Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to <6 [intravenous (i.v.) only], 6 to <12, and 12 to <18 years), receiving 10 mg/kg body weight (maximum, 372 mg) isavuconazonium sulfate either i.v. or orally.

Pediatric patients with invasive fungal infections are often fragile hosts with multiple underlying conditions. Safety is an important feature of antifungal agents to be used in this setting. This study aims to evaluate safety of micafungin in pediatric patients (<16 years of age), enrolled in different studies including pharmacokinetic evaluations and clinical trials for invasive aspergillosis, candidiasis, and antifungal prophylaxis. Adverse event (AE) data were pooled from 6 clinical trials conducted in Europe, the Americas, and Asia. A total of 296 patients with a mean ± standard deviation age of 6.5 ± 5.1 years received ≥1 dose of micafungin; 66 were <1 year of age; 38 were premature. Other common underlying conditions were hematopoietic stem cell transplantation (33.8%) and hematologic malignancy (29.1%). Approximately 40% of patients were neutropenic at baseline (absolute neutrophil count <500 cells/mm). Median daily micafungin dose was 1.7 mg/kg overall (range, 0.4-8.6 mg/kg) and 2.0 mg/kg (range, 0.8-7.7 mg/kg) for neonates <4 weeks old. Median treatment duration was 15 days (range, 1-425 days). During the study, AEs regardless of causality were recorded in 93.2% of subjects; 26.7% were classified as at least possibly related to study drug; and 34% of subjects had AEs meeting criteria for serious AE; of which, 4.7% of subjects experienced serious AEs at least possibly related to study drug. Study drug was discontinued because of AEs in 7 patients (2.4%). No trends were observed with respect to analysis of AEs by dose or duration of treatment. Micafungin was well tolerated by children of all ages including those with life-threatening underlying conditions. AEs thought to be drug related occasionally lead to discontinuation of the treatment.

Congenital syphilis still represents a worldwide public health problem. If left untreated, it can lead to fetal demise and high neonatal morbidity and mortality. Unfortunately, in the last decade, there has been a resurgence of cases in the U.S. This review discusses the ongoing problem of this preventable congenital infection, vertical transmission and clinical manifestations while providing a guidance for the evaluation and management of infants born to mothers with reactive serologic tests for syphilis.

Invasive aspergillosis (IA) and mucormycosis (IM) cause significant morbidity and mortality in immunocompromised and/or hospitalized patients. Isavuconazonium sulfate, a prodrug of the antifungal triazole isavuconazole, has been approved for treatment of IA and IM in adults; and was recently approved in children. This study describes the outcomes, safety, and pharmacokinetics of isavuconazole for the treatment of proven, probable, or possible IA or IM in children. In this phase 2, open-label, non-comparative study, patients aged 1 to <18 years with at least possible invasive mold disease were enrolled across 10 centers in the US, Spain, and Belgium from 2019 to 2022. Patients received 10 mg/kg isavuconazonium sulfate daily (maximum 372 mg; equivalent to 5.4 mg/kg or 200 mg isavuconazole) for up to 84 (IA) or 180 days (IM). Outcomes included rates of all-cause case fatality, overall response, treatment-emergent adverse events (TEAEs), and pharmacokinetics. Of 31 patients enrolled, 61.3% were 1–<12 years old; 58.1% had underlying hematologic malignancies. The successful overall response rate at the end of treatment was 54.8%. Day 42 all-cause case fatality was 6.5%; 93.5% experienced TEAEs, and two patients discontinued treatment due to drug-related TEAEs. Dosing at 10 mg/kg (maximum dose: 372 mg) met the pre-defined exposure threshold of above the 25th percentile for the area under the concentration-time curve (≥60 mg·h/L). Simulated doses of 15 mg/kg improved drug exposures in patients aged 1–<3 years. Isavuconazole was well tolerated in children, with exposure consistent with adult studies. Successful response was documented in 54.8% of patients. CLINICAL TRIALS: This study is registered at ClinicalTrials.gov as NCT03816176 .

Recurrent and persistent acute otitis media (AOM) is a common problem, affecting close to 20% of children in their first years of life. It presents a therapeutic challenge to physicians, particularly as beta-lactamase-producing Haemophilus influenzae, as well as penicillin- and, more recently, macrolide-resistant Streptococcus pneumoniae are often responsible for AOM in these patients. Intramuscular ceftriaxone (50 mg/kg, once daily for 3 days) has been shown to be effective in treating nonresponsive AOM, but there have been relatively few clinical trials exploring oral antibiotic regimens. Higher doses of commonly used antibiotics (amoxicillin-clavulanate ratio, 14:1 ratio and azithromycin 60 mg/kg divided into three equal once daily doses) have demonstrated high rates of clinical success. These studies will be discussed together with a review of the clinical and microbiologic characteristics of this disease. We will also address the impact that the pneumococcal conjugate vaccine may have on the microbiology of recurrent and persistent AOM.