Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease

Abstract

The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE CI ‫؍‬ 0.69 to 1.07, P ‫؍‬ 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR ‫؍‬ 1.33, 95% CI ‫؍‬ 1.17 to 1.52, P < 0.0001), especially in the digestive system (mITT population, OR ‫؍‬ 2.41, 95% CI ‫؍‬ 1.67 to 3.46, P < 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.The threat of antimicrobial resistance has been identified as one of the major challenges facing public health, and antimicrobial resistance has increased rates of morbidity and mortality and socioeconomic costs. The rapid rate of microbial evolution underscores the urgent need for development of new agents that overcome existing mechanisms of resistance displayed by multidrug-resistant bacteria.Tigecycline is a first-in-class expanded-broad-spectrum glycylcycline. It inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit but with a five times higher affinity than that for the tetracyclines (4). In vitro studies demonstrate that it has good activity against many commonly encountered respiratory bacteria, including multiple resistant Gram-positive, Gram-negative, anaerobic, as well as multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), and ␤-lactamase-producing Haemophilus influenzae, among others (5). Tigecycline overcomes the two key tetracycline resistance mechanisms (efflux pumps and ribosomal protection) and is unaffected by other bacterial mechanisms of resistance, such as extended-spectrum ␤-lactamases (32).Tigecycline was first approved for use for indications of complicated skin and skin structure infections (cSSSIs) and complicated intra-abdominal infections (cIAIs). Currently, it is approved for use for community-acquired pneumonia (CAP). It has also been found to be effective for the trea...

Is there a future for tigecycline?

“…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.…”

Skin and Soft Tissue Infections

“…47 Tigecycline use has been associated with higher all cause mortality rates, though it was not statistically significant, FDA has issued a warning. 48 No dosage adjustment of tigecycline is necessary in patients with renal insufficiency or mild to moderate hepatic impairment and the aged population, although in patients with severe hepatic impairment, the initial dose should be 100 mg, followed by a reduced maintenance dose of 25 mg every 12 hrs. 49 …”

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

“…and Morganella spp. 22,38,54,55 However, evidence of increased mortality, compared to other antibiotic therapies, especially in ventilator-associated pneumonia 48 leads to caution in its use. Moreover, a serious drawback, at least for monotherapy in bacteremia, is the low serum level obtained.…”