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

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.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.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).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

Quantitative Human Immunodeficiency Virus (HIV)-1 Antibodies Correlate With Plasma HIV-1 RNA and Cell-associated DNA Levels in Children on Antiretroviral Therapy

BackgroundThis study measured serial plasma human immunodeficiency virus (HIV)-1-specific antibody (Ab) levels in children who initiated antiretroviral therapy (ART) prior to 2 years of age, and evaluated their relationship to peripheral blood HIV-1 RNA and DNA levels.MethodsWe studied 46 HIV-1-infected children, stratified by age at ART initiation (<3 mo, early therapy [ET]; >3 mo-2 years, late therapy [LT]) and by virologic response (R) or non-response (NR), before and up to 4 years following ART. We studied 20 HIV-1-uninfected children born to HIV-1-infected mothers (seroreverters [SR]) as controls. Plasma immunoglobulin G (IgG) Ab levels directed against HIV-1 envelope (gp160, gp41), gag (capsid, p24; matrix, p17), reverse transcriptase (p66/51), and integrase (p31) were serially measured using quantitative enzyme-linked immunosorbent assays. HIV-1 Ab rates of decline were estimated over the first 15 months of the study.ResultsThe HIV-1 Ab rates of decline in the ET-R group were similar to those in the SR group for all Ab specificities, except for p17 (P = .01). Ab decline rates in the LT-R group and the NR group were significantly slower than in the SR group for all tested Ab specificities. After 1 year of age, Ab levels to p31 and p17 were significantly associated with HIV-1 RNA levels (P < .001); Ab levels to gp160 (P < .001) and gp41 (P < .001) were significantly associated with cell-associated HIV-1 DNA levels.ConclusionsQuantitative HIV-1-specific Ab levels may be useful for screening children on ART for viral suppression or for residual, cell-associated HIV-1 DNA levels.Clinical trials registrationNCT00000872

Safety, Efficacy and Pharmacokinetics of Anidulafungin in Patients 1 Month to <2 Years of Age with Invasive Candidiasis, including Candidemia

Nineteen patients 1 month to &lt;2 years of age with (n = 16) or at high risk of (n = 3) invasive candidiasis received anidulafungin for 5-35 days (3 mg/kg day 1, 1.5 mg/kg daily thereafter) followed by optional fluconazole (NCT00761267). Most treatment-emergent adverse events were mild/moderate, and no treatment-related deaths occurred. End of intravenous therapy global response success rate was 68.8%. Pharmacokinetics were similar to adult patients

Markers of Spontaneous Preterm Delivery in Women Living With HIV: Relationship With Protease Inhibitors and Vitamin D

Background: Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. Design: Plasma was obtained from 103 WLHIV with SPTD (= 37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNF alpha, IFNy gamma, IL6, IL8, IL1 beta, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Ra, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GRO alpha, MMP9, IL10, TGF beta, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. Results: Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Ra was associated with increased risk of SPTD. High sCD14, GCSF, PGF2 alpha, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2 alpha, and lower anti-inflammatory 5-HEPE. Conclusions: The best plasma predictor of SPTD in WLHIV was sIL2R alpha, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder

Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women

Objective.To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum. Methods.HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated. Results.Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, 60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing. Conclusions.Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy. Clinical Trials Registration.NCT00825929 and NCT000422890.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe