Is there a future for tigecycline?

Excerpt

In 2010 and 2013, the US Food and Drug Administration (FDA) reported an increased risk of mortality associated with tigecycline use in comparison with other drugs in the treatment of serious infections. The analysis used a pooled group of randomized clinical trials including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), complicated skin and soft tissue infections (cSSTI), complicated intra-abdominal infections (cIAI), and diabetic foot infections [1, 2]. On the basis of the pooled data analysis, the FDA recommended that alternatives to tigecycline should be considered in patients with severe infections. After the FDA warning several meta-analysis were published; obviously using different methodologies and selecting different studies. Yahav et al. [3] meta-analysis reported statistically higher all-cause 30-day mortality in the tigecycline arms. On the other hand, Cai et al. [4] found no difference in all-cause mortality and drug-related mortality between tigecycline and the comparators, whereas Tasina et al. [5] demonstrated reduced clinical efficacy and increased mortality for tigecycline, but the difference was not statistically significant. The FDA alert has been further jeopardized by two more studies. McGovern et al. [6] performed an all-cause mortality analysis by use of logistic regression and classification and regression tree analyses on study-level and patient-level data in an effort to find a reason for the increase in mortality. Deaths were attributed to infections or underlying co-morbidities and not to tigecycline. Subsequently, Vardakas et al. [7] separately analyzed studies involving infections for which tigecycline has approval and reported no statistical difference in clinical efficacy and no significant increase in mortality. On the other hand, analyzed data from non-approved indications showed that the tigecycline arm was statistically less effective. Finally, meta-analyses of study-level data suggested decreased clinical efficacy as a possible explanation for the demonstrated imbalance in mortality [3, 8]. …