Journal article
Influence of Macrolide Susceptibility on Efficacies of Clarithromycin and Azithromycin against Streptococcus pneumoniae in a Murine Lung Infection Model
Antimicrobial agents and chemotherapy, Vol.47(2), pp.739-746
02/01/2003
DOI: 10.1128/AAC.47.2.739-746.2003
PMCID: PMC151733
PMID: 12543686
Abstract
We evaluated the activities of clarithromycin and azithromycin against 19 isolates of
Streptococcus pneumoniae
using a neutropenic lung infection model. The isolates included five susceptible isolates (clarithromycin and azithromycin MICs, ≤0.12 μg/ml), nine isolates exhibiting low-level,
mefA
-mediated resistance (clarithromycin and azithromycin MICs, 0.5 to 32 μg/ml), and five isolates expressing high-level,
ermB
-mediated macrolide resistance (clarithromycin and azithromycin MICs, ≥64 μg/ml). Infected mice were administered either saline (control), clarithromycin (4, 40, or 200 mg/kg of body weight twice daily or 200 mg/kg once daily), or azithromycin (4, 40, or 200 mg/kg once daily or 40 mg/kg twice daily) by oral gavage for 72 h. Mortality was assessed at regular intervals for 10 days, and survival in each group was compared to that of untreated controls. Animals infected with susceptible isolates demonstrated significant improvement in survival compared to the controls following treatment with either agent at doses of ≥40 mg/kg. In contrast, none of the regimens improved the survival of animals infected with isolates exhibiting high-level macrolide resistance. Among mice infected with strains expressing low-level resistance, significant improvement in survival compared to the controls was noted among isolates treated with clarithromycin at 40 (seven of nine isolates) and 200 (nine of nine isolates) mg/kg twice a day and with azithromycin at 40 (one of nine isolates) and 200 (three of nine isolates) mg/kg once a day. Animals infected with isolates of
S. pneumoniae
exhibiting low-level,
mefA
-mediated macrolide resistance responded to treatment with clarithromycin at rates similar to those observed among mice infected with fully susceptible isolates.
Details
- Title: Subtitle
- Influence of Macrolide Susceptibility on Efficacies of Clarithromycin and Azithromycin against Streptococcus pneumoniae in a Murine Lung Infection Model
- Creators
- Holly L. Hoffman - Colleges of Pharmacy, Medicine, University of Iowa, Iowa City, Iowa, Ferris State University College of Pharmacy, Big Rapids, MichiganMichael E. Klepser - Ferris State UniversityErika J. Ernst - American Association of Colleges of PharmacyC. Rosemarie Petzold - American Association of Colleges of PharmacyLoai Mohammed Sa'adah - Colleges of Pharmacy, Medicine, University of Iowa, Iowa City, Iowa, Ferris State University College of Pharmacy, Big Rapids, MichiganGary V. Doern - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.47(2), pp.739-746
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/AAC.47.2.739-746.2003
- PMID
- 12543686
- PMCID
- PMC151733
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Language
- English
- Date published
- 02/01/2003
- Academic Unit
- Epidemiology; Pathology; Pharmacy Practice and Science
- Record Identifier
- 9984366016902771
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