Efficacy and safety of high-dose tigecycline for the treatment of infectious diseases

Abstract

Background:High-dose (HD) tigecycline regimen is increasingly used in infectious diseases, however its efficacy and safety versus low-dose (LD) is still unclear.Methods:A systematic review and meta-analysis was performed; PubMed, Embase, Cochrane Library, ScienceDirect, Web of Science, clinicalTrials.gov, Wanfang, VIP, and China National Knowledge Infrastructure (CNKI), were searched using terms “tigecycline” AND “dose” up to October 31, 2018. Eligible studies were randomized trials or cohort studies comparing mortality, clinical response, microbiological eradication and safety of different tigecycline dose regimens for any bacterial infection. The primary outcome was mortality, and the secondary outcomes were clinical response rate, microbiological eradiation rate and adverse events (AEs). Meta-analysis was done with random-effects model, with risk ratios (RR) and 95% confidence intervals (CI) calculated for all outcomes.Results:Of 951 publications retrieved, 17 studies (n = 1041) were pooled in our meta-analysis. The primary outcome was available in 11 studies, and the RR for mortality was 0.67 (95% CI 0.53–0.84, P < .001). Clinical response (RR 1.46, 95% CI 1.30–1.65, P < .001) and microbiological eradication rate (RR 1.61, 95% CI 1.35–1.93, P < .001) were both higher in HD than in LD tigecycline regimen. However, non-Chinese study subgroup presented no statistical significance between HD and LD regimen, RR for mortality, clinical response and microbiological eradication were 0.79 (95% CI 0.56–1.14, P = .21), 1.35 (95% CI 0.96–1.92, P = .26), 1.00 (95% CI 0.22–4.43, P = 1.00), respectively. AEs did not differ between HD and LD tigecycline (RR 1.00, 95% CI 0.80–1.26, P = .97).Conclusion:HD tigecycline regimen reduced mortality meanwhile improved clinical efficacy and should be considered in serious infections caused by multidrug-resistant and extensively drug-resistant (MDR/XDR) bacteria.

Pharmacokinetics of high-dose tigecycline in critically ill patients with severe infections

“…3 Institute of Farmacologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome, Italy. 4 Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 5 Dipartimento di Scienze di Laboratorio e Infettivologiche, UOC di Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.…”

“…Tigecycline (TGC), the first antimicrobial of glycilcycline class, has shown an expanded-spectrum activity against gram-positive, gram-negative, aerobic, anaerobic and atypical bacterial species, including antibiotic-resistant strains [ 1 ]. Indeed, it has been demonstrated that methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae , vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL)/carbapenem-producing Enterobacterales and extensively drug-resistant (XDR) Acinetobacter baumannii are susceptible to TGC [ 2 – 4 ].…”

Successful High-Dosage Monotherapy of Tigecycline in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia–Septicemia Model in Rats

“…Additionally, the administration of tigecycline treatment has been associated with an increased death rate [5], and a number of case reports have indicated serious complications in patients as a consequence of tigecycline treatment [36][37][38][39][40]. On the other hand, a meta-analysis by Falagas et al in 2014 concluded that high-dose tigecycline regimens may be effective for the treatment of severe bacterial infections [9], and a meta-analysis by Gong et al concluded that high-dose tigecycline regimens did not elevate the risk of toxic side effects [41]. Further, pharmacokinetic and pharmacodynamic studies have indicated that higher dosages of tigecycline can be administered to humans, resulting in improved therapeutic efficacy [6,42,43].…”

Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting—Focus on ICU Patients and Gram-Negative Strains

“…The increasing incidence of MDR and extensively drug resistant (XDR) strains causing infections has recently renewed the use of tigecycline, often in combination chemotherapy. A recent metanalysis including 17 studies with 1104 pts has demonstrated that high doses of tigecycline (150–200 mg loading dose and then 75–100 mg BID) are more effective both microbiologically and clinically than standard doses without a significant impairment of safety [ 64 ].…”