Antimicrobial activity of solithromycin and levofloxacin against a murine pneumonia mixed-infection model caused by Streptococcus pneumoniae and anaerobic bacteria

[[[ Introduction: ]]] Solithromycin is a novel fluoroketolide developed to treat pneumonia. But, few studies evaluating its antimicrobial activity against S. pneumoniae in a mixed-infection model with anaerobes are available, while community-acquired pneumonia can involve mixed-infection of Streptococcus pneumoniae and anaerobic bacteria. This study evaluated the antimicrobial activity of solithromycin against macrolide-resistant S. pneumoniae and anaerobic bacteria with a murine pneumonia mixed-infection model. [[[ Material and methods: ]]] We evaluated antimicrobial activity of solithromycin (10 and 20 mg/kg) and levofloxacin (126 mg/kg) against S. pneumoniae with a three-point mutation in penicillin-binding protein and an ermB gene, and Parvimonas micra. Antimicrobial efficacy was calculated for each isolate as the change in bacterial count (Δlog_{10} CFU/mL) obtained in the treated mice after 24 h compared with the count in the starting control animals. [[[ Results: ]]] The solithromycin and levofloxacin minimum inhibitory concentrations (MICs) for S. pneumoniae were 0.03 and 0.5 μg/mL, respectively. The solithromycin and levofloxacin MICs for P. micra were 0.015 and 0.12 μg/mL, respectively. In a mixed-infection model, solithromycin showed significantly higher antimicrobial activity against S. pneumoniae than levofloxacin (solithromycin 20 mg/kg; -2.87 ± 1.33 log_{10} CFU/mL vs. levofloxacin; -1.35 ± 0.37 log_{10} CFU/mL, p = 0.0397). Similarly, solithromycin showed significantly higher antimicrobial activity against P. micra than levofloxacin (solithromycin 20 mg/kg; -2.78 ± 0.98 log_{10} CFU/mL vs. levofloxacin; -1.57 ± 0.47 log_{10} CFU/mL, p = 0.0400). [[[ Discussion: ]]] Solithromycin showed higher antimicrobial activities against macrolide-resistant S. pneumoniae and P. micra than levofloxacin, even though they were coexisted in murine lung tissue. Our results suggest that solithromycin could be effective for pneumonia patients due to S. pneumoniae to reduce bacterial density in lung tissue.