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Tigecycline in Vitro Activity Against Often Difficult to Treat Pathogens: Presented at ECCMID

By Chris Berrie

NICE, FRANCE -- April 4, 2006 -- The activity of the new glycylcycline antibiotic tigecycline (GAR-936) against a wide spectrum of pathogens shows promise for enhanced coverage of serious nosocomial/community pathogens, according to a study presented here at the 16^th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

Tigecycline acts via inhibition of protein synthesis, through its binding to the 30S ribosomal subunit, and although seen as a new glycylcycline agent, "Essentially, tigecycline is a modification of an older tetracycline called minocycline, which was itself based on tetracycline originally," said researcher Robert E. Badal, director, New Business and Project Development, International Health Management Associates, Schaumburg, United States.

Although tigecycline was developed to provide activity against tetracycline and multi-drug-resistant Gram-positive pathogens, it has demonstrated significant activity against aerobic and anaerobic Gram-positive and -negative microorganisms, he said during his presentation on April 2^nd.

As tigecycline resistance is infrequent and difficult to induce in the laboratory, Dr. Badal and his colleagues conducted their study to expand the agent's pathogen profile through a better definition of its in vitro activity against a number of clinical isolates collected from study centres across Asia and the Pacific Rim regions.

All of the isolates tested (N = 1088) were derived from blood, respiratory tract, urine, skin, wound and other defined sources, with only one isolate used per patient. Isolates, which were collected from January 2004 to January 2006, were identified to genus and species, and tested in 6 study centres across Asia and the Pacific Rim.

The custom broth microdilution panels of the agents tested comprised: tigecycline, amikacin, amoxclav, ampicillin, cefepime, ceftazidime, ceftriaxone, imipenem, levofloxacin, minocycline and piptazo.

The panel of pathogens included a range of Enterobacteriaceae (n = 458), non-fastidious Gram-positive pathogens (n = 339), fastidious respiratory pathogens (n = 157), and Acinetobacter baumannii (n = 75) and Pseudomonas aeruginosa (n = 118).

The broad spectrum of activity of tigecycline was seen in its inhibition of 98.2% of all of the Enterobacteriaceae and 96.9% of the ESBL-producing isolates at a MIC of 2 mcg/mL. Similarly, it showed potent activity against A. baumannii, with its limited activity against P. aeruginosa being similar to that seen for other tetracyclines.

Tigecycline also showed potent inhibition of Staphylococcus aureas, Enterococcus faecium and Streptococcus pneumoniae, with little effects seen for methicillin-, vancomycin- and penicillin-resistant isolates, respectively. Its potent activity was also unchanged by beta-lactamase positivity of Haemophilus influenza.

Thus, in presenting the wide range of data obtained across the full spectrum of pathogens from these clinical isolates, and with a consideration of the further emerging clinical relevance of tigecycline, Mr. Badal indicated that this suggests that tigecycline is a promising agent for the treatment of serious infections caused by the most commonly encountered nosocomial and community-acquired pathogens.

"If you are in an institution with a severe resistance problem to a certain agent, without knowing if you have a Gram-positive or Gram-negative pathogen, [tigecycline] would be one of your top choices to consider, for the initial therapy at least, because you can be reasonably confident that it will take care of whatever [pathogen] you are likely to have come up with," he said.

Wyeth Pharmaceuticals provided financial support for this study.


[Study title: Tigecycline in Vitro Activity Against Often Difficult to Treat Pathogens From Centres in Asia/ Pacific Rim – T.E.S.T. Programme 2006. Abstract P494]

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