Antibiotic Resistance and Typhoid

Dyson, Zoe A.; Klemm, Elizabeth J.; Palmer, Sophie; Dougan, Gordon

doi:10.1093/cid/ciy1111

Cited by 128 publications

(112 citation statements)

References 24 publications

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“…Salmonella Typhi continues to pose a major challenge in treatment as it causes invasive infections and acquires antimicrobial resistance (AMR) genes to become non-susceptible to available drugs 79 . As the pipeline for new antityphoidal drugs are exhausted, it has become imperative to explore whole genomes to understand the characteristics and search for novel diagnostic targets.…”

Section: Discussionmentioning

confidence: 99%

Genomic profiling of antimicrobial resistance genes in clinical isolates of Salmonella Typhi from patients infected with Typhoid fever in India

Katiyar

Sharma

Dahiya

et al. 2020

Sci Rep

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The development of multidrug resistance in Salmonella enterica serovar Typhi currently forms a major roadblock for the treatment of enteric fever. This poses a major health problem in endemic regions and extends to travellers returning from developing countries. The appearance of fluoroquinolone non-susceptible strains has resulted in use of ceftriaxone as drug of choice with azithromycin being recommended for uncomplicated cases of typhoid fever. A recent sporadic instance of decreased susceptibility to the latest drug regime has necessitated a detailed analysis of antimicrobial resistance genes and possible relationships with their phenotypes to facilitate selection of future treatment regimes. Whole genome sequencing (WGS) was conducted for 133 clinical isolates from typhoid patients. Sequence output files were processed for pan-genome analysis and prediction of antimicrobial resistance genes. The WGS analyses disclosed the existence of fluoroquinolone resistance conferring mutations in gyrA, gyrB, parC and parE genes of all strains. Acquired resistance determining mechanisms observed included catA1 genes for chloramphenicol resistance, dfrA7, dfrA15, sul1 and sul2 for trimethoprim-sulfamethoxazole and bla TEM-116 /bla TEM-1B genes for amoxicillin. No resistance determinants were found for ceftriaxone and cefixime. The genotypes were further correlated with their respective phenotypes for chloramphenicol, ampicillin, co-trimoxazole, ciprofloxacin and ceftriaxone. A high correlation was observed between genotypes and phenotypes in isolates of S. Typhi. The pangenome analysis revealed that core genes were enriched in metabolic functions and accessory genes were majorly implicated in pathogenesis and antimicrobial resistance. The pan-genome of S. typhi appears to be closed (B pan = 0.09) as analysed by Heap's law. Simpson's diversity index of 0.51 showed a lower level of genetic diversity among isolates of S. Typhi. Overall, this study augments the present knowledge that WGS can help predict resistance genotypes and eventual correlation with phenotypes, enabling the chance to spot AMR determinants for fast diagnosis and prioritize antibiotic use directly from sequence. Typhoid fever, a multisystemic disease related to Salmonella enterica serovar Typhi (S. Typhi) infection is a global threat due to increasing antibiotic resistance to antityphoidal agents in practice 1,2. Antimicrobial-non-susceptible Salmonella infections not only increase disease severity, but also enhance cost of antibiotic treatment and need for hospitalization resulting in economic losses 3,4. Resistance in typhoidal salmonellae surfaced majorly after introduction of therapy with chloramphenicol 5. The emergence of multiple drug resistant isolates collectively resistant to chloramphenicol, ampicillin and co-trimoxazole made ciprofloxacin the drug of choice to treat enteric fever. Wide overuse of this drug generated non-susceptible strains due to appearance of mutations in the target enzyme, DNA gyrase and topoisomerase IV 6,7. Discontinuation ...

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Section: Discussionmentioning

confidence: 99%

Genomic profiling of antimicrobial resistance genes in clinical isolates of Salmonella Typhi from patients infected with Typhoid fever in India

Katiyar

Sharma

Dahiya

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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“…Until multidrug resistant strains emerged and spread in the second half of the 1980s, chloramphenicol, ampicillin, and co-trimoxazole were considered the first-line therapy of typhoid fever globally [58]. The indiscriminate use of antibiotics, particularly in low-income areas, has favored the selection and spread of antimicrobial resistant strains [59].…”

Section: Antimicrobial Resistance and Typhoid Fevermentioning

confidence: 99%

Travel-Related Typhoid Fever: Narrative Review of the Scientific Literature

Muresu

Sotgiu

Are

et al. 2020

IJERPH

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Enteric fever is a foodborne infectious disease caused by Salmonella enterica serotypes Typhi and Paratyphi A, B and C. The high incidence in low income countries can increase the risk of disease in travelers coming from high income countries. Pre-travel health advice on hygiene and sanitation practices and vaccines can significantly reduce the risk of acquiring infections. Although the majority of the cases are self-limiting, life-threatening complications can occur. Delayed diagnosis and cases of infections caused by multi-drug resistant strains can complicate the clinical management and affect the prognosis. More international efforts are needed to reduce the burden of disease in low income countries, indirectly reducing the risk of travelers in endemic settings. Surveillance activities can help monitor the epidemiology of cases caused by drug-susceptible and resistant strains.

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“…Today, in addition to the bioburden of enteric fever already present in South Asia, there is evidence of an emergence of a cephalosporin-resistant strain of Salmonella typhi. Although the first outbreak has been reported in Sindh, it is not just a concern for Pakistan, as cephalosporin-resistant strains of Salmonella typhi have also been recorded in India, Bangladesh, Philippines, Iraq, and Guatemala [11][12][13]. Figure 1describes a brief recollection of major events pertaining to antimicrobial resistance in Salmonella typhi.…”

Section: Evolution Of Antimicrobialmentioning

confidence: 99%

“…With ever-decreasing treatment options for typhoid fever, XDR typhoid presents itself as a grave concern that commands serious attention before it becomes a global health concern. Reports indicate decreased susceptibility to azithromycin [24], which clinicians are using as a last resort for treatment for XDR typhoid fever, along with tigecycline and carbapenems [12].…”

Section: Professional Health Care Managementmentioning

confidence: 99%

Extensively Drug-Resistant (XDR) Typhoid: Evolution, Prevention, and Its Management

Akram

Khan

et al. 2020

BioMed Research International

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Typhoid fever is the result of a human host-restricted Salmonella enteric serotype typhi infection that causes enteric fever. Around 21 million people contract typhoid annually, with Pakistan’s inhabitants at most risk amongst Asian countries where typhoid remains prevalent. Decades of indiscriminate antibiotic usage has driven the evolution of multidrug-resistant strains and more recently, extensively drug-resistant (XDR) strains of Salmonella enteric serotype typhi. Current reports of extensively drug-resistant typhoid fever outbreak in Pakistan are not only a major concern for Pakistan but also for health authorities worldwide: intercontinental transmission, spread, and replacement of native strains in neighboring countries and a major impediment to Pakistani health care management. The WHO records that there are 5274 cases of extensively drug-resistant (XDR) typhoid fever out of a total of 8188 total cases of typhoid fever reported in Pakistan. The last remaining feasible oral antibiotic that XDR typhoid remains susceptible to is azithromycin; this is a cause of major concern. Additionally, several cases of XDR typhoid fever have also been reported in patients travelling from Pakistan to the USA, UK, and Canada. This review article attempts to raise the issue of XDR typhoid with respect to its epidemiology, prevention, management, and future outlook and stresses a better understanding of antimicrobial stewardship and general surveillance of the disease. Although progress is being made to combat XDR typhoid locally, efficient, unified efforts on a national and international scale are required to contain the XDR outbreak before it is no longer manageable and leads us back to the preantibiotic era.

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Antibiotic Resistance and Typhoid

Cited by 128 publications

References 24 publications

Genomic profiling of antimicrobial resistance genes in clinical isolates of Salmonella Typhi from patients infected with Typhoid fever in India

Genomic profiling of antimicrobial resistance genes in clinical isolates of Salmonella Typhi from patients infected with Typhoid fever in India

Travel-Related Typhoid Fever: Narrative Review of the Scientific Literature

Extensively Drug-Resistant (XDR) Typhoid: Evolution, Prevention, and Its Management

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