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JAC Advance Access published online on October 14, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh465
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received June 13, 2004
Revised September 14, 2004
Accepted September 14, 2004

Original article

Treatment of experimental osteomyelitis by liposomal antibiotics

Ashraf A. Kadry 1*, Saleh A. Al-Suwayeh 2, Adel R. A. Abd-Allah 3, and Mohsen A. Bayomi 2

1 Microbiology Division, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Pharmaceutics Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia
2 Pharmaceutics Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia
3 Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia

* To whom correspondence should be addressed. E-mail: kadry57{at}yahoo.com.


  Abstract

Objectives: Traditional antibiotic therapy of staphylococcal osteomyelitis by a single drug or a drug combination is ineffective in producing complete sterilization of infected bones. The aim of this study was to develop a non-traditional delivery system of antibiotics for treatment of chronic experimental osteomyelitis.

Methods: In the current work, ciprofloxacin and vancomycin were encapsulated in a cationic, anionic or neutral liposomal formulation. For prolonged circulation in serum, liposomal dispersions (<100 nm in diameter) were sonicated for different times (20, 40, 60 or 80 s), and tested for antibacterial activities.

Results and conclusions: Liposomes sonicated for 40 s gave the highest antibacterial activities in vitro. Since cationic liposomes trapped the highest percentage of antibiotics, and enhanced antibacterial activity above that of the free drugs, they were used for therapeutic trials to treat chronic staphylococcal osteomyelitis induced in rabbits. Therapeutic trials with antibiotics given intravenously revealed that, free ciprofloxacin or vancomycin given alone for 14 days was ineffective in sterilizing bone. Combination therapy with free ciprofloxacin and vancomycin for 14 days was more effective. However, this group showed renal dysfunction and severe diarrhoea, which resulted in loss of 33.3% of treated animals. Treatment with liposomal forms of either drug for 7 days was ineffective. Meanwhile, combination therapy in liposomal form for 7 days was more effective. Complete sterilization of bone tissues on cultures (100% cure) was obtained only in the group treated for 14 days with the combination of both drugs in liposomal form. Moreover, liposomal formulations showed much lower nephrotoxicity and a lower incidence of severe diarrhoea than that induced by free drugs.

Keywords: S. aureus; liposomes; ciprofloxacin; vancomycin.
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