Mike Sharland1, Keith A Rodvold2, Hal R Tucker3, Nathalie Baillon-Plot4, Margaret Tawadrous5, M Anne Hickman6, Susan Raber7, Joan M Korth-Bradley8, Humberto Díaz-Ponce9, Michele Wible10. 1. From the Paediatric Infectious Diseases Research Group, St. George's, University of London, London, United Kingdom. 2. Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois. 3. Established Products Business Unit, Pfizer Inc., Collegeville, Pennsylvania. 4. Antibacterials Europe, Pfizer PFE, Paris, France. 5. Clinical Research and Development, Pfizer Inc., Groton, Connecticut. 6. Worldwide Safety and Regulatory, Pfizer Inc., Groton, Connecticut. 7. Clinical Pharmacology, Pfizer Essential Health, Pfizer Inc., La Jolla, California. 8. Clinical Pharmacology, Pfizer Inc., Collegeville, Pennsylvania. 9. LATAM Anti-infectives, Pfizer México, Mexico City, Mexico (affiliation at the time when the study was conducted). 10. Biostatistics, Pfizer Inc., Collegeville, Pennsylvania.
Abstract
BACKGROUND: The need for antimicrobial therapies effective against multidrug resistant 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, complicated intra-abdominal infections and, in the United States, community-acquired bacterial pneumonia 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 METHODS: Data on tigecycline use in children were identified from published and unpublished sources including clinical trials, expanded access and compassionate use programs, databases of healthcare records and patient safety monitoring.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 to <18 years would achieve exposure similar to adults receiving 50 mg q12h. Available phase 2 pediatric clinical trial data and data from other sources demonstrated similar clinical efficacy between adult and pediatric patients treated with tigecycline. These data showed no new or unexpected safety concerns with tigecycline in children. CONCLUSIONS: Information presented here may help guide the appropriate use of tigecycline in children with multidrug resistant infections. Continued pharmacovigilance from real-world observational studies may also further refine appropriate use of tigecycline.
BACKGROUND: The need for antimicrobial therapies effective against multidrug resistant 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, complicated intra-abdominal infections and, in the United States, community-acquired bacterial pneumonia 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 to <18 years would achieve exposure similar to adults receiving 50 mg q12h. Available phase 2 pediatric clinical trial data and data from other sources demonstrated similar clinical efficacy between adult and pediatric patients treated with tigecycline. These data showed no new or unexpected safety concerns with tigecycline in children. CONCLUSIONS: Information presented here may help guide the appropriate use of tigecycline in children with multidrug resistant infections. Continued pharmacovigilance from real-world observational studies may also further refine appropriate use of tigecycline.
Authors: Laura Folgori; Irja Lutsar; Joseph F Standing; A Sarah Walker; Emmanuel Roilides; Theoklis E Zaoutis; Hasan Jafri; Carlo Giaquinto; Mark A Turner; Mike Sharland Journal: BMJ Open Date: 2019-12-31 Impact factor: 2.692