Incidence and risk factors influencing the development of vancomycin nephrotoxicity in children.

OBJECTIVE: To determine the incidence of vancomycin-associated nephrotoxicity in children and to examine potential risk factors for nephrotoxicity, including average serum trough concentrations ≥ 15 mg/L. STUDY DESIGN: Patients ≥ 1 week old to ≤ 19 years with normal baseline serum creatinine values who received vancomycin for ≥ 48 hours between December 2007 and April 2009 were retrospectively evaluated. Nephrotoxicity was defined as a serum creatinine increase of ≥ 0.5 mg/dL or ≥ 50% baseline increase over 2 days. Patients with average serum trough concentrations ≥ 15 mg/L were compared with a lower trough group. RESULTS: Nephrotoxicity occurred in 14% of 167 patients. More patients who attained high average (≥ 15 mg/L) rather than low average (<15 mg/L) vancomycin troughs had nephrotoxicity (28% versus 7.3%, P = .0001). Using multivariable regression analysis, patients with high troughs and those receiving furosemide in the intensive care unit were more likely to have nephrotoxicity (OR, 3.27 [95% CI, 1.19 to 8.95], P = .021, and odds ratio, 9.45 [95% confidence interval, 3.44 to 26.00], P < .0001, respectively). CONCLUSIONS: Renal function and serum troughs in children receiving vancomycin, especially those with targeted troughs of ≥ 15 mg/L, in intensive care, and receiving furosemide, should be closely monitored.

Phase I/II trial of intravenous recombinant interleukin-2 in HIV-infected children.

OBJECTIVES: To define the tolerated dose of recombinant interleukin-2 (rIL-2) in HIV-infected children (part A), and to determine the safety and immunologic effects of the tolerated rIL-2 dose in a cohort of HIV-infected children (part B). DESIGN: Open-label, dose-escalation. SETTING: Multiple center study. SUBJECTS: Twenty HIV-infected children, aged 3-12 years. INTERVENTION: In part A six subjects received 1 x 10(6) IU/m2 and four subjects received 4 x 10(6) IU/m2 rIL-2 by continuous intravenous infusion for 5 days every 8 weeks for three cycles. In part B 10 different subjects received 1 x 10(6) IU/m2 for 5 days every 8 weeks for six cycles. MAIN OUTCOME MEASURES: Toxicity, CD4 cell count and percentage, and viral load. RESULTS: The tolerated dose of rIL-2 was 1 x 10(6) IU/m2. The most common side effects were fever and vomiting. Of 10 subjects enrolled in part B of the study, five discontinued rIL-2 therapy for a variety of reasons, most related to administration of study drug. Comparable rises in CD4 cell count and percentage were observed in each of the treatment arms. Six cycles of rIL-2 therapy did not appear to be better than three cycles with respect to improvement of CD4 parameters. Transient rises in plasma HIV-1 RNA levels were detected in some subjects. CONCLUSIONS: These results suggest that rIL-2 therapy can raise CD4 cell counts and percentages in some HIV-infected children, although a high proportion of HIV-infected children may have to discontinue intravenous therapy because of drug- or administration-related toxicity. Controlled trials of rIL-2 in this patient population are warranted.

Two-dimensional 1H MR spectroscopy of the brain in human immunodeficiency virus (HIV)-infected children.

PURPOSE: To measure cerebral metabolites in brains of human immunodeficiency virus (HIV)-infected patients using two-dimensional (2D) proton ((1)H) magnetic resonance spectroscopy (MRS), which enables more sensitive detection of metabolites at lower concentrations and delineation of the components of the different choline (Ch) groups in the frequency domain when compared to one dimensional (1D) (1)H-MRS. MATERIALS AND METHODS: We examined metabolite/creatine (Cr) and metabolite/Ch ratios in the left frontal brain of 10 HIV-infected (mean age 13.7 +/- 4.7 years) and 11 control (mean age 15.3 +/- 4.6 years) adolescents and children using 2D localized chemical shift correlated spectroscopy (L-COSY). The integrated volume under each 2D metabolite peak was calculated with reference to the diagonal creatine methyl peak (Cr_d) or the diagonal choline trimethylamine peak (Ch_d). RESULTS: In the HIV-infected patients, myoinositol (mI)/Cr_d (P = 0.009) and mI/Ch_d (P = 0.006) were elevated. The ratios of the following metabolites were also significantly elevated (P < 0.05): mI-Ch/Cr_d, gamma-aminobutyrate (GABA)/ Cr_d, GABA/Ch_d, threonine-lactate (Thr-Lac)/Cr_d, Thr-Lac/Ch_d, and N-acetyl aspartate (NAA)/Cr_d. CONCLUSION: We have demonstrated for the first time the feasibility of 2D-MRS in HIV-infected children and adolescents to assess cerebral metabolites and found elevated mI and elevated GABA, in the left frontal brain of clinically stable HIV-infected patients. A larger study population is needed to confirm these pilot GABA findings.