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Mechanisms of Macrolide Resistance in Clinical Isolates of Haemophilus influenzae with Higher Macrolide MICs than Baseline Strains from Alexander Project (1997-2000).

PERIC M, BOZDOGAN B, JACOBS MR, APPELBAUM PC; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. C1-1613.

Hershey Medical Center, Hershey, PA.

Background. Macrolides have limited activity against H. influenzae. Occasional isolates are found with higher macrolide MICs than those of baseline strains. The purpose of this study was to determine the changes that lead to such macrolide resistance in clinical strains of H. influenzae. Materials and methods. Clinical strains of H. influenzae used in this study were collected within the Alexander Project during 1997-2000. Macrolide resistant strains, defined as isolates with azi MICs of >4 microg/ml or cla MICs of >16 microg/ml, were studied for the presence of genes conferring resistance to macrolides and mutations in the genes coding for 23S rRNA, and L4 and L22 ribosomal proteins in H influenzae. Results. A total of 43 strains among 11 734 strains screened had azi (24 strains) and/or cla (42 strains) MICs that met the criteria set. No acquired macrolide resistance (erm, mef) genes were detected. From genomic sequence analysis it was found that 10 strains had L4 ribosomal protein mutations (63[GT] insertion, [K]61[Q], [T]64[K],[ G]65[D] or [D]139[G] substitution), 11 had L22 ribosomal protein mutations ([G]91[D] substitution, 77[DEGPSM] insertion, 88[RAKG] insertion, 81[S], 95[RI] or 96[ILK] deletion) and 6 had 23S ribosomal RNA A2058G, G2160T, G2161A, A2162T, or C2164G, base substitutions. One strain with [G]65[D] mutation in L4 had a raised MIC to cla (32 microg/ml) but not to azi (4 microg/ml). Conclusion. High level macrolide resistance in H. influenzae is rare. Alterations in ribosomal proteins L4 and L22 and in 23S rRNA are associated with high level resistance in H. influenzae and were found in 19 of the 43 isolates studied.

Publication Types:
  • Meeting Abstracts
Keywords:
  • Anti-Bacterial Agents
  • BaseLine
  • Glass Ionomer Cements
  • Haemophilus Infections
  • Haemophilus influenzae
  • Macrolides
  • Microbial Sensitivity Tests
  • Mutation
  • RNA, Ribosomal, 23S
  • Ribosomal Proteins
  • genetics
  • ribosomal protein L4
Other ID:
  • GWAIDS0028534
UI: 102268158

From Meeting Abstracts




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