Tygacil (tigecycline)

Commentary

Tigecycline is an expanded, broad spectrum glycocycline. It is a tetracycline analog with an expanded spectrum. It is indicated for treatment in adults with complicated skin and soft tissue infections, complicated intraabdominal infection and community-acquired pneumonia.

It has activity against gram positive bacteria, most notably MRSA and Enterococcus faecalis as well as anaerobes including Bacteroides fragilis. It is only available in intravenous form.

Patients treated with tigecycline at MD Anderson Cancer Center were reviewed. Almost all patients received tigecycline as a second line agent after failure to respond to other broad spectrum antibiotics. Clinical response was noted in 64% of the patients. No serious adverse effects related to tigecycline were noted. The combination of tigecycline plus an antipseudomonal drug may be appropriate therapy for treating refractory infection in multi drug resistant organisms in cancer patients and stem cell transplant recipients.

Clinical Studies

Khanna N, Inkster T. Methicillin-resistant Staphylococcus aureus hepatic abscess treated with tigecycline. J Clin Pathol. 2008 Aug;61(8):967-8. Epub 2008 May 21.

Tigecycline was used to treat a liver abscess caused by MRSA that was refractory to therapy with standard gram positive antimicrobial agents. Tigecycline was highly active against S. pneumoniae and H. influenza even if resistant in vitro to beta lactam agents.

Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections.  Metan G, Alp E, Yildiz O, Percin D, Aygen B, Sumerkan B.  J Chemother. 2010 Apr;22(2):110-4.

81% of patients infected with carbapenem-resistant acinetobacter species responded to tigecycline. Clinical cure rates were 81.3% for tigecycline and 78.5% for the comparator. Tigecycline was safe and well tolerated in the treatment of secondary bacteremia associated with complicated SSTI, complicated intraabdominal infections and CAP.

Influence of tigecycline on expression of virulence factors in biofilm-associated cells of methicillin-resistant Staphylococcus aureus. Smith K, Gould KA, Ramage G, Gemmell CG, Hinds J, Lang S. Antimicrob Agents Chemother. 2010 Jan;54(1):380-7.

Tigecycline may reduce the expression of important zero factors in S. aureus.

The expression of toxic shock syndrome toxin genes encoding, biofilm development, in genes which encode adhesions which attach to human proteins.

Systemic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Diseases. Cai Y, Wang R, Liang B, Bai N, Liu Y.  Antimicrob Agents Chemother. 2011;55(3):1162-1172.

Tigecycline monotherapy was found to be as effective as standard therapy for skin and soft tissue infections, intraabdominal infections, and community-acquired pneumonia.  It also covered MRSA and VRE effectively. Tigecycline for the treatment of severe Clostridium difficile infection.

Tigecycline for the treatment of severe Clostridium difficile infection.  Larson KC, Belliveau PP, Spooner LM. Ann Pharmacother 2011;

45(7-8):1005-10. 

Tigecycline was used for 6 anecdotal cases of Clostridium difficile colitis refractory to metronidazole and vancomycin.  All were successfully treated with no recurrences.  Given its excellent fecal penetration, tigecycline has potential utility in refractory cases.

Laboratory Studies

Jump RLP, Li Y, Pultz MJ, Kypriotakis G, Donskey CJ. Tigecycline exhibits inhibitory activity against Clostridium difficile in the colon of mice and does not promote growth or toxin production.  Antimicrob Agents Chemother 2011;55(2):546-549.

In a mouse model of Clostridium difficile, tigecycline did not suppress anaerobes nor promote the growth of Clostridium difficile or its toxin as compared to clindamycin. In fact, tigecycline prevented clindamycin-induced Clostridum difficile colitis.

Adverse Drug Reactions and Warnings

FDA Information

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