XDR Typhoid Fever Research Articles

Fighting XDR Typhoid: A Hospital Based Study on Clinical Aspects and Treatment Outcome in Tertiary Care Hospital

Objective: The main aim of this study is to find Clinical Aspects and Treatment Outcome in drug resistant Typhoid. Methodology: Total 120 patients participated in this study. Individuals who received a diagnosis of XDR S.Typhi through a blood culture test were identified from the registry of both healthcare facilities. The medical data of patients suffering from typhoid fever who received treatment as either a hospital inpatient or outpatient between April 1, 2022, and June 30, 2022, were examined for the purpose of screening for inclusion in this investigation. Only typhoid patients who tested positive for S.Typhi in a test to culture blood and the manifestation of insusceptibility to the five classifications of antimicrobials (ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, fluoroquinolone, and 3rd generation cephalosporin (ceftriaxone or cefixime) were examined for potential incorporation in this inquiry. Results: Among the 120 cases of XDR Typhoid, n= 35 (29.16%) were managed exclusively with azithromycin, while 40 (33.33%) were solely administered meropenem. The remaining 45(37.5%) received a combination of both azithromycin and meropenem. Two patients could not recover after receiving Azithromycin. Full recovery seen in Meropenem. Four patients couldn’t recover from combination therapy. Conclusion: Escalating antibiotic resistance in Salmonella enterica has rendered it a complex ailment to address. Measures ought to be implemented to enhance antibiotic prescription protocols and establish consistent recommendations for the management of highly resistant strains of Salmonella enterica.

Disseminated Salmonella Typhi Infection Presenting with Slurred Speech and Encephalopathy: An Unusual Presentation

Abstract: Salmonella enterica serovar Typhi causes systemic infections and typhoid fever in humans, mainly affecting infants and children. It presents mostly with fever, malaise, anorexia, abdominal pain, constipation, and/or diarrhoea. Complications of the disease include intestinal perforation and haemorrhage. However, sometimes extra-intestinal complications are also reported, which rarely include encephalopathy. This report presents a case of a 28-year-old male who presented with somnolence and later developed slurred speech. A week before his current admission, he was admitted with abdominal pain and underwent a laparoscopic appendectomy, and was discharged uneventfully. Now after eight days he presented with somnolence. His neurological examination was otherwise unremarkable. Imaging studies helped to rule out ischaemic stroke. A detailed system-wise examination revealed mild right upper quadrant tenderness and hepatosplenomegaly on abdominal examination. Imaging revealed hepatosplenomegaly with gallbladder wall oedema and mesenteric lymphadenopathy. Blood culture was reviewed, revealing extensively drug-resistant (XDR) Salmonella Typhi. A diagnosis of XDR Salmonella bacteraemia leading to encephalopathy was made. The patient responded well to antibiotic therapy guided by the culture and sensitivity. Keywords: Salmonella, Complicated typhoid, XDR typhoid, Food hygiene, Speech disturbance, Ischaemic stroke.

Extensively drug-resistant Salmonella typhi Infection in Adults; Experience from A Tertiary Care Hospital.

This study aimed to determine the epidemiology, clinical features, and complications of extensively drug-resistant Salmonella typhi (XDR S. typhi) infection in adults. This cross-sectional study enrolled adults with culture-proven XDR S. typhi admitted to Hayatabad Medical Complex, Peshawar from 1st March to 10th September 2022. Their demographic characteristics, clinical features, treatment, and complications were recorded. Out of 84 patients, 68 (80.9%) were male. The mean age of enrolled patients was 25.2 ± 11.3 years. The mean duration of fever at the time of admission was 13.6 ± 8.2 days, respectively. The most common symptom was loose stools (n=25, 29.8%). Most of the patients (n=69, 82.1%) had received empirical treatment before hospitalization. The majority of the patients (n=42, 50%) received meropenem and a combination of meropenem and azithromycin (n=35, 41.7%) during the study. The time to defervescence for both regimens was similar. Five patients (6%) developed complications of enteric fever. There was no mortality among the participants. Diarrhea was the most common associated clinical feature in XDR typhoid fever. Most of the patients received meropenem alone or in combination with azithromycin with a comparable time to defervescence. The majority of the patients recovered uneventfully and there was no mortality among the study participants.

Knowledge, Attitude, and Practices (KAPS) of the Inhabitants of Punjab, Pakistan toward XDR Typhoid Outbreak During COVID-19

Background Typhoid fever, caused by the bacterium Salmonella typhi, is the most prevalent in areas that have poor hygienic conditions. The most alarming situation is the development of the resistant strains of Salmonella typhi, first reported in 2016 in Hyderabad, Sindh. Later, there was a widespread outbreak of extensively drug-resistant (XDR) typhoid. This survey aims to investigate the risk factors for the spread of XDR typhoid in Pakistan based on the knowledge, attitude, and practices (KAPs) of the affected or at-risk population to help plan preventive actions. Method For this purpose, a community-based random KAP study was conducted in Punjab, Pakistan. Data was collected online and also by face-to-face interaction from those who had no access to the Internet. Result More than half of the respondents were aware of the fact that bacteria is the causative agent (60.6%) of XDR. Similarly, with regard to practice, it was found that 67.7% of them washed their hands before eating and 88.8% washed their hands after using the toilet. A common practice in the form of using filtered water for drinking purposes was adhered to by 73.8% of respondents. Conclusion The study concluded that preventative and control measures are necessary to avoid XDR typhoid pandemic spread.

Trends in typhoid fever during the COVID-19 pandemic in Pakistan.

Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.

Drug Resistant XDR Typhoid in Children Admitted in a Tertiary Care Hospital

Objective: To evaluate the prevalence and patterns of drug-resistant typhoid fever, including extensively drug-resistant (XDR) and multidrug-resistant (MDR) strains, among children admitted to a tertiary care Hospital. Methodology: This descriptive observational study was done at Paediatric department of LUMHS from May 2022-november 2022. Children aged 1-12 years, both gender and with confirmed diagnosis of typhoid fever based on positive blood cultures were included. Blood culture samples were collected from pediatric patients presenting with suspected typhoid fever are processed according to standard microbiological techniques. Isolation and identification of Salmonella Typhi are performed using appropriate culture media and biochemical tests. Antimicrobial susceptibility testing was conducted using standardized methods. Drug resistance patterns, including multidrug resistance (MDR) and extensively drug-resistant (XDR) phenotypes, are determined based on susceptibility testing results. MDR was defined as resistance to at least three classes of antibiotics commonly used for typhoid fever treatment, while XDR indicates additional resistance to fluoroquinolones and third-generation cephalosporins, which are frontline treatment options for typhoid fever. Data was entered and analyzed using SPSS version 26. Results: A total of 43 patients were studied, their mean age was 5.91 years. Boys were 72.15 and girls were 27.9%. Most of the cases 65.1% were consuming tap water. MDR resistance was observed in 9.4% of the cases, while XDR resistance was highly frequent among 83.7% of the patients. Very few cases 16.3% had history of typhoid vaccination. However, MDR and XDR resistance were statistically insignificant according to type of water consumption (p->0.05). Conclusion: In conclusion, the study revealed alarmingly high prevalence rates of extensively drug-resistant (XDR) typhoid with multidrug-resistant (MDR) strains observed in 9.4% of cases. These findings emphasize the urgent need for comprehensive strategies that address both antimicrobial resistance and vaccination efforts to combat the increasing burden of XDR typhoid in children.

The frightening disease burden of blood culture proven XDR Typhoidal isolates in pediatric population in a tertiary care hospital in Islamabad; Time to implement a holistic approach countrywide

Background: Typhoid fever is a deadly enteric bacterial infection and millions of people all over the globe are endangered of acquiring it. Since the first outbreak of XDR typhoid in Pakistan in 2016, the ever-rising resistance of typhoid has become a major threat faced by the pediatric population of Pakistan. There is a dearth of available data in children harboring this extensively drug resistant pathogen countrywide. The objective of this study is to highlight the alarmingly increasing prevalence of XDR S. typhi in pediatric population in Federal territory in Pakistan. Material and Methods: This Cross-sectional study was conducted at Microbiology Lab, Children Hospital, PIMS from June 2022 to May 2023. Blood culture samples of children (with strong clinical suspicion of typhoid) ranging one till 12 years (both genders). Result: Out of a total of 245 typhoid suspected blood culture samples, 153 (62%) samples yielded growth of typhoidal Salmonella isolates with 109 (71 %) isolates proved as XDR Salmonella Typhi ,35 (23%) as MDR Salmonella Typhi and the rest 09 cases (6 %) were Salmonella paratyphi A. There was a male predominance of 96(63%) and the rest 57(37%) were females. Age range most commonly affected was 5-8 years followed by 9-12 yrs. There was 100% susceptibility to Meropenem in XDR typhoid cases and 99% XDR cases were susceptible to Azithromycin. Conclusion: We concluded that there is widespread existence of MDR/ XDR S.typhi in pediatric population in federal territory as well as all over Pakistan but there is scarcity of documented data nationwide. Hence, our study signifies that a holistic approach should be implemented along with continuous ongoing surveillance to combat this frightening MDR/ XDR disease burden in this particular population. Key Words: Salmonella Typhi, Extensively Drug Resistant (XDR), Typhoidal isolates

Extensive Drug-Resistant Typhoid Fever Prevention and Management in Pakistan: A Challenge to Public Health

Typhoid fever is a bacterial infection that largely spreads through contamination in food and water, as well as close contact, and displays many cold-like symptoms in addition to more severe gastrointestinal, muscle, and life-threatening states. The emergence of a new, extensive drug-resistant (XDR) strain in Hyderabad, Pakistan in 2016 resulted in the need for stronger antimicrobials to combat the pathogen. Despite vaccination and contact tracing interventions, the multi-drug resistance and fitness of the H58 strain Salmonella enterica serovar Typhi contributed to rapid spread of typhoid fever in Pakistan. Vaccination is at the forefront of efforts attempting to combat XDR typhoid fever cases in Pakistan, and public education systems and schools should prioritize health classes that pertain to the spread of disease, and what steps individuals can take to be safe, as well as social media infographics circulated through Instagram and Facebook with popular hashtags to reach target audiences. A robust and forward-thinking approach needs to be taken by the Pakistani government to use its budget and international funding in the sectors of health and education to ensure disease prevention.

2803. The Medical Trends and Economic Burden of XDR Typhoid Compared to Non-XDR Typhoid: A Single Center Retrospective Study from Karachi, Pakistan

Abstract Background In 2016, Pakistan reported the first outbreak of an Extensively Drug Resistant (XDR) typhoid showing susceptibility only to Meropenem and Azithromycin which created a treatment dilemma and raised concerns not only in developing countries but also globally. In this study, we compared the medical trends and economic burden of XDR typhoid with non-XDR typhoid at a tertiary care hospital of Karachi, Pakistan. Methods A retrospective study was conducted at the Sindh Infectious Diseases Hospital & Research Centre Karachi, Pakistan from June 2022 to April 2023. All hospitalized patients 14 years and above with confirmed Salmonella typhi on blood culture were included. Medical records were reviewed for clinical data and antibiotic cost. Statistical analysis was done using SPSS. Results Thirty-five patients were included of which 23 (65.7%) had XDR typhoid while 12 (34.3%) patients had non-XDR typhoid. Of the 12 non-XDR typhoid cases, nine were MDR (Multi Drug Resistant) while three had ampicillin sensitive strain. The mean age was 21.14 years with 27 (77.1%) males. Compared to non-XDR, majority of the XDR typhoid patients had diarrhea (60.9% vs. 16.7%, p-value= 0.02, OR 7.7, 95% CI: 1.3-44.0). XDR typhoid was treated with either Meropenem alone or Meropenem and Azithromycin combination while MDR typhoid was treated with Ceftriaxone. The time to defervescence was prolonged in XDR typhoid compared to non-XDR typhoid (7.95 days vs. 4.67 days, p-value= 0.007, OR 1.6, 95% CI: 1.14-2.3), with higher per day cost of antibiotics and total inpatient-antibiotic cost (US$20.3 vs. US$11, p-value= 0.006, OR 1.4, 95%CI 1.1-1.9) and (US$193 vs. US$139, p-value= 0.048] respectively. Within XDR group, the mean defervescence time was more in patients who received combined Meropenem and Azithromycin compared to Meropenem alone group (10.1 days vs 6.4 days, p-value=< 0.001) with a consequent higher per day in-patient antibiotic cost (USD$22 vs USD$ 18.8, p-value= < 0.001) and total in-patient cost (USD$ 235 vs. USD$ 158K, p-value= 0.009). Conclusion XDR typhoid has emerged not only as a heath care but also as an economic challenge owing to its prolonged defervescence time and increased per day/ total in-patient antibiotic cost. Disclosures All Authors: No reported disclosures

Assessing the global risk of typhoid outbreaks caused by extensively drug resistant Salmonella Typhi

Since its emergence in 2016, extensively drug resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) has become the dominant cause of typhoid fever in Pakistan. The establishment of sustained XDR S. Typhi transmission in other countries represents a major public health threat. We show that the annual volume of air travel from Pakistan strongly discriminates between countries that have and have not imported XDR S. Typhi in the past, and identify a significant association between air travel volume and the rate of between-country movement of the H58 haplotype of S. Typhi from fitted phylogeographic models. Applying these insights, we analyze flight itinerary data cross-referenced with model-based estimates of typhoid fever incidence to identify the countries at highest risk of importation and sustained onward transmission of XDR S. Typhi. Future outbreaks of XDR typhoid are most likely to occur in countries that can support efficient local S. Typhi transmission and have strong travel links to regions with ongoing XDR typhoid outbreaks (currently Pakistan). Public health activities to track and mitigate the spread of XDR S. Typhi should be prioritized in these countries.

Drug resistant typhoid fever; its clinical spectrum and management in different age groups.

Objective: To describe the clinical spectrum of MDR and XDR typhoid fever in different age groups of pediatric population as the disease is generally more common in children with higher rates of complications and mortality. Study Design: Prospective Cross-sectional study. Setting: Department of Pediatric, Government Teaching Hospital Shahdara, Lahore. Period: July 2020 to July 2021. Material & Methods: 211 patients with suspected/confirmed enteric fever between 6 months to 5 years were initially enrolled. Blood culture was performed in all cases. Only culture confirmed cases (143/211) were included. Data was entered and analyzed using SPSS version 23. Quantitative variables like age group, fever defervescence time and duration of hospital stay were calculated as mean and standard deviations while qualitative variables like gender, clinical symptoms and signs, types of typhoid and response to antibiotics were calculated as percentages. Chi-square test was used taking P value <0.05 as statistically significant. Results: Mean age of study population was 6.8 ± 3.1 years. Majority (44.1%) of patients belonged to age group >5-10 years and were males (54.5%). Anorexia, coated tongue and hepatomegaly was prevalent among all age groups. High grade fever, loose motions and splenomegaly were common in children <5 years as were anemia, leukocytosis and enteric hepatitis. Children >5-10 years of age had more frequency of abdominal pain (P value <0.03), toxic look (P value <0.04) and leucopenia. While vomiting and thrombocytopenia were common in children >10-15 years of age. MDR typhoid was common in young children (<5 years) while XDR typhoid was common in children of >5-15 years. All MDR patients responded to ceftriaxone while XDR patients responded to either monotherapy or a combination of drugs. Age and gender did not affect antibiotic resistance in both MDR and XDR typhoid (P value >0.05). Fever defervescence time (FDT) was 3-5 days in both MDR and XDR typhoid and it was not significantly different with either monotherapy or a combination of drugs (P value 0.40). Conclusion: There are age related differences in clinical spectrum and lab parameters of drug resistant typhoid fever (MDR & XDR). Resistance to antibiotics in both MDR and XDR typhoid was not significantly affected by age and gender.

Extensively Drug Resistance Enteric Fever in Tertiary Care Hospital

Background: Salmonella enterica causes typhoid and paratyphoid fevers. Pakistan and other South Asian nations with little resources, including those with poor sanitation and hygiene, are particularly susceptible to enteric fever. Enteric fever is a disease which is extensively resistant to majority of antibiotics and these strains are rapidly spreading in Pakistan, raising concerns about the global failure of antibiotics. Study design: Descriptive cross-sectional study. Place and duration of study: Department of Pediatrics, CMH Quetta from 1st July 2022 to 31st December 2022. Methodology: A hospital based study in which history of fever for minimum of three days in the previous seven days, and blood test recommendation from a doctor were requirements for enrolment in the study. Individuals who had blood cultures that tested positive for enteric fever were enrolled. Results: Salmonella Typhi made up 52(94%) of the isolates and S. Para typhi made up 6%. 33(60%) of isolates were extensively drug-resistant (XDR), resistant to first-line antibiotics, fluoroquinolones, and third generation cephalosporin’s, and 8(15%) of isolates were extremely drug-resistant (MDR) to first-line antibiotics. Conclusion: In the current region of Pakistan, enteric fever is widespread. Over the course of the monitoring period, the incidence of typhoid fever has risen. With the advent of XDR typhoid, resistance to antimicrobial agents has also increased. Keywords: Enteric fever, Burden, Salmonella typhi, Typhoid fever

Molecular Characterization of Extensively Drug Resistant Salmonella Enterica Serovar Typhi Clinical Isolates from Lahore, Pakistan.

The emergence of extensively drug-resistant (XDR) typhoid in Pakistan has endangered the treatment options available to manage this infection. Third generation cephalosporin were the empiric choice to treat typhoid fever in Pakistan, but acquisition of ESBLs have knocked them out of the arsenal. The current empiric choice is azithromycin which is vulnerable to resistance too. This study aimed to assess the burden of XDR typhoid and the frequency of resistance determinants in blood culture samples collected from different hospitals in Lahore, Pakistan. A total of 835 blood cultures were collected from different tertiary care hospitals in Lahore during January 2019 to December 2021. Among 835 blood cultures, 389 Salmonella Typhi were identified, and 150 were XDR S. Typhi (resistant to all recommended antibiotics). Antibiotics resistance genes of the first-line drugs (blaTEM-1, catA1, sul1, and dhfR7) and second line drugs (gyrB, gyrA, qnrS, ParC and ParE) were investigated among XDR S. Typhi. There were different CTX-M genes isolated using the specific primers, blaCTX-M-U, blaCTX-M-1, blaCTX-M-15, blaCTX-M-2, blaCTX-M-8 and blaCTX-M-9. Antibiotic resistant genes of the first-line drugs were isolated with different frequency, blaTEM-1 (72.6%), catA1 (86.6%), sul1 (70%), and dhfR7 (56%). Antibiotics resistance genes of second-line drugs were isolated as: gyrB (60%), gyrA (49.3%), qnrS (32.6%), parC (44%) and parE (28%). Among CTX-M genes, blaCTX-M-U (63.3%) was the most frequent followed by blaCTX-M-15 (39.3%) and blaCTX-M-1 (26%). Our study concluded that XDR isolates circulating in Pakistan have acquired first-line and second-line antibiotic resistant genes quite successfully along with CTX-M genes (ESBLs) rendering them resistant to the third generation cephalosporins as well. Emergence of azithromycin resistance in XDR S. Typhi which is currently used as an empiric treatment option is worrisome and needs to be monitored carefully in endemic countries like Pakistan.

Identification of Multiple Variant Extensively Drug-Resistant Typhoid Infections across Pakistan.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening bacterial infection. Recently, an outbreak of a new sublineage of extensively drug resistant (XDR) S. Typhi emerged in Pakistan in the province of Sindh. This sublineage had both a composite multidrug resistance transposon integrated on the chromosome and an acquired IncY plasmid carrying the extended spectrum beta-lactamase, blaCTX-M-15, which conferred resistance to third-generation cephalosporins. We observed previously that XDR typhoid had spread beyond the originating southern Sindh Province. Thus, we sought to determine the genetic diversity of 58 ceftriaxone-resistant S. Typhi clinical isolates by whole genome sequencing collected across Pakistan from November 2018 to December 2020 to provide insights into the molecular epidemiology of the evolving outbreak. We identify multiple novel genomic integrations of the extended spectrum beta-lactamase gene into the chromosome in S. Typhi, revealing the existence of various XDR typhoid variants circulating in the country. Notably, the integration of the IncY plasmid bearing antibiotic resistance genes may allow for subsequent plasmid acquisition by these variants, potentially leading to further plasmid-borne multidrug resistance. Our results can inform containment initiatives, help track associated outcomes and international spread, and help determine how widespread the risk is.

A frightening outbreak of Extensive drug resistant-Typhoid in Karachi, Pakistan: A threat to future generation

Aim Laboratory of Jinnah Medical College Hospital identified an outbreak of Extensive drug-resistant (XDR)-Typhoid in Karachi, Pakistan. The frightening rise in the number of XDR typhoid cases observed here demands the need for urgent intervention and prevention for disease control. Recently a threat to future generations in terms of healthcare burden, antibiotic resistance, and public health is also digital diagnosis and self medication which also increases the resistance. Methods A descriptive, cross-sectional survey was conducted to measure the XDR-cases flare-up. Data was collected from Jinnah Medical College Hospital from 1st February-30th September 2019. Out of 175 blood cultures suspected for typhoid, only 65 XDR cases were included by non-probability consecutive sampling. Patients showing no growth on culture, growth of organisms other than Salmonella Typhi and Salmonella Typhi which was not XDR, were excluded. All data were analyzed using SPSS Software 25.0. Results: 65 XDR cases had been reported in 8 months. 36 (55.4%) females and 24 (37%) young adults, aged between 20-29 years, were most affected. A few patients developed complications including intestinal perforation (n=1), acute hepatitis (n=7), and free peritoneal fluid (n=3). A number of cases reported were as low as 2 (3.1%) in February to as high as 11 (16.9%) in August. Conclusions: With declining antibiotic arsenal and evolution from Multidrug-resistant (MDR) to XDR typhoid, treating typhoid has become quite challenging. This adds insistence to the need for typhoid preventive measures including community awareness and education, and vaccination.

Travel-associated extensively drug-resistant typhoid fever: a case series to inform management in non-endemic regions.

Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use. Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim-sulfamethoxazole. Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade. XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.

Frequency of leukocytosis in culture proven enteric fever in children.

Objective: To determine the frequency of leukocytosis in patients of culture proven enteric fever in children over one year period. Study Design: Retrospective Cross-sectional study. Setting: Department of Paediatrics, at Fatima Memorial Hospital, Shadman Lahore. Period: January 2020 to December 2020. Material & Methods: The case record of patients diagnosed with enteric fever on blood culture were reviewed. All patients in the age group of one year to 15 years with a discharge diagnosis of enteric fever for admitted inpatient or from Outpatient Department (OPD) were included in the study. Results: Median age was 61.3 (IQR 38) months and slight female preponderance 61 out of 110 patients (55.5%) was observed. Median duration of fever before presentation was eight days with IQR of 7.3 days and 95 patients has shown anorexia (86.4%), which was the most common symptom after fever. S. Typhi was found in 76.4% (84 patients out of 110) of positive blood cultures and 23.6% of positive culture (26 cases) found S. Paratyphi A,B,C. Only 8 cases (5 %) of enteric fever were multisensitive with 93% of isolates (102 cases) were either multidrug resistant (45 cases (41%) or 57 cases Extended drug resistant (52%).18 out of 110 patients (16%) has shown leukocytosis and leukocyte count was normal in 73% patients (80 out of 110). Among leukocytosis group strikingly, 89% of patients (16 out of 18) had shown extended drug resistant pattern (XDR). Conclusion: Leukocytosis in Typhoid fever is not uncommon and culture proven Typhoid Fever can be associated with leukocytosis in children. Once there is leukocytosis in culture proven Typhoid fever, there is a high incidence of XDR typhoid.

Extensively Drug-Resistant Typhoid Fever in the United States.

Cases of extensively drug-resistant (XDR) typhoid fever have been reported in the United States among patients who did not travel internationally. Clinicians should consider if and where the patient traveled when selecting empiric treatment for typhoid fever. XDR typhoid fever should be treated with a carbapenem, azithromycin, or both.

Antibiotic Resistance Pattern of Salmonella Species in Children in a Tertiary Care Hospital

Objective: To determine the recent antibiotic resistance patterns of Salmonella species in children in a tertiary care hospital.
 Materials and Methods: This descriptive cross-sectional study was conducted in the Department of Pediatrics of Akbar Niazi Teaching Hospital, Bhara Kahu, from 18th March 2020 to 31st January 2021. A total of one hundred and seventy-eight (n=178) patients of either gender having age between 1 month to 12 years who had signs and symptoms of enteric fever and positive blood culture report of Salmonella species were enrolled in this study through non-probability, consecutive sampling. The demographic characteristics of patients along with the antibiotic sensitivity pattern of the Salmonella species were recorded on the predesigned proforma and analyzed through SPSS version 25.
 Results: Out of the total of 178 patients, reports of blood cultures of 164(92.1%) patients showed Salmonella Typhi while those of 14(7.9%) patients showed Salmonella Paratyphi. Out of the total of 178 Salmonella cases, 11(6.2%) were extensively drug-resistant and 58(32.6%) were multidrug-resistant. All XDR cases were of Salmonella Typhi. Out of 14 Salmonella Paratyphi, 2(14%) were MDR but no XDR Salmonella Paratyphi was found. Nalidixic acid had the highest resistance (96.4%) followed by sulphamethoxazole (65.5%). Azithromycin had the least resistance (0%) followed by imipenem (1.8%), piperacillin-tazobatam (1.9%), and meropenem (2%). Resistance of ceftriaxone was 20.8% and that of ciprofloxacin was 28.2%.
 Conclusion: No resistance of Salmonella species against azithromycin was found in our study. The presence of XDR typhoid fever cases and the rising resistance of Salmonella species to ceftriaxone and carbapenems are very alarming. To prevent this resistance, we should reserve carbapenems for complicated cases of resistant typhoid fever only. Minocycline and pipercillin-tazobactam are two other good cost-effective drugs in resistance to typhoid fever.

Treatment of 21st-Century typhoid fever in children; open-label mono versus combination drug therapy: A multicenter randomized control study.

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.