Microbes, Infection and Chemotherapy LETTERS TO THE EDITOR Authors Andrew W. Taylor-Robinson College of Health Sciences, Vin University, Hanoi, Vietnam. Center for Global Health, University of Pennsylvania, Philadelphia, USA. https://orcid.org/0000-0001-7342-8348 Saima Mohsin Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Pakistan. https://orcid.org/0000-0002-1487-3545 Corresponding author: Andrew W. Taylor-Robinson Vin University, Hanoi, Vietnam. andrew.tr@vinuni.edu.vn Copyright © 2022 the Author(s) Submitted: January 10, 2022 Reviewed : January 14, 2022 Approved : January 14, 2022 How to cite: Taylor-Robinson AW, Mohsin S. Response to Letter to the Editor: Typhoid fever in Pakistan: a recurrent challenge? Microb Infect Chemother es . 2022; 2: e1336. Dear Editor We thank Modesto dos Santos et al. (1) for drawing our attention to a recently published study (2), conducted in a different tertiary care center in the same city of Karachi to that of our own research discussed in Microbes, Infection and Chemotherapy (3). The findings corroborate our conclusions regarding patterns of sensitivity and resistance by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) to antibiotic therapy among pediatric patients (4). As the study of Saleem and colleagues indicates, the formerly effective drugs ampicillin, cotrimoxazole, chloramphenicol and ceftriaxone are now each ineffective in treating four in every five children presenting with typhoid fever (TF) (2). The knock-on effect is this will impose a massive selection pressure for bacterial resistance to emerge to those antibiotics that are now used as first-line replacements; meropenem, azithromycin and ciprofloxacin. Collectively, these investigations highlight the pressing need for a coordinated and multifaceted national policy for antimicrobial stewardship of TF in countries where multidrug- resistant (MDR) strains of S. Typhi are endemic and where extensively drug-resistant (XDR) strains are increasingly emerging. Pakistan is foremost among these nations. S. Typhi is constantly evolving to evade the twin threats of the human immune response and antibiotic treatment. The take-home message could not be clearer: what is a tailored regimen today may not be as effective tomorrow. Hence, vigilance should be maintained by treating physicians in known hotspots for TF to confirm the sensitivity of a patient's specimen to the prescribed antibiotic. To use a football analogy, we need to stay in a game in which the goal posts are constantly moving. This extreme task requires commitment by individual hospitals and concerted effort by local health authorities. This process should be orchestrated as an ongoing public health response at regional and national levels, with provision for data collection of notified cases of MDR and XDR S. Typhi. Conict of interest The authors declare that there is no conflict of interest. Funding None Authors' contributions Both authors wrote the draft, reviewed the manuscript, and approved the final version. References 1. Modesto dos Santos V, Modesto dos Santos LA, Campos- Modesto L, Campos-Modesto, J. Typhoid fever in Pakistan: a recurring challenge? Microbes Infect Chemother. 2022; 2: e1331 2. Saleem S, Parkash A, Jalil M, Mubashir F. Sensitivity pattern of Salmonella typhi from blood culture in paediatric population. Liaquat Nat J Prim Care. 2021; 3(2): 77-81. doi.org/10.37184/lnjpc.2707-3521.3.24. 3. Mohsin S, Taylor-Robinson AW. Persistence of first-line antibiotic-resistant typhoid fever among Pakistani children: a growing concern for regional antimicrobial stewardship. Microbes Infect Chemother. 2022; 2: e1301. doi.org/10.54034/mic.e1301. 4. Mohsin S, Aziz Q, Muurlink OT, Taylor-Robinson AW. Burden of antibiotic resistance among children with typhoid in Gadap Town, Karachi, Pakistan. Microbes Infect Dis. 2022; in press. doi: 10.21608/mid.2021.87000.1174. Microbes Infect Chemother, 2022, v.2, 1, e1336 Response to Letter to the Editor: Typhoid fever in Pakistan: a recurrent challenge? 1