing strains, with efficacy comparable to Gentamicin, highlighting its potential as a natural therapeutic option.