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The first Canadian pediatric case of extensively drug-resistant Salmonella Typhi originating from an outbreak in Pakistan and its implication for empiric antimicrobial choices.

ABSTRACT: We report on a three year-old male who contracted enteric fever during a visit to the Sindh province of Pakistan in the summer of 2018. He was diagnosed after returning to Canada and blood cultures isolated Salmonella enterica serovar Typhi which harbored extensive drug-resistance (XDR) to all first-line antibiotics including ceftriaxone. Empiric ceftriaxone was switched to meropenem and he was successfully treated with a two-week course. An outbreak of XDR typhoid is currently emerging from Pakistan and several outbreak-related cases have been identified in the U.K and U.S. Whole genome sequencing confirmed that our child was infected with the XDR outbreak-strain. Current empiric antimicrobial choices will result in treatment failure if an XDR strain is encountered, therefore clinicians must adapt their empiric approach for those returning from high risk regions. This is the first XDR typhoid case in Canada and the first pediatric case to be diagnosed and treated outside of Pakistan. Clinicians must be vigilant of future cases.

SUBMITTER: Wong W

PROVIDER: S-EPMC6378779 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The first Canadian pediatric case of extensively drug-resistant <i>Salmonella</i> Typhi originating from an outbreak in Pakistan and its implication for empiric antimicrobial choices.

Wong Waison W Rawahi Hatem Al HA Patel Samir S Yau Yvonne Y Eshaghi Alireza A Zittermann Sandra S Tattum Leah L Morris Shaun K SK

IDCases 20190115

We report on a three year-old male who contracted enteric fever during a visit to the Sindh province of Pakistan in the summer of 2018. He was diagnosed after returning to Canada and blood cultures isolated <i>Salmonella enterica</i> serovar Typhi which harbored extensive drug-resistance (XDR) to all first-line antibiotics including ceftriaxone. Empiric ceftriaxone was switched to meropenem and he was successfully treated with a two-week course. An outbreak of XDR typhoid is currently emerging f ...[more]

PMID: 30815359

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Project description:IntroductionSalmonella Typhi is one of the leading health problems in Pakistan. With the emergence of extensively drug resistant (XDR) Salmonella Typhi, 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.MethodsWe 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.ResultsRecords 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.ConclusionPatients 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.

Project description:BackgroundSalmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan.MethodsThis cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174 005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207 000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, culture-confirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20 847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated.Findings23 407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13 436 (57·4%) children were vaccinated, 12 214 (52·2%) were male, and 10 168 (43·4%) were aged 6-59 months. 5378 (23·0%) of 23 407 children had suspected S Typhi, among whom 775 (14·4%) had culture-confirmed S Typhi and 361 (68·6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52-57) against suspected S Typhi (regardless of culture confirmation), 95% (93-96) against culture-confirmed S Typhi, and 97% (95-98) against XDR S Typhi.InterpretationTypbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance.FundingBill & Melinda Gates Foundation.

Dataset Information

The first Canadian pediatric case of extensively drug-resistant Salmonella Typhi originating from an outbreak in Pakistan and its implication for empiric antimicrobial choices.

Publications

The first Canadian pediatric case of extensively drug-resistant <i>Salmonella</i> Typhi originating from an outbreak in Pakistan and its implication for empiric antimicrobial choices.

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