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An intrinsic pattern of reduced susceptibility to fluoroquinolones in pediatric isolates of Streptococcus pyogenes
S Steve Yan1, Paul C Schreckenberger, Xiaotian Zheng
1Food and Drug Administration, DHHS, Rockville, MD 20855, USA.
Insights
Pediatric Streptococcus pyogenes isolates show reduced fluoroquinolone susceptibility due to parC mutations. Monitoring genetic changes in parC and gyrA can predict high-level resistance emergence.
Area of Science:
- Microbiology
- Genetics
- Pharmacology
Background:
- Fluoroquinolones are critical antibiotics.
- Emergence of antimicrobial resistance is a growing concern.
- Understanding resistance mechanisms in pediatric pathogens is vital.
Purpose of the Study:
- To investigate fluoroquinolone susceptibility in pediatric Streptococcus pyogenes isolates.
- To identify genetic mutations associated with reduced susceptibility.
- To compare genotypic and phenotypic resistance patterns.
Main Methods:
- Disc diffusion and Etest for susceptibility testing.
- Analysis of point mutations in parC and gyrA genes.
- Molecular typing including M/emm typing, rep-PCR, and PFGE.
Main Results:
- Nine percent of isolates exhibited reduced susceptibility to fluoroquinolones.
- A single point mutation (Ser-79) in parC was linked to reduced susceptibility.
- PFGE with SgrAI was more discriminatory than SmaI for strain typing.
Conclusions:
- A population of pediatric S. pyogenes with intrinsic reduced fluoroquinolone susceptibility exists.
- parC mutations are key drivers of reduced susceptibility.
- Monitoring parC and gyrA mutations aids in predicting fluoroquinolone resistance.
Abstract:
A total of 116 clinical isolates collected in 2003 from a tertiary pediatric hospital and a primary pediatric department in Chicago, IL, 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 was evaluated, and point mutations were compared with other reports of isolates derived from adult or mixed patient populations. Nine percent of isolates had reduced susceptibility to 1 or more of these fluoroquinolones by Etest: ciprofloxacin, levofloxacin, and moxifloxacin. A single point mutation (Ser-79) in parC seemed responsible for the reduced susceptibility. Resistant Streptococcus pyogenes isolates were compared using M/emm type, repetitive sequence-based PCR (rep-PCR), and pulsed-field gel electrophoresis (PFGE). Rep-PCR provided no more separation of strains than M/emm typing, and PFGE results with SgrAI were more discriminatory than with SmaI. The majority of these isolates were M/emm type 6. PFGE analysis using SgrAI 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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