Impact of model-informed precision dosing in adults receiving vancomycin via continuous infusion: a randomized, controlled clinical trial.

BACKGROUND: Vancomycin is a commonly prescribed antibiotic to treat gram-positive infections. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. However, in most countries, steady-state plasma concentrations are used as a surrogate parameter of target AUC/MIC, but this practice has some drawbacks. Hence, direct AUC-guided monitoring of vancomycin using model-informed precision dosing (MIPD) tools has been proposed for earlier attainment of target concentrations and reducing vancomycin-related nephrotoxicity. However, solid scientific evidence for these benefits in clinical practice is still lacking. This randomized controlled trial (RCT) aims to investigate the clinical utility of MIPD dosing of vancomycin administered via continuous infusion in hospitalized adults. METHODS: Participants from 11 wards at two Belgian hospitals are randomly allocated to the intervention group or the standard-of-care comparator group. In the intervention group, clinical pharmacists perform dose calculations using CE-labeled MIPD software and target an AUC24h of 400 to 600 mg × h/L, whereas patients in the comparator group receive standard-of-care dosing and monitoring according to the institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400-600 between 48 and 72 h after start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury (AKI) during and until 48 h after stop of vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400-600 between 72 and 96 h after start of vancomycin treatment, and the proportion of time within the target AUC24h/MIC of 400-600. DISCUSSION: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment. TRIAL REGISTRATION: EudraCT number: 2021-003670-31. Registered June 28, 2021. CLINICALTRIALS: gov identifier: NCT05535075. Registered September 10, 2022. Protocol version 3, protocol date: April 21, 2023.

High-risk alcohol use and associated socio-demographic, health and psychosocial factors in patients with HIV infection in three primary health care clinics in South Africa.

Alcohol use may have a negative impact on the course of HIV disease and the effectiveness of its treatment. We studied patients with HIV who use alcohol and associated socio-demographic, health and psychosocial factors. Outcomes from this study may help in selecting patients from clinical practice with high-risk alcohol use and who are likely to benefit most from alcohol reduction interventions. In a cross sectional study in three primary health care clinics in Pretoria, South Africa, from January 2012 to June 2012, patients with HIV infection were interviewed and patients' medical files were reviewed to obtain data on levels of alcohol use (Alcohol Use Disorder Identification Test), patients' socio-demographic characteristics, HIV-related information, health related quality of life (WHOQoL-HIVBref), internalized AIDS stigma, symptoms of depression and adherence to antiretroviral therapy. Analyses consisted of descriptive statistics, bi- and multivariate logistic regression models. A total of 2230 patients (1483 [66.5%] female) were included. The median age was 37 years (interquartile range 31-43), 99.5% were black Africans, 1975 (88.6%) had started ART and the median time on ART was 22 months (interquartile range 9-40). No alcohol was used by 64% of patients, 8.9% were low risk drinkers, 25.1% of patients were hazardous or harmful drinkers and 2.0% had possible alcohol dependence. In multivariate analysis high-risk drinking was positively associated with male gender, never being married, tobacco use, a higher score for the 'level of independence'-domain measured with the WHOQoL-HIVBref questionnaire, and with more depressive symptoms compared to low-risk drinking. This study shows a high prevalence of hazardous or harmful drinking in patients with HIV infection (especially men) attending primary health care clinics in South Africa. Routine screening for alcohol use should be introduced in these clinics and harm reduction interventions should be evaluated, taking into account associated factors.