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There are limited data to guide treatment recommendations for children with acute, symptomatic coronavirus disease 2019 (COVID-19). This review outlines a proposed management approach for children based on the published evidence to date and the approval of medications through drug regulatory agencies, as well as the known safety profile of the recommended drugs in this age group.

Therapeutic drug monitoring (TDM) of voriconazole is recommended to achieve trough concentrations of 1-5 mg/L. In children, this is challenging due to age-related variability in voriconazole pharmacokinetics. This study describes our experience with voriconazole, focusing on dosing regimens, dose adjustment and TDM.We reviewed the medical records of immunocompromised children who received voriconazole from July 2009 to January 2015 and had TDM. Demographic, clinical and voriconazole dosing and monitoring data were collected.Fifty-five children received 62 courses of voriconazole and had TDM, with a total of 256 samples taken. Only 71.0% of courses (44/62) had TDM at the correct time, and at least one therapeutic level was achieved in only 52.3% (23/44) of these. Twenty-six courses had at least one sub-therapeutic level and in only 61.5% was the dose adjusted. Patients aged6, 6-12 and12 years required median intravenous doses of 8.8, 7.5 and 4.0 mg/kg twice daily, respectively (P 0.001). With oral administration, patients aged 6-12 and12 years required median doses of 4.7 and 4.3 mg/kg twice daily, respectively (P = 0.307). Levels within the target range were observed to fall below 1 mg/L in 36.4% of unchanged dosing regimens. Photosensitive skin reactions (20.0%) and hepatotoxicity (12.7%) were the most frequent adverse events and occurred in children with voriconazole levels5 mg/L.There is significant intra- and inter-individual variability in voriconazole concentrations in children, particularly in children6 years of age. This warrants repeated TDM throughout treatment. Standardized guidelines for TDM and dose adjustment are required in children.

Our proposal to perform a randomised trial of antiviral treatments for children with moderate to severe COVID-19 has frequently been met with the view that it is not ethical. Central concerns have been that children frequently have no symptoms (when in fact symptoms occur in 21% of children), that severe presentations are rare (2%)1 and that treatments should only be evaluated in children once the results of adult trials are available. Certainly, medical research involving children raises distinctive ethical issues. Children are more vulnerable than most adults, and many lack capacity to provide informed consent to potentially harmful research.2 As with all human research, the risks of a trial in children must be carefully weighed against the possible benefits to …

Itraconazole is a broad-spectrum antifungal agent used for prophylaxis and treatment of fungal infections in immunocompromised children. Achieving the recommended target serum itraconazole trough concentration of ≥0.5 mg/L is challenging in children because of variation in itraconazole pharmacokinetics with age. We studied itraconazole use and treatment outcomes in a tertiary children's hospital.We did a 10-year retrospective review of medical records of children at the Royal Children's Hospital Melbourne who received oral itraconazole and had therapeutic drug monitoring (TDM).Overall, 81 children received 92 courses of oral itraconazole and had TDM. Of 222 TDM samples, 183 (82.4%) were taken at the appropriate time (trough level at steady state). Patients ≤12 and12 years of age required median doses of 6.2 and 3.9 mg/kg/d, respectively, to attain target trough levels (P0.001). Of children ≤12 years of age, 71.4% required doses above the recommended dose of 5 mg/kg/d to achieve therapeutic levels, compared with 17.4% of those12 years of age. At least 1 subtherapeutic trough concentration was reported in 63 (76.8%) courses; in only 18 (28.6%) of these was the dose adjusted. Gastrointestinal symptoms [14/92 (15.2%) courses] and hepatotoxicity [6/92 (6.5%)] were the most frequent adverse events. Neither was associated with elevated trough levels.The poor attainment of target levels with current recommended dosing in children12 years of age suggests that higher empiric doses are needed in this age group. The poor compliance with TDM guidelines highlights the need for better education about appropriate timing of sampling and dose adjustment.

A 6-year-old girl presents with fever, rash and arthralgia 1 week after returning from a camping trip to South Africa. After exclusion of other potential diagnoses, her rickettsia serology is found to be positive and you decide to prescribe a course of doxycycline. However, the package insert states that doxycycline is contraindicated in children

While covering the paediatric haematology–oncology ward, you are asked to prescribe co-trimoxazole for prophylaxis against Pneumocystis jirovecii pneumonia (PJP). You refer to your usual drug resources discovering a variety of different dosing options and wonder which regimen you should prescribe. In immunocompromised children and adolescents without HIV infection (patient), which co-trimoxazole dosing regimen (intervention) is most effective in preventing PJP and best tolerated (outcome)? We searched Medline (1946 to current) and Embase (1974 to current) via the OVID interface in July 2015. The following keywords were used: trimethoprim (TMP)–sulfamethoxazole combination, TMP, sulfamethoxazole, drug combinations, pneumocystis infections, pneumocystis, pneumocystis pneumonia, chemoprevention, prophylaxis, chemoprophylaxis, prevention and control, infant, newborn, neonate, babies or baby, toddler, preschooler, child, adolescent, or paediatric. The search was limited to English language studies in humans aged 0–18 years. This identified a total of 972 publications. Articles were included if the specific dosing regimen of TMP–sulfamethoxazole was stated and outcomes were reported separately for patients under 18 years of age. Only studies examining PJP as an outcome were included. Studies of children with HIV infection and those without a robust case definition for PJP were excluded. Eleven articles fulfilled the inclusion criteria (table 1). The references of all articles were reviewed and no additional studies were identified. View this table: Table 1 Summary of evidence PJP is an opportunistic fungal infection that occurs in primary or acquired immunodeficiency syndromes. Prior to the widespread use of PJP prophylaxis, 15%–43% of children treated for haematological malignancies were affected.1 ,2 Combination TMP and sulfamethoxazole (co-trimoxazole) is effective in preventing PJP and is now the preferred prophylactic agent.3 ,4 However, there is significant variation in recommended dosing regimens. These range from doses on 1–3 consecutive or non-consecutive days per week, administered in 1–2 doses/day, calculated either by weight (usually 5 mg/kg/day TMP component) or body surface area …