Vancomycin efficiency and safety of a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis.

Background: Optimal vancomycin trough concentrations and dosages remain controversial in sepsis children. We aim to investigate vancomycin treatment outcomes with a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis from a clinical perspective. Methods: Children diagnosed with Gram-positive bacterial sepsis and received intravenous vancomycin therapy between January 2017 and June 2020 were enrolled retrospectively. Patients were categorized as success and failure groups according to treatment outcomes. Laboratory, microbiological, and clinical data were collected. The risk factors for treatment failure were analyzed by logistic regression. Results: In total, 186 children were included, of whom 167 (89.8%) were enrolled in the success group and 19 (10.2%) in the failure group. The initial and mean vancomycin daily doses in failure group were significantly higher than those in success group [56.9 (IQR =42.1-60.0) vs. 40.5 (IQR =40.0-57.1), P=0.016; 57.0 (IQR =45.8-60.0) vs. 50.0 (IQR =40.0-57.6) mg/kg/d, P=0.012, respectively] and median vancomycin trough concentrations were similar between two groups [6.9 (4.0-12.1) vs.7.3 (4.5-10.6) mg/L, P=0.568)]. Moreover, there was no significant differences in treatment success rate between vancomycin trough concentrations ≤15 mg/L and >15 mg/L (91.2% vs. 75.0%, P=0.064). No vancomycin-related nephrotoxicity adverse effects occurred among all enrolled patients. Multivariate analysis revealed that a PRISM III score ≥10 (OR =15.011; 95% CI: 3.937-57.230; P<0.001) was the only independent clinical factor associated with increased incidence of treatment failure. Conclusions: Vancomycin dosages of 40-60 mg/kg/d are effective and have no vancomycin-related nephrotoxicity adverse effects in children with Gram-positive bacterial sepsis. Vancomycin trough concentrations >15 mg/L are not an essential target for these Gram-positive bacterial sepsis patients. PRISM III scores ≥10 may serve as an independent risk factor for vancomycin treatment failure in these patients.

Effects of continuous venovenous hemofiltration on vancomycin trough concentrations in critically ill children.

BACKGROUND: Vancomycin trough concentrations are associated with clinical outcomes and drug adverse effects. This study investigates the effects of continuous venovenous hemofiltration (CVVH) on vancomycin trough concentrations in critically ill children with a vancomycin dosage of 40-60 mg/kg/day. METHODS: Children with steady-state vancomycin trough concentrations admitted to the pediatric intensive care unit (PICU) between January 2016 and December 2019 were retrospectively enrolled. Patients were divided into CVVH and non-CVVH groups according to treatment differences and renal function. Vancomycin trough concentrations were then compared between the groups, and risk factors for supratherapeutic trough concentrations (>20 mg/L) were analyzed with logistic regression. RESULTS: Of the 119 patients included, 35 were enrolled in the CVVH group and 84 in the non-CVVH group. Median vancomycin trough concentrations were significantly higher in the CVVH group than those in the non-CVVH group [14.9 (IQR =9.6-19.6) vs. 9.3 (IQR =7.0-13.4), P<0.001] and the proportion of therapeutic trough concentrations (10-20 mg/L) was similar between CVVH and non-CVVH groups (54.3% vs. 39.3%, P=0.133). However, CVVH therapy patients had a significantly higher proportion of supratherapeutic trough concentrations (20.0% vs. 1.2%, P=0.001) compared to the non-CVVH group. Multivariate analysis demonstrated that the Pediatric Risk of Mortality (PRISM) III score ≥28 (OR =13.7; 95% CI, 1.4-137.0; P=0.026] was an independent risk factor for supratherapeutic trough concentrations in critically ill patients. CONCLUSIONS: CVVH therapy affects vancomycin trough concentrations and is associated with supratherapeutic concentrations with a 40-60 mg/kg/day vancomycin dosage. PRISM III scores ≥28 may serve as an independent risk factor for supratherapeutic trough concentrations in children receiving CVVH therapy.

Adjunctive rifampin for the treatment of Staphylococcus aureus bacteremia with deep infections: A meta-analysis.

BACKGROUND: Staphylococcus aureus (S. aureus) bacteremia (SAB) has high morbidity and mortality, with the development of methicillin-resistant S. aureus (MRSA) and the recognized shortcomings of vancomycin, its management is becoming more complicated. Considering the capability to penetrate cells, tissues and biofilms, rifampin has been used as adjunctive agent to against staphylococcal activity. OBJECTIVES: We performed this meta-analysis, aimed to explore the efficacy of adjunctive rifampin for the treatment of SAB. METHODS: Medical literatures were searched in the Pubmed, Medline, Embase and Cochrane databases up to October 2018. Patients with SAB received treatment with or without rifampin were included. The risk ratio (RR) and 95% confidence intervals (CI) of mortality, rate of bacteriological failure and relapse were estimated. RESULTS: Seven articles (five randomized controlled trials and two retrospective cohort studies) enrolling 979 and 636 patients of SAB treated with and without rifampin, respectively, were included. There was no difference of mortality between the adjunctive rifampin therapy and standard therapy on SAB (RR: 0.771, 95% CI: 0.442 to 1.347, I2 = 70.4%). In the subgroup analyses, the decreased mortality was observed in the adjunctive rifampin treatment for patients without MRSA infection (RR: 0.509, 95% CI: 0.372 to 0.697, I2 = 8.8%). In addition, there was no difference of the rate of bacteriologic failure (RR: 0.602, 95% CI: 0.198 to 1.825, I2 = 0.0%) or relapse (RR: 0.574, 95% CI: 0.106 to 3.112, I2 = 77.9%) between the adjunctive rifampin therapy and standard therapy on SAB. CONCLUSIONS: In general, insufficient evidence supported the efficacy of adjunctive use of rifampin for treatment of SAB, adding rifampin to standard therapy didn't decrease the incidence of death, rate of bacteriologic failure and relapse.