Use of a bioabsorbable polymer for the delivery of ofloxacin during experimental osteomyelitis treatment.
This study was performed to investigate the potential utility of ofloxacin-impregnated bioabsorbable polymers for osteomyelitis therapy. Pseudomonas aeruginosa osteomyelitis was induced in 48 New Zealand White rabbits. Four weeks after infection, the animals were randomized to one of four treatment groups: drug-free polymer, ofloxacin polymer, systemic ofloxacin, or ofloxacin polymer plus systemic ofloxacin. Twenty-eight days later, radiographs were taken of the affected area, the animals were killed, and bone was obtained for histologic evaluation, culture, and determination of ofloxacin concentrations. The percentage of sterile bone cultures was 33, 83, 75, and 91 for the groups treated with drug-free polymer, ofloxacin polymer, systemic ofloxacin, and ofloxacin polymer plus systemic ofloxacin, respectively. When compared with the drug-free polymer, both the ofloxacin polymer and the ofloxacin polymer plus systemic ofloxacin significantly improved the rate of sterilization. The mean concentrations of the drug in bone for the groups treated with ofloxacin polymer, systemic ofloxacin, and ofloxacin polymer plus systemic ofloxacin were 34.9 (range: 2-160), 1.9 (range: 0.8-3), and 26.0 microg/g (range: 9-100 microg/g), respectively. These data suggest that the DL-lactide:glycolide polymer studied is a suitable vehicle for the delivery of high local concentrations of ofloxacin and that these concentrations result in eradication of the bacterial pathogen in this rabbit model.
Nie
L
L
Department of Orthopedic Surgery, Hartford Hospital, Connecticut 06102, USA.
Nicolau
D P
DP
Tessier
P R
PR
Kourea
H P
HP
Browner
B D
BD
Nightingale
C H
CH
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D005260:Female; D015242:Ofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010019:Osteomyelitis / Q000188:drug therapy*; D014677:Pharmaceutical Vehicles; D011108:Polymers; D011817:Rabbits
D000890:Anti-Infective Agents; D014677:Pharmaceutical Vehicles; D011108:Polymers; D015242:Ofloxacin