title: Tigecycline Treatment for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review and Meta-Analysis.
abstract: Carbapenem-resistant Enterobacteriaceae (CRE) infections are prevalent worldwide; they have few effective treatments and this jeopardizes public health. Clinicians often use tigecycline to combat CRE, but its clinical efficacy remains controversial. Therefore, to compare the efficacy and safety of tigecycline in treating CRE infections compared with that of other antimicrobial agents, and to evaluate whether combination therapy and high-dose regimens are beneficial, we performed a systematic review and meta-analysis. PubMed and Embase were searched for controlled trials or cohort studies reporting the efficacy and/or safety of tigecycline-based regimens to treat CRE infections. Statistical analyses were performed using the Comprehensive Meta-Analysis V2.2. All meta-analyses were performed based on fixed- or random-effects model, and the I method was used to assess heterogeneity. Twenty-one controlled studies and 5 single-arm studies were included in this systematic review. With regard to the controlled studies, the tigecycline groups did not differ significantly from the control groups in terms of overall mortality (Odds ratio (OR) = 0.96 [95% confidence interval (CI) = 0.75-1.22; P = 0.73]), clinical response rate (OR = 0.58 [95% CI = 0.31-1.09; P = 0.09]), or microbiological response rate (OR = 0.46 [95% CI = 0.15-1.44; P = 0.18]). Subgroup analyses showed that 30-day mortality was significantly lower in patients who received tigecycline combination therapy than in those who received monotherapy (OR = 1.83 [95% CI = 1.07-3.12; P = 0.03]) and other antibiotic regimens (OR = 0.59 [95% CI = 0.39-0.88; P = 0.01]), respectively. In addition, high-dose tigecycline regimens differed significantly from standard dose schedules in terms of ICU mortality (OR = 12.48 [95% CI = 2.06-75.43; P = 0.006]). The results of the 5 single-arm studies corroborated the findings of the controlled studies. Our results indicated that the efficacy of tigecycline in treating CRE infections is similar to that of other antibiotics. Tigecycline combination therapy and high-dose regimens may be more effective than monotherapy and standard-dose regimens, respectively. Nonetheless, considering that the current available evidence is limited, well-designed randomized controlled trials are urgently needed to clarify the comparative efficacy of tigecycline in treating CRE infections.
authors.affiliation: From the Department of Respiratory Diseases (WN, CW, JZ, JC, YL), Chinese PLA General Hospital; Department of Neurology (YH), Chinese PLA 305 Hospital; Department of Vascular and Endovascular Surgery (JL); and Department of Clinical Pharmacology (RW), Chinese PLA General Hospital, Beijing, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Ni
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Wei
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.forename: Junchang
authors.initials: J
authors.lastname: Cui
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Youning
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015780:Carbapenems; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008911:Minocycline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000078304:Tigecycline; D008911:Minocycline