X-DR (Drug Resistant) typhoid fever in children

DRUG RESISTANT IN TYPHOID FEVER The Professional Medical Journal www.theprofesional.com ORIGINAL PROF-0-4563 DOI: 10.29309/TPMJ/2020.27.09.4563 X-DR (DRUG RESISTANT) TYPHOID FEVER IN CHILDREN. Muhammad Sohail1, Zahid Mahmood Anjum2, Jaweeria Masood3, Iram Iqbal4, Jawaria Khalid5, Hina Ayesha6 1. MBBS, FCPS Senior Registrar Paediatrics Children Hospital and ICH, Faisalabad. 2. MBBS, FCPS Assistant Professor Children Hospital and ICH, Faisalabad. 3. MBBS, FCPS Assistant Professor Children Hospital and ICH, Faisalabad. 4. MBBS, FCPS Senior Registrar Paediatrics Children Hospital and ICH, Faisalabad. 5. MBBS, FCPS Senior Registrar Paediatrics Children Hospital and ICH, Faisalabad. 6. MBBS, FCPS Professor Paediatrics Faisalabad Medical University. Correspondence Address: Dr. Muhammad Sohail 136-B Sheikh Colony, Jhang Road Faisalabad. [email protected] Article received on: 11/02/2020 Accepted for publication: 20/04/2020 ABSTRACT… Objectives: To study antibiotic sensitivity pattern of Salmonella typhi in children with enteric fever. Study Design: Prospective, Consecutive sampling. Setting: Children Hospital and Institute of Child Health, Faisalabad. Period: 6 Months June 2019 to November 2019. Material & Methods: All admitted children of age 1-16 years with strong clinical suspicion of typhoid fever and with no comorbidities were included in this study. Blood cultures and other relevant investigations were performed to rule out other causes of fever. After identification of organism as Salmonella typhi, antibiotics susceptibility testing was done by disk diffusion technique and zones of inhibition were interpreted according to clinical and Lab standard (CLSI) guidelines. Results: Out of 60 patients maximum children were < 5 year and >10 year of age. Maximum cases were admitted during July to September. Male to female ratio was 1.6:1. We were able to send blood cultures of 31 cases (51%) only. Out of them 14 cases (45%) were found culture positive. All culture positive (100%) were found sensitive to meropenem. 92.8% were found sensitive to azithromycin and 7.1% were found sensitive to amikacin. Overall 16 cases treated with meropenem, 10 cases (16%) with azithromycin and one with amikacin. However, 33 cases (55%) responded to ceftriaxone alone. Conclusion: Sensitivity pattern of Salmonella typhi revealed significant proportion of multidrug and extensive drug resistant strain. So, continue surveillance is needed in this regard to find actual burden of XDR typhoid fever. We recommend local district administration and health authorities to launch an awareness campaign regarding sanitation, good hygiene, use of safe of water and mass vaccination of children with conjugated vaccine against typhoid. Alongwith above measures antibiotic stewardship should be started. Key words: Children, Drug Resistance, Typhoid Fever, Antibiotic Sensitivity. Article Citation: Sohail M, Anjum ZM, Masood J, Iqbal I, Khalid J, Ayesha H. X-DR (Drug Resistant) typhoid fever in children. Professional Med J 2020; 27(9):19471951. DOI: 10.29309/TPMJ/2020.27.09.4563 INTRODUCTION Enteric fever caused by Salmonella enterica serovar typhi (S.Typhi) is serious and occasionally fatal disease, more prevalent in developing countries attributed to poor sanitation facilities and lack of clean drinking water supply. Approximately 21.6 million people are infected by S.Typhi yearly leading to around two hundred thousands deaths with more than 90% burden of morbidity and mortality shared by Asian countries.1,2 India and Pakistan are ranked first and second in Enteric fever prevalence respectively.3 Drug resistance is emerging as a great problem in managing cases of enteric fever leading to increasing cost of treatment, morbidity and complications.3,4,5 It started in early 70’s.5 Professional Med J 2020;27(9):1947-1951. Over past 2 decades, emergence of MDR (chloramphenicol, amoxicillin, TMP) strains has necessitated use of fluroquinolones as drug of choice with cephalosporins as alternative.6 But recent reports of XDR (chloramphenicol, amoxicillin, TMP, fluroquinolones and ceftriaxone) strains of Salmonella in areas of Sindh (Pakistan) have been alarming.7,9,10 International Surveillance has also identified XDR strains in patients in UK, USA and Canada with all of them having travelled to Pakistan in recent past.8,9 Pakistan health authorities have reported an outbreak of extensively (XDR) typhoid fever that begin in Hyderabad district of Sindh province in November, 2016.11 Since then, number of patients with XDR typhoid fever are remarkably increasing. www.theprofesional.com 1947 DRUG RESISTANT IN TYPHOID FEVER We think that XDR typhoid fever is not confined to Sindh Province only and is spreading all over the Pakistan, we have observed a surge of typhoid fever cases in our setup. We are conducting this study with objective to evaluate antibiotic sensitivity pattern in patients presenting with clinical suspicion of enteric fever at Children hospital, Faisalabad which will help us to formulate management guidelines for drug resistant patients and to stress on need of vaccination against S.Typhi. MATERIAL & METHODS This was Prospective, consecutive sampling conducted for 6 months. Study was conducted from June 2019 to November 2019 at Children Hospital and Institute of Child Health, Faisalabad. Inclusion Criteria • Patients having febrile illness more than five days and there is no other observed cause of fever. Exclusion Criteria • Age less than one year and more than sixteen year. • Patients having other comorbidities were also excluded from study. After admitting the patients blood culture and sensitivity, CBC and other relevant investigations were carried out to exclude other causes of fever like Malaria, Dengue, UTI etc. Those patients who received antibiotics for more than 5 days their blood culture was not sent. Blood samples were cultured on blood agar and MacConkey agar plates. After identification of organism as Salmonella Typhi, antibiotic susceptibility testing was done by disk diffusion technique and zones of inhibition were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Isolates were tested for ampicillin, co-trimoxazole, ceftriaxone, cefixime, chloramphenicol, ciprofloxacin, amikacin, azithromycin and meropenem susceptibility. We were able to send culture of 31 patients only due to one or more reason. All patients were given intravenous ceftriaxone 75mg/kg/day in two 1948 www.theprofesional.com 2 divided doses empirically after sending blood culture. The patients whose culture sent were later treated according to sensitivity pattern if they have not responded to empirical therapy. However, culture negative and all those patients whose culture were not sent and who did not respond to intravenous ceftriaxone after 7 days were switched to meropenem or azithromycin depending upon susceptibility patterns. No complication was observed in any patient. All patients were treated successfully. Frequencies and percentages were calculated for gender and XDR isolates. Mean was calculated for age distribution of culture positive patients. RESULTS We studied 60 patients admitted with clinical suspicion of enteric fever from June 2019 – November 2019.Out of these 60 patients, 37 patients (61.6%) were males and 23 (38.4%) were females. Among them 47 (78.3%) patients were urban residents while 6 (10%) and 7 (11.6%) were from peri-urban and rural areas respectively. Maximum cases were admitted during July to September. Most common presentation was fever (100%), abdominal pain (68.33%), vomiting (60%) followed by Diarrhea (25%) (Table-I) Common signs seen were tachycardia (75%), pallor (25%), Hepatosplenomegaly (16.6%), coated tongue (8.3%), Hepatomegaly (10%) and Splenomegaly (1.6%) (Table-II). Out of 31 patients, 14(45%) were culture positive and 17 (55%) were culture negative. Among 14 culture positive patients, 12 patients (85.7%) turned out to be XDR strains of Salmonella typhi, only sensitive to Meropenem and Azithromycin. One patient (7.1%) was sensitive to Meropenem only and one patient (7.1%) to Amikacin and Co-trimoxazole only (Table-III) Mean age of culture positive patients was 7.2 years (TableIV). All these 14 patients were empirically treated with ceftriaxone. Those who didn’t responded to empirical therapy switched to Meropenem or azithromycin depending upon susceptibility patterns. Of the remaining 46 culture negative patients Professional Med J 2020;27(9):1947-1951. DRUG RESISTANT IN TYPHOID FEVER 3 (including 29 patients whose cultures were not sent), 33(71.7%) patients responded to ceftriaxone alone. Out of remaining 13 patients, 10 patients (76.9%) responded to azithromycin and 3(23.1%) patients responded to meropenem only. None of these 46 patients developed any complication and were discharged. Overall sensitivity/response rate of 60 patients to various antibiotics was observed as, ceftriaxone 33/60(55%), meropenem 16/60(26.6%), azithromycin 10/60(16.6%) and amikacin 1/60(1.6%). Symptoms Percentage Fever 100% Abdominal pain 68.33% Vomiting 60% Diarrhea 25% Anorexia 13.33% Constipation 1.6% Table-I. Symptoms observed in patients Signs Percentage Tachycardia 75% Pallor 25% Hepatosplenomegaly 16.6% Hepatomegaly 10% Coated Tongue 8.3% Splenomegaly 1.6% Table-II. Signs observed in patients Number Percentage (n=14) Meropenem 14 100% Azithromycin 13 92.8% Ceftriaxone, Cefixime 0 0% Ampicillin, Ciprofloxacin 0 0% Chloramphenicol 0 0% Amikacin, Co-trimoxazole 1 7.1% Table-III. Antibiotic sensitivity pattern of Salmonella Typhi Antibiotic Age at the Time of Presentation Frequency of Patients Percentage of Patients < 5years 5 35.7% 5 to 10years 4 28.5% 10 to 15years 5 35.7% Table-IV. Age distribution of patients with XDR Salmonella Typhi (n=14) Professional Med J 2020;27(9):1947-1951. No. of Cases (n=60) Percentage June 08 13.3% July 14 23.3% August 14 23.3% September 11 18.3% October 08 13.3% November 05 8.3% Months Table-V. Month wise distribution of cases Number of Patients Admitted (n=60) Number of Blood Cultures sent (n=31) Positive Blood Cultures (n=14) Percentage of Positive Blood Cultures June 08 01 01 100% July 14 06 03 50% August 14 08 02 25% September 11 05 02 40% October 08 07 05 71.4% November 05 04 01 25% Total 60 31 14 45.1% Month Table-VI. Month wise distribution of culture positive patients DISCUSSION Most of the studies already done on typhoid fever includes age group of 5 to 15 years. However, in studies from Bangladesh and India higher trends are seen in children younger than 5 years.12 So, we included age group 1 to 15 years and found that the maximum children affected were in age groups less than 5 years and greater than 10 years. Perhaps it is difficult to maintain hygiene in these age groups as less than 5 years demand continue surveillance by elders and age group greater than 10 years are school going and have easy access to food stuff at school canteens. Male to female ratio is 1.6:1 and this is very similar to a study done in Bangladesh.13 Greater percentage of patients belong to urban areas12and only a small percentage was found resident of rural areas indicating poor hygienic conditions and sanitation of our urban areas, inviting attention of health authorities to promote public awareness and guide government officials to work on this. www.theprofesional.com 1949 DRUG RESISTANT IN TYPHOID FEVER 4 Maximum cases were admitted during July to September. We know this period coincides with moon-soon season and increase in house fly population, hence facilitating feco-oral transmission. Same phenomena was observed in most of studies done in Asia.3,14 which has already initiated in district Hyderabad. Along with these, injudicious use of antibiotics should be banned and it can be safely prevented by sensitising general practitioners and clinicians on the rational use of antimicrobials for typhoid fever. Most common presentation was fever (100%), abdominal pain (68.33%), vomiting (60%) followed by Diarrhea (25%) which was very similar to a study done by Habte, L., Tadesse, E., Ferede, G., et al Ethiopia at University of Gondar, Ethiopia.15 CONCLUSION Emergence and spread of XDR typhoid fever is on the rising trend. Surveillance studies are required at all levels for risk stratification and control of this disease. Our study also signifies the role of preventive measures, better health care facilities, antibiotic stewardship and vaccination, at a national level to restrict this menace. Copyright© 20 Apr, 2020. Common signs seen were tachycardia (75%), pallor (25%), Hepatosplenomegaly (16.6%), coated tongue (8.3%), Hepatomegaly (10%) and Splenomegaly (1.6%).14 REFERENCES In this study we were able to send culture of 51% of patients (31 cases) only. Out of them 45% of patients (14 cases) were found culture positive. Our culture positivity rate was very high as compare to studies done in other parts of Asia and Pakistan that showed a range of 5 to 33.1%.3,16 In an analysis, based on antibiotic susceptibility from 2012-2014, prevalence of MDR salmonella typhi was 52%, fluoroquinolone resistance was 90% and there was no cephalosporin resistance.17 But the recent trends seen in studies from 2015-2019, showed a decline in MDR strains and rising trends of resistance against cefixime and ceftriaxone.18,19 In our study there were 100% MDR strains and only 7.1% were sensitive to amikacin and cotrimoxazole and no isolate was found sensitive to ceftriaxone, cefixime, ampicillin or ciprofloxacin. We have reported only 14 culture positive patients. As this number is very small to make any solid conclusion. So, continue surveillance should be in place to find the actual burden of XDR typhoid fever in Faisalabad. For this, we may need collaboration with other medical institutes of Faisalabad for collection of data regarding XDR typhoid fever. Considering the reports from Hyderabad, Sindh, we recommend local district administration and health authorities to launch an awareness campaign regarding sanitation, good hygiene, use of safe water and mass vaccination of children with conjugated vaccine against typhoid 1950 www.theprofesional.com 1. Ali MK, Sultana S. Antimicrobial sensitivity pattern of Salmonella Typhi in children. Bangladesh J. Med Sci 2016; 15:416-8. 2. Nagshetty K, Channappa ST, Gaddad SM. Antimicobial susceptibility of Salmonella Typhi in India. J infect Dev Ctries 2009; 4:070-3. 3. Ochial RL, Acosta CJ, Denovaro-Holliday M, Baiqing D, Bhattacharya SK, Agtini MD, et al. A study of typhoid fever in five Asian countries. Disease burden and implications for controls. Bull World health Organ 2008; 86:260-8. 4. Hasan B,Nahar SG, Akter L, Saleh AA. 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AUTHORSHIP AND CONTRIBUTION DECLARATION Sr. # Author(s) Full Name Contribution to the paper 1 Muhammad Sohail 1st Author 2 Zahid Mahmood Anjum 2nd Author 3 Jaweeria Masood 3rd Author 4 Iram Iqbal 4th Author 5 Jawaria Khalid 5th Author 6 Hina Ayesha 6th Author Professional Med J 2020;27(9):1947-1951. Author(s) Signature www.theprofesional.com 1951