health-services/patient-care/perinatal-reproductive/neonatal-ehandbook/ conditions/hypothyroidism#lp-h-0 [accessed 14 August 2018]. 2 National Health and Medical Research Council, Australian Government. Nutrient Reference Values for Australia and New Zealand. Canberra: The Council; 2014. Available from: https://www.nrv.gov.au/nutrients/ iodine [accessed 14 August 2018]. 3 Connelly KJ, Boston BA, Pearce EN et al. Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion. J. Pediatr. 2012; 161: 760–2. 4 Thaker VV, Leung AM, Braverman LE, Brown RS, Levine B. Iodine- induced hypothyroidism in full-term infants with congenital heart dis- ease: More common than currently appreciated? J. Clin. Endocrinol. Metab. 2014; 99: 3521–6. Dear Editor, FLUCLOXACILLIN THERAPEUTIC DRUG MONITORING IN A NEONATE ON EXTRACORPOREAL MEMBRANE OXYGENATION Extracorporeal membrane oxygenation (ECMO) is an advanced life support system providing cardiorespiratory support for patients requiring advanced intensive care. 1,2 ECMO is associated with altered pharmacokinetic (PK) parameters, changes in drug plasma concentrations and potentially unpredicted pharmacologi- cal effects. Definitive antibiotic dosing guidelines for patients on ECMO are not yet available. 1 In June 2016, an 11-day-old term infant was admitted to a ter- tiary paediatric hospital intensive care unit with cardiogenic shock secondary to enteroviral cardiomyopathy, for which he required ECMO. His stay was complicated by disseminated methicillin- susceptible Staphylococcus aureus infection, with bacteraemia, bilateral pneumonia, liver abscess and atrial clot, suggesting intravascular infection while on ECMO. The infant commenced intravenous flucloxacillin 50 mg/kg/dose every 4 h, and trough flucloxacillin plasma concentration was collected given the serious infection and uncertainty about flucloxacillin PK during ECMO. Linezolid (10 mg/kg 8 hourly) was added pending flucloxacillin therapeutic drug-monitoring (TDM) results. The infant’s total flu- cloxacillin plasma concentration was 22.2 mg/L, with an esti- mated free drug concentration of 5.6 mg/L. This was deemed to be adequate, and linezolid was ceased while flucloxacillin contin- ued at the original dosing for 6 weeks. The infant recovered, with no further S. aureus grown from blood culture or clinical evidence of ongoing infection. ECMO was ceased at 14 days, and the infant was discharged home at 172 days following prolonged rehabilita- tion unrelated to S. aureus infection. Both severe infection and ECMO have been reported to affect antibiotic PK, the latter related to direct extraction by the circuit, increased volume of distribution and altered clearance, but antibiotic-specific information is limited. 1–3 A systematic review found neonatal data on altered PK in sepsis, mainly from 1980s– 1990s, and thus perhaps not valid for new ECMO technology, although there is emerging data from adults and older children. 1,2 The largest number of studies has been conducted with gentami- cin and vancomycin. 1,2 According to Pullen et al., plasma concentrations of free flu- cloxacillin should exceed 2.0 mg/L for methicillin-sensitive Staphylococcus aureus for at least 40% of the time based on the breakpoint minimum inhibitory concentration (MIC) value of flucloxacillin for S. aureus (2.0 mg/L). 4 There is some evidence that plasma concentrations, using commonly recommended dos- ages of flucloxacillin, remain well above MIC for S. aureus when used for prophylaxis throughout cardiopulmonary bypass surgery in neonates with weight < 5 kg. 5 No studies have examined ECMO on flucloxacillin PK in critically ill patients, and no specific flucloxacillin dosing recommendations are given in the literature for neonates and children on ECMO. 2 Beta-lactam antibiotics are hydrophilic and significantly affected by priming/transfusion haemodilution and other patho- physiological changes that occur during ECMO. 3 Neonates have a high concentration of total body water, which results in a higher volume of distribution for hydrophilic drugs. Antibiotic regimens for patients on ECMO should be individualised whenever possible through TDM for optimal antibiotic efficacy and patient outcome. We recommend further studies be conducted on TDM of fluclox- acillin in critically ill neonates managed with ECMO to ensure that recommended regimens are adequate to achieve desired concentrations and optimise patient outcomes. Dr Laila S Al Yazidi 1,2,3 Dr Sofia A Badran 4 Dr Indy Sandaradura 5,6 Dr Kevin Swil 2,7 Dr Brendan McMullan 1,2 1 Immunology and Infectious Diseases Department, 7 Intensive Care Unit Sydney Children’s Hospital 2 The School of Women’s and Children’s Health, University of New South Wales 4 Infectious Diseases and Microbiology Department The Children’s Hospital at Westmead 5 Centre for Infectious Diseases and Microbiology Westmead Hospital 6 St. Vincent’s Clinical School, University of New South Wales Sydney, New South Wales Australia 3 Sultan Qaboos University, College of Medicine Muscat Sultanate of Oman Conflict of interest: None declared. References 1 Mousavi S, Levcovich B, Mojtahedzadeh M. A systematic review on pharmacokinetic changes in critically ill patients: Role of extracorporeal membrane oxygenation. Daru 2011; 19: 312–21. 2 Sherwin J, Heath T, Watt K. Pharmacokinetics and dosing of anti- infective drugs in patients on extracorporeal membrane oxygenation: A review of the current literature. Clin. Ther. 2016; 38: 1976–94. 3 Shekar K, Fraser JF, Smith MT, Roberts JA. Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation. J. Crit. Care 2012; 27: 741.e9–18. 4 Pullen J, Stolk LML, Degraeuwe PLJ, Tiel FHV, Neef C, Zimmermann LJI. Protein binding of flucloxacillin in neonates. Ther. Drug Monit. 2007; 29: 279–83. 5 Vargas MRA, Dantona MH, Javaida SM et al. Pharmacokinetics of intravenous flucloxacillin and amoxicillin in neonatal and infant 246 Journal of Paediatrics and Child Health 55 (2019) 245–251 © 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians) Letters to the Editor