Pre-extensively Drug-Resistant Congenital Tuberculosis in an Extremely Premature Baby.

We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-extensively drug-resistant (XDR) pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital tuberculosis (TB).

Corrigendum to "Lower risk of multi-system Inflammatory Syndrome in Children (MIS-C) with the Omicron variant" [The Lancet Regional Health - Western Pacific 27 (2022) 100604].

[This corrects the article DOI: 10.1016/j.lanwpc.2022.100604.].

Geographic Expansion of Japanese Encephalitis Virus to Australia: Neuroinflammatory Sequelae and Consideration of Immunomodulation.

We report a child from Southern Australia (New South Wales) who presented during a La Niña event with encephalopathy and acute flaccid paralysis. Magnetic resonance imaging suggested Japanese encephalitis (JE). Steroids and intravenous immunoglobulin did not improve symptoms. Therapeutic plasma exchange (TPE) resulted in rapid improvement and tracheostomy decannulation. Our case illustrates the complex pathophysiology of JE, its' geographic expansion into Southern Australia and potential use of TPE for neuroinflammatory sequelae.

An Approach to the Treatment of Children With COVID-19.

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.

Candidemia in Children: A 16-year Longitudinal Epidemiologic Study.

BACKGROUND: Candida species are the most common cause of systemic fungal infections in children. Risk factors for candidemia vary in different patient populations, posing challenges for clinical prediction of infection. We describe the epidemiology and clinical disease of candidemia in children admitted to a tertiary pediatric hospital. METHODS: Retrospective audit of children ≤18 years of age with candidemia at a tertiary pediatric hospital over a 16-year period. RESULTS: There were 139 episodes of candidemia in 124 children. A central venous catheter was present in 94% of episodes, prior antibiotic exposure in 86% and parenteral nutrition in 43%. During the study period, the proportion of candidemia due to non-albicans Candida spp. increased primarily due to a rise in C. krusei. Colonization with Candida spp. in the 30 days before developing candidemia was identified in 40% of episodes and the species was concordant in 60%. Infection at other sites was rare, including pulmonary dissemination (9/38, 24%), renal fungal disease (9/114, 8%), fungal endophthalmitis (8/102, 8%) and hepatosplenic nodules (5/92, 5%). Overall, 8/127 (6%) isolates were fluconazole-resistant (7 C. krusei and 1 C. glabrata) and 7/127 (6%) had intermediate susceptibility to fluconazole. The overall 30-day mortality was 12% and significant risk factors for mortality on multivariate analysis were male sex, liver disease and mucositis. CONCLUSIONS: Our study outlines low rates of disseminated candidiasis and low mortality associated with candidemia at our institution. Additionally, it suggests that prior colonization may be an important risk factor, however, this should be validated in large prospective controlled studies.

Itraconazole Dosing and Drug Monitoring at a Tertiary Children's Hospital.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 and >12 years of age required median doses of 6.2 and 3.9 mg/kg/d, respectively, to attain target trough levels (P < 0.001). 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 those >12 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. CONCLUSIONS: The poor attainment of target levels with current recommended dosing in children <12 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.

Voriconazole dosing and therapeutic drug monitoring in children: experience from a paediatric tertiary care centre.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 aged <6, 6-12 and >12 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 and >12 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 levels <5 mg/L. CONCLUSIONS: There is significant intra- and inter-individual variability in voriconazole concentrations in children, particularly in children <6 years of age. This warrants repeated TDM throughout treatment. Standardized guidelines for TDM and dose adjustment are required in children.