No abstract

Background The need for antimicrobial therapies effective against multidrug resistant (MDR) organisms for children remains unmet. Tigecycline shows antibacterial activity across a broad spectrum of bacteria and is approved for treating complicated skin and skin-structure infections (cSSSI), complicated intraabdominal infections (cIAI), and, in the US, community-acquired bacterial pneumonia (CAP) for adult patients. No blinded, randomized Phase 3 tigecycline clinical trials on neonates or children have been completed or planned. This review aimed to provide a comprehensive synthesis of all the existing data sources, both on-label and off-label, for tigecycline use in children. Methods Data on tigecycline use in children were identified from published and unpublished sources including clinical trials, expanded access and compassionate use programs, databases of healthcare records and patient safety monitoring. Results Pharmacokinetic simulations predicted that tigecycline 1.2 mg/kg (maximum dose 50 mg) every 12 hours (q12h) in children 8-11 years and 50 mg q12h in children 12-<18 years would achieve exposure similar to adults receiving 50 mg q12h. Available Phase 2 paediatric clinical trial data and data from other sources demonstrated similar clinical efficacy between adult and paediatric patients treated with tigecycline. These data showed no new or unexpected safety concerns with tigecycline in children. Conclusions 4 Information presented here may help guide the appropriate use of tigecycline in children with MDR infections. Continued pharmacovigilance from real-world observational studies may also further refine appropriate use of tigecycline.

BackgroundAcinetobacter infections, especially multidrug-resistant (MDR) Acinetobacter infections, are a global health problem. This study aimed to describe clinical outcomes in patients with confirmed Acinetobacter spp. isolates who were treated with tigecycline in randomized clinical trials.Materials and methodsData from 14 multinational, randomized (open-label or double-blind), and active-controlled (except one) Phase III and IV studies were analyzed using descriptive statistics.ResultsA total of 174 microbiologically evaluable patients with Acinetobacter spp. infections (including MDR infections) were identified, and 95 received tigecycline to treat community-acquired pneumonia (CAP), diabetic foot infections (DFIs), hospital-acquired pneumonia (HAP), complicated intra-abdominal infections (cIAIs), infections with resistant pathogens (RPs), or complicated skin and skin-structure infections. The rate of cure of tigecycline for most indications was 70%–80%, with the highest (88.2%) in cIAIs. The rate of cure of the comparators was generally higher than tigecycline, but within each indication the 95% CIs for clinical cure for each treatment group overlapped. For most Acinetobacter isolates, the minimum inhibitory concentration of tigecycline was 0.12–2 μg/mL, with seven at 4 μg/mL and one at 8 μg/mL. The cure rate by tigecycline was 50% (95% CI 12.5%–87.5% in CAP) to 88.2% (95% CI 66.2%–97.1% in cIAIs) for all Acinetobacter, and 72.7% (95% CI 54.5%–93.2% in HAP) to 100% (95% CI 25%–100.0% in cIAIs) for MDR Acinetobacter. For the comparators, it was 83.8% (95% CI 62.8%–95.9% in HAP) to 100% (95% CI 75%–100% in cIAIs and 25%–100.0% in RPs) and 88% (95% CI 66%–97% in HAP) to 100% (95% CI 25%–100% in cIAIs and 75%–100% in DFIs), respectively.ConclusionThese findings suggest that with appropriate monitoring, tigecycline may be a useful consideration for Acinetobacter infections alone or in combination with other anti-infective agents when other therapies are not suitable.

Background Risk minimization measures (RMM) were implemented from February 2011 in the European Union to address risks of superinfection, off-label use and lack of efficacy associated with tigecycline. The objective of this study was to evaluate RMM effectiveness by describing prescription patterns among adults and children treated with any dose of tigecycline for any indication pre-and post-RMM implementation; incidence proportions of superinfection and lack of efficacy among adults treated with approved doses of tigecycline for complicated intraabdominal infection and complicated skin and soft tissue infection were also evaluated. Methods This was an observational, retrospective chartabstraction study, including charts from 777 patients (399 pre-RMM, 378 post-RMM) at 13 sites across Austria, Germany, Italy, Greece and the United Kingdom (UK). Potential superinfection and lack of efficacy cases among those using tigecycline for on-label indication, age, dose, and duration were adjudicated. The distribution of indications for tigecycline was analyzed overall (i.e. across both study periods) and stratified by study period. Numbers and incidence proportions of superinfection and lack of efficacy cases (potential and adjudicated) were calculated overall and by study period. Results Off-label use (indication or age) decreased from 54.2% [95% confidence interval (95% CI): 49.0, 59.3%] pre-RMM to 35.7% (95% CI 30.4, 41.2%) post-RMM. Overall, 45.7% (95% CI 41.9, 49.5%) of patients were prescribed tigecycline off-label; the most commonly reported off-label indications were characterized as ''other'' (25.5%), hospital acquired pneumonia (8.2%), other pneumonia (6.3%), bacteremia (5.2%) and diabetic foot infection (1.5%). Across study periods, incidence proportions of definite or probable superinfection and lack of efficacy in adults treated for approved indications, authorized treatment doses and duration were 4.5% (95% CI 2.1, 8.4%) and 5.5% (95% CI 2.8, 9.7%), respectively. Conclusions Off-label use of tigecycline decreased following RMM implementation. Overall incidence proportions of definite or probable superinfection and lack of efficacy were low. EU PAS register number: EUPAS3674 Key PointsThe proportion of off-label tigecycline use decreased across five EU countries following implementation of a healthcare provider educational program Proportions of definite and probable superinfection and lack of efficacy were low across both study periods & Vera Frajzyngier

No abstract