Fluoroquinolone Resistance in<i>Streptococcus pyogenes</i>

Richter, Sandra; Diekema, Daniel J.; Heilmann, Kristopher P.; Almer, Laurel S.; Shortridge, Virginia D.; Zeitler, Rodney R.; Flamm, Robert K.; Doern, Gary V.

doi:10.1086/345904

Cited by 33 publications

(30 citation statements)

References 23 publications

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“…Using this cut-off for screening clinical isolates, as many as 14 mutations have been described in the QRDRs of parC, parE, gyrA and gyrB [4,[7][8][9][10]12,[14][15][16]29] and 4 new mutations were encountered in the present study. The QRDR sequence comparison M a n u s c r i p t of susceptible and non-susceptible isolates of the same emm types revealed that the S79F in parC is a relevant mutation for ciprofloxacin non-susceptibility.…”

Section: Discussionmentioning

confidence: 73%

“…The first description of a GAS clinical isolate resistant to ciprofloxacin [minimal inhibitory concentration (MIC) >32 mg/L) was reported in 2000 [7]. So far, seven cases of highly resistant strains have been described [7][8][9][10][11]. At the same time, GAS with reduced susceptibility to FQs have been increasingly reported worldwide [4,12,13].…”

Section: Introductionmentioning

confidence: 99%

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Emerging fluoroquinolone-non-susceptible group A streptococci in two different paediatric populations

Smeesters¹,

Vergison²,

Campos³

et al. 2009

International Journal of Antimicrobial Agents

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Clonal emergence of group A streptococci (GAS) with reduced susceptibility to fluoroquinolones (FQs) has been increasingly reported. Non-susceptibility is associated with various point mutations in the target-encoding genes and has only been described in a few emm types. We used a well characterised GAS clinical paediatric collection from Brussels (Belgium) and Brasília (Brazil) to analyse the molecular basis of FQ non-susceptibility. GAS strains were tested for ciprofloxacin susceptibility and were screened for mutations in DNA gyrase-and topoisomerase IV-encoding genes. Genetic relationships between the different emm types were assessed by phylogenetic analysis of the whole surface-exposed part of the M protein. A high proportion (22.5%) of ciprofloxacin-non-susceptible isolates (minimal inhibitory concentration ≥ 2 mg/L) was found among the Belgian strains. They belonged mostly to emm type 6 (87%). In Brazil, 6% of the isolates, belonging to seven distantly related emm types, were non-susceptible. Our phylogenetic analysis showed that non-susceptibility may arise in various genetic backgrounds. Sequence comparison of the quinolone resistance-determining regions (QRDRs) of the ParCand ParE-encoding genes from susceptible and non-susceptible isolates revealed that most of the mutations were found in both classes of isolates, indicating an emm type-linked polymorphism. In conclusion, we observed a clonal spreading of nonsusceptible emm type 6 GAS strains in Brussels and a polyclonal distribution of nonsusceptible isolates in Brazil. All the Brazilian and Belgian emm type 6 strains displayed a S79A/F mutation in parC that convincingly explains the non-susceptible phenotype.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Emerging fluoroquinolone-non-susceptible group A streptococci in two different paediatric populations

Smeesters¹,

Vergison²,

Campos³

et al. 2009

International Journal of Antimicrobial Agents

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“…Our data from pediatric isolates of S. pyogenes confirmed this M/emm 6 predominance finding. However, it is interesting to note that although M/emm 6 isolates have intrinsic fluoroquinolone resistance, the highly resistant isolates reported in the literature have been M/ emm types 2, 12, and 89 rather than M/emm type 6 (Yan et al, 2000b;Reinert etal., 2004;Richter et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in naturally arising resistant isolates of S. pyogenes occur in the QRDR of gyrA at Ser-81 with or without replacement at Met-99 and in the QRDR of parC at Ser-79 with or without change at Ala-121 (Yan et al, 2000b;Richter et al, 2003;Yan et al, 2000a;Alonso et al, 2002). The point mutation patterns among the pediatric isolates are similar to those previously documented in adult isolates and somewhat similar to those key residue replacements in S. pneumoniae but with much less variety of amino acid substitutions (Boos et al, 2001;Janoir et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, susceptibility testing of S. pyogenes isolates is not routinely performed. In the past six years, a few highly fluoroquinolone-resistant isolates of S. pyogenes have been reported (Yan et al, 2000b;Reinert etal., 2004;Richter et al, 2003). Analyses of the gyrA and parC gene sequences from these organisms indicate that point mutations along the quinolone resistance-determining regions (QRDRs) were the mechanisms for resistance (Yan et al, 2000b;Reinert et al, 2004;Orscheln et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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An intrinsic pattern of reduced susceptibility to fluoroquinolones in pediatric isolates of Streptococcus pyogenes

Yan¹,

Schreckenberger

Zheng

et al. 2008

Diagnostic Microbiology and Infectious Disease

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A total of 116 clinical isolates collected in 2003 from a tertiary pediatric hospital and a primary pediatric department in Chicago, Illinois were screened for reduced susceptibility to selected fluoroquinolones by disc diffusion. Correlation between reduced susceptibility and point mutations in the quinolone resistance-determining region of parC and gyrA genes were evaluated, and point mutations were compared with other reports of isolates derived from adult or mixed patient populations. 9% of isolates had reduced susceptibility to one or more of these fluoroquinolones by Etest: ciprofloxacin, levofloxacin, moxifloxacin. A single point mutation (Ser-79) in parC seemed responsible for the reduced susceptibility. Resistant S. pyogenes isolates were compared using M/ emm type, RepPCR, and pulsed-field gel electrophoresis (PFGE). RepPCR provided no more separation of strains than M/emm typing and PFGE results with SgrA1 were more discriminatory than with SmaI. The majority of these isolates were M/emm type 6. PFGE analysis using SgrA1 demonstrated 2 different resistant strains among the M/emm type 6 isolates. The findings suggest that a population of S. pyogenes with an intrinsic reduced susceptibility to fluoroquinolones exists in pediatric clinical isolates. Monitoring of amino acid changes in both parC and gyrA will assist in the prediction of emergence of high level fluoroquinolone resistance.

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What Antimicrobial Resistance Has Taught Us About Horizontal Gene Transfer

Barlow

2009

Methods in Molecular Biology

225

146

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Horizontal gene transfer (HGT) has been responsible for the dissemination of numerous antimicrobial-resistance determinants throughout diverse bacterial species. The rapid and broad dissemination of resistance determinants by HGT, and subsequent selection for resistance imposed by the use of antimicrobials, threatens to undermine the usefulness of antimicrobials. However, vigilant surveillance of the emerging antimicrobial resistance in clinical settings and subsequent studies of resistant isolates create a powerful system for studying HGT and detecting rare events. Two of the most closely monitored phenotypes are resistance to beta-lactams and resistance to fluoroquinolones. Studies of resistance to these antimicrobials have revealed that (1) transformation occurs between different species of bacteria including some recipient species that were not previously known to be competent for natural transformation; (2) transduction may be playing an important role in generating novel methicillin-resistant Staphylococcus aureus (MRSA) strains, although the details of transferring the SCCmec element are not yet fully understood; (3) Resistance genes are probably moving to plasmids from chromosomes more rapidly than in the past; and (4) Resistance genes are aggregating upon plasmids. The linkage of numerous resistance genes on individual plasmids may underlie the persistence of resistance to specific antimicrobials even when use of those antimicrobials is discontinued. Further studies of HGT and methods for controlling HGT may be necessary to maintain the usefulness of antimicrobials.

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Fluoroquinolone Resistance inStreptococcus pyogenes

Cited by 33 publications

References 23 publications

Emerging fluoroquinolone-non-susceptible group A streptococci in two different paediatric populations

Emerging fluoroquinolone-non-susceptible group A streptococci in two different paediatric populations

An intrinsic pattern of reduced susceptibility to fluoroquinolones in pediatric isolates of Streptococcus pyogenes

What Antimicrobial Resistance Has Taught Us About Horizontal Gene Transfer

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