Pediatric Infectious Disease

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VOLUME 4 , ISSUE 2 ( April-June, 2022 ) > List of Articles

REVIEW ARTICLE

Off-label Use of Antibiotics in Pediatrics

Jeeson C Unni

Keywords : Antibiotics, Drug formulary, Neonate, Off-label antibiotics, Off-label medications, Pediatric

Citation Information : Unni JC. Off-label Use of Antibiotics in Pediatrics. Pediatr Inf Dis 2022; 4 (2):43-46.

DOI: 10.5005/jp-journals-10081-1315

License: CC BY-NC 4.0

Published Online: 01-06-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Abstract

Usage of antibiotics off-label, in neonates and children, is an important public health issue. An overwhelming number of antibiotics are marketed and prescribed without clear labeling for use in pediatrics. It presents an even larger and more complex issue in neonates, children younger than 2 years, and those with chronic and/or rare diseases due to a lack of good clinical trials in these pediatric subgroups. The purpose of off-label use is to benefit an individual patient. The article details the prevalence of off-label antibiotic use in pediatrics and the reasons for the same. An attempt is made to highlight the different recommendations for antibiotic use in two pediatric drug formularies, the non-availability of child-friendly formulations and the lack of studies on newer antibiotics in neonates and children that necessarily results in antibiotics being prescribed off-label in children.


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  1. Corny J, Lebel D, Bailey B, et al. Unlicensed and off-label drug use in children before and after pediatric governmental initiatives. J PediatrPharmacol Ther 2015;20(4):316–328. DOI: 10.5863/1551-6776-20.4.316.
  2. Unni JC, Joseph RB. Off-label medications in pediatrics. Indian J Pediatr 2019;86(12):1149. DOI: 10.1007/s12098-019-03029-9.
  3. Joint Formulary Committee. British National Formulary for Children. London: BMJ Group and Pharmaceutical Press; 2019–2020.
  4. IAP Drug Formulary 2019. IAP drug formulary with IAP recommendations for drug therapy of pediatric illnesses Unni JC, Nair MKC, Menon PSN, ed. 5th ed., Cochin: Publication of Indian Academy of Pediatrics. Pixel Studio; 2019.
  5. Frattarelli DA, Galinkin JL, Green TP, et al. American Academy of Pediatrics Committee on Drugs. Off-label use of drugs in children. Pediatrics 2014;133(3):563–567. DOI: 10.1542/peds.2013-4060.
  6. Yen E, Davis JM, Milne CP. Impact of regulatory incentive programs on the future of pediatric drug development. Ther Innov Regul Sci 2019;53(5):609–614. DOI: 10.1177/2168479019837522.
  7. McLay JS, Tanaka M, Ekins-Daukes S, et al. A prospective questionnaire assessment of attitudes and experiences of off label prescribing among hospital based paediatricians. Arch Dis Child 2006;91(7):584–587. DOI: 10.1136/adc.2005.081828.
  8. Porta A, Esposito S, Menson E, et al. Off-label antibiotic use in children in three European countries. Eur J Clin Pharmacol 2010;66(9):919–927. DOI: 10.1007/s00228-010-0842-1.
  9. Zingg W, Posfay-Barbe KM. Antibiotic use in children- Off-label use. Curr Drug Targets 2012;13(7):885–892. DOI: 10.2174/138945012800675777.
  10. Mukattash TL, Hayajneh WA, Ibrahim SM, et al. Prevalence and nature of off-label antibiotic prescribing for children in a tertiary setting: a descriptive study from Jordan. Pharm Pract (Granada) 2016;14(3):725. DOI: 11.18549/PharmPract.2016.03.725.
  11. Laforgia N, Nuccio MM, Schettini F, et al. Off-label and unlicensed drug use among neonatal intensive care units in Southern Italy. Pediatr Int 2014;56(1):57–59. DOI: 10.1111/ped.12190.
  12. Kouti L, Aletayeb M, Aletayeb SMH, et al. Pattern and extent of off-label and unlicensed drug use in neonatal intensive care units in Iran. BMC Pediatr 2019;19(1):3. DOI: 10.1186/s12887-018-1370-x.
  13. Casañ VA, Escribano BC, Garrido-Corro B. Off-label and unlicensed drug use in a Spanish neonatal intensive care unit. Artículo de opinión 2017;41:371–381.
  14. Puja, Dhasmana DC, Kohli S, et al. Off-label use of antibiotics in hospitalised children in a tertiary care teaching hospital. Int J Basic Clin Pharmacol 2018;7(10):1970–1973. DOI: 10.18203/2319-2003.ijbcp20183932.
  15. Saiyed MM, Lalwan T, Rana D. Off-label medicine use in pediatric inpatients: a prospective observational study at a tertiary care hospital in India. Int J Pediatr 2014;2014:415815. DOI: 10.1155/2014/415815.
  16. Miao R, Wan C, Wang Z, et al. Inappropriate antibiotic prescriptions among pediatric inpatients in different type hospitals. Medicine (Baltimore) 2020;99(2):e18714. DOI: 10.1097/MD.0000000000018714.
  17. Ratjen F, Brockhaus F, Angyalosi G. Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: a review. J Cystic Fibro 2009;8(6):361–369. DOI: 10.1016/j.jcf.2009.08.004.
  18. Streptomycin. TB drug monographs. http://www.tbdrugmonographs.co.uk/streptomycin.html. Accessed on 17/4/20.
  19. Second Meeting of the Subcommittee of the Expert Committee on the Selection and Use of Essential Medicines. Use of carbapenems in children. http://origin.who.int/selection_medicines/committees/subcommittee/2/Carbapenems.pdf. Accessed on 17/4/20.
  20. CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morbid Mortal Wkly Rep 2012;61:590–594.
  21. Tristram S, Jacobs MR, Appelbaum PC. Antimicrobial resistance in haemophilus influenza. Clin Microbiol Rev 2007;20(2):368–389. DOI: 10.1128/CMR.00040-06.
  22. Integrated Management of Childhood Illness for High HIV Geneva: World Health Organizationhttps://www.ncbi.nlm.nih.gov/books/NBK144140/.
  23. Rathi N, Kulkarni A, Yewale V. IAP guidelines on rickettsial diseases in children; For Indian academy of pediatrics guidelines on rickettsial diseases in children committee. Ind Pediatr 2017;54(3):223–229. DOI: 10.1007/s13312-017-1035-0.
  24. Gaillard T, Briolant S, Madamet M, et al. The end of a dogma: the safety of doxycycline use in young children for malaria treatment. Malar J 2017;16(1):148. DOI: 10.1186/s12936-017-1797-9.
  25. Garazzino S, Tovo P. Clinical experience with linezolid in infants and children. J Antimicro Chemother 2011;66(Supplement 4):iv23–iv41. DOI: 10.1093/jac/dkr074.
  26. Batchelor HK, Marriott JF. Formulations for children: problems and solutions. Br J Clin Pharmacol 2015;79(3):405–418. DOI: 10.1111/bcp.12268.
  27. Richey RH, Shah UU, Peak M, et al. Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence. BMC Pediatr 2013;13(1):81. DOI: 10.1186/1471-2431-13-81.
  28. Ainscough LP, Ford JL, Morecroft CW, et al. Accuracy of intravenous and enteral preparations involving small volumes for paediatric use: a review. Eur J Hosp Pharm 2018;25(2):66–71. DOI: 10.1136/ejhpharm-2016-001117.
  29. Thompson G, Barker CI, Folgori L, et al. Global shortage of neonatal and paediatric antibiotic trials: rapid review. BMJ Open 2017;7(10):e016293. DOI: 10.1136/bmjopen-2017-016293.
  30. Unni JC. Newer antibiotics: need for more studies in neonates and children. Pediatr Inf Dis 2019;1(4):164–168. DOI: 10.5005/jp-journals-10081-1212.
  31. Mastrolia MV, Galli L, De Martino M, et al. Use of tigecycline in pediatric clinical practice. Expert Rev Anti Infect Ther 2017;15(6):605–612. DOI: 10.1080/14787210.2017.1318064.
  32. Iosifidis E, Violaki A, Michalopoulou E, et al. Use of tigecycline in pediatric patients with infections predominantly due to extensively drug-resistant gram-negative bacteria. J Pediatric Infect Dis Soc 2017;6(2):123–128. DOI: 10.1093/jpids/piw009.
  33. Silvia G, Elio C, Maria DG, et al. Daptomycin for children in clinical practice experience. Pediat Infect Dis J 2016;35(6):639–641. DOI: 10.1097/INF.0000000000001121.
  34. De Cock PAJG, van Dijkman SC, Jaeger AE, et al. Dose optimization of piperacillin/tazobactam in critically ill children. J Antimicrob Chemother 2017;72(7):2002–2011. DOI: 10.1093/jac/dkx093.
  35. Knoderer CA, Karmire LC, Andricopulos KL, et al. Extended infusion of piperacillin/tazobactam in children. J Pediatr Pharmacol Ther 2017;22(3):212–217. DOI: 10.5863/1551-6776-22.3.212.
  36. Jan S, Ragunanthan B, DiBrito SR, et al. Cefepime efficacy and safety in children: a systematic review and meta-analysis. Front Pediatr 2018;6:46. DOI: 10.3389/fped.2018.00046.
  37. Dassner AM, Girotto JE. Evaluation of a second-sign process for antimicrobial prior authorization. J Pediat Infect Dis Soc 2018;7(2):113–118. DOI: 10.1093/jpids/pix015.
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