Efficacy of quinupristin-dalfopristin against methicillin-resistant Staphylococcus aureus and vancomycin-insensitive S. aureus in a model of hematogenous pulmonary infection.
BACKGROUND
Quinupristin-dalfopristin (Q-D) is a mixture of quinupristin and dalfopristin, which are semisynthetic antibiotics of streptogramin groups B and A, respectively.


METHODS
We compared the effect of Q-D to that of vancomycin (VCM) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA).


RESULTS
Treatment with Q-D resulted in a significant decrease in the number of viable bacteria in the lungs of mice in an MRSA infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 2.99 +/- 0.44, 6.38 +/- 0.32, 5.75 +/- 0.43 and 8.40 +/- 0.14 log10 CFU/lung, respectively]. Compared with VCM, high-dose Q-D significantly reduced the number of bacteria detected in the VISA hematogenous infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 5.17 +/- 0.52, 7.03 +/- 0.11, 7.10 +/- 0.49 and 7.18 +/- 0.36 log10 CFU/lung, respectively]. Histopathological examination confirmed the effect of Q-D.


CONCLUSIONS
Our results suggest that Q-D is potent and effective in the treatment of MRSA and VISA hematogenous pulmonary infections.
Yanagihara
Katsunori
K
Second Department of Internal Medicine, Nagasaki University Graduate School of Pharmaceutical Sciences, Nagasaki, Japan. kyana-ngs@umin.ac.jp
Okada
Makiko
M
Fukuda
Yuichi
Y
Imamura
Yoshifumi
Y
Kaneko
Yukihiro
Y
Ohno
Hideaki
H
Higashiyama
Yasuhito
Y
Miyazaki
Yoshitsugu
Y
Tsukamoto
Kazuhiro
K
Hirakata
Yoichi
Y
Tomono
Kazunori
K
Kadota
Jun-Ichi
J
Tashiro
Takayoshi
T
Murata
Ikuo
I
Kohno
Shigeru
S
D000818:Animals; D016470:Bacteremia / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004352:Drug Resistance, Microbial; D007564:Japan; D008168:Lung / Q000382:microbiology / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D016106:Methicillin Resistance / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D011023:Pneumonia, Staphylococcal / Q000150:complications* / Q000188:drug therapy*; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D020713:Vancomycin Resistance / Q000187:drug effects* / Q000235:genetics; D014769:Virginiamycin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D014769:Virginiamycin; C062940:quinupristin-dalfopristin