Safety and Efficacy of Tigecycline to Treat Multidrug-resistant Infections in Pediatrics: An Evidence Synthesis

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 Methods Data on tigecycline use in children were identified from published and unpublished sources including clinical trials, expanded access and compassionate use programs, databases of healthcare records and patient safety monitoring.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.

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

“…and anaerobic and atypical bacteria. [67][68][69] The U.S. Food and Drug Administration (FDA) has approved tigecycline for adults with complicated intra-abdominal and skin/skin structure infections or community-acquired bacterial pneumonia. However, pediatric use has been very limited, and there have been no phase 3 clinical trials of children.…”

“…70 In 2019, tigecycline safety and efficacy were studied at 1.2 mg/kg (maximum 50 mg) every 12 hours in children aged 8 to 11 years and at 50 mg every 12 hours in children older than 12 years. 69 Although not FDA approved to treat VRE, use of the drug via the IV and IVT routes should be considered when a child is diagnosed with MDR ventriculitis. 66 Tissue drug distribution is rapid, but the CSF concentrations are low when the IV route is used.…”

Clinical and laboratory responses to tigecycline in children

“…Clinical evidence of safety or efficacy in paediatric patients under 18 years of age is lacking. However, tigecycline can be used as a salvage treatment in children when options are limited 9–15 . Because pharmacokinetic safety and efficacy data are not available for children, clinical trials are required to identify the most appropriate therapeutic strategies.…”

“…However, tigecycline can be used as a salvage treatment in children when options are limited. [9][10][11][12][13][14][15] Because pharmacokinetic safety and efficacy data are not available for children, clinical trials are required to identify the most appropriate therapeutic strategies. We present our experience with the use of tigecycline in critically ill children to guide future studies.…”

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view

“…The establishment of a network of different stakeholders (academics, physicians, regulators and industry) involving centres in all regions across the world would allow the conduct of prospective cohort studies using electronic data records as part of post-marketing surveillance (as has already been set up with paediatric HIV registries). Such approach could potentially allow data to be collected and easily pooled out at a relatively low cost 11…”