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In Vitro Activity of Tigecycline Against Rapidly Growing Mycobacteria
Abstract and Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University, School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Dr. Winslow serves as a consultant for Siemens Diagnostics, and is on the speaker's bureau for Boehringer-Ingelheim and GSK.
Synopsis: The in vitro activities of tigecycline and 10 other antimicrobials were examined against 165 clinical isolates of rapidly growing mycobacteria. Tigecycline was the most active agent studied and inhibited all strains at ≤ 1 ug/mL.
Source: Fernandez-Roblas R, et al. In vitro activities of tigecycline and 10 other antimicrobials against non-pigmented rapidly growing mycobacteria. Antimicrob Agents Chemother. 2008;52:4184-4186.
In this study, 165 clinical isolates of rapidly growing mycobacteria (including M. abscessus, M. chelonae, M. peregrinum, M. fortuitum, M. mucogenicum, M. mageritense, M. alvei, M. smegmatis, M. porcinum, M. septicum, and M. wolinskyi) were tested for in vitro susceptibility to tigecycline and 10 other antibiotics (erythromycin, clarithromycin, azithro-mycin, ciprofloxacin, levofloxacin, amikacin, tobra-mycin, cefoxitin, doxycycline, and trimethoprim-sulfamethoxazole) using a broth microdilution method. All isolates were inhibited in vitro by ≤ 1 ug/mL of tigecycline. Against some of the more common rapidly growing mycobacterial species, impressively low MICs were seen (M. abscessus MIC50 0.06 ug/mL, M. chelonae MIC50 0.12 ug/mL, M. fortuitum MIC50 ≤ 0.03 ug/mL).
Rapidly growing mycobacteria are not uncommonly encountered as significant pathogens by infectious disease clinicians. Over my own 30-year career, I have been involved in the management of numerous serious infections due to rapidly growing mycobacteria. In addition to the commonly encountered skin and soft-tissue infections due to local inoculation of tissue with these organisms, more complicated infections included patients who had developed sternotomy infections possibly related to contaminated bone wax, a handful of progressive pulmonary infections, orthopedic device-related infections, and even infections of indwelling venous lines. The last case I saw just a couple of months ago was a child with acute lymphoblastic leukemia who developed bacteremia due to M. chelonae from an infected tunneled central-venous catheter.
Obviously, removal of infected devices is of paramount importance, but antimicrobial therapy is often critically important as well. While there are no data from prospective, controlled trials to support the use of any given antimicrobial agent in the treatment of rapidly growing mycobacterial infections, most clinicians who have treated these infections believe that in vitro susceptibility testing is useful in guiding the selection of appropriate antimicrobials. The newer macrolide antibiotics (clarithromycin and azi-thromycin) have become mainstays of treatment of rapidly growing mycobacterial infections, but these agents are not uniformly active. In fact, some isolates of M. fortuitum in the present study had MIC90 values of > 64 ug/mL with azithromycin and 16 ug/mL with clarithromycin, levels unlikely to be achieved with normal dosing. Tigecycline is a drug with which I honestly have little personal clinical experience. However, it is definitely an agent that we will use with increasing frequency in the future, particularly as we encounter multi-drug resistant pathogens such as Acinetobacter baumannii. Tigecycline's dramatic activity in vitro against rapidly growing mycobacteria should be kept in mind, and this agent should be considered as part of our arsenal to treat infections caused by these organisms.