Emergence of Resistance Mutations in Salmonella enterica Serovar Typhi Against Fluoroquinolones

Matono, Takashi; Morita, Masatomo; Yahara, Koji; Lee, Ken-ichi; Izumiya, Hidemasa; Kaku, Mitsuo; Ohnishi, Makoto

doi:10.1093/ofid/ofx230

Cited by 19 publications

(17 citation statements)

References 35 publications

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“…Such a phenomenon was found, for example, in Salmonella enterica serovar Typhi ( S. Typhi ). Strains with MIC ≤ 0.06 mg/L had a point mutation associated with the gyrA gene, which further led to the development of resistance of this strain to fluoroquinolones [ 42 , 45 ]. The relationship between the MIC value of susceptible strain and the effectiveness of the medicine is also described when vancomycin is used in S. aureus infections.…”

Section: The Importance Of Mic Values In Clinical Practicementioning

confidence: 99%

The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance

2021

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Inefficiency of medical therapies used in order to cure patients with bacterial infections requires not only to actively look for new therapeutic strategies but also to carefully select antibiotics based on variety of parameters, including microbiological. Minimal inhibitory concentration (MIC) defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotic. Reliable assessment of MIC has a significant impact on the choice of a therapeutic strategy, which affects efficiency of an infection therapy. In order to obtain credible MIC, many elements must be considered, such as proper method choice, adherence to labeling rules, and competent interpretation of the results. In this paper, two methods have been discussed: dilution and gradient used for MIC estimation. Factors which affect MIC results along with the interpretation guidelines have been described. Furthermore, opportunities to utilize MIC in clinical practice, with pharmacokinetic /pharmacodynamic parameters taken into consideration, have been investigated. Due to problems related to PK determination in individual patients, statistical estimation of the possibility of achievement of the PK/PD index, based on the Monte Carlo, was discussed. In order to provide comprehensive insights, the possible limitations of MIC, which scientists are aware of, have been outlined.

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Section: The Importance Of Mic Values In Clinical Practicementioning

confidence: 99%

The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance

2021

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“…Interestingly, accumulating mutations in the QRDR caused Salmonella Typhi to incrementally evolve towards increasing MIC values. Ciprofloxacin-susceptible strains (MIC≤0.06 µg ml −1 ) acquired a gyrA Ser83Phe single mutation causing DCS (MIC=0.12–0.5 µg ml −1 ) and additional gyrA and parC mutations, encoding Asp87Asn and Ser80Ile, respectively, caused high-level FQ resistance (MIC≥4 µg ml −1 ) [ 40 ]. Strains with multiple gyr and par mutations were reported from Cambodia, India and Nepal [ 36–39 ] ( Table 1 ).…”

Section: Fq Resistance In Typhoidal Salmonellamentioning

confidence: 99%

Fluoroquinolone resistance in Salmonella: insights by whole-genome sequencing

et al. 2018

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Fluoroquinolone (FQ)-resistant Salmonella spp. were listed by the WHO in 2017 as priority pathogens for which new antibiotics were urgently needed. The overall global burden of Salmonella infections is high, but differs per region. Whereas typhoid fever is most prevalent in South and South-East Asia, non-typhoidal salmonellosis is prevalent across the globe and associated with a mild gastroenteritis. By contrast, invasive non-typhoidal Salmonella cause bloodstream infections associated with high mortality, particularly in sub-Saharan Africa. Most Salmonella strains from clinical sources are resistant to first-line antibiotics, with FQs now being the antibiotic of choice for treatment of invasive Salmonella infections. However, FQ resistance is increasingly being reported in Salmonella, and multiple molecular mechanisms are already described. Whole-genome sequencing (WGS) is becoming more frequently used to analyse bacterial genomes for antibiotic-resistance markers, and to understand the phylogeny of bacteria in relation to their antibiotic-resistance profiles. This mini-review provides an overview of FQ resistance in Salmonella, guided by WGS studies that demonstrate that WGS is a valuable tool for global surveillance.

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“…The primary targets for the fluoroquinolones are the subunits of DNA gyrase (GyrA and GyrB) and the topoisomerase IV (ParC and ParE). Nonsynonymous single nucleotide substitutions in the quinolone resistance-determining regions of chromosome genes gyrA, gyrB, parC and parE decrease the fluoroquinolone susceptibility [1,9,19,26,28,31,42]. Single nucleotide substitutions, mainly in gyrA, leads to low-level resistance (MIC of ciprofloxacin 0.12-0.5 mg/l), the most common nucleotide substitutions in S. Typhi are in the codons 83 and 87 of gyrA, leading to amino acid substitu-tions Ser83Phe or Asp87Asn.…”

Section: Discussionmentioning

confidence: 99%

The antimicrobial susceptibility, resistance mechanisms and phylogenetic structure of S. Typhi isolated in 2005-2018 in the Russian Federation

Egorova

Kuleshov

Кафтырева

et al. 2020

Russian Journal of Infection and Immunity

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Here we present current global epidemiological and microbiological trends for typhoid fever, as well as describe antimicrobial susceptibility and resistance mechanisms of S. Typhi. The data on examining 299 S. Typhi isolates collected in 2005—2018 in the Russian Federation were analyzed from the Russian S. Typhi Reference Center. It was found that S. Typhi population consisted of the isolates with different resistance phenotypes and mechanisms as well as genetic heterogeneity. Moreover, antimicrobial susceptibility was detected in as low as 10.4% S. Typhi strains, whereas 89.6% isolates showed fluoroquinolone resistance (including 7.3% high-level resistance) and 3.0% — multidrug resistance to am-picillin, chloramphenicol, trimethoprim/sulfamethoxazole, tetracycline and fluoroquinolones. All strains preserved susceptibility to extended-spectrum cephalosporins and azithromycin. Fluoroquinolone low-level resistance in S. Typhi was due to single nucleotide substitutions in the gyrA: Asp87Asn (78.7%) Ser83Tyr (5.0%) and Ser83Phe (3.2%). In addition, a plasmid-mediated low-level fluoroquinolone resistance (qnrS) was found in one isolate. In contrast, a fluoroquinolone high-level resistance in S. Typhi was due to accumulation of three single nucleotide substitutions in the genes gyrA (Asp87Asn+Ser83Phe) andparC (Ser80Ile). In multidrug resistant S. Typhi isolates, pHCMl plasmids of incompatibility group IncHI1B(R27) (consisted of blaTEM.1, catA1, dfrA7 and tetB) and single nucleotide substitutions Ser83Tyr or Asp87Asn in gene gyrA were detected. The data of phylogenetic reconstruction based on the analysis of core singlenucleotide variations among examined and previously sequenced S. Typhi genomes, demonstrated that more than 80.0% of S. Typhi isolated in Russia were referred to the Asian genotype as they belonged to subclade 4.3.1 (by Wong et al.) or dominant H58 clade (H58 haplotype by Roumagnac et al.). More than 60.0% isolates in this dominant phylogenetic group possessed a fluoroquinolone low-level resistance due to gyrA Asp87Asn. Less than 20.0% of S. Typhi strains isolated in Russia phylogenetically belonged to the subclades other than 4.3.1 (non-H58) and differed from the major S. Typhi population by lacked antibiotic resistance or exerted fluoroquinolone resistance due to gyrA Ser83Phe. The study data allowed to expand our understanding on genetic diversity in S. Typhi strains isolated recently and pinpoint features of phylogenetic structure for S. Typhi population in the Russian Federation.

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Emergence of Resistance Mutations in Salmonella enterica Serovar Typhi Against Fluoroquinolones

Cited by 19 publications

References 35 publications

The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance

The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance

Fluoroquinolone resistance in Salmonella: insights by whole-genome sequencing

The antimicrobial susceptibility, resistance mechanisms and phylogenetic structure of S. Typhi isolated in 2005-2018 in the Russian Federation

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