Tigecycline In-vitro Surveillance in Taiwan (TIST)

Abstract

The last half of the 20th century has seen significant progress in the development of antibacterial agents. This progress fostered the perception that bacterial diseases were more readily cured than any other major disorder. However, in the last decade, the emergence of multidrug-resistant organisms has resulted in serious public health implications. Currently, resistance has spread to previously susceptible organisms, and some organisms are essentially resistant to all approved antibacterial agents. In Taiwan, the strikingly high prevalence of resistance to macrolides and streptogramin in clinical isolates of Grampositive bacteria correlates with the widespread use of these agents in the medical and farming communities, respectively. The increasing rate of enterococci that are resistant to glycopeptides does parallel the high use of glycopeptides and extended-spectrum b-lactams in hospitals. The evolving problem of extended-spectrum b-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates is substantial, and some unique enzymes have been reported. Recently, some Gram-negative bacteria (e.g., Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) that are resistant to nearly all available antimicrobial agents (susceptible to only polymyxin B or E [colistin] or tigecycline) have become widespread in the hospitals. Tigecycline is a glycylcycline antibiotic and an analog of the semisynthetic tetracycline, minocycline. This agent was developed in order to restore therapeutic utility to this tetracycline class by overcoming tetracycline resistance mechanisms. It demonstrates a broad spectrum of antibacterial activity by inhibiting multiple resistant Gram-positive, Gramnegative, anaerobic, and atypical bacteria. Tigecycline does not demonstrate significant in-vitro activity against Pseudomonas aeruginosa, Proteus species, or Providencia species. Tigecycline has shown to be efficacious in a variety of animal models of infections. This agent has been approved for clinical use for intra-abdominal infection and skin and skinstructure infections in humans. Investigators from 20 major hospitals in Taiwan are participating in a multi-center surveillance study to demonstrate the in-vitro potency of tigecycline against a wide variety of pathogens from both nosocomial and communityacquired infections, using the disk diffusion method, the Etest (Epsilometer test), and the broth microdilution method in Taiwan. This study will be completed in approximately five years (2006 2010). Up to 20,100 isolates in total (3,000 isolates in year 2006; 3,000 isolates in year 2007; up to 4,700 isolates in each year from 2008 to 2010) will be collected in this study. For the years 2006 2007, each site will collect approximately 150 isolates per year. For the years 2008 2010, each site will collect up to 235 isolates per year. All the isolates are clinically relevant organisms (no duplicates) and must meet the laboratory criteria of “significant pathogens” and be considered the “probable causative agents” of hospitalor communityacquired infections. Minimum inhibitory concentrations (MICs) are determined by the Etest (Epsilometer test) and the disk diffusion method at each site’s laboratory; determination by the broth microdilution method is performed at the central laboratory (National Taiwan University Hospital). The purpose of this study is to determine the in-vitro activity of tigecycline against a variety of resistant Gram-positive and -negative bacteria from patients with various clinical infections in Taiwan. This study also aims to evaluate the suitability of three susceptibility testing methods for routine use in clinical microbiology laboratories.