Abstract: Poster Presentations |

Short-course Gemifloxacin Therapy is Effective Against Streptococcus pneumoniae in a Murine Model of Pneumonia FREE TO VIEW

Darrin J. Bast, PhD*; Xueynn Chen, BS; Ryan Goren, BSc; Mei Yue, MD; Carla L. Duncan, BSc; Linda Dresser, PharmD; Lionel A. Mandell, MD; Donald E. Low, MD; Joyce C. de Azavedo, PhD
Author and Funding Information

Toronto Centre for Antimicrobial Research & Evaluation, Toronto, ON, Canada


Chest. 2004;126(4_MeetingAbstracts):847S. doi:10.1378/chest.126.4_MeetingAbstracts.847S
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PURPOSE:  Inappropriate use of antibiotics like fluoroquinolones (FQ) has led to rising rates of resistance among clinical isolates of Streptococcus pneumoniae (SPN). Short-course FQ therapy using the most potent agent in the class has been advocated for treatment of community-acquired pneumonia on the basis that rapid bacterial eradication likely minimizes resistance. In an effort to address this issue, we investigated FQ treatment of pneumococcal pneumonia in mice comparing 2-day (d) versus 5d treatment with gemifloxacin (GEM), which has the highest in vitro activity against SPN.

METHODS:  Thirty Swiss Webster mice were inoculated endotracheally with 5-log10 cfu of a SPN serotype 3 strain, fully susceptible in vitro to levofloxacin (MIC 1 mg/L)and GEM (MIC 0.03 mg/L). The surface temperature (ST) of a mouse has been previously shown to predict pulmonary bacterial load & histologic changes indicative of the severity of pneumonia. ST at 24 h was used to assess disease severity & stratify the mice prior to drug treatment (moderately ill: ≥ 32°C; severely ill: <32°C). GEM was administered subcutaneously OD (50 mg/kg) at 24-h post-infection to 10 mice each for 2d and 5d and taking into account numbers of moderately & severely ill mice in each group. An additional 10 mice were left untreated & served as our positive control. Viable counts for whole-lung homogenate (limit of detection of < 1.7 log10 cfu) was determined for all mice. This experiment was done twice.

RESULTS:  GEM was exceptionally effective in the complete eradication of SPN from all mice, independent of disease severity prior to treatment & the length of treatment. By comparison, untreated mice had a mean bacterial count of 8.4 + 0.4 log10 at their time of death, which generally preceded the time point for euthanasia (median time to death 65h).

CONCLUSION:  GEM completely eradicates SPN in mouse lung whether it is 2d or 5d course therapy.

CLINICAL IMPLICATIONS:  Short-course therapy with GEM may be effective in the treatment of pneumococcal pneumonia in patients independent of disease severity.

DISCLOSURE:  D.J. Bast, None.

Wednesday, October 27, 2004

12:30 PM- 2:00 PM




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