Efficacy of tedizolid against methicillin-resistant Staphylococcus aureus and Peptostreptococcus anaerobius in thigh mixed-infection mouse model.
OBJECTIVE
The purpose of this study is to compare the antimicrobial activity of human simulated exposures of tedizolid 200 mg daily, and linezolid 600 mg every 12 h for the treatment of complicated skin and skin structure infection (cSSSI) caused by MRSA and Peptostreptococcus anaerobius in both the neutropenic mice thigh mixed-infection models.


METHODS
Tedizolid phosphate and linezolid were used for all in vivo testing. A total of one MRSA and two P. anaerobius isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the change in bacterial numbers (Δlog10CFU/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. Tedizolid MIC for P. anaerobius was 0.12 μg/ml, and linezolid MICs for two P. anaerobius isolates were 0.5 and 1 μg/ml. In mixed infection model, tedizolid therapy showed similar antimicrobial activities for one MRSA and two P. anaerobius isolates evaluated, compared with linezolid therapy. Additionally, 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.


CONCLUSIONS
In the neutropenic murine thigh infection 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. anaerobius in the treatment of cSSSI.
Department of Clinical Infectious Diseases, Aichi Medical University School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Yuka
Y
Yamagishi
Department of Clinical Infectious Diseases, Aichi Medical University School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Hiroshige
H
Mikamo
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Pharmacy, Aichi Medical University Hospital, Japan.
Hideo
H
Kato
Department of Clinical Infectious Diseases, Aichi Medical University School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Naoya
N
Nishiyama
Department of Clinical Infectious Diseases, Aichi Medical University School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Nobuhiro
N
Asai
Department of Clinical Infectious Diseases, Aichi Medical University School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Yusuke
Y
Koizumi
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Daisuke
D
Sakanashi
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Hiroyuki
H
Suematsu
Department of Pharmacy, Aichi Medical University Hospital, Japan.
Katsuhiko
K
Matsuura
Department of Clinical Infectious Diseases, Aichi Medical University School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Pharmacy, Aichi Medical University Hospital, Japan. Electronic address: hagimao@aichi-med-u.ac.jp.
Mao
M
Hagihara
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D010755:Organophosphates / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D010080:Oxazoles / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D010462:Peptostreptococcus / Q000187:drug effects*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013848:Thigh / Q000382:microbiology
D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; C515040:tedizolid phosphate
Methicillin-resistant Staphylococcus aureus; Peptostreptococcus anaerobius; Tedizolid; Thigh mixed-infection mouse model