Antimicrobial Resistance of Shigella flexneri in Pakistani Pediatric Population Reveals an Increased Trend of Third-Generation Cephalosporin Resistance

The rapid emergence of resistance to third-generation cephalosporins in Shigella flexneri is crucial in pediatric shigellosis management. Limited studies have been conducted on molecular pattern of antibiotic resistance of S. flexneri in diarrhea endemic areas of Pakistan. The aim of the study was to analyze the antimicrobial resistance of S. flexneri isolated from pediatric diarrheal patients in Peshawar, Pakistan. A total of 199 S. flexneri isolates (clinical, n = 1 55 and non-clinical, n = 44) were investigated for drug resistance and mutational analysis of selected drug resistance genes. All isolates were found to be highly resistant to amoxicillin/clavulanic acid (88%), followed by trimethoprim-sulfamethoxazole (77%), chloramphenicol (43%), and quinolones (41.6%). About 34.5% S. flexneri isolates were found to be resistant to third-generation cephalosporin. None of the isolates was resistant to imipenem, piperacillin-tazobactam, and amikacin. Interestingly high frequency of third-generation cephalosporin resistance was observed in S. flexneri isolated from non-clinical samples (49%) when compared to clinical samples (30.5%). Furthermore, the most prevalent phenotypic-resistant patterns among third-generation cephalosporin-resistant isolates were AMC,CAZ,CPD,CFM,CRO,SXT (13%) followed by OFX,AMC,CAZ,CPD,CFM,CRO,SXT,NA,CIP (10%). The most frequently detected resistance genes were trimethoprim-sulfamethoxazole (sul2 = 84%), beta-lactamase genes (blaOXA = 87%), quinolones (qnrS = 77%), and chloramphenicol (cat = 64%). No mutation was detected in any drug-resistant genes. We are reporting for the first time the sequence of the blaTEM gene in S. flexneri. Furthermore, high third-generation cephalosporin resistance was observed in the patients who practiced self-medication as compared to those who took medication according to physician prescription. This study shows the high emergence of third-generation cephalosporin-resistant S. flexneri isolates, which is a potential threat to the community in the country. This finding will be helpful to develop a suitable antibiotic prescription regime to treat shigellosis.