Antimicrobial and immunomodulatory effects of tedizolid against methicillin-resistant Staphylococcus aureus in a murine model of hematogenous pulmonary infection.
Tedizolid (TZD) is a second-generation oxazolidinone and demonstrates potent in-vitro activity against multidrug-resistant Gram-positive bacteria. Phase III studies in patients with acute bacterial skin and skin structure infections (ABSSSI) have demonstrated the non-inferiority of TZD to linezolid (LZD). However, there are only a few studies that show the effect of TZD in pulmonary infections. In this study, we investigated the effect of TZD in a murine model of hematogenous pulmonary infection caused by methicillin-resistant Staphylococcus aureus (MRSA). The mice were treated either twice daily with saline (control), 25mg/kg of vancomycin (low-VAN), 110mg/kg of vancomycin (high-VAN), 120mg/kg of LZD or once daily with 20mg/kg of TZD. As compared to the control, the low- and high-VAN treatment groups, LZD and TZD significantly improved the survival rate, reduced the bacterial count in the lungs. Furthermore, TZD decreased the area of central bacterial colony zone (CBCZ) at 36h post-inoculation, compared with the control. In addition, we investigated the immunomodulatory effect of TZD by evaluating the plasma concentrations of the inflammatory cytokines. Although there were no significant differences in the bacterial count in the lungs amongst the drugs at 26h post-inoculation, TZD and LZD significantly improved the plasma concentrations of TNF-alpha, IL-6 and MIP-2, in comparison with the control. In this study, both TZD and LZD demonstrated antimicrobial and immunomodulatory efficacy in a murine model of hematogenous pulmonary infection caused by MRSA.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan. Electronic address: kaku-ngs@umin.ac.jp.
Norihito
N
Kaku
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Yoshitomo
Y
Morinaga
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan; Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Kazuaki
K
Takeda
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Kosuke
K
Kosai
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Naoki
N
Uno
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Hiroo
H
Hasegawa
Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Taiga
T
Miyazaki
Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Koichi
K
Izumikawa
Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Hiroshi
H
Mukae
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Katsunori
K
Yanagihara
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D058491:Bacterial Load; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000382:microbiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D010755:Organophosphates / Q000008:administration & dosage* / Q000494:pharmacology; D010080:Oxazoles / Q000008:administration & dosage* / Q000494:pharmacology; D010949:Plasma / Q000737:chemistry; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D016019:Survival Analysis; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D016207:Cytokines; D007155:Immunologic Factors; D010755:Organophosphates; D010080:Oxazoles; C515040:tedizolid phosphate
Methicillin-resistant Staphylococcus aureus; Murine model; Oxazolidinone; Pulmonary infection