Abstract
Introduction SalmonellaTyphi is one of the leading health problems in Pakistan. With the emergence of extensively drug resistant (XDR)SalmonellaTyphi, treatment options are limited. Here we report the clinical manifestations and the response to treatment of patients with XDR Typhoid fever. The patients were treated with either Meropenem or Azithromycin or a combination of both. Methods We reviewed the records of culture confirmed XDR typhoid who visited Aga Khan University Hospital (AKUH), Karachi and Aga Khan Secondary Care Hospital, Hyderabad from April 2017 to June 2018. Symptoms developed during disease, unplanned treatment extension and complications developed while on antimicrobials was recorded. Means with standard deviation were calculated for duration of treatment, time to defervescence, and cost of treatment. Results Records of 81 culture confirmed XDR typhoid patients admitted at the AKU hospitals were reviewed. Most, (n = 45; 56%) were male. Mean age of the cases was 8.03 years with range (1-40). About three quarter (n = 66) of the patients were treated as inpatient. Fever and vomiting were the most common symptoms at the time of presentation. Oral azithromycin alone (n = 22; 27%), intravenous meropenem alone (n = 20; 25%), or a combination of azithromycin and meropenem (n = 39; 48%) were the options used for treatment. Average (95% confidence interval) time to defervescence was 7.1(5.5-8.6), 6.7(4.7-8.7), and 6.7(5.5-7.9) days for each treatment option respectively whereas there were 1,0 and 3 treatment failures in each treatment option respectively. Average cost of treatment per day for azithromycin was US$5.87 whereas it was US$88.46 for meropenem. Conclusion Patients treated with either Azithromycin, Meropenem alone or in combination showed similar time to defervescence. Because of the lower cost of azithromycin, it is preferable in lower socio-economic areas. Background estimates for power calculation can be made for more robust clinical trials using this observational data.
Author summary Ever since the emergence of Extensively Drug Resistant (XDR) Typhoid fever in Pakistan, which is resistant to all but two classes of anti-microbials, we need to find an effective treatment plan so thatS.Typhi does not also make these anti-microbials redundant in the future. In this retrospective case series review, we observed the response of XDR Typhoid fever patients treated with meropenem or azithromycin or combination of both. All 3 groups showed a similar therapeutic response based on number of complications developed and time taken for fever clearance. The higher price of meropenem however could become a deterrent to its use in poor socio-economic areas. This new knowledge may contribute to better treatment plans in handling XDR enteric fever in the future whilst also serving as a rough guide in how to treat patients with XDR Typhoid fever in the present.