Telithromycin and azithromycin pharmacodynamics vs. genotypically characterised (mefA and ermB) macrolide-resistant strains of Streptococcus pneumoniae simulating free serum and free epithelial lining fluid concentrations
Abstract number: 1134_02_105
Hoban D.J., Noreddin A., Hisanaga T., DeCorby M., Laing N., Wierzbowski A., Zhanel G.G.
Telithromycin (Teli) is a new ketolide with in vitro activity against macrolide resistant SPN. The purpose of this study was to compare the pharmacodynamics (PD) of Teli and azithromycin (Azi) versus macrolide-resistant SPN simulating free serum (S) and free epithelial lining fluid (ELF) concentrations in an in vitro model.
Five PCR-positive mefA, one PCR-positive ermB and a control PCR-negative mefA, ermB strain of SPN were studied. A one compartment in vitro pharmacodynamic model was used with starting inocula 1 × 106 CFU/ml. Teli was added to the model simulating a dosage of 800 mg PO OD (S: free drug Cpmax 0.7 mg/ml, t1/2 10 hr, free AUC ~4; ELF: free drug Cmax 6 mg/ml, t1/2 10 hr, free AUC ~35). Azi was added simulating a dosage of 500/250 mg PO OD (S: free drug Cpmax 0.2 mg/ml, t1/2 68 hr, free AUC ~2; ELF: free drug Cmax 1 mg/ml, t1/2 68 hr, free AUC ~10). Samples were obtained over 24 hours to assess viable growth and selection of resistance.
Both S and ELF Teli concentrations eradicated (lowered inoculum below level of detection) all PCR-positive mefA, ermB and wild type SPN from the model within 6 hours. No difference in the rate or extent of killing (>3 log10 reduction) occurred between the test and control strains or between S and ELF concentrations. Azi S and ELF concentrations eradicated macrolide-susceptible SPN but did not eradicate macrolide-resistant SPN regardless of resistance phenotype.
Both Teli and Azi eradicated macrolide-susceptible SPN. Teli but not Azi, completely eradicated both mefA and ermB SPN from the model with no regrowth over 24 hour. Teli offers promise for the management of respiratory infections caused by macrolide-resistant SPN.
|Session name:||XXIst ISTH Congress|
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