Abstract

In developing countries, typhoid fever is mostly seen due to poor public health and low socioeconomic indices. Currently Pakistan is going through the largest outbreak of XDR typhoid fever which has resulted in increased morbidity and mortality especially in pediatric population. Objectives: To see the pattern of extended drug resistant typhoid fever in different areas of Karachi. Study Design: Cross sectional study. Setting: Department of pediatrics, Ziauddin Hospital (KDLB, NORTH, CLIFTON campus). Period: 6 months from October 2018 till March 2019. Material & Methods: All patients who presented with history of fever for 3 or more days with signs and symptoms of typhoid fever were recruited. For data collection a self-structured questionnaire was used. Age, gender, socioeconomic status, personal hygiene, water supply and sanitation were taken into account. Blood samples were sent for cultures. Salmonella isolates were tested for antibiotic susceptibility. Tested antimicrobials were ampicillin, TMP/SMX, cefixime, ceftriaxone, aztreonam, ciprofloxacin, azithromycin, meropenem. For data analysis SPSS version 22 was used. Results: Out of 415 patients, 235 had culture proven typhoid fever. Salmonella typhi was isolated in 94.4%of the patients and salmonella paratyphi was isolated in 5.57%. Of the 235, Males were 62% and females were 42.4%. Major determinants associated with acquiring salmonella infection were young age (74%), male sex (62%), middle and low socioeconomic status (83.8%), living in west district of Karachi (54.9%) and drinking line water (79.2%). Extended drug resistance was encountered in 69.5%. Most of the isolates were sensitive to meropenem and azithromycin (96.7 %, and 95.5% respectively). Ceftriaxone resistance was prevelant in all three districts of Karachi (p value <0.001), in different age groups 1-6yrs (98%), 7-12 yrs(91%), 13-18 yrs (100%) and in males(58%) predominantly. Conclusion: Karachi is facing an outbreak of XDR typhoid fever. Risk of acquiring extended drug resistant typhoid fever is increased in younger age group 1-6 yrs, males, west district of Karachi and poor socioeconomic status. Drinking unboiled water is identified as one of the major culprits. Actions should be taken at all health care levels to monitor the judicious use of antibiotics, and preventive strategies like safe water supply, improved sanitation along with typhoid vaccination are suggested to overcome this outbreak.

Background: The treatment of 21st Century XDR typhoid fever is potentially life-threatening and endemic in Pakistan, presents a therapeutic challenge as currently there is no universal treatment strategy whether to use monotherapy with meropenum or a combination of meropenum and azithromycin. Our objective was to compare the efficacy of both therapies in complicated XDR typhoid fever in children, regarding defervescence, bacterial clearance time, resolution of complications, hospital stay, and relapse.  Methodology: This open-label randomized comparative trial was conducted over 18 months at the Department of Pediatrics, Kemari, Clifton and North Campuses, Ziauddin University Hospital Karachi, Pakistan, in which children (aged 6 months to 18 years) with positive blood culture for XDR enteric fever, were recruited into 2 parallel treatment groups (meropenum) and (meropenum+azithromycin combined). Primary outcome viz clinical improvement (resolution of defervescence, complications, and hospital stay) and lab improvement (negative repeat blood culture, 5 days post-treatment), as well as secondary outcome i.e. treatment failure, adverse drug reactions, and relapse of typhoid within 2 weeks post-treatment were monitored. Results: In the combination group, there was a quicker resolution of fever (5.40 ± 2.17 days vs 6.55 ± 2.77 days in the monotherapy group) as well as complications (3.42 ± 1.97 days vs 4.31 ± 2.71 days in the monotherapy group), resulting in shorter hospital stay (6.94 ± 2.63 days vs 8.08 ± 3.16 days in monotherapy group). 20% had treatment failure in the monotherapy group with a relative risk of 3.55 times more than that in the combination group.   Conclusion: Combination therapy with meropenum and azithromycin is more efficacious in treating complicated XDR typhoid fever in children than meropenum alone.