Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi Louis Ates a, c , Christa Hanssen-H ¨ ubner a , Douglas E. Norris b , Dania Richter d , Peter Kraiczy a , Klaus-Peter Hunfeld c,Ã a Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt/Main, Germany b The Harry W. Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland c Institute of Laboratory Medicine, Northwest Medical Centre, Academic Teaching Hospital, Medical Faculty, University of Frankfurt, Steinbacher Hohl 2–26, D-60488 Frankfurt/Main, Germany d Abt. Parasitologie, Institut f¨ ur Pathologie, Charite´ Universit¨ atsmedizin Berlin, Malteserstrasse 74–100, 12249 Berlin, Germany article info Article history: Received 23 August 2009 Received in revised form 22 November 2009 Accepted 23 November 2009 Available online 7 January 2010 Keywords: Borrelia burgdorferi Tetracyclines Tigecycline Susceptibility testing Lyme borreliosis abstract Tigecycline is a new glycylcycline that has recently been revealed to be very effective in vitro against a variety of Gram-negative and Gram-positive bacteria including multi-drug resistant microorganisms. Using a standardized microdilution susceptibility testing method, we determined the minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) of tigecycline, in parallel with doxycycline, tetracycline, and other antibiotic agents relevant for Lyme borreliosis treatment such as ceftriaxone and cefotaxime. The activity of all agents against 16 different Borrelia isolates belonging to all borrelial genospecies known to be pathogenic for humans was investigated and analyzed under standardized conditions. The overall rank order of MIC 90 s was tigecycline ( r0.016 mg/L) 4 ceftriaxone (0.03 mg/L) 4 cefotaxime ( r0.125 mg/L) 4 doxycycline (0.25 mg/L) 4 tetracycline (0.25 mg/L). The rank order of MBC 90 s was tigecycline (0.5 mg/L) 4 ceftriaxone (2 mg/L) 4 tetracycline (16 mg/L) 4 doxycycline (16 mg/L) 4 cefotaxime ( 416 mg/L). High in vitro activity of the new glycylcycline against Borrelia was further substantiated by time-kill experiments performed with B. afzelii isolate EB1. Parallel testing of tigecycline and ceftriaxone demonstrated a bacteriostatic effect for 0.016 mg/L of tigecycline and for 0.03 mg/L for ceftriaxone after 72 h of incubation. Moreover, tigecycline was bactericidal at a concentration of 0.25 mg/L showing a 43 log 10 unit reduction of the initial inoculum, whereas for ceftriaxone a concentration of 2 mg/L was needed. & 2009 Elsevier GmbH. All rights reserved. Introduction Lyme borreliosis is a vector-borne disease that is transmitted by ixodid ticks and is caused by the spirochete Borrelia burgdorferi sensu lato (s.l.) complex. The 5 genospecies that are currently considered to be human pathogens are B. burgdorferi sensu stricto (s.s.), B. afzelii, B. garinii, and B. spielmanii, and the proposed but not yet validated novel species B. bavariensis (Margos et al., 2009). In Europe, the incidence of Lyme borreliosis is estimated to range from 3.9 to 168/ 100,000 (Hunfeld et al., 2005; Stanek et al., 1996). The disease can manifest itself progressively as a multisystem disorder exhibiting a large variety of clinical symptoms (Steere, 2001). Early on in the course of the infection, a bull’s-eye rash called erythema migrans is the most common disease manifestation appearing in 80–90% of the patients. If left untreated, however, the infection may cause neurological disorders and late manifestations including acroderma- titis chronica atrophicans or chronic arthritis (Steere, 2001; Weinstein and Britchkov, 2002). Lyme borreliosis is frequently treated by orally administered doxycycline or intravenous ceftriaxone, which appear to be equally effective in European patients (Ljostad et al., 2008; Loewen et al., 1999). Other often administered antibiotics are penicillin, amoxicillin, cefuroxime, cefotaxime, and tetracycline. Although these drugs have been reported to be clinically effective in the majority of cases under controlled study conditions, treatment failures have been repeatedly published for most of these compounds (Hodzic et al., 2008; Hunfeld et al., 2005; Miklossy et al., 2008; Preac-Mursic et al., 1989). Tigecycline, a glycylcycline and structural analog of minocycline is a relatively new antibiotic agent that has been found to be effective against many Gram-positive and Gram-negative bacteria including multi-drug resistant pathogens such as ESBL-producing enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multi-drug resistant Acinetobacter baumanii (Jamal et al., 2009; Zhanel et al., ARTICLE IN PRESS Contents lists available at ScienceDirect journal homepage: www.elsevier.de/ttbdis Ticks and Tick-borne Diseases 1877-959X/$ - see front matter & 2009 Elsevier GmbH. All rights reserved. doi:10.1016/j.ttbdis.2009.11.004 Ã Corresponding author. Tel.: + 49 69 7601 3252; fax: + 49 69 7601 3907. E-mail address: K.Hunfeld@em.uni-frankfurt.de (K.-P. Hunfeld). Ticks and Tick-borne Diseases 1 (2010) 30–34