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In Vitro Development of Resistance to Five Quinolones and Amoxicillin/Clavulanate in Streptococcus pneumoniae.

DAVIES T, PANKUCH G, DEWASSE B, JACOBS M, APPELBAUM P; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 111 (abstract no. 828).

Hershey Med. Ctr., Hershey, PA

Ability of 50 sequential subculutes in subMICs of ciprofloxacin, levofloxacin, grepafloxacin, sparfloxacin, trovafloxacin and amoxicillin/ clavulanate to select for resistance was studied in 6 penicillin susceptible (S) and 4 penicillin intermediate (I) pneumococci. Subculturing in the presence of cipro, grepa, levo, and spar led to raised MICs in all 10 strains with MICs rising from: cipro, 0.5-4.0 to 4.0-32.0 mg/ml (7-12 passages); grepa, 0.06-0.25 to 0.5-8.0 microg/ml (5-23 passages); levo, 0.5-1.0 to 4.0-64 microg/ml (14-49 passages); and spar, 0.125-0.25 to 1.0-16.0 microg/ml (8-26 passages). Trova led to raised MICs in 8 strains with MICs rising from 0.06-0.125 microg/ml to 0.5-8.0 microg/ml (6-28 passage). Amox/ clav led to raised MICs in only 1 strain with the MIC rising from 0.15 microg/ml to 0.125 microg/ml (24 passages). Subculturing in amox/clav did not lead to raised MICs to any of the fluoroquinolones (FQ) and conversely subculturing in any of the FQs did not lead to raised amox/clav MICs. Low-level FQ resistance was associated with single mutations of S79->F or Y or D83->A in ParC or S83->F or Y or E87->K or Q in GyrA. Double mutations in both ParC and GyrA led to high-level FQ resistance when ParC mutations were at S79. Trova MICs were 1-2 microg/ ml in double mutatns with ParC mutations at positions other than S79 (e.g. D83). Mutations in ParE (D435->N) and Gyr B (D435->N or E) were also associated with resistance and found in two and four mutants respectively. In the presence of reserpine 29 mutants had lower cipro MICs (2-16x); 8 mutants had lower levo MICs (2x); and one mutant had lower trova MICs (2x), suggesting that an efflux mechanism contributed to the raised MICs. In contrast to FQs, subculturing in the presence of amox/clav did not select for resistance to this drug.

Publication Types:
  • Meeting Abstracts
Keywords:
  • Amoxicillin
  • Amoxicillin-Potassium Clavulanate Combination
  • Ciprofloxacin
  • Clavulanic Acid
  • Fluoroquinolones
  • In Vitro
  • Microbial Sensitivity Tests
  • Naphthyridines
  • Ofloxacin
  • Penicillins
  • Quinolones
  • Streptococcus pneumoniae
  • grepafloxacin
  • sparfloxacin
  • trovafloxacin
Other ID:
  • GWAIDS0007415
UI: 102244911

From Meeting Abstracts




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