scholarly journals First Case of Typhoid Fever due to Extensively Drug-resistant Salmonella enterica serovar Typhi in Italy

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 151 ◽  
Author(s):  
Michela Procaccianti ◽  
Alice Motta ◽  
Stefano Giordani ◽  
Sara Riscassi ◽  
Battista Guidi ◽  
...  

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 β-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.

Author(s):  
Umar Saeed ◽  
◽  
Sara Rizwan Uppal ◽  
Zahra Zahid Piracha ◽  
Rizwan Uppal ◽  
...  

There have been several outbreaks of antimicrobial resistant (AMR) strains of Salmonella enterica serovar Typhi that cause extensively drug resistant (XDR) typhoid fever in Pakistan. It has been observed that many clinicians use serological diagnostic tests such as Widal agglutination, and TyphiDOT that detects IgM and IgG antibodies against the outer membrane protein of S. Typhi. However, it has been confirmed by many scientists that these test may lead to misdiagnosis against XDR S. Typhi. Due to lack of implementation strategies health authorities are unable to hamper Widal or TyphiDOT tests which are still practiced in many rural and urban areas.


2020 ◽  
Vol 9 (31) ◽  
Author(s):  
Samantha Hao ◽  
Tess Veuthey ◽  
Saharai Caldera ◽  
Paula Hayakawa Serpa ◽  
Barbara Haller ◽  
...  

ABSTRACT 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.


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


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257744
Author(s):  
Chanmi Kim ◽  
Iqra Latif ◽  
Durga P. Neupane ◽  
Gi Young Lee ◽  
Ryan S. Kwon ◽  
...  

Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized antibiotic-resistance profiles of XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients (n = 45, 68.89% male and 31.11% female) and determined antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients of 18 XDR S. Typhi representing all 45 isolates. Their ages were 1–13 years old: toddlers aging 1–2 years old (n = 9, 20%), pre-schoolers aging 3–5 years old (n = 17, 37.78%), school-age children aging 6–12 years old (n = 17, 37.78%), and adolescents aging 13–18 years old (n = 2, 4.44%). Through analyzing blaTEM1, dhfR7, sul1, and catA1genes for multidrug-resistance, qnrS, gyrA, gyrB, parC, and parE for fluoroquinolone-resistance, blaCTX-M-15 for XDR, and macAB and acrAB efflux pump system-associated genes, we showed the phenotype of the XDR S. Typhi isolates matches with their genotypes featured by the acquisitions of the genes blaTEM1, dhfR7, sul1, catA1, qnrS, and blaCTX-M-15 and a point mutation on gyrA. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and treatment strategies for XDR S. Typhi.


Author(s):  
Sadia Hameed

Introduction: Typhoid fever is a public health issue, burdening many regions of the world with poor socioeconomic background. Management of this disease faces the major hurdle of antimicrobial resistance. The present study reveals current pattern of antimicrobial susceptibility among Salmonella enterica (Salmonella typhi & Salmonella paratyphi A) blood culture isolates from typhoid fever cases. Regular data collection about Salmonella infections and their response to antimicrobial agents, coupled with a long term commitment to providing adequate health information systems, is the key to effective planning and policy formation against typhoid fever. Aims & Objectives: To evaluate the prevalence of ceftriaxone resistant Salmonella enterica isolates from blood cultures in Shaikh Zayed Medical Complex for updating nosocomial antimicrobial resistance data. Place and duration of study: This research study was conducted at Shaikh Zayed Medical Complex, Lahore from March 2018 to May 2019. Material & Methods: Blood cultures positive for Salmonella enterica were analyzed, taking into consideration the gender & age of patients with typhoid fever. Antimicrobial susceptibility testing was carried out through disc diffusion method. The recommended antimicrobial agents for S. typhi (Salmonella typhi) & S. paratyphi A (Salmonella Parathyphi A) (as per CLSI, USA 2018/2019 guidelines; described later), were tested and analyzed during this study with the main focus on 3rd generation cephalosporin resistance pattern. Among second line treatment options, meropenem and azithromycin were selected for study. Results: Out of 899 isolates of Salmonella enterica (from 13964 samples for blood culture), 849 (94.4%) were S. typhi and 50 (5.6%) were S. paratyphi A. Of these, 57.1% isolates were from males, 42.9% from females, 81.7% from children (age less than 12 years) and 18.3% were from adults (age more than 12 years). A continuously rising resistance percentage was observed for 3rd generation cephalosporins over the span of fifteen months. It was 43.4% for ceftriaxone (CRO). No case of meropenem and azithromycin resistance was observed during study period. Conclusion: Demographic information was provided by this study regarding high level of resistance among Salmonella enterica isolates particularly S. typhi .The first line antibiotic drugs were a complete failure in ongoing outbreak of typhoid fever. The novel results of this study are the high resistance percentages for 3rd generation cehalosporins, whether oral or parenteral. This result is worrisome as it will leave us with no option but to resort to second line drugs. However, an increasing trend of blood culturing was observed in this research. Extensively drug resistant (XDR) Salmonella infection has definitely highlighted the importance of blood culture and its use as a more preferred diagnostic tool. Key words: Typhoid fever, Extensively drug resistant (XDR) Salmonella enterica, (S. typhi & S. paratyphi A), Antimicrobial Resistance, CRO (Ceftriaxone) resistance.


mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Elizabeth J. Klemm ◽  
Sadia Shakoor ◽  
Andrew J. Page ◽  
Farah Naz Qamar ◽  
Kim Judge ◽  
...  

ABSTRACT 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 bla CTX-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.


2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Alireza Eshaghi ◽  
Sandra Zittermann ◽  
Amrita Bharat ◽  
Michael R. Mulvey ◽  
Vanessa G. Allen ◽  
...  

ABSTRACT 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.


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