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.
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.
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).
GEM completely eradicates SPN in mouse lung whether it is 2d or 5d course therapy.
Short-course therapy with GEM may be effective in the treatment of pneumococcal pneumonia in patients independent of disease severity.
D.J. Bast, None.