Emergence of Novel Mutations in Extensively Drug-Resistant Salmonella enterica Serovar Typhi from Pakistan.
Ontology highlight
ABSTRACT:
SUBMITTER: Amir A
PROVIDER: S-EPMC7526821 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
Emergence of Novel Mutations in Extensively Drug-Resistant Salmonella enterica Serovar Typhi from Pakistan.
Amir Afreenish A Ikram Aamer A Salman Muhammad M
Antimicrobial agents and chemotherapy 20200722 8
Similar Datasets
Project description:A strain of extensively drug-resistant (XDR) Salmonella enterica serovar Typhi has caused a large ongoing outbreak in Pakistan since 2016. In Ontario, Canada, 10 cases of mainly bloodstream infections (n = 9) were identified in patients who traveled to Pakistan. Whole-genome sequencing showed that Canadian cases were genetically related to the Pakistan outbreak strain. The appearance of XDR typhoid cases in Ontario prompted a provincial wide alert to physicians to recommend treatment with carbapenems or azithromycin in suspected typhoid cases with travel history to Pakistan.
| S-EPMC7179602 | biostudies-literature
Project description:We report a draft genome sequence of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi isolated from a returned traveler from Pakistan who developed sepsis. Whole-genome sequencing revealed relatedness to a previously reported outbreak in Pakistan and identified the blaCTX-M-15 and qnrS resistance genes.
| S-EPMC7393959 | biostudies-literature
Project description:A chloramphenicol-resistant strain of Salmonella enterica serovar Typhi was first noted in Korea in 1992, when a resistant isolate was detected in a returned traveler. Continued isolation of multidrug-resistant (MDR) strains thereafter in other settings prompted a retrospective analysis of laboratory records and phenotypic and genotypic analyses of 12 chloramphenicol-resistant isolates. Among these, one isolate was resistant only to chloramphenicol, and the other isolates were also resistant to ampicillin and co-trimoxazole. MDR was transferred by conjugation from 9 of the 11 isolates. PCR showed that all isolates had an incompatible group HI1 plasmid, and oriT was detected in 10 isolates, which included strains with an unsuccessful transfer of resistance. All of the ampicillin-resistant isolates had a beta-lactamase band of pI 5.4 and bla(TEM) alleles. A PCR amplicon from an isolate showed that the sequences were identical to those of bla(TEM-1), suggesting that all isolates had a TEM-1 beta-lactamase. All isolates had class 1 integrons: 10 isolates had integrons of ca. 1.2 kb with dhfr7 gene cassettes, and 1 isolate had an integron of ca. 2.3 kb with aacA4 and bla(OXA-1)-like gene cassettes. The pulsed-field gel electrophoresis patterns of 7 of 11 MDR isolates were identical and indistinguishable from those reported for isolates in India and Indonesia. In conclusion, some of the MDR strains in Korea are related to those in other Asian countries. Susceptibility testing became necessary for selection of antimicrobial agents for the optimal treatment of patients with the emergence of MDR Salmonella serovar Typhi in Korea.
| S-EPMC525459 | biostudies-literature
Project description:Typhoid fever is a potentially severe and occasionally life-threatening bacteraemic illness caused by Salmonella enterica serovar Typhi (S. Typhi). In Pakistan, an outbreak of extensively drug-resistant (XDR) S. Typhi cases began in November 2016. We report on a five-year-old boy who contracted enteric fever while travelling in Pakistan and was diagnosed after returning to Italy in September 2019. Blood culture isolated Salmonella enterica serovar Typhi that was XDR to all first-line antibiotics, including ceftriaxone and fluoroquinolones. Empiric therapy was switched to meropenem, and the patient recovered completely. Whole-genome sequencing showed that this isolate was of haplotype H58. The XDR S. Typhi clone encoded a chromosomally located resistance region and harbored a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum ?-lactamase and the qnrS fluoroquinolone resistance gene. This is the first case of typhoid fever due to XDR S. Typhi detected in Italy and one of the first paediatric cases reported outside Pakistan, highlighting the need to be vigilant for future cases. While new vaccines against typhoid are in development, clinicians should consider adapting their empiric approach for patients returning from regions at risk of XDR S. Typhi outbreak with typhoid symptoms.
| S-EPMC7168590 | biostudies-literature
Project description:Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S Typhi observed here adds urgency to the need for typhoid prevention measures.
| S-EPMC5821095 | biostudies-literature
Project description:BackgroundLittle is known about the evolutionary process and emergence time of resistance mutations to fluoroquinolone in Salmonella enterica serovar Typhi.MethodsWe analyzed S. Typhi isolates collected from returned travelers between 2001 and 2016. Based on ciprofloxacin susceptibility, isolates were categorized as highly resistant (minimum inhibitory concentration [MIC] ≥ 4 μg/mL [CIPHR]), resistant (MIC = 1-2 μg/mL [CIPR]), intermediate susceptible (MIC = 0.12-0.5 μg/mL [CIPI]), and susceptible (MIC ≤ 0.06 μg/mL [CIPS]).ResultsA total of 107 isolates (33 CIPHR, 14 CIPR, 30 CIPI, and 30 CIPS) were analyzed by whole-genome sequencing; 2461 single nucleotide polymorphisms (SNPs) were identified. CIPS had no mutations in the gyrA or parC genes, while each CIPI had 1 of 3 single mutations in gyrA (encoding Ser83Phe [63.3%], Ser83Tyr [33.3%], or Asp87Asn [3.3%]). CIPHR had the same 3 mutations: 2 SNPs in gyrA (encoding Ser83Phe and Asp87Asn) and a third in parC (encoding Ser80Ile). CIPHR shared a common ancestor with CIPR and CIPI isolates harboring a single mutation in gyrA encoding Ser83Phe, suggesting that CIPHR emerged 16 to 23 years ago.ConclusionsThree SNPs-2 in gyrA and 1 in parC-are present in S. Typhi strains highly resistant to fluoroquinolone, which were found to have evolved in 1993-2000, approximately 10 years after the beginning of the ciprofloxacin era. Highly resistant strains with survival advantages arose from strains harboring a single mutation in gyrA encoding Ser83Phe. Judicious use of fluoroquinolones is warranted to prevent acceleration of such resistance mechanisms in the future.
| S-EPMC5726467 | biostudies-literature
Project description:ObjectivesTo highlight the importance of molecular testing in characterizing extensively drug-resistant (XDR) Salmonella Typhi (S. Typhi), and linking it to the current outbreak in Sindh, Pakistan.MethodsOur study reports three travel-related typhoid fever cases caused by XDR S. Typhi that presented between January 2019 and August 2019. Antimicrobial susceptibility and genotyping with pulse-field gel electrophoresis (PFGE) were carried out. Whole-genome sequencing (WGS) was performed to characterize the genomic clonality in relation to the emerging outbreak of S. Typhi in Sindh, Pakistan, and to study the molecular resistance profiles.ResultsLaboratory testing revealed resistance to all first-line antibiotics (i.e ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole), as well as to quinolones and third-generation cephalosporins, leading to a change in the patients' therapy to the use of carbapenems. Classical MLST (cMLST) revealed that the strains were of sequence type 1 (ST1) and the core genome sequence (cgWGS) analysis closely clustered our strains with internationally reported strains from Pakistan, India, and the UK. The strains were found to carry a bla CTX-15 gene-harbouring IncY plasmid, which encodes resistance to ceftriaxone.ConclusionsOur report alerts clinicians to the use of appropriate empirical treatments in such scenarios, and highlights the significance of the global spread of XDR S. Typhi.
| S-EPMC9216381 | biostudies-literature
Project description:A large outbreak of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi infections is ongoing in Pakistan, predominantly in Sindh Province. Here, we report the sequencing and characterization of five XDR Salmonella Typhi isolates from the Punjab province of Pakistan that are closely related to the outbreak strain and carry the same IncY plasmid.
| S-EPMC7098906 | biostudies-literature
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.
| S-EPMC7561124 | biostudies-literature
Project description:Global travel has led to intermittent importation of multidrug-resistant Salmonella enterica serovar Typhi into industrialized countries. We detected azithromycin-resistant Salmonella Typhi in Singapore, of which 2 isolates were likely locally acquired. Ongoing vigilance and surveillance to minimize the public health risk for this serious pathogen is needed.
| S-EPMC7853538 | biostudies-literature