International Journal of Antimicrobial Agents 28 (2006) 460–464 Short communication Activity of tigecycline in the treatment of acute Burkholderia pseudomallei infection in a murine model Marshall Feterl a , Brenda Govan a,∗ , Cathy Engler b , Robert Norton b,c , Natkunam Ketheesan a,b a School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Qld 4811, Australia b School of Medicine, James Cook University, Townsville, Qld 4811, Australia c Queensland Health Pathology Services, Townsville Hospital, Qld 4811, Australia Received 5 June 2006; accepted 20 July 2006 Abstract Burkholderia pseudomallei is the causative agent of melioidosis. Standard therapy includes ceftazidime alone or in combination with co- trimoxazole. Tigecycline, a novel agent, has displayed activity against B. pseudomallei. We evaluated the in vivo efficacy of tigecycline using a murine model of melioidosis. Mice were infected with either a high or low virulence B. pseudomallei isolate followed by administration of antibiotics alone or in combination (tigecycline, ceftazidime, tigecycline plus ceftazidime) for 7 days. Bacterial loads were assessed up to 7 days and survival was determined up to 7 days post infection. Tigecycline in combination with ceftazidime was the most effective and conferred the lowest mortality, suggesting the use of this new agent in B. pseudomallei infection. © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Burkholderia pseudomallei; Tigecycline; Therapy 1. Introduction Burkholderia pseudomallei, a Gram-negative soil sapro- phyte, is the causative agent of melioidosis. Endemic foci of the disease are typically found in tropical and subtropical regions of Southeast Asia and Australia [1]. Acute infection is associated with a high incidence of mortality and a slow to minimal response to antibiotic therapy following primary infection. Treatment of the acute septicaemic form of the dis- ease involves the use of ceftazidime or the carbapenem class of antimicrobials. Despite the initiation of intensive therapy, mortality remains at 21% in septicaemic patients with melioi- dosis in Australia [2] and up to 40% in Thailand [3]. The mortality associated with severe melioidosis coupled with the intrinsic antibiotic resistance of the organism has focused attention on the need to develop novel treatment protocols. ∗ Corresponding author. Present address: School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Qld 4811, Aus- tralia. Tel.: +61 7 4781 5607; fax: +61 7 4779 1526. E-mail address: Brenda.govan@jcu.edu.au (B. Govan). Tigecycline, the newest member of the glycylcycline class, has displayed a broad spectrum of activity against clinically important pathogens, including methicillin-, penicillin- and vancomycin-resistant organisms [4]. Tigecycline has been found to be active against 98% of the B. pseudomallei strains tested using standard in vitro susceptibility assays [5]. There- fore, tigecycline has potential for use as a therapeutic agent for melioidosis. In this investigation, we evaluated the in vivo efficacy of tigecycline alone and in combination with ceftazidime using the well characterised murine model of melioidosis [6]. 2. Materials and methods 2.1. Origin of B. pseudomallei isolates Fifty-five clinical B. pseudomallei isolates were obtained from the Townsville Culture Collection. The identity of the isolates was determined by colonial morphology on Ashdown agar and API 20NE (bioM´ erieux, La Balme, 0924-8579/$ – see front matter © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2006.07.022