Comparison of the In Vitro Activity of the Glycylcycline Tigecycline (Formerly GAR-936) with Those of Tetracycline, Minocycline, and Doxycycline against Isolates of Nontuberculous Mycobacteria

Abstract

We compared the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, doxycycline, and minocycline by broth microdilution against 76 isolates belonging to seven species of rapidly growing mycobacteria (RGM) and 45 isolates belonging to five species of slowly growing nontuberculous mycobacteria (NTM). By using a resistance breakpoint of >4 g/ml for tigecycline and >8 g/ml for tetracycline, all RGM were highly susceptible to tigecycline, with inhibition of 50% of isolates at <0.12 g/ml and inhibition of 90% of isolates at 0.25 g/ml for Mycobacterium abscessus and inhibition of both 50 and 90% of isolates at <0.12 g/ml for M. chelonae and the M. fortuitum group. The MICs of tigecycline were the same for tetracycline-resistant and -susceptible strains, and RGM isolates were 4-to 11-fold more susceptible to tigecycline than to the tetracyclines. In contrast, no slowly growing NTM were susceptible to tigecycline, and isolates of M. marinum and M. kansasii were less susceptible to this agent than to minocycline. This new antimicrobial offers exciting therapeutic potential for the RGM, especially for isolates of the M. chelonae-M. abscessus group, against which the activities of the currently available drugs are limited.Treatment of infections due to rapidly growing mycobacteria (RGM) remains difficult, in part because of resistance to the first-line antituberculous agents and also in part because of resistance to almost all antibacterial agents (3, 21). The only drugs with activity against all three major pathogenic species (Mycobacterium chelonae, M. abscessus, and M. fortuitum) are amikacin (13) and clarithromycin (4). In vitro studies with prior glycylcyclines (N,N-dimethylglycylamido-minocycline ) have shown this class of agents to be extremely active against this group of organisms, including tetracycline-resistant strains (1, 3). The latest glycylcycline, tigecycline (GAR-936), has shown excellent activity against many tetracycline-resistant bacterial species (1, 8, 17; R. N. Jones, A. C. Gales, L. M. Deshpande, D. M. Johnson, and D. J. Biedenbach, poster 407, 39th Intersci. Conf. Antimicrob. Agents Chemother., 1999). With this in mind, we undertook a comparative study of the in vitro susceptibilities of multiple species of nontuberculous mycobacteria (NTM) to tetracycline, minocycline, doxycycline, and tigecycline.(A portion of this study was presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, 16 to 19 December 2001, Chicago, Ill.) MATERIALS AND METHODSOrganisms. Clinical mycobacterial isolates submitted to the Mycobacterial/ Nocardia Laboratory at The University of Texas Health Center for susceptibility testing and selected reference strains were chosen for testing. Clinical isolates were tested upon receipt in the laboratory, while the reference strains were taken from frozen stocks stored at Ϫ70°C in Trypticase soy broth with 15% glycerol. We also tested 45 isolates of slowly growing NTM that included 11 M. avium complex, 10 M. ...

Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis

“…Tigecycline (GAR-936) is a new semisynthetic glycylcycline (tetracycline analogue) and is effective against intra-abdominal, skin and soft-tissue infections caused by staphylococci, enterococci or streptococci, as well as most Enterobacteriaceae and anaerobic pathogens [29,52]. Tigecycline is effective against rapid-growing mycobacteria (Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium abscessus) but showed no activity against more slow-growing mycobacteria (M. tuberculosis) [52,53].…”

Clinical characteristics of nontuberculosis mycobacterial pulmonary infection in immunocompetent adult patients: 6 cases

“…Although combination therapies including amikacin and clarithromycin are generally used, the treatment of Mycobacterium abscessus can be very difficult due to development of high resistance against antituberculous drugs (9). Some studies reported the efficiency of tigecycline in the treatment of M. abscessus (10). In another study, patients with M. abscessus pulmonary disease who were treated with multi-drug antibiotic therapy and surgery or antibiotic therapy alone had similar clinical outcomes (11).…”

Non-Tuberculous Mycobacterial Lung Diseases: Retrospective Analysis of 42 Cases

“…9 Tigesiklinin M. abscessus tedavisinde etkin olduğunu gösteren bazı araştırmalar bulunmaktadır. 29 Leber ve ark. tarafından gerçekleş-tirilen çok-değişkenli analizde, M. abscessus enfeksiyonu, intravenöz tedavi ve M. xenopi enfeksiyonunun, aylık tedavi maliyetlerinde artış ile yakından ilişkili olduğu gösterilmiştir.…”