Session: P066 Various agents against Gram-positive bacteria

Category: 2e. Skin, soft tissue, bone & joint & central nervous system infections

24 April 2017, 12:30 - 13:30 P1341

Efficacy of tedizolid against methicillin-resistant Staphylococcus aureus and Peptostreptococcus anaerobiuse in thigh mixed-infection mouse model

Hiroshige Mikamo*1, Mao Hagihara2, Hideo Kato2, Naoya Nishiyama2, Nobuhiro Asai2, Yuseke Koizumi2, Daisuke Sakanashi2, Hiroyuki Suematsu2, Katsuhiko Matsuura2, Yuka Yamagishi3

1Aichi Medical University

2Aichi Medical University

3Aichi Medical University Graduate School of Medicine; Department of Clinical Infectious Diseases

Background: To explore the best treatment of complicated skin and soft tissue infection (cSSSI), especially for necrotizing fasciitis (NF), it is important to evaluate antimicrobial activity with mixed- infection model of aerobic-anaerobic floras. The purpose of this study is to compare the antimicrobial activity of human simulated exposures of tedizolid 200 mg daily, and linezolid 600mg every 12 hours for the treatment of cSSSI caused by MRSA and Peptostreptococcus anaerobius in both the neutropenic mice thigh mixed-infection models.

Material/methods: Tedizolid phosphate (Bayer Pharma AG, Leverkusen, Germany) and linezolid (Sigma, Japan) were used for all in vivo testing. A total of 1 MRSA and 2 Peptostreptococcus anaerobius isolates were utilized. Specific-pathogen-free, ICR mice (20-25 g) was used. Antimicrobial efficacy was calculated for each isolate as the change in bacterial numbers (△log10CFU/ml) obtained in the treated mice after 24 h compared with the numbers in the starting control animals (0 h).

Results: The tedizolid and linezolid MICs for MRSA was 0.25 and 2 μg/ml, respectively. Tedizolid MIC for P. anaerobiuse was 0.12 μg/ml, and linezolid MICs for two P. anaerobiuse isolates were 0.5 and 1 μg/ml, respectively. The MRSA densities of thighs from 0 h control mice ranged from 6.52 to 6.64 log10 CFU/ml. Isolates grew to 8.13 to 9.15 log10 CFU/ml after 24 h in untreated control animals. Numerically better activity was noted for linezolid therapy for the isolates evaluated, compared with tedizolid therapy. When comparing the antimicrobial activity of tedizolid and linezolid monotherapy between single infection and mixed infection model, antimicrobial activities of both antimicrobials were attenuated when mixed infection model was used.

The P. anaerobiuse densities of thighs from 0 h control mice ranged from 6.74 to 7.36 log10 CFU/ml. Isolates grew to 7.55 to 8.13 log10 CFU/ml after 24 h in untreated control animals. Any statistically significant differences in efficacy between the agents were transient. While numerically better activity was noted for tedizolid therapy for P. anaerobiuse, compared with linezolid therapy. When comparing the activity of tedizolid and linezolid monotherapy between single infection and mixed infection model, antimicrobial activities of both antimicrobials were attenuated when mixed infection model was used. Significantly incensement of bacteria burden of P. anaerobiuse was noted for the mixed infection model after 24 h incubation (p < 0.05).

Conclusions: We suggest that “P. anaerobiuse” virulence is enhanced by the presence of the aerobe MRSA. In the neutropenic murine thigh model, human simulated exposures of tedizolid and linezolid resulted in similar efficacies against MRSA, even though single and mixed infection models were used. These data support the clinical utility of tedizolid for use against MRSA and P. anaerobiuse in the treatment of cSSSI.