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Objective: The number of extremely drug-resistant (XDR) Salmonella typhi isolates is growing in the northwest of Pakistan, where health-care facilities are already under strain due to the coronavirus disease 2019 (COVID-19) issue. In Khyber Pakhtunkhwa, Pakistan, we currently describe the first widespread appearance of an XDR Salmonella typhi epidemic during the COVID-19 pandemic. This strain of Salmonella typhi is resistant to all first- and second-line drugs and even the third-generation cephalosporin. Methods: Salmonella species isolated from pediatric blood samples shown a high level of resistance to the various antibiotic classes evaluated between November and December 2020. Gender, age, address, and clinical symptoms were among the demographic information that was recorded. A total of 562 blood cultures from symptomatic patients have been collected by the Pathology Laboratory at a tertiary care institution of Rehman Medical Institute, Peshawar. All samples have been processed in accordance with regulatory requirements and incubated in BacT/ALERT 3D. Results: Of the 562 blood samples, 71 included Salmonella typhi, of which 66 (92.9%) and 5 (7%) were multidrug resistant (MDR) and XDR, respectively. Ciprofloxacin (100%), chloramphenicol (100%), ceftriaxone (100%), ampicillin (100%), and cotrimoxazole (93%) were completely resistant to all isolates. Azithromycin and carbapenems were effective against every Salmonella typhi isolate that was MDR or XDR. Males (76%) were more commonly affected than females (24%), and the frequency was substantially higher in children under 15 years of age (88%) than in adults (P = 0.0016). Conclusion: The emergence of XDR Salmonella typhi with a high level of resistance is in fact alarming. Due to the lack of viable treatment alternatives, the current situation necessitates the immediate implementation of efficient preventive measures, such as campaigns for typhoid vaccination and food and water safety. [ABSTRACT FROM AUTHOR]