scholarly journals A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug-resistant (XDR) Salmonella Typhi isolates in children in Karachi

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saba Shahid ◽  
Marvi Mahesar ◽  
Nida Ghouri ◽  
Saba Noreen

Abstract Background Enteric fever is a systemic infection caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A, B, and C. There is an emergence of Typhoid fever caused by extensively drug-resistant Salmonella Typhi strain called XDR S.Typhi. This strain is resistant to recommended first-line antibiotics and cephalosporins. WHO estimated 5274 cases of XDR S.Typhi in Karachi from November 2016 to December 2019. This study aims to determine clinical course, complications and response to treatment of XDR S.Typhi among the pediatric population coming to Indus Hospital. Method We reviewed the records of children who had culture-proven XDR S.Typhi infection at Indus Hospital from July 2017 to December 2018. A pre-designed data abstraction form was used to record information about seasonality, demographic details, clinical features and course, treatment, complications and outcomes of the cases of XDR S.Typhi. Results The records of 680 children were reviewed. The median (IQR) age of the patients was 5 (2–8) years. More than half (n = 391, 57.5%) of the patients were males. The outcomes were recorded in 270 (40%) patients. Out of these, 234 (86.7%) children got cured within 14 days, while a delayed response to antibiotics was noted in 32 (11.9%) children. Seventy-six (29%) children recovered on a combination of meropenem and azithromycin, 72 (27%) got cured on azithromycin alone, while 15 (6%) responded to meropenem alone. Conclusion Our review indicated that children under 5 years of age were affected more with XDR S.Typhi. Azithromycin alone or in combination with meropenem were effective antibiotics for treating XDR S.Typhi in children.

2020 ◽  
Author(s):  
Saba Shahid ◽  
Marvi Mahesar ◽  
Nida Ghouri ◽  
Saba Noreen

Abstract Background: Enteric fever is a systemic infection, which can be caused by Salmonella enterica; Typhi and Paratyphi A. Over time, Salmonella Typhi has developed resistance to antibiotics resulting in the emergence of extensively drug-resistant (XDR) enteric fever. WHO estimated 5274 cases of XDR Enteric fever in Karachi from November 2016 to December 2019. This study aims to determine clinical course, complications and outcomes of XDR enteric fever among the pediatric population coming to Indus HospitalMethods: A retrospective chart review of pediatric patients (aged one month to 15 years) seen in Indus Hospital between July 2017 to December 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about seasonality and distribution of cases, demographic details, signs and symptoms, clinical course, treatment, complications and outcomes of the cases treated for XDR Enteric feverResults: Six hundred and eighty children were included in the study. The median (IQR) age of the patients was 5 (2-8) years. More than half (n=391, 57.5%) of the patients were males. Most common clinical manifestations included fever, vomiting and diarrhea, noted in 680 (100%), 242 (35%) and 174 (25%) patients. Outcomes of 270 (39.7%) patients were recorded. Others were lost to follow up [351 (51.6%)], referred out [52 (7.6%)] or left against medical advice [7 (1%)]. 266 (39.1%) patients were cured, and four children (0.6%) expired. Seventy-eight patients (82%) and 15 patients (16.3%) got cured on Azithromycin and Meropenem alone while 157 on a combination of drugs.Conclusion: Our review indicated that children under five years of age were affected more with XDR Enteric fever. Meropenem and Azithromycin, either alone or in combination were the most effective antibiotics for treating XDR Enteric fever in children coming to Indus hospital


2020 ◽  
Author(s):  
Saba Shahid ◽  
Marvi Mahesar ◽  
Nida Ghouri ◽  
Saba Noreen

Abstract Background: Enteric fever is a systemic infection, which can be caused by Salmonella enterica; Typhi and Paratyphi A. Over a period of time Salmonella Typhi has developed resistance to many antibiotics which has resulted in emergence of extensively drug resistant (XDR) enteric fever. WHO estimated 5274 cases of XDR Enteric fever in Karachi from November 2016 to December 2019.This study aims to determine clinical course, complications and outcomes of XDR enteric fever among the pediatric population coming to Indus HospitalMethods: A retrospective chart review of pediatric patients (aged 1 month–15 years) seen in Indus Hospital between July 2017 to December 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about seasonality and distribution of cases, demographic details, signs and symptoms, clinical course, treatment, complications and final outcomes of the cases treated for XDR Enteric feverResults: Six hundred and eighty children were included in the study. The median (IQR) age of the patients was 5 (2-8) years. More than half (n=391, 57.5%) of the patients were males. Most common clinical manifestations included fever vomiting and diarrhea which were noted in 680 (100%), 242 (35%) and 174 patients (25%) Final outcomes of 270 (39.7%) patients have been recorded; 351 (51.6%) were lost to follow up, 52 (7.6%) were referred out and 7 (1%) left without medical advice. 266 (39.1%) patients were cured and 4 children (0.6%) expired. Seventy eight patients (82%) and 15 patients (16.3%) got cured on Azithromycin and Meropenum alone while 157 patients got cured on combination of drugs.Conclusion: Our review indicated that children under 5 years of age were affected more with XDR Enteric fever. Meropenum and Azithromycin, either alone or in combination were the most effective antibiotics for treating XDR Enteric fever in children coming to Indus hospital


2022 ◽  
Author(s):  
Kokab Jabeen ◽  
Sidrah Saleem ◽  
Faiqa Arshad ◽  
Zill-e-Huma ◽  
Shah Jahan ◽  
...  

Abstract Typhoid fever is a significant health problem in developing countries like Pakistan. Salmonella Typhi the causative agent of typhoid has developed resistant to almost all recommended antibiotics. Emergence of resistance to third generation cephalosporins has further complicated the situation and such strains are called as extensively drug resistant (XDR) Salmonella Typhi. Currently only available options are azithromycin and cabapenems. Recently few reports of azithromycin resistance have emerged from countries like Pakistan, India, Bangladesh and Nepal. As azithromycin is the only oral option available to treat XDR Typhoid, development of resistance may change treatment strategy altogether from out patient management to hospitalization of every patient. This may increase the burden on already weak health care system of countries like Pakistan. So there is dire need to look for the alternative treatment options. Manuka honey is well known for its therapeutic potential against wide range of bacteria including Salmonella Typhimurium. In this study 3 azithromycin resistant isolates were isolated and identified using disc diffusion, E-test and broth micro dilution methods and antibacterial activity, MIC and MBC of manuka honey was performed by agar well diffusion assay and broth micro dilution assay respectively. Manuka honey manifested significant antibacterial activity against all test isolates with zone of inhibition ranging from 7.3mm to 7.5mm, MIC and MBC values were between 10 to 15% v/v Here, we conclude that Manuka honey possess potent antibacterial activity and might be used as an alternative treatment option against azithromycin resistant XDR Typhid. However, further clinical trials are mandatory to validate our initial findings.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S99-S100
Author(s):  
Felicita Medalla ◽  
Louise Francois Watkins ◽  
Michael Hughes ◽  
Meseret Birhane ◽  
Layne Dorough ◽  
...  

Abstract Background Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions. Methods Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin. Results During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states. Conclusion Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq. Disclosures All Authors: No reported disclosures


2021 ◽  
Author(s):  
Elli Mylona ◽  
Phat Voong Vinh ◽  
Sonia Qureshi ◽  
Abhilasha Karkey ◽  
Sabina Dongol ◽  
...  

Abstract The emergence of multi-drug (MDR) and extensive-drug resistance (XDR) in Salmonella Typhi and Paratyphi A hinder efficacious out-patient enteric fever treatment. We show that non-XDR and XDR S. Typhi and S. Paratyphi A are susceptible to the carbapenem tebipenem in vitro. Tebipenem demonstrated partial synergy with antimicrobials including azithromycin, signifying combination therapy may limit the emergence of resistance. Given recent evidence on tebipenem inhibitory activity against MDR Shigella, its broad-spectrum activity against MDR/XDR organisms renders it a good clinical trial candidate.


2021 ◽  
Vol 118 (48) ◽  
pp. e2110227118
Author(s):  
Melissa J. Martin ◽  
Brendan W. Corey ◽  
Filomena Sannio ◽  
Lindsey R. Hall ◽  
Ulrike MacDonald ◽  
...  

A protracted outbreak of New Delhi metallo-β-lactamase (NDM)–producing carbapenem-resistant Klebsiella pneumoniae started in Tuscany, Italy, in November 2018 and continued in 2020 and through 2021. To understand the regional emergence and transmission dynamics over time, we collected and sequenced the genomes of 117 extensively drug-resistant, NDM-producing K. pneumoniae isolates cultured over a 20-mo period from 76 patients at several healthcare facilities in southeast Tuscany. All isolates belonged to high-risk clone ST-147 and were typically nonsusceptible to all first-line antibiotics. Albeit sporadic, resistances to colistin, tigecycline, and fosfomycin were also observed as a result of repeated, independent mutations. Genomic analysis revealed that ST-147 isolates circulating in Tuscany were monophyletic and highly genetically related (including a network of 42 patients from the same hospital and sharing nearly identical isolates), and shared a recent ancestor with clinical isolates from the Middle East. While the blaNDM-1 gene was carried by an IncFIB-type plasmid, our investigations revealed that the ST-147 lineage from Italy also acquired a hybrid IncFIB/IncHIB–type plasmid carrying the 16S methyltransferase armA gene as well as key virulence biomarkers often found in hypervirulent isolates. This plasmid shared extensive homologies with mosaic plasmids circulating globally including from ST-11 and ST-307 convergent lineages. Phenotypically, the carriage of this hybrid plasmid resulted in increased siderophore production but did not confer virulence to the level of an archetypical, hypervirulent K. pneumoniae in a subcutaneous model of infection with immunocompetent CD1 mice. Our findings highlight the importance of performing genomic surveillance to identify emerging threats.


Cureus ◽  
2021 ◽  
Author(s):  
Said Amin ◽  
Mohammad Noor ◽  
Fawad Rahim ◽  
Muhammad Yasir Khan ◽  
Raza Ullah

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