Factors predicting efficacy of ethanol lock therapy as catheter salvage strategy for pediatric catheter-related infections.

AIM: Catheter-related infections are difficult to cure, and failure rates are high. We aimed to evaluate the efficacy and safety of ethanol lock therapy (ELT) as catheter salvage strategy in children with central-line-associated bloodstream infection (CLABSI), and to identify factors associated with treatment failure. METHODS: Data were collected of all the children who received ELT for treatment of CLABSI during 2013-2018 due to failure of standard therapy or multiple catheter-related infections. Univariate and multivariate analyses of risk-factors for ELT failure were performed. Catheter salvage rates were compared to those achieved using systemic antimicrobials alone in an historical control group. RESULTS: A total of 123 ELT episodes among 95 patients were analyzed. The majority of patients had underlying hemato-oncological disorders. Approximately half the episodes occurred in patients with implantable ports. Early and late treatment failure rates of ELT were 16% (20/123) and 7% (9/123), respectively. Overall, successful catheter salvage was achieved in 78% (96/123) of episodes, compared to 54% using systemic antimicrobials alone (P < .001), including mycobacterium, candida, and most staphylococcus aureus infections. Adverse events were reported in 9% (11/123) of episodes and were mostly mechanical. Multivariate analysis identified four risk factors for ELT failure: Gram-positive bacteria, elevated C-reactive protein, signs of tunnel infection, and low absolute neutrophil counts. CONCLUSIONS: Our findings support the use of ELT for catheter salvage in children with CLABSI who failed standard therapy or had multiple catheter-related infections. The identified variables associated with ELT failure may help identify patients who can most benefit from ELT.

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antipsychotic Medications Palliate Symptoms in Children with Cancer.

Objectives: The present study characterized the psychiatric diagnoses and symptoms that led to the administration of antipsychotic medications in children and adolescents with cancer, and to evaluate the benefits and tolerability of these drugs in a large hospital-based pediatric hematology-oncology practice. Methods: Efficacy and adverse effects of two second-generation antipsychotics were retrospectively analyzed in 43 patients 2.9-19.6 (mean 12.1) years of age. The Clinical Global Impression-Severity (CGI-S) Scale and Improvement (CGI-I) Scale were used to evaluate psychiatric symptom severity before and following treatment, while the incidence of side effects and drug-drug interactions were collected from medical records. Results: Olanzapine was administered to 58% of patients and risperidone to 42%; the choice of drug was at the discretion of the treating psychiatrist. The common psychiatric diagnoses among these patients included adjustment disorder (37%) and medication-induced psychiatric disorders (23%). The most common psychiatric-medical symptoms included irritability/agitation (79%) and depressed mood (74%). CGI-S improved significantly (p < 0.001) between assessments, with no statistically significant difference between olanzapine- and risperidone-treated patients. CGI-I scores at reassessment indicated superiority of olanzapine as compared with risperidone. Adverse effects of treatment were mild. Conclusions: Olanzapine and risperidone can be well tolerated and ameliorate severe psychiatric-medical symptoms in children and adolescents with cancer. The potential palliative benefits of these second-generation antipsychotics (e.g., rapid onset of action, antiemesis, sedation, and appetite stimulation) increase the utility of their use in children treated in oncology and bone marrow transplant units.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study.

BACKGROUND: Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens. METHODS: The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated. RESULTS: Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given. CONCLUSIONS: The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.