Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis.
In the field of local application of antimicrobials, a number of novel drugs and/or new drug delivery systems have been developed in recent years. The present study aimed to investigate hydroxyapatite cement (HAC) as a carrier for vancomycin in the treatment of chronic osteomyelitis due to Staphylococcus aureus strains with various mechanisms of resistance. The release of vancomycin from standard test cylinders was determined in vitro and the efficacy of the delivery system was measured in vivo using a rabbit model of chronic osteomyelitis. First, powdered HAC was mixed with vancomycin at 80, 160 and 240 mg/g. After hardening, formed cylinders were eluted in phosphate buffer and antibiotic release was measured by agar diffusion. High levels of release (1512+/-318 to 1937+/-336 microg/ml) were obtained for 12 to 20 days depending on the dosage of vancomycin. Additionally, bone infection was induced in the tibia of 30 New Zealand white rabbits by injecting either a methicillin-resistant S. aureus strain (MRSA) or a S. aureus strain with a small colony variant (SCV) phenotype. After 3 weeks (chronic infection), all animals were treated by debridement. Moreover, group 1 (challenged with SCVs) and group 2 (challenged with MRSA) were treated by filling the marrow with HAC alone, whereas in groups 3 (SCVs) and 4 (MRSA) the marrow was filled with HAC/vancomycin (160 mg/g). After 6 weeks all animals were sacrificed. At 3 weeks, pathogens were detected in 24 of 30 animals. All swabs of the control groups, positive for S. aureus on day 21, were also positive on day 42 and S. aureus strains recovered were shown to be clonal to the strains used for induction of osteomyelitis. By contrast, no growth was found in the treatment group following 7 days of incubation in BHI bouillon. HAC/vancomycin-treated animals showed no histological evidence of infection on day 42. In the other groups, different stages of chronic osteomyelitis were found histologically. No local or systemic side effects due to HAC or vancomycin were seen. HAC is an effective carrier material for antibiotic compounds even in refractory infections due to MRSA or S. aureus SCVs.
Joosten
Uwe
U
Department of Trauma and Orthopaedic Surgery, Munarienhospital Osnabrück, Johannisfreiheit 2-4, 49074 Osnabrück Germany. unfallchirurgie@mhos.de
Joist
Alexander
A
Gosheger
G
G
Liljenqvist
Ulf
U
Brandt
Burkhard
B
von Eiff
Christof
C
D000818:Animals; D001682:Biological Availability; D001835:Body Weight / Q000187:drug effects; D001843:Bone Cements / Q000737:chemistry*; D002097:C-Reactive Protein / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry; D007958:Leukocyte Count; D010019:Osteomyelitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus; D016896:Treatment Outcome; D014640:Vancomycin / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
D001843:Bone Cements; D004337:Drug Carriers; D014640:Vancomycin; D002097:C-Reactive Protein; D017886:Durapatite