Comparative evaluation of tigecycline and vancomycin, with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model.
OBJECTIVE
Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis.


METHODS
A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed.


RESULTS
Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones.


CONCLUSIONS
Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.
Yin
Li-Yan
LY
Department of Orthopaedic Surgery, University of Missouri, Columbia, MO, USA.
Lazzarini
Luca
L
Li
Fan
F
Stevens
C Melinda
CM
Calhoun
Jason H
JH
D000818:Animals; D001842:Bone and Bones / Q000382:microbiology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D016106:Methicillin Resistance; D008911:Minocycline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010019:Osteomyelitis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits; D011859:Radiography; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000302:isolation & purification; D000078304:Tigecycline; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D014640:Vancomycin; D000078304:Tigecycline; D008911:Minocycline; D012293:Rifampin