HALF OF ALL GRAM-NEGATIVE ISOLATES ARE EXTENSIVELY DRUG-RESISTANT: A CROSS-SECTIONAL INSIGHT FROM A PAKISTANI TERTIARY CARE HOSPITAL.

The alarming global spread of antimicrobial resistance (AMR) is particularly severe in low- and middle-income countries (LMICs), where overburdened health systems and widespread antibiotic misuse fuel the emergence of extensively drug-resistant (XDR) pathogens. XDR Gram-negative organisms—resistant to all but one or two classes of antimicrobials—pose serious therapeutic challenges in hospital settings. Despite this growing threat, few local studies in Pakistan have systematically documented the burden and distribution of these organisms, particularly in high-risk tertiary care public hospitals. Objective: this study aimed to determine the prevalence, organism-specific distribution, and demographic associations of XDR Gram-negative bacterial isolates among hospitalized patients in a large public sector tertiary hospital in northern Pakistan. The findings are intended to inform local antimicrobial stewardship efforts and guide empirical therapy. Methods: A descriptive cross-sectional study was conducted over six months (August 2024 to February 2025) at Ayub Teaching Hospital, a 1500-bed tertiary care referral center in Abbottabad, Pakistan. All culture-positive clinical specimens yielding Gram-negative bacilli from the medical, surgical, and burn units were included. Duplicate isolates, Gram-positive bacteria, and outpatient specimens were excluded. Bacterial identification and antimicrobial susceptibility testing were performed using standard biochemical methods and Kirby-Bauer disk diffusion in accordance with CLSI 2024 guidelines. XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories. Data were analyzed using SPSS version 26.0, with chi-square tests to determine statistically significant associations. Results: Out of 540 Gram-negative isolates, 267 (49.4%) met the criteria for XDR. The most commonly isolated pathogens were Klebsiella pneumoniae (31.1%), Acinetobacter baumannii (26.3%), Escherichia coli (23.9%), and Pseudomonas aeruginosa (18.7%). XDR prevalence was highest among K. pneumoniae (50%) and A. baumannii (48.6%), followed closely by P. aeruginosa (57.4%) and E. coli (43.4%). The medical unit accounted for the highest number of XDR cases (45.7%), followed by surgical (31.8%) and burn units (22.5%). Wound swabs, urine, and pus were the leading specimen types associated with XDR isolates. Elderly patients (≥61 years) showed the highest proportion of XDR infections (26.6%), and a statistically significant correlation was observed between XDR status and unit of admission (p = 0.03), organism type (p = 0.01), and age group (p = 0.04). No significant association was found with gender (p = 0.28). Conclusion: This study reveals a disturbingly high prevalence of XDR Gram-negative organisms in a major public hospital in Pakistan, with nearly every second isolate demonstrating resistance to nearly all available antimicrobial options. The dominance of XDR K. pneumoniae and A. baumannii, coupled with high infection rates in medical and burn units, reflects inadequate infection control measures and irrational antibiotic use. These findings emphasize the urgent need for hospital-wide antimicrobial stewardship programs, regular surveillance of resistance patterns, and evidence-based updates to empirical treatment protocols. Without immediate and coordinated interventions, the burden of XDR organisms will continue to rise, threatening the efficacy of last-resort antibiotics and patient safety across the healthcare system.