Efficacy of linezolid against Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) in a mouse model of haematogenous pulmonary infection.
Many strains of community-acquired meticillin-resistant Staphylococcus aureus (MRSA) have a pore-forming leukotoxin, known as Panton-Valentine leukocidin (PVL), which can cause severe necrotising pneumonia. Linezolid (LZD) is a new antibacterial agent with potent antibacterial activity against MRSA. In this study, a mouse model of haematogenous pulmonary infection was used to compare the efficacies of LZD and vancomycin (VAN) against pulmonary infection caused by PVL-positive S. aureus. Following antibiotic administration for 3 days, the number of viable bacteria (mean+/-standard error of the mean) in the control, VAN and LZD groups was 6.77+/-0.14, 5.29+/-0.27 and 4.25+/-0.33 log colony-forming units/lung, respectively. LZD significantly decreased the number of viable bacteria in the lungs compared with the control and VAN groups (P<0.05). The survival rate at Day 7 post-inoculation was higher in the LZD group (100%) than in the VAN group (50%) or the control group (0%). Histopathological examination and cytokine analysis also showed the beneficial efficacy of LZD compared with VAN. In conclusion, LZD significantly reduced bacterial numbers and inflammation in a mouse model of PVL-positive S. aureus haematogenous infection and improved the survival rate of infected mice compared with VAN. LZD is clinically effective against PVL-positive S. aureus.
Yanagihara
Katsunori
K
Department of Laboratory Medicine, Nagasaki University Graduate School of Medical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. kyana-ngs@umin.ac.jp
Kihara
Rie
R
Araki
Nobuko
N
Morinaga
Yoshitomo
Y
Seki
Masafumi
M
Izumikawa
Koichi
K
Kakeya
Hiroshi
H
Yamamoto
Yoshihiro
Y
Yamada
Yasuaki
Y
Kohno
Shigeru
S
Tsukamoto
Kazuhiro
K
Kamihira
Shimeru
S
D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000150:complications*; D001427:Bacterial Toxins / Q000096:biosynthesis*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000032:analysis; D005098:Exotoxins / Q000096:biosynthesis*; D006651:Histocytochemistry; D007956:Leukocidins / Q000096:biosynthesis*; D000069349:Linezolid; D008168:Lung / Q000737:chemistry / Q000382:microbiology / Q000473:pathology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D051379:Mice; D023303:Oxazolidinones / Q000627:therapeutic use*; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D016019:Survival Analysis; D016896:Treatment Outcome; D037521:Virulence Factors / Q000096:biosynthesis*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D016207:Cytokines; D005098:Exotoxins; D007956:Leukocidins; D023303:Oxazolidinones; C078284:Panton-Valentine leukocidin; D037521:Virulence Factors; D000069349:Linezolid