Recommendations for managing Aspergillus osteomyelitis and joint infections based on a review of the literature Andrew Kirby a, * , Ibrahim Hassan a , James Burnie a,b a Department of Microbiology, Clinical Sciences Building, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK b NeutecPharma PLC, Clinical Sciences Building, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK Accepted 18 August 2005 Available online 18 October 2005 KEYWORDS Aspergillus; Osteomyelitis; Anti-fungal pharmacology Summary Objectives: To produce recommendations for the management of Aspergillus osteomyelitis and joint infections. Methods: Published literature was surveyed to identify both case reports of Aspergillus osteomyelitis and joint infections and anti-fungal pharmacology of anti-fungal agents. Included in the pharmacological review was an assessment of new and investigational anti-fungals to consider their potential role in the management of this infection. Results: Successful treatments, identified from the cases reviewed, were based on combination anti-fungal therapy with one agent having good bone penetration and one having reliable anti-Aspergillus activity. Conclusions: For the management of serious Aspergillus osteomyleitis/joint infections amphotericin B in combination with flucytosine is recommended. A number of second line treatment combinations are identified. Monotherapy is appropriate with an azole in clinically stable patients. Q 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved. Introduction Osteomyelitis is the fourth most common site of infection for aspergillosis following pulmonary, sinus and cerebral infections. 1 Bone and joint infections occur mainly as a result of dissemination in immunocompromised patients. Infections of bone and joint caused by Aspergillus are recognised as being difficult to treat and often requiring prolonged medical therapy. Medical options for treatment include: Amphotericin B (AMB) and its lipid formulations liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC); triazoles: Itraconazole and voriconazole; flucytosine and rifampicin. New and developmental anti-fungals Journal of Infection (2006) 52, 405–414 www.elsevierhealth.com/journals/jinf 0163-4453/$30.00 Q 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2005.08.016 * Corresponding author. Address: 232 Berry Hill Lane, Mans- field, Notts NG18 4JP, UK. Tel.: C44 1623 627344. E-mail address: kirbyandrew@doctors.org.uk (A. Kirby).