Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatmen t of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin ). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.
Papageorgiou, A. and Pelausa, E. (2014) Management and Outcome of Extremely Low Birth Weight Infants. Journal of Pediatric and Neonatal Individualized Medicine, 3, e030209.
Marchant, E.A., Boyce, G.K., Sadarangani, M. and Lavoie, P.M. (2013) Neonatal Sepsis Due to Coagulase-Negative Staphylococci. Clinical and Developmental Immunology, 2013, Article ID: 586076. https://doi.org/10.1155/2013/586076
Tsai, M.H., Hsu, J.F., Chu, S.M., Lien, R., Huang, H.R., Chiang, M.C., et al. (2014) Incidence, Clinical Characteristics and Risk Factors for Adverse Outcome in Neonates with Late Onset Sepsis. The Pediatric Infectious Disease Journal, 33, e7-e13. https://doi.org/10.1097/INF.0b013e3182a72ee0
Fairchild, K.D. (2013) Predictive Monitoring for Early Detection of Sepsis in Neonatal ICU Patients. Current Opinion in Pediatrics, 25, 172-179. https://doi.org/10.1097/MOP.0b013e32835e8fe6
Kuppala, V.S., Meinzen-Derr, J., Morrow, A.L. and Schibler, K.R. (2011) Prolonged Initial Empirical Antibiotic Treatment Is Associated with Adverse Outcomes in Premature Infants. Journal of Pediatrics, 159, 720-725. https://doi.org/10.1016/j.jpeds.2011.05.033
Smith, P.B. and Benjamin Jr., D.K. (2011) Choosing the Right Empirical Antibiotics for Neonates. ADC Fetal & Neonatal Edition, 96, F2-F3. https://doi.org/10.1136/adc.2010.188938
Russell, A.B., Sharland, M. and Heath, P.T. (2012) Improving Antibiotic Prescribing in Neonatal Units: Time to Act. ADC Fetal & Neonatal Edition, 97, F141-F146. https://doi.org/10.1136/adc.2007.120709
Pandolfini, C., Kaguelidou, F., Sequi, M., Jacqz-Aigrain, E., Choonara, I., Turner, M.A., et al. (2013) Wide Intra- and Inter-Country Variability in Drug Use and Dosage in Very-Low-Birth-Weight Newborns with Severe Infections. European Journal of Clinical Pharmacology, 69, 1031-1036. https://doi.org/10.1007/s00228-012-1415-2
Leroux, S., Zhao, W., Betremieux, P., Pladys, P., Saliba, E., Jacqz-Aigrain, E., The French Society of Neonatology (2015) Therapeutic Guidelines for Prescribing Antibiotics in Neonates Should Be Evidence-Based: A French National Survey. Archives of Disease in Childhood, 100, 394-398. https://doi.org/10.1136/archdischild-2014-306873
Metsvaht, T., Nellis, G., Varendi, H., Nunn, A.J., Graham, S., Rieutord, A., et al. (2015) High Variability in the Dosing of Commonly Used Antibiotics Revealed by a Europe-Wide Point Prevalence Study: Implications for Research and Dissemination. BMC Pediatrics, 15, 41-51. https://doi.org/10.1186/s12887-015-0359-y
Spyridis, N., Syridou, G., Goossens, H., Versporten, A., Kopsidas, J., Kourlaba, G., et al. (2016) ARPEC Project Group Members. Variation in Paediatric Hospital Antibiotic Guidelines in Europe. Archives of Disease in Childhood, 101, 72-76. https://doi.org/10.1136/archdischild-2015-308255
de Jong, J., van den Berg, P.B., Visser, S.T., de Vries, T.W. and de Jong-van den Berg, L.T. (2009) Antibiotic Usage, Dosage and Course Length in Children between 0 and 4 Years. Acta Paediatrica, 98, 1142-1148. https://doi.org/10.1111/j.1651-2227.2009.01309.x
Porta, A., Esposito, S., Menson, E., Spyridis, N., Tsolia, M., Sharland, M., et al. (2010) Off-Label Antibiotic Use in Children in Three European Countries. European Journal of Clinical Pharmacology, 66, 919-927. https://doi.org/10.1007/s00228-010-0842-1
Zingg, W. and Posfay-Barbe, K.M. (2012) Antibiotic Use in Children: Off-Label Use. Current Drug Targets, 13, 885-892. https://doi.org/10.2174/138945012800675777
Kadambari, S., Heath, P.T., Sharland, M., Lewis, S., Nichols, A. and Turner, M.A. (2011) Variation in Gentamicin and Vancomycin Dosage and Monitoring in UK Neonatal Units. Journal of Antimicrobial Chemotherapy, 66, 2647-2650. https://doi.org/10.1093/jac/dkr351
Cuzzolin, L. and Agostino, R. (2016) Off-Label and Unlicensed Drug Treatments in Neonatal Intensive Care Units: An Italian Multicentre Study. European Journal of Clinical Pharmacology, 72, 117-123. https://doi.org/10.1007/s00228-015-1962-4
Pediatric Formulary Committee (2016) The BNF for Children 2016-2017. Pharmaceutical Press, BMJ Group, London.
Agostino, R., Braguglia, A., Caccamo, M.L, Dotta, A., Massenzi, L., Messner, H., et al. (2009) Farmacoterapia Neonatale: Guida Pratica (Con Software Interattivo). Biomedia, Milan.
Tripathi, N., Cotton, C.M. and Smith, P.B. (2012) Antibiotic Use and Misuse in the Neonatal Intensive Care Unit. Clinics in Perinatology, 39, 61-68. https://doi.org/10.1016/j.clp.2011.12.003
Cheng, C.L., Yang, Y.H., Lin, S.J., Lin, C.H. and Lin, Y.J. (2010) Compliance with Dosing Recommendations from Common References in Prescribing Antibiotics for Preterm Neonates. Pharmacoepidemiology and Drug Safety, 19, 51-58. https://doi.org/10.1002/pds.1858
Cuzzolin, L. (2014) Off-Label Drug in the Newborn. Journal of Pediatric and Neonatal Individualized Medicine, 3, e030224.
Kaguelidou, F., Turner, M.A., Choonara, I., van den Anker, J., Manzoni, P., Alberti, C., et al. (2013) Randomized Controlled Trials of Antibiotics for Neonatal Infections: A Systematic Review. British Journal of Clinical Pharmacology, 76, 21-29. https://doi.org/10.1111/bcp.12113
Olski, T.M., Lampus, S.F., Gherarducci, G. and Saint Raymond, A. (2011) Three Years of Paediatric Regulation in the European Union. European Journal of Clinical Pharmacology, 67, 245-252. https://doi.org/10.1007/s00228-011-0997-4
Garazzino, S., Lutsar, I., Bertaina, C., Tovo, P.-A. and Sharland, M. (2013) New Antibiotics for Paediatric Use: A Review of a Decade of Regulatory Trials Submitted to the European Medicines Agency from 2000—Why Aren’t We Doing Better? International Journal of Antimicrobial Agents, 42, 99-118. https://doi.org/10.1016/j.ijantimicag.2013.05.001
Laughon, M.M., Avant, D., Tripathi, N., Hornik, C.P., Cohen-Wolkowiez, M., Clark, R.H., et al. (2014) Drug Labelling and Exposure in Neonates. JAMA Pediatrics, 168, 130-136. https://doi.org/10.1001/jamapediatrics.2013.4208
Knoderer, C.A., Everett, J.A. and Buss, W.F. (2003) Clinical Issues Surrounding Once-Daily Aminoglycoside Dosing in Children. Pharmacotherapy, 23, 44-56. https://doi.org/10.1592/phco.23.1.44.31924
Rao, S.C., Srinivasjois, R. and Moon, K. (2016) One Dose per Day Compared to Multiple Doses per Day of Gentamicin for Treatment of Suspected or Proven Sepsis in Neonates. Cochrane Database of Systematic Reviews, 12, CD005091.
NICE Clinical Guidance (2012) Antibiotics for Early-Onset Neonatal Infections.
Jacqz-Aigrain, E., Leroux, S., Zhao, W., van den Anker, J.N. and Sharland, M. (2015) How to Use Vancomycin Optimally in Neonates: Remaining Questions. Expert Review of Clinical Pharmacology, 8, 635-648. https://doi.org/10.1586/17512433.2015.1060124
Principi, N. and Marchisio, P. (1998) Meropenem Compared with Ceftazidime in the Empiric Treatment of Acute Severe Infections in Hospitalized Children. Journal of Chemotherapy, 10, 108-113.
de Hoog, M., Mouton, J.W. and van den Anker, J.N. (2005) New Dosing Strategies for Antibacterial Agents in the Neonate. Seminars in Fetal & Neonatal Medicine, 10, 185-194. https://doi.org/10.1016/j.siny.2004.10.004