gms | German Medical Science

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Deutsche Gesellschaft für Infektiologie,
Deutsche AIDS-Gesellschaft,
Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit,
Paul-Ehrlich-Gesellschaft für Chemotherapie

23.06. - 26.06.2010, Köln

Prevalence of first-step parC mutants with amino acid alterations at resistance hot spots S79 and D83 among Streptococcus pneumoniae isolates in Germany

Häufigkeit von S79- und D83-Mutationen im parC-Gen von Streptococcus-pneumoniae-Stämmen, isoliert von Patienten aus dem ambulanten Bereich in Deutschland

Meeting Abstract

  • B. Körber-Irrgang - Antiinfectives-Intelligence GmbH, Rheinbach, Germany
  • A. Röhrig - Antiinfectives-Intelligence GmbH, Rheinbach, Germany
  • M.W. Pletz - Hannover Medical School, Department of Pulmonary Medicine, Hannover, Germany
  • M. Kresken - Antiinfectives-Intelligence GmbH, Rheinbach, Germany

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP3

DOI: 10.3205/10kit059, URN: urn:nbn:de:0183-10kit0596

Published: June 2, 2010

© 2010 Körber-Irrgang et al.
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Outline

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Objectives: Resistance (R) of S. pneumoniae (SPN) to fluoroquinolones (FQ) is mainly associated with mutations in the genes parC and gyrA encoding for the ParC subunit of topoisomerase IV and the GyrA subunit of DNA gyrase, respectively. Complete R to anti-pneumococcal FQs such as levofloxacin (LVX) requires alterations in both enzymes, while single mutations (first-step mutants) are often associated with susceptibility to LVX. However, a first-step mutation increases the likelihood for the acquisition of a second mutation resulting in complete R. Among first-step mutants, those with an alteration in ParC predominate. The aim of this study was to evaluate the prevalence of isolates with a first step mutation at the resistance hot spots S79 or D83 in parC among SPN recovered from outpatients with respiratory tract infections (RTIs).

Methods: 296 isolates consecutively collected in 29 laboratories between Jan-Apr 2007 were studied. MICs of LVX, ciprofloxacin (CIP), moxifloxacin (MFX) and norfloxacin (NOR) were determined by the broth microdilution method according to the standard ISO 20776-1:2006. EUCAST clinical breakpoints were applied to interpret MICs of LVX, CIP and MFX. PCR-RFLP analyses were performed to screen the isolates for mutations at amino acid positions S79 and D83 of parC. Isolates harbouring mutations at the respective positions were further analysed by sequencing.

Results: All isolates were susceptible to LVX and MFX, while 18/296 (6.1%) were R to CIP. The peak MIC of NOR was 8 mg/L. Isolates exhibiting NOR MICs of >8 mg/L (n=72) were included in the PCR-RFLP analyses. RFLP screening indicated that 10/72 isolates harboured a mutation in parC. In nine isolates only synonymous nucleotide exchanges at D83 were found. MICs of NOR, CIP, LVX and MFX for these isolates were 16–32, 2–4, 1–2 and 0.125–0.25 mg/L, respectively. One isolate, with MICs of 64, 4, 2 and 0.25 mg/l for NOR, CIP, LVX and MFX, respectively, had an amino acid exchange at position 79 (serine to phenylalanine). This resulted in an overall prevalence of first-step parC mutants with exchanges at amino acid positions S79 or D83 of 0.3% (1/296).

Conclusions: Based on our data, first-step parC mutants with alterations at amino acid positions S79 and D83 are rare among SPN isolates recovered from outpatients with RTIs in Germany. Regular screening for such mutants, however, is important because they are precursors of complete FQ-resistant isolates.