title: Local treatment of experimental Pseudomonas aeruginosa osteomyelitis with a biodegradable dilactide polymer releasing ciprofloxacin.
abstract: A biodegradable system of poly-D,L-dilactide releasing ciprofloxacin was assessed in a Pseudomonas aeruginosa osteomyelitis model after inoculation of the test pathogen into the left tibia of 76 New Zealand White rabbits; 31 were controls (group A), and 45 were implanted with the polymer at the infection site (group B). The rabbits were killed on a weekly basis, and cancellous bone was harvested for histopathology and for estimation of bacterial growth and the concentrations of ciprofloxacin. Tibial X ray was performed immediately before the animals were killed. The total number of fistulas with purulent discharge that developed after inoculation of the pathogen was counted, and fistulas with purulent discharge were found in 16 animals in group A (51.6%) and 3 animals in group B (6.7%) (P < 0.0001). The animals in group A had a profound loss of body weight compared to the animals in group B. The main radiological finding was the presence of sequestra in 25 animals (80.6%) in group A and 6 animals in group B (13.3%) (P < 0.0001). The bacterial load in group B was significantly reduced compared to that in group A, possibly due to the prolonged local antibiotic release at concentrations exceeding even 80 times the MIC for the test pathogen. The histology of animals killed after week 49 revealed a mild inflammatory reaction accompanied by diffuse fibrosis and new bone formation in group A animals and the presence of small polymer particles in group B animals. It is concluded that the system described achieved eradication of the pathogen, accompanied by clinical and radiologically confirmed benefits, so this treatment may be a candidate for the management of difficult orthopedic infections.
authors.affiliation: 4th Department of Internal Medicine, Attikon University Hospital, 1 Rimini Str., Athens 124 62, Greece. kyrkanel@yahoo.gr
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Kanellakopoulou
authors.forename: George C
authors.initials: GC
authors.lastname: Thivaios
authors.forename: Maria
authors.initials: M
authors.lastname: Kolia
authors.forename: Ismini
authors.initials: I
authors.lastname: Dontas
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakopoulou
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Dounis
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Andreas
authors.initials: A
authors.lastname: Andreopoulos
authors.forename: Panayotis
authors.initials: P
authors.lastname: Karagiannakos
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004343:Drug Implants; D006801:Humans; D008297:Male; D010019:Osteomyelitis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011091:Polyesters; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D011817:Rabbits; D013977:Tibia
chemical_list: D000900:Anti-Bacterial Agents; D004343:Drug Implants; D011091:Polyesters; C033616:poly(lactide); D002939:Ciprofloxacin