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New Data Highlight Tygacil (tigecycline) in Vitro Activity Against Resistant Gram-Negative and Extended-Spectrum Beta-Lactamase-Producing Bacteria

Recently Approved I.V. Antibiotic Demonstrates Expanded Broad Spectrum In Vitro Activity

WASHINGTON, DC -- January 4, 2006 -- Wyeth Pharmaceuticals, a division of Wyeth, presented data from multiple studies that indicate the in vitro activity of Tygacil(R) (tigecycline) against many resistant Gram-negative bacteria, including Extended-Spectrum Beta-Lactamase (ESBL)-producing organisms.

Nearly 99% of Acinetobacter isolates tested were susceptible to Tygacil. These data were among 39 tigecycline abstracts and posters presented at the 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C., U.S.A.

"While much has been reported on the rising rates of Gram-positive organisms, such as methicillin -resistant Staphylococcus aureus (MRSA), there is increasing concern throughout the global medical community over resistant Gram-negative organisms, especially those that are ESBL producing," says David Wu, MD, Assistant Vice President, Clinical Affairs, Global Medical Affairs at Wyeth.

Extended-Spectrum Beta Lactamases, known as ESBLs, are enzymes produced by Gram-negative bacteria that make the organisms drug resistant. Tigecycline is not affected by these enzymes.

Among the data presented are results from the Tigecycline Evaluation Surveillance Trial (T.E.S.T.) demonstrating tigecycline's in vitro activity against commonly encountered Gram-negative bacteria strains, such as Acinetobacter baumannii, that are found in certain community- and hospital- acquired infections. Other data demonstrated tigecycline's in vitro activity against important ESBL-producing bacteria such as Klebsiella pneumoniae and Escherichia coli isolates.

About Resistant Gram-Negative Bacteria
Data have shown a marked rise in resistant strains of Gram-negative bacteria such as Klebsiella, Enterobacter, and E. coli over the past decade. A high rate of ESBL-producing Gram-negative bacteria has been detected in Latin America, and, since 2001, ESBL production has risen sharply in the UK and Ireland. According to data from the Centers for Disease Control and Prevention, Klebsiella pneumoniae isolates resistant to certain antibiotics have increased in the U.S. within the past few years.

About Tygacil
Tygacil, a first-in-class glycylcycline, is an I.V. antibiotic with an expanded broad spectrum of in vitro activity against Gram positives, Gram negatives, anaerobes, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE); Tygacil is unaffected by Extended- Spectrum Beta Lactamases (ESBLs).

Tygacil is indicated for the treatment of adults with:

Complicated skin and skin structure infections (cSSSI) caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, and Bacteroides fragilis.

Complicated intra-abdominal infections (cIAI) caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

Tygacil was approved in the United States on June 16, 2005, and can be used as an empiric monotherapy to treat a variety of cIAI and cSSSI, both hospital- and community-acquired, including complicated appendicitis, infected burns, intra-abdominal abscesses, deep soft-tissue infections, and infected ulcers.

In addition, Tygacil has been shown to have in vitro activity against the indicated organisms above and the following organisms: Enterococcus avium, Enterococcus casseliflavus, Enterococcus faecalis (vancomycin-resistant isolates), Enterococcus faecium (vancomycin-susceptible and -resistant isolates), Enterococcus gallinarum, Listeria monocytogenes, Staphylococcus epidermidis (methicillin-susceptible and -resistant isolates), Acinetobacter baumannii, Aeromonas hydrophila, Citrobacter koseri, Enterobacter aerogenes, Pasteurella multocida. The clinical significance of in vitro activity is unknown.

Tygacil provides clinicians with a novel, expanded broad-spectrum antibiotic option that can be used at the onset of treatment when the specific bacteria present are not yet known. In addition, Tygacil does not require dosage adjustment in patients with impaired renal function, and is conveniently dosed every 12 hours.

Important Tygacil Safety Information
* To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tygacil and other antibacterial drugs, Tygacil should be used only to treat infections proven or strongly suspected to be caused by susceptible bacteria.

* Tygacil is contraindicated in patients with known hypersensitivity to tigecycline.

* Tygacil should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics.

* Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, pancreatitis, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hypophosphatemia).

* In clinical trials, the most common treatment-emergent adverse events in patients treated with Tygacil were nausea (29.5%) and vomiting (19.7%).

* Tygacil may cause fetal harm when administered to a pregnant woman.

* The safety and effectiveness of Tygacil in patients below age 18 and lactating women have not been established.

* Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening.

* Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective.

* The use of Tygacil during tooth development may cause permanent discoloration of the teeth. Tygacil should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated.

* Prothrombin time or other suitable anticoagulant test should be monitored if Tygacil is administered with warfarin.

* Monotherapy should be used with caution in patients with clinically apparent intestinal perforation.

* In patients with severe hepatic impairment (Child Pugh C), the initial dose of Tygacil should be 100 mg followed by 25 mg every 12 hours. Patients should be treated with caution and monitored for treatment response.

* The following drugs should not be administered simultaneously through the same Y-site as Tygacil: amphotericin B, chlorpromazine, methylprednisolone, and voriconazole.


SOURCE: Wyeth

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