Background Voriconazole pharmacokinetic (PK) and pharmacodynamic (PD) data are lacking in children. Methods Records at the Childrens Hospital Los Angeles were reviewed for children with ≥1 serum voriconazole concentration obtained between May 1, 2006 and June 1, 2007. Demographics, dosing histories, serum concentrations, toxicity/survival data and outcomes were obtained. Analysis was with R 2.9.1 and the non-parametric modeling and simulation MM-USCPACK software. Results There were 207 voriconazole concentrations obtained from 46 patients (0.8 – 20.5 years). A 2-compartment Michaelis-Menten PK model fit the data best, but only explained 80% of the observed variability. Crude mortality was 13 (28%), and each trough serum voriconazole concentration <1,000 ng/mL was associated with a 2.6-fold increased odds of death (95% CI 1.6 – 4.8, P=0.002). Serum voriconazole concentrations were not associated with hepatotoxicity. Simulations predicted an intravenous dose of 7 mg/kg or oral dose of 200 mg twice daily would achieve a trough >1,000 ng/mL in the majority of patients, but with a very wide range of possible concentrations. Conclusions We found a PD association between a voriconazole trough >1,000 ng/mL and survival, and marked PK variability, particularly after enteral dosing, justifying measurement of serum concentrations.

Objectives: To use the ethanol-lock technique (in conjunction with systemic antibiotics) to salvage central lines from removal and to prevent persistence of catheterrelated infections among pediatric patients with longterm intravascular devices. Patients: Forty children with diverse underlying disorders were treated for 51 catheter-related infections using the Childrens Hospital Los Angeles ethanol-lock technique.Interventions: Eligible infected central lines were instilled with a dose volume of 0.8 to 1.4 mL of 70% ethanol into the catheter lumen during 12 to 24 hours and then withdrawn. The volume of ethanol used was based on the type of intravascular device. Main Outcome Measures:Clearance of infection and incidence of recurrence.Results: Of the 51 ethanol-lock treatments in 40 children, no catheters were removed because of persistent infection. Eighty-eight percent (45/51) of the treated episodes cleared without recurrence (defined as a relapse within 30 days with the same pathogen). Twelve (75%) of 16 polymicrobial isolates and 33 (94%) of 35 monomicrobial isolates were successfully treated. There were no adverse reactions or adverse effects reported. Conclusion:This retrospective study supports the use of the ethanol-lock technique in conjunction with systemic antibiotics as an effective and safe method to retain the use of a previously infected central venous catheter, decrease the need for line removal, and eradicate persistent pathogens in catheter-related infections.

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Graft-versus-host disease (GVHD) is a cause of serious morbidity and mortality in >50% of recipients of unrelated hematopoietic stem cell transplantation (HSCT). We performed a trial using Campath 1 H pre- and post-HSCT in an attempt to decrease the incidence of GVHD without increasing the risk of infection or relapse. Patients were retrospectively compared to a population of patients who received antithymocyte globulin (ATG) pre- and post-HSCT. Twenty-seven patients were evaluated for this study. Fourteen patients received Campath 1H and 13 patients received ATG. Demographics of patients who received Campath 1H consisted of 9 males and 5 females, with a median age of 13 years (3-17.8 years). Thirteen patients received unrelated bone marrow and 1 patient received unrelated PBSC. Demographics of patients receiving ATG consisted of 9 males, 4 females with a median age of 7.4 years (21 months-19 years). Twelve patients received unrelated bone marrow and 1 patient received unrelated PBSC. Diagnoses were similar between the 2 groups. Patients who received Campath1H received a total dose of 52 mg/m(2) pre-HSCT and 20 mg/m(2) post-HSCT. Patients who received ATG received a total dose of 60 mg/kg pre-HSCT and 100 mg/kg post-HSCT. GVHD prophylaxis and supportive care measures were similar in both groups, including aggressive antimicrobial therapy. There was a significant difference in the incidence of severe (grade III and grade IV) GVHD between the 2 groups (Campath [0 of 14] versus ATG [6 of 13], P = .006). Among the patients who were transplanted for leukemia, there was no significant difference between the 2 groups in terms of relapse (Campath [2 of 14] versus ATG [4 of 9], P = 0.16). The 100-day survival between the 2 groups was not significantly different. Patients receiving Campath 1H had the presence of CD3(+) T cells (>30 cells/mL) in their peripheral blood later than in those who received ATG (64.5 days [Campath 1H] versus 27days [ATG], P = .001). The median time to the development of a normal PHA response occurred later in the Campath 1H arm (283 days[(Campath 1H] versus 88 days [ATG], P = .0001). The median time to an antigen specific response also occurred later in those receiving Campath 1H (365 days [Campath 1H] versus 150 days [ATG], P = .004). There was no significant difference between the 2 groups in terms of fungal or viral infections. Campath 1H is effective in decreasing the incidence of GVHD without increasing the risk of relapse. Although there is a significant delay in immune reconstitution, there was no increase in infectious complications or relapse in recipients of Campath 1H. Further studies are warranted to assess if a lack of difference in infection rates are still demonstrated in larger cohorts.

CPx neither alter the incidence of overall bacteremia nor change the pattern of fever or use of supportive care. Our experience supports further investigation into the use of extended-spectrum quinolone prophylaxis during therapy for pediatric AML.