The clinical impact of ST131 H30-Rx subclone in urinary tract infections due to multidrug-resistant Escherichia coli

Can, Füsun; Azap, Özlem Kurt; Ispir, Pelin; Nurtop, Elif; Şeref, Ceren; Loçlar, İlayda; Aktaş, Ozge Nur; Orhan, Yelda; Ergönül, Önder

doi:10.1016/j.jgar.2015.10.006

Cited by 18 publications

(12 citation statements)

References 14 publications

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“…In particular, E . coli 025b:H4/ST131 is now prevalent in long term care facilities, exhibits co-resistance to the fluoroquinolones, aminoglycosides and TMP-SMX, and now represents a considerable public health concern [11, 12]. The factors responsible for the successful global dissemination of E .…”

Section: Discussionmentioning

confidence: 99%

“…A particular driver of the rapid rise of ESBL-based resistance is the expansion of the ST131-H30 clone of E . coli that is well established as a globally disseminated multidrug resistant clone [11, 12]. The ST131 clone is frequently associated with the CTX-M-15 ESBL which is now the most prevalent ESBL in the US and many other countries [13, 14].…”

Section: Introductionmentioning

confidence: 99%

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The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017

et al. 2019

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Urinary tract infections (UTIs) caused by Escherichia coli have been historically managed with oral antibiotics including the cephalosporins, fluoroquinolones and trimethoprim-sulfamethoxazole. The use of these agents is being compromised by the increase in extended spectrum β-lactamase (ESBL)-producing organisms, mostly caused by the emergence and clonal expansion of E. coli multilocus sequence typing (ST) 131. In addition, ESBL isolates show co-resistance to many of oral agents. Management of UTIs caused by ESBL and fluoroquinolone-resistant organisms is becoming increasingly challenging to treat outside of the hospital setting with clinicians having to resort to intravenous agents. The aim of this study was to assess the prevalence of ESBL phenotypes and genotypes among UTI isolates of E. coli collected in the US during 2017 as well as the impact of co-resistance to oral agents such as the fluoroquinolones and trimethoprim-sulfamethoxazole. The national prevalence of ESBL phenotypes of E. coli was 15.7% and was geographically distributed across all nine Census regions. Levofloxacin and trimethoprim-sulfamethoxazole-resistance rates were ≥ 24% among all isolates and this co-resistance phenotype was considerably higher among isolates showing an ESBL phenotype (≥ 59.2%) and carrying blaCTX-M-15 (≥ 69.5%). The agents with the highest potency against UTI isolates of E. coli, including ESBL isolates showing cross-resistance across oral agents, were the intravenous carbapenems. The results of this study indicate that new oral options with the spectrum and potency similar to the intravenous carbapenems would address a significant unmet need for the treatment of UTIs in an era of emergence and clonal expansion of ESBL isolates resistant to several classes of antimicrobial agents, including oral options.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017

et al. 2019

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“…Epidemiologically, the 172 isolates consisted of mostly those from North America obtained between 1948 and 2011, with most collected between 2000 and 2010, irrespective of the clade and subclade types. Since the first description of the fimH lineage in 2013 [3], the fimH type has been found in several epidemiological studies published on ExPEC or fecal ST131 isolates [8–17]. However, these have mostly concerned fluoroquinolone-resistant and /or ESBL-producing isolates.…”

Section: Introductionmentioning

confidence: 99%

The ST131 Escherichia coli H22 subclone from human intestinal microbiota: Comparison of genomic and phenotypic traits with those of the globally successful H30 subclone

et al. 2017

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BackgroundIn 2006, we found healthy subjects carrying ST131 Escherichia coli in their intestinal microbiota consisting of two populations: a subdominant population of fluoroquinolone-resistant E. coli belonging to subclone H30 (H30-R or subclade C1), the current worldwide dominant ST131 subclone, and a dominant E. coli population composed of antibiotic-susceptible E. coli belonging to subclone H22 (clade B), the precursor of subclone H30. We sequenced the whole genome of fecal H22 strain S250, compared it to the genomes of ExPEC ST131 H30-Rx strain JJ1886 and commensal ST131 H41 strain SE15, sought the H22-H30 genomic differences in our fecal strains and assessed their phenotypic consequences.ResultsWe detected 173 genes found in the Virulence Factor Database, of which 148 were shared by the three ST131 genomes, whereas some were genome-specific, notably those allowing determination of virotype (D for S250 and C for JJ1886). We found three sequences of the FimH site involved in adhesion: two in S250 and SE15 close and identical, respectively, to that previously reported to confer strong intestinal adhesion, and one in JJ1886, corresponding to that commonly present in uropathogenic E. coli. Among the genes involved in sugar metabolism, one encoding a gluconate kinase lacked in S250 and JJ1886. Although this gene was also absent in both our fecal H22 and H30-R strains, H22 strains showed a higher capacity to grow in minimal medium with gluconate. Among the genes involved in gluconate metabolism, only the ghrB gene differed between S250/H22 and JJ1886/H30-R strains, resulting in different gluconate reductases. Of the genes involved in biofilm formation, two were absent in the three genomes and one, fimB, in the JJ1886 genome. Our fecal H30-R strains lacking intact fimB displayed delayed biofilm formation relative to our fecal H22 strains. The H22 strains differed by subclade B type and plasmid content, whereas the H30-R strains were identical.ConclusionsPhenotypic analysis of our fecal strains based on observed genomic differences between S250 and JJ1886 strains suggests the presence of traits related to bacterial commensalism in our H22 strains and traits commonly found in uropathogenic E. coli in our H30-R strains.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-0984-8) contains supplementary material, which is available to authorized users.

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“…Statistical analysis was performed using the computing environment R [3]. -ΔΔ(ct) values of efflux pump genes were normalized to generate a heat map with dendrogram of rows and columns.…”

Section: Discussionmentioning

confidence: 99%

“…H30 clonal subset of ST131 contains allele 30 of the type-1 fimbriae adhesin gene fimH. Recently described H30Rx clade of ST131-H30 is associated with fluoroquinolone resistance and usually produces CTX-M-15 [3].…”

Section: Introductionmentioning

confidence: 99%

The Role of AcrAB–TolC Efflux Pumps on Quinolone Resistance of E. coli ST131

et al. 2018

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E.coli ST131 is a global concern because of its high multi-drug resistance and several virulence factors. In this study, the contribution of acrAB-TolC efflux system of E.coli ST131 to fluoroquinolone resistance was evaluated. A total of non-repetitive 111 ciprofloxacin resistant E.coli isolates were included in the study. Multi-locus sequence typing (MLST) was used for genotyping. Expressions of acrA, acrB and tolC efflux pump genes were measured by RT-PCR. Mutations in marA, gyrA, parC, and aac(6')-lb-cr positivity were studied by Sanger sequencing. Sixty-four (57.7%) of the isolates were classified as ST131 and 52(81.3%) of the ST131 isolates belonged to H30-Rx subclone. In ST131, CTX-M 15 positivity (73%) and aac(6')-lb-cr carriage (75%) were significantly higher than non-ST131 (12.8% and 51%, respectively) (p<0.05). The ampicillin-sulbactam (83%) resistance was higher, gentamicin resistance (20%) was lower in ST131 than non-ST131 (64% and 55%, respectively) (p=0.001 and p=0.0002). Number of the isolates with MDR or XDR profiles did not differ in both groups. Multiple in-dels (up to 16) were recorded in all quinolone resistant isolates. However, marA gene was more overexpressed in ST131 compared to non-ST131 (median 5.98 vs 3.99; P=0.0007). Belonging to H30-Rx subclone, isolation site, ciprofloxacin MIC values did not correlate with efflux pump expression. In conclusion, the marA regulatory gene of AcrAB-TolC efflux pump system has a significant impact on quinolone resistance and progression to MDR profile in ST131 clone. Efflux pump inhibitors might be alternative drugs for the treatment of infections caused by E.coli ST131 if used synergistically in combination with antibiotics.

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The clinical impact of ST131 H30-Rx subclone in urinary tract infections due to multidrug-resistant Escherichia coli

Cited by 18 publications

References 14 publications

The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017

The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017

The ST131 Escherichia coli H22 subclone from human intestinal microbiota: Comparison of genomic and phenotypic traits with those of the globally successful H30 subclone

The Role of AcrAB–TolC Efflux Pumps on Quinolone Resistance of E. coli ST131

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