Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial

Abstract

BackgroundTigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.MethodsIn this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for ≤2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes.ResultsOne hundred ninety-nine patients received ≥1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (P < 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005).ConclusionsClinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.Trial RegistrationClinicalTrials.gov NCT00136201

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

“…Data regarding the success of treatment with the administered antimicrobial regimens for CE and c-mITT patients were reported in seven RCTs (2,3,6,7,35,43,45). The treatment success of one RCT (16) was based on ME and m-mITT populations, so it was not included here.…”

Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology

“…234,235 Tigecycline was also found to be associated with higher rate of adverse events. [230][231][232] No differences in microbiological eradication in E. coli 222,233 or K. pneumoniae 233 were observed. One of the studies also found a higher rate of clinical failure with tigecycline among patients with Gram-negative infections.…”

“…Regarding the severity of the infections, most were moderate, and immunocompromised patients were excluded. [221][222][223][224][225][226][227][228][229][230][231] Therefore, from the evidence provided by these studies it cannot be inferred that the efficacy of tigecycline in monotherapy would be the same in more severe infections.…”

“…[221][222][223][224][225][226][227][228][229][230][231] The tigecycline dose used was 100 mg loading-dose followed by 50 mg/12 h. From the published clinical trials, information can be obtained about the clinical response in Enterobacteriaceae infections. Overall, 92% of potentially susceptible Enterobacteriaceae (excluding Proteeae tribe) were E. coli and Klebsiella spp.…”

Prise en charge des infections intra-abdominales

“…Quelques rapports font état d'utilisation de la tigécycline [12][13][14]. R42 -Lors du traitement probabiliste du premier épisode d'IIA associée aux soins et en l'absence de facteurs de risque de BMR, il faut probablement utiliser une association pipéra-cilline/tazobactam + amikacine (optionnel en l'absence de signes de gravité).…”