Efficacy of Azithromycin and Meropenem in Pediatric XDR Salmonella Typhi: A Retrospective Study from Abbottabad, Pakistan
Keywords:
Antibiotic Resistance, Azithromycin, Meropenem, Salmonella Typhi, Typhoid FeverAbstract
Objective: To evaluate the efficacy of azithromycin as a first-line therapy and the combination of meropenem and azithromycin as the second-line therapy in treating pediatric patients with extensively drug-resistant (XDR) Salmonella Typhi in Abbottabad, Pakistan.
Methods: This retrospective cross-sectional study was conducted at Department of Pediatrics, Abbottabad International Medical Complex, Pakistan from May 2022 to January 2024. Children aged 1-15 years clinically diagnosed with typhoid fever were enrolled if subsequent blood cultures confirmed XDR Salmonella Typhi infection. Initial treatment comprised azithromycin. If there was no response to azithromycin, patients received a combination therapy of meropenem alongside continued azithromycin. Primary outcomes were clinical recovery, recurrence within 30 days post-treatment, and treatment-related adverse effects.
Results: Of total 67 pediatric patients, the mean age of the patients was 10.02 ±2.76 years. The overall mean duration of defervescence was 6.01 ±2.98 days. Initially, all patients were treated with azithromycin alone. Most patients recovered clinically 57 (85.1%). For the 10 (14.9%) who did not respond, meropenem was added to azithromycin, resulting in recovery for all. The mean duration of defervescence found significantly low in patients who received azithromycin monotherapy as compared to patients who received combination therapy i.e., 4.80 ±0.58 days vs. 12.90 ±1.10 days (p-value <0.001). Mild nausea was the only adverse event observed in 29 patients (43.3%) during treatment.
Conclusion: Azithromycin monotherapy demonstrated a high clinical recovery rate, with a significant reduction in fever duration compared to combination therapy with meropenem. Mild nausea was the only treatment-related adverse effect observed.
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References
World Health Organization. Typhoid [Internet]. 2023 [cited 2024 May 17]. Available from: https://www. who.int/news-room/fact-sheets/detail/typhoid
Imran H, Saleem F, Gull S, Khan Z. Uncovering the grow-ing burden of enteric fever: A molecular analysis of Salmonella Typhi antimicrobial resistance. Microb Pathog 2024; 191:106676. doi:10.1016/j.micpath.2024.106676
Marchello CS, Carr SD, Crump JA. A systematic review on antimicrobial resistance among Salmonella Typhi worldwide. Am J Trop Med Hyg 2020; 103:2518-27. doi:10.4269/ajtmh.20-0258
Kim C, Latif I, Neupane DP, Lee GY, Kwon RS, Batool A, et al. The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients. PLoS One 2021; 16:e0257744. doi:10.1371/journal.pone.0257744
Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nat Genet 2015; 47:632-9. doi:10.1038/ng.3281
Baig U, Mehdi SM, Iftikhar N. A pattern of antibiotic drug resistance of Salmonella Typhi and Salmonella Paratyphi among children with enteric fever in a tertiary care hospital in Lahore, Pakistan. Croat Med J 2023; 64:256-64. doi:10.3325/cmj.2023.64.256
Zakir M, Khan M, Umar MI, Murtaza G, Ashraf M, Shamim S. Emerging trends of multidrug-resistant (mdr) and extensively drug-resistant (xdr) salmonella typhi in a tertiary care hospital of lahore, pakistan. Microorganisms 2021; 9:2484. doi:10.3390/microorganisms9122484
Qureshi S, Naveed AB, Yousafzai MT, Ahmad K, Ansari S, Lohana H, et al. Response of extensively drug resistant Salmonella Typhi to treatment with meropenem and azithromycin, in Pakistan. PLoS Negl Trop Dis 2020; 14:e0008682. doi:10.1371/journal.pntd.0008682
Qamar FN, Yousafzai MT, Khalid M, Kazi AM, Lohana H, Karim S, et al. Outbreak investigation of ceftriaxone-resistant Salmonella enterica serotype Typhi and its risk factors among the general population in Hyderabad, Pakistan: A matched case-control study. Lancet Infect Dis 2018; 18:1368-76. doi:10.1016/S1473-3099(18)30483-3
Batool R, Qureshi S, Yousafzai MT, Kazi M, Ali M, Qamar FN. Risk factors associated with extensively drug-resistant typhoid in an outbreak setting of lyari town karachi, Pakistan. Am J Trop Med Hyg 2022; 106:1379-83. doi:10.4269/ajtmh.21-1323
Shahid S, Mahesar M, Ghouri N, Noreen S. A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug-resistant (XDR) Salmonella Typhi isolates in children in Karachi. BMC Infect Dis 2021; 21:900. doi:10.1186/s12879-021-06599-2
Ishaque S, Syed B, Dodani SK, Anwar S. Comparison of single vs combination drug therapy in extensively drug resistant salmonella typhi: an observational study from Pakistan. Infect Drug Resist 2022; 15:6093-6100. doi:10.2147/IDR.S372136
Aslam A, Kharal SA, Aslam M, Raza A. Trends of antimicrobial resistance in typhoidal strains of salmonella in a tertiary care hospital in Pakistan. Cureus 2021; 13:e12664. doi:10.7759/cureus.12664
Carey ME, Dyson ZA, Ingle DJ, Amir A, Aworh MK, Chattaway MA, et al. Global typhoid genomics consortium group authorship. Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes. Elife 2023; 12:e85867. doi:10.7554/eLife.85867
Shah SA, Nadeem M, Syed SA, Abidi FT, Khan N, Bano N. Antimicrobial sensitivity pattern of salmonella typhi: emergence of resistant strains. Cureus 2020; 12:e11778. doi:10.7759/cureus.11778
Rahim F, Amin S, Noor M, Naeem M, Bangash A. Extensively drug-resistant typhoid fever; it's not that simple: A case report. J Pak Med Assoc 2023; 73:1320-2. doi:10.47391/JPMA.6918
Langah A, Nadeem MC, Radhan AH, Asif M. Defervescence period of azithromycin versus ceftriaxone in children with enteric fever. Khyber Med Univ J 2020; 12:192-6. doi:10.35845/kmuj.2020.19085
Izhar K, Ahmed K, Rehan M, Umar M, Ikram N, Izhar NA, et al. Extensively drug-resistant Salmonella Typhi XDR infection at Rawalpindi medical university and allied hospitals. J Rawal Med Coll 2020; 24:406-11. doi:10.37939/jrmc.v24i4.1493
Frenck RW Jr, Nakhla I, Sultan Y, Bassily SB, Girgis YF, David J, et al. Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children. Clin Infect Dis 2000; 31:1134-8. doi:10.1086/317450
Anwar T, Rais H, Jamil MF, Safdar S, Amir MR, Altaf A, et al. Extended drug resistance in children with typhoid fever. Professional Med J 2020; 27:581-7. doi:10.29309/TPMJ/2020.27.3.3695
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