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Antimicrobial Agents and Chemotherapy, July 2008, p. 2335-2339, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.01360-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Local Treatment of Experimental Pseudomonas aeruginosa Osteomyelitis with a Biodegradable Dilactide Polymer Releasing Ciprofloxacin{triangledown}

Kyriaki Kanellakopoulou,1* George C. Thivaios,2 Maria Kolia,1,2 Ismini Dontas,3 Lydia Nakopoulou,4 Eleftherios Dounis,2 Evangelos J. Giamarellos-Bourboulis,1 Andreas Andreopoulos,5 Panayotis Karagiannakos,3,6 and Helen Giamarellou1

4th Department of Internal Medicine, University of Athens Medical School,1 Department of Orthopaedics, Laikon Athens General Hospital,2 Department of Experimental Surgery and Surgical Research, University of Athens Medical School,3 1st Department of Pathology, University of Athens Medical School,4 Department of Chemical Engineering, National Polytechnic School,5 Academy of Athens, Institute of Biomedical Research, Athens, Greece6

Received 23 October 2007/ Returned for modification 28 December 2007/ Accepted 5 April 2008

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.

* Corresponding author. Mailing address: 4th Department of Internal Medicine, Attikon University Hospital, 1 Rimini Str., Athens 124 62, Greece. Phone: 30210 5831665. Fax: 30210 5326446. E-mail: kyrkanel{at}yahoo.gr

{triangledown} Published ahead of print on 14 April 2008.

Antimicrobial Agents and Chemotherapy, July 2008, p. 2335-2339, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.01360-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kanellakopoulou, K., Panagopoulos, P., Giannitsioti, E., Tsaganos, T., Carrer, D.-P., Efstathopoulos, N., Giamarellos-Bourboulis, E. J. (2009). In Vitro Elution of Daptomycin by a Synthetic Crystallic Semihydrate Form of Calcium Sulfate, Stimulan. Antimicrob. Agents Chemother. 53: 3106-3107 [Abstract] [Full Text]  


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