Conclusion and future directions

The study demonstrates a high prevalence of multidrug- and extensively drug-resistant [8] ESKAPEE pathogens in Hyderabad clinical settings, posing a significant threat to treatment efficacy and infection-control programs. Among Gram-negative isolates, E. coli and K. pneumoniae were the predominant MDR and ESCR producers, while A. baumannii and P. aeruginosa showed substantial carbapenem resistance, reflecting declining effectiveness of frontline and last-line antibiotics. Gram-positive pathogens, including MRSA and VRE, further challenge clinical management, although linezolid and vancomycin largely retained activity. The predominance of urinary isolates highlights urinary tract infections as the principal source of multidrug-resistant ESKAPEE isolates in this study, suggesting that reducing urinary tract infections could substantially lessen the overall burden of antimicrobial resistance.

These findings emphasize the urgent need for robust antimicrobial stewardship, continuous susceptibility surveillance, and stringent infection-control measures. Targeted preventive strategies, particularly among older adults, who represented the largest proportion of cases in this study, may help reduce this burden before antibiotic treatment becomes necessary. In line with IDSA and CDC recommendations for catheter-associated urinary tract infection prevention [38], these include minimizing unnecessary or prolonged urinary catheterization, aseptic catheter insertion and care, improved personal hygiene, appropriate diagnosis and prompt treatment of symptomatic urinary tract infections, and avoidance of antimicrobial prophylaxis for asymptomatic bacteriuria. Evaluating the specific effectiveness of such interventions within Pakistan's health care context falls outside the scope of the present study and warrants dedicated future research.

Future research should focus on molecular characterization of resistance determinants, plasmid profiling, and genomic mapping to clarify transmission dynamics. Investigating novel therapeutic combinations and re-evaluating older agents such as fosfomycin or minocycline may offer interim treatment options. National surveillance programs, enhanced clinician awareness, and targeted public health initiatives are critical to mitigating this escalating antimicrobial resistance crisis in Pakistan.