NEW YORK (Reuters Health) – The authors of a systematic review and meta-analysis of relevant studies encourage clinicians to exercise good judgment in using the injectable antibiotic tigecycline due to an increased risk of adverse events and death.

Tigecycline (Tygacil; Wyeth Pharmaceuticals) is an efficacious antibiotic in appropriate patients with severe infections, but clinical use should be “prudent,” write Yun Cai and colleagues of the PLA General Hospital, Beijing, People’s Republic of China, in the December 20 online issue of Antimicrobial Agents and Chemotherapy.

Tigecycline — a first-in-class expanded broad-spectrum glycylcycline antibiotic — is approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated intra-abdominal infections, complicated skin and skin structure infections and community acquired pneumonia.

It has also been shown to be effective for the treatment of hospital-acquired and ventilator-associated pneumonia and bacteremia, sepsis with shock and urinary tract infections. It is active against pathogens that are susceptible and resistant to other antibiotics.

In several comparative randomized clinical trials, tigecycline proved at least as effective as comparator antibiotics, but the results were “not completely consistent” and bias could not be ruled out, Cai and colleagues say. This prompted them to conduct a meta-analysis of eight high-quality randomized controlled trials.

Their aim was to clarify whether use of tigecycline is associated with improved outcomes in comparison to the use of other empirical antibiotic regimens reported to have “good efficacy” for complicated skin and skin structure infections, complicated intra-abdominal infections, community-acquired pneumonia, and other infections caused by multidrug-resistant pathogens.

They found that tigecycline monotherapy was clinically as effective as vancomycin and aztreonam for complicated skin and skin structure infections, impenam/cilastin or ceftriazone plus metronidazole for complicated intra-abdominal infections, and levofloxacin for community-acquired pneumonia. This was true in both the clinically evaluable population and the intention-to-treat population.

Tigecycline monotherapy also had similar microbiological treatment success rates as comparator antibiotic regimens.

The researchers defined clinical treatment success as complete resolution or substantial improvement of symptoms and signs of infection and no further antimicrobial therapy or surgical intervention for infection. They defined microbiological treatment success as eradication of baseline pathogens or as presumed eradication based on the clinical outcomes when post-treatment cultures were not performed.

Despite the similar efficacy, an increased incidence of all adverse events (including fever, headache, infection, abdominal pain, chills, and pain), and in particular those involving the digestive system, was seen with tigecycline treatment. Mirroring prior studies, nausea and diarrhea were the most commonly reported adverse events.

Taken together, the data highlight the need for clinicians to monitor for signs and symptoms of digestive problems in tigecycline-treated patients, the researchers say.

The meta-analysis also showed numerically but not significantly higher mortality rates with tigecycline relative to comparator regimens, both for all-cause mortality and possibly-drug related mortality.

In a September 2010 safety alert to clinicians on their website, the U.S. FDA noted an increased risk of death associated with the use of tigecycline compared with other antibiotics used to treat a variety of serious infections for which tigecycline is approved.

The increased mortality risk, the agency reported, was seen most clearly in patients treated for hospital-acquired pneumonia, especially ventilator-associated pneumonia, but was also seen in patients with complicated skin and skin structure infections, complicated intra-abdominal infections and diabetic foot infections.

Specifically, they cited data from a pooled analysis of 13 trials in which patients were given tigecycline for both approved and unapproved indications. In the analysis, 150 of 3,788 patients treated with tigecycline died compared with 110 of 3,646 patients who received other antibiotics (4.0% vs 3.0%). The adjusted risk difference for all-cause mortality based on a random effects model was 0.6% between tigycycline and comparator antibiotics.

Based on their analysis, Cai and colleagues encourage clinicians to “carefully consider” the benefits and risks of tigecycline before using it.

Reference:

Effectiveness and safety of tigecycline for the treatment of infectious disease: a systematic review and meta-analysis

Antimicrob Agents Chemother 2010. Published online December 20, 2010.