Clonal spread of fluoroquinolone non-susceptible Streptococcus pyogenes.

BACKGROUND Fluoroquinolones are an important group of antibiotics widely used in adults, and, despite the absence of official approval, these drugs are also used in children. So far, resistance to fluoroquinolones in Streptococcus pyogenes is very rare. METHODS During a national surveillance programme in Belgium from 1999 to 2002, 2793 non-duplicate S. pyogenes recovered from tonsillopharyngitis patients were screened for fluoroquinolone resistance. Mutations in topoisomerase genes and the presence of any efflux pump activity were investigated to elucidate the fluoroquinolone resistance mechanisms. Clonality was assessed by pulsed-field gel electrophoresis (PFGE) and emm typing. RESULTS Non-susceptibility to fluoroquinolones, defined as ciprofloxacin MIC > or = 2 mg/L, was identified in 152 (5.4%) of 2793 S. pyogenes. Fifty-five (36%) fluoroquinolone non-susceptible isolates were investigated for known resistance mechanisms; all showed mutations in parC, and 29 (19%) isolates also in parE; antibiotic efflux was not noted. Two major PFGE types comprised 88% of fluoroquinolone non-susceptible S. pyogenes and belonged to serotypes emm6 and emm75. Overall, emm6 and emm75 constituted >90% of all fluoroquinolone non-susceptible isolates and showed a significant temporal and geographical shift within Belgian provinces. Although fluoroquinolone-susceptible S. pyogenes also showed fluctuations in the predominant S. pyogenes serotypes, emm6 or emm75 were under-represented in this population. Approx. 55% of the fluoroquinolone non-susceptible isolates were recovered from children ( < or =16 years). CONCLUSIONS We show here, for the first time, a multi-clonal spread of fluoroquinolone non-susceptible S. pyogenes exhibiting a known resistance mechanism. Non-susceptibility to fluoroquinolones in paediatric isolates is of concern.

[1]  R. Lütticken,et al.  High-level fluoroquinolone resistance in a clinical Streptoccoccus pyogenes isolate in Germany. , 2004, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[2]  I. Morrissey,et al.  Antibacterial resistance among children with community-acquired respiratory tract infections (PROTEKT 1999-2000). , 2004, The Journal of infection.

[3]  P. Roland,et al.  Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes. , 2004, Pediatrics.

[4]  D. Gendrel,et al.  Fluoroquinolones in paediatrics: a risk for the patient or for the community? , 2003, The Lancet. Infectious diseases.

[5]  M. Gill,et al.  A multidrug efflux phenotype mutant of Streptococcus pyogenes. , 2003, The Journal of antimicrobial chemotherapy.

[6]  S. Richter,et al.  Fluoroquinolone resistance in Streptococcus pyogenes. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  E. Goldstein,et al.  Widespread use of fluoroquinolones versus emerging resistance in pneumococci. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  P. Courvalin,et al.  parC Mutation Conferring Ciprofloxacin Resistance in Streptococcus pyogenes BM4513 , 2002, Antimicrobial Agents and Chemotherapy.

[9]  D. Hooper Fluoroquinolone resistance among Gram-positive cocci. , 2002, The Lancet. Infectious diseases.

[10]  C. Daniels,et al.  Pharmacodynamic characterization of efflux and topoisomerase IV-mediated fluoroquinolone resistance in Streptococcus pneumoniae. , 2002, The Journal of antimicrobial chemotherapy.

[11]  E. Cercenado,et al.  Activity of six quinolones against 226 recent clinical isolates of Streptococcus pyogenes with reduced susceptibility to ciprofloxacin. , 2002, The Journal of antimicrobial chemotherapy.

[12]  Dwight R. Johnson,et al.  Dynamic epidemiology of group A streptococcal serotypes associated with pharyngitis , 2001, The Lancet.

[13]  A. Noreddin,et al.  Pharmacokinetics and pharmacodynamics of the new fluoroquinolones: focus on respiratory infections. , 2001, Current opinion in pharmacology.

[14]  A. Orrling,et al.  Penicillin Treatment Failure in Group A Streptococcal Tonsillopharyngitis: No Genetic Difference Found between Strains Isolated from Failures and Nonfailures , 2001, The Annals of otology, rhinology, and laryngology.

[15]  S. Holland,et al.  Resistance to Multiple Fluoroquinolones in a Clinical Isolate of Streptococcus pyogenes: Identification of gyrA and parC and Specification of Point Mutations Associated with Resistance , 2000, Antimicrobial Agents and Chemotherapy.

[16]  L. Mandell,et al.  Fluoroquinolone Resistance in Clinical Isolates ofStreptococcus pneumoniae: Contributions of Type II Topoisomerase Mutations and Efflux to Levels of Resistance , 2000, Antimicrobial Agents and Chemotherapy.

[17]  D. Hooper,et al.  Mechanisms of action and resistance of older and newer fluoroquinolones. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[18]  D. Hooper New uses for new and old quinolones and the challenge of resistance. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  A. Noorani,et al.  Isolation rates of Streptococcus pyogenes in patients with acute pharyngotonsillitis and among healthy school children in Iran , 2000, Epidemiology and Infection.

[20]  H. Goossens,et al.  Macrolide resistance and erythromycin resistance determinants among Belgian Streptococcus pyogenes and Streptococcus pneumoniae isolates. , 2000, The Journal of antimicrobial chemotherapy.

[21]  C. Deangelis,et al.  Incidence of streptococcal carriers in private pediatric practice. , 1999, Archives of pediatrics & adolescent medicine.

[22]  H. Nsanze,et al.  The prevalence of group A streptococcal throat carriage in Al Ain, United Arab Emirates. , 1996, Annals of tropical paediatrics.

[23]  D H Persing,et al.  Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing , 1995, Journal of clinical microbiology.

[24]  Rapid typing of group A streptococci by the use of DNA amplification and non-radioactive allele-specific oligonucleotide probes. , 1994, FEMS microbiology letters.

[25]  S. Schuldiner,et al.  Mutants of the Bacillus subtilis multidrug transporter Bmr with altered sensitivity to the antihypertensive alkaloid reserpine. , 1993, The Journal of biological chemistry.

[26]  R. Chaisson,et al.  Infectious complications with respiratory pathogens despite ciprofloxacin therapy. , 1991, The New England journal of medicine.

[27]  E. Bruck,et al.  National Committee for Clinical Laboratory Standards. , 1980, Pediatrics.

[28]  E. Kaplan,et al.  The dynamics of streptococcal infections in a defined population of children: serotypes associated with skin and respiratory infections. , 1976, American journal of epidemiology.