Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2–10 mg/L, but was adjusted to 2–5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5–15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2–21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug–drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ.

Relapse of neonatal meningitis is most commonly caused by Escherichia coli. Management to prevent relapse varies and evidence is limited. We present four cases of relapsing neonatal E. coli meningitis in Denmark in 2016–2017 and review the current literature on this subject. During the primary episodes, our patients received cephalosporin for 3 weeks and gentamicin for the first 3 days. The only identified risk factor was delayed CSF sterilization in three of four cases and no repeated lumbar puncture. Relapse occurred after 2–28 days; one case with ventriculitis and one with empyema. Relapses were treated for 6–14 weeks with monotherapy. No children had an underlying disease predisposing to E. coli meningitis. There is generally a trend towards reducing invasive procedures, e.g., lumbar puncture and the length of intravenous antibiotics in pediatric infectious diseases, but our cases highlight a condition where the opposite might be needed.

Liposomal amphotericin-B (L-AmB) prophylaxis is used in children with leukemia when azoles are contraindicated, but its effect is debated. We reviewed cases of invasive aspergillosis despite L-AmB 2.5 mg/kg twice weekly in children with high-risk leukemia during 2012-2019. Ten (16%) of 62 children had proven or probable aspergillosis. Thus, L-AmB prophylaxis offered insufficient protection for Aspergillus, in particular for Aspergillus flavus.

Childhood illness is extremely common and imposes a considerable economic burden on society. We aimed to quantify the overall economic burden of childhood illness in the first three years of life and the impact of environmental risk factors. The study is based on the prospective, clinical mother–child cohort Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) of 700 children with embedded randomized trials of fish-oil and vitamin D supplementations during pregnancy. First, descriptive analyses were performed on the total costs of illness, defined as both the direct costs (hospitalizations, outpatient visits, visit to the practitioner) and the indirect costs (lost earnings) collected from the Danish National Health Registries. Thereafter, linear regression analyses on log-transformed costs were used to investigate environmental determinants of the costs of illness. The median standardized total cost of illness at age 0–3 years among the 559 children eligible for analyses was EUR 14,061 (IQR 9751–19,662). The exposures associated with reduced costs were fish-oil supplementation during pregnancy (adjusted geometric mean ratio (GMR) 0.89 (0.80; 0.98), p = 0.02), gestational age in weeks (aGMR = 0.93 (0.91; 0.96), p < 0.0001), and birth weight per 100 g (aGMR 0.98 (0.97; 0.99), p = 0.0003), while cesarean delivery was associated with higher costs (aGMR = 1.30 (1.15; 1.47), p < 0.0001). In conclusion, common childhood illnesses are associated with significant health-related costs, which can potentially be reduced by targeting perinatal risk factors, including maternal diet during pregnancy, cesarean delivery, preterm birth and low birth weight.

Improved methods are needed for diagnosing infectious diseases in children with cancer. Most children have fever for other reasons than bacterial infection and are exposed to unnecessary antibiotics and hospital admission. Recent research has shown that host whole blood RNA transcriptomic signatures can distinguish bacterial infection from other causes of fever. Implementation of this method in clinics could change the diagnostic approach for children with cancer and suspected infection. However, extracting sufficient mRNA to perform transcriptome profiling by standard methods is challenging due to the patient’s low white blood cell (WBC) counts. In this prospective cohort study, we succeeded in sequencing 95% of samples from children with leukaemia and suspected infection by using a low-input protocol. This could be a solution to the issue of obtaining sufficient RNA for sequencing from patients with low white blood cell counts. Further studies are required to determine whether the captured immune gene signatures are clinically valid and thus useful to clinicians as a diagnostic tool for patients with cancer and suspected infection.