Does mutation in gyrA and/or parC or efflux pump expression play the main role in fluoroquinolone resistance in Escherichia coli urinary tract infections?: A statistical analysis study

Shigemura, Katsumi; Tanaka, Kazushi; Yamamichi, Fukashi; Shirakawa, Toshiro; Fujisawa, Masato

doi:10.1016/j.ijantimicag.2012.07.019

Cited by 26 publications

(18 citation statements)

References 22 publications

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“…Sulfonamide and trimethoprim resistance genes were typically coresident (occurring together in 12 of 15 isolates with either type of gene) and in close proximity on the same contig. One strain (SF-264) was also resistant to fluoroquinolones due to the presence of typical chromosomal mutations (in gyrA , Ser83-to-Leu and Asp87-to-Asn; in parC , Ser80-to-Ile) encountered in fluoroquinolone-resistant clinical E. coli isolates (21). …”

Section: Resultsmentioning

confidence: 99%

Genomic Analysis of Factors Associated with Low Prevalence of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli Sequence Type 95 Strains

Stephens

Adams‐Sapper

Sekhon

et al. 2017

mSphere

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Antibiotic resistance in bacterial pathogens is a major public health concern. This work was motivated by the observation that only a small proportion of ST95 isolates, a major pandemic lineage of extraintestinal pathogenic E. coli, have acquired antibiotic resistance, in contrast to many other pandemic lineages. Understanding bacterial genetic factors that may prevent acquisition of resistance could contribute to the development of new biological, medical, or public health strategies to reduce antibiotic-resistant infections.

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Section: Resultsmentioning

confidence: 99%

Genomic Analysis of Factors Associated with Low Prevalence of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli Sequence Type 95 Strains

Stephens

Adams‐Sapper

Sekhon

et al. 2017

mSphere

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“…High-level fluoroquinolone resistance in Enterobacteriaceae is mainly via mutations in gyrA or parC. 27 The 8-and 16-plex MTPCRs accurately predicted ciprofloxacin resistance for E. coli from the Tm of the gyrA product. With the 16-plex assay, 89.3% sensitivity and 100% specificity were achieved for prediction of resistance in E. coli in urine; however, resistance was not predictable for other Enterobacteriaceae, some of which also gave products for gyrA in the assay.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of multiplex tandem PCR (MT-PCR) assays for the detection of bacterial resistance genes among Enterobacteriaceae in clinical urines

Schmidt

Stanley²,

Hale³

et al. 2018

Journal of Antimicrobial Chemotherapy

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Background: Increasing resistance drives empirical use of less potent and previously reserved antibiotics, including for urinary tract infections (UTIs). Molecular profiling, without culture, might better guide early therapy. Objectives: To explore the potential of AusDiagnostics multiplex tandem (MT) PCR UTI assays. Methods: Two MT-PCR assays were developed successively, seeking 8 or 16 resistance genes. Amplification was tracked in real time, with melting temperatures used to confirm product identity. Assays were variously performed on: (i) extracted DNA; (ii) cultured bacteria; (iii) urine spiked with reference strains; and (iv) bacteria harvested from clinical urines. Results were compared with those from sequencing, real-time SybrGreen PCR or phenotypic susceptibility. Results: Performance was similar irrespective of whether DNA, cultures or urines were used, with .90% sensitivity and specificity with respect to common b-lactamases, dfr genes and aminoglycoside resistance determinants except aadA1/A2/A3, for which carriage correlated poorly with streptomycin resistance. Fluoroquinolonesusceptible and-resistant Escherichia coli (but not other species) were distinguished by the melting temperatures of their gyrA PCR products. The time from urine to results was ,3 h. Conclusions: The MT-PCR assays rapidly identified resistance genes from Gram-negative bacteria in urines as well as from cultivated bacteria. Used directly on urines, this assay has the potential to guide early therapy.

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“…It has been shown that increased expression of efflux pumps such as acrAB or transcriptional regulators of efflux pumps such as marA is significantly correlated with increased fluoroquinolone MIC in E. coli . 107,108 Secondly, complex combinations of resistance determinants such as combinations of gyrA / parC mutations with plasmid-mediated resistance determinants have been reported sparsely in the experimental data. Therefore, the comparison of experimental and observational data for these combinations of resistance determinants is impossible using this dataset.…”

Section: Discussionmentioning

confidence: 99%

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

Remondini

Pasquini

et al. 2018

Preprint

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SynopsisIntroductionCiprofloxacin resistance in Escherichia coli is widespread and adds to the burden of E. coli infections. Reviews assessing the genetic basis of ciprofloxacin resistance have mostly been qualitative. However, to allow for the prediction of a resistance phenotype of clinical relevance based on genotypic characteristics, it is essential to quantify the contribution of prevalent genotypic determinants to resistance. We carried out a systematic review to assess the relative contribution of currently known genomic resistance determinants to the minimum inhibitory concentration (MIC) of ciprofloxacin in E. coli.MethodsPubMed and Web of Science were searched for English language studies that assessed both ciprofloxacin MIC and the presence or introduction of genetic determinants of ciprofloxacin resistance in E. coli. We included experimental and observational studies without time restrictions. Medians and ranges of MIC fold changes were calculated for each resistance determinant and for combinations of determinants.ResultsWe included 66 studies, describing 604 E. coli isolates that carried at least one genetic resistance determinant. Genes coding for targets of ciprofloxacin (gyrA and parC) are strongest contributors to ciprofloxacin resistance, with median MIC fold increases ranging from 24 (range 4-133) for single Ser83Leu (gyrA) mutants to 1533 (range 256-8533) for triple Ser83Leu, Asp87Asn/Gly (gyrA) and Ser80Ile/Arg (parC) mutants. Other resistance mechanisms, including efflux, physical blocking or enzymatic modification, conferred smaller increases in ciprofloxacin MIC (median MIC fold increases typically around 15, range 1-125). However, the (combined) presence of these other resistance mechanisms further increases resistance with median MIC fold increases of up to 4000, and even in the absence of gyrA and parC mutations up to 250.ConclusionThis report provides a comprehensive and quantitative overview of the contribution of different genomic determinants to ciprofloxacin resistance in E. coli. Additionally, the data demonstrate the complexity of resistance phenotype prediction from genomic data and could serve as a reference point for studies aiming to address ciprofloxacin resistance prediction using genomics, in E. coli.

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Does mutation in gyrA and/or parC or efflux pump expression play the main role in fluoroquinolone resistance in Escherichia coli urinary tract infections?: A statistical analysis study

Cited by 26 publications

References 22 publications

Genomic Analysis of Factors Associated with Low Prevalence of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli Sequence Type 95 Strains

Genomic Analysis of Factors Associated with Low Prevalence of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli Sequence Type 95 Strains

Evaluation of multiplex tandem PCR (MT-PCR) assays for the detection of bacterial resistance genes among Enterobacteriaceae in clinical urines

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

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