Optimizing vancomycin dosage regimens in relation to high-flux haemodialysis.

Objectives: To develop a population pharmacokinetic (PK) model for vancomycin in adults receiving high-flux haemodialysis (HFHD) in an effort to optimize vancomycin dosing in this population. Methods: A population PK model using NONMEM was developed using retrospective data collected from 48 vancomycin courses administered to patients (n = 37) receiving HFHD. Fixed-dose [1.5 g loading dose (LD), 1 g maintenance dose (MD)], literature-adapted weight-based (WBL; 20 mg/kg LD, 10 mg/kg MD) and hospital-adapted weight-based (WBH; 25-30 mg/kg LD, 20-25 mg/kg MD) dosage regimens were then simulated using the Monte Carlo method. The PTA was an AUC24/MIC ≥400 with success being a PTA ≥90%. Results: The data were best described using a two-compartment model. It was observed that fixed-dose and WBL dosage regimens resulted in a PTA ≤90% for most days. The WBH dosing achieved a PTA ≥90% on most days, but there were supratherapeutic concentrations with repeated dosing of vancomycin. If HFHD was delayed by 48-72 h after the LD, the PTA would fall below 90%. A dose-optimized regimen was developed: 30 mg/kg LD and 10 mg/kg MD given on HFHD days. An additional dose of 500 mg or 1 g was administered 24 h after the LD if HFHD occurred 48-72 h post-LD. This dose-optimized regimen afforded a PTA ≥90% on all days of therapy and achieved clinically acceptable pre-haemodialysis concentrations. Conclusions: Current vancomycin dosage regimens used clinically do not achieve a PTA ≥90% for most days of therapy for people receiving HFHD. A dose-optimized regimen was developed, which could be implemented in clinical practice.

Patterns of use and appropriateness of antibiotics prescribed to patients receiving haemodialysis: an observational study.

BACKGROUND: There are limited published data on the types and appropriateness of oral and intravenous (IV) antibiotics prescribed to patients receiving haemodialysis. This information is critical to optimise antibiotic prescribing. Therefore this study aims to describe the patterns of use and the appropriateness of oral and IV antibiotics prescribed to patients receiving haemodialysis. METHODS: This was a prospective, observational study across four community and two hospital inpatient haemodialysis units in Melbourne, Australia. Data were collected from July 2014 to January 2015 from participants. Antibiotic regimens prescribed were compared with nationally available antibiotic guidelines and then classified as being either appropriate, inappropriate or not assessable by an expert multidisciplinary team using the National Antimicrobial Prescribing Survey tool. RESULTS: Overall, 114 participants consented to this study where 55.3% (63/114) received antibiotics and 235 antibiotic regimens were prescribed at a rate of 69.1 antibiotic regimens/100 patient-months. The most common oral antibiotics prescribed were amoxycillin/clavulanic acid and cephalexin. The most common IV antibiotics prescribed were vancomycin, piperacillin/tazobactam, cephazolin and ceftriaxone. The percentage of inappropriate antibiotic regimens prescribed were 34.9% (15/43) in the community setting and 22.1% (40/181) in the hospital setting. Furthermore, 29.4% (30/102) of oral and 20.5% (25/122) of IV antibiotic regimens were inappropriate with incorrect dosing as the primary reason. CONCLUSION: Although this study is limited by the sample size, it describes the high antibiotic exposure that patients receiving haemodialysis experience. Of concern is inappropriate dose and frequency being a major issue. This requires interventions focused on the quality use of medicines and antimicrobial stewardship aspects of prescribing in this population.

Infliximab Trough Levels Are Associated With Transmural Sonographic Healing in Inflammatory Bowel Disease.

BACKGROUND: Mucosal healing improves clinical outcomes in patients with inflammatory bowel disease (IBD) and is associated with higher infliximab trough levels (ITLs). Transmural healing, assessed by intestinal ultrasound (IUS), is emerging as an objective target in Crohn's disease (CD) and ulcerative colitis (UC). This study explores the correlation between maintenance ITLs and sonographic transmural healing. METHODS: Patients on maintenance infliximab therapy were prospectively enrolled to undergo paired IUS examination and serum ITL. Infliximab trough levels were compared between patients with and without sonographic markers of inflammation using the Mann-Whitney U test. RESULTS: A prospective cohort of 103 patients (51% male; 79 CD; 24 UC; median duration of disease 8 years) underwent IUS and serum ITL testing. Forty-one percent of CD and 66% of UC patients demonstrated sonographic healing (bowel wall thickening ≤3 mm with no increase in color Doppler signal). Crohn's disease patients with sonographic healing had higher median ITL compared with those with sonographic inflammation (4.8 µg/mL vs 3.1 µg/mL; P = .049). Additionally, the presence of hyperemia on Doppler was independently associated with lower ITL compared with those without hyperemia (2.1 µg/mL vs 4.2 µg/mL, respectively; P = .003). There was no significant association between ITL and other sonographic markers of inflammation. In UC, lower ITL was associated with hyperemia on Doppler imaging (P = .04). There was no association between ITL and sonographic healing or any other individual sonographic parameter of inflammation. CONCLUSIONS: Lower maintenance infliximab levels are associated with sonographic parameters of inflammation in UC and CD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.

Transmural healing assessed by intestinal ultrasound allows for objective assessment of disease activity. Lower maintenance infliximab levels were associated with sonographic parameters of inflammation in IBD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.

Pharmacist-Facilitated Interactive E-Learning for Patients Newly Initiated on Warfarin: A Randomised Controlled Study.

It is not known whether electronic-learning (e-learning) is effective for educating hospital inpatients about complex medications such as warfarin. This prospective randomised controlled study compared pharmacist-facilitated e-learning with standard pharmacist-delivered face-to-face education on patients' or their unpaid carers' knowledge of warfarin and satisfaction with warfarin education as well as the time that was spent by pharmacists in delivering warfarin education. Adult English-speaking patients (or their carers) who had been prescribed warfarin were randomised to receive standard pharmacist face-to-face education (control) or an e-learning module on a tablet device facilitated by a pharmacist (intervention). All of the participants received written warfarin information and were presented with the opportunity to ask any questions that they may have had to a pharmacist. Fifty-four participants completed the study (27 per group). The participants who received e-learning had median correct Oral Anticoagulation Knowledge (OAK) test scores of 85% compared to 80% for standard education (p = 0.14). The participants in both groups were satisfied with the information that they received. There was a trend towards pharmacists spending less time on warfarin education for the e-learning group than in the standard education group (25.5 vs. 33 min, respectively, p = 0.05). Education delivered via pharmacist-facilitated e-learning was non-inferior in terms of patient or carer warfarin knowledge compared to standard pharmacist-delivered education.

Improving medication adherence in adult kidney transplantation (IMAKT): A pilot randomised controlled trial.

Resources to support long-term medication adherence in kidney transplantation are limited. This study aimed to determine the efficacy of an intervention designed for kidney transplant recipients to enhance medication adherence. A single-blind, multi-site, 12-month pilot randomised controlled trial was conducted at all five public hospitals providing adult kidney transplantation in Victoria, Australia. Participants were recruited at 4 to 6 weeks post-transplantation. Thirty-five participants were randomly assigned to a 3-month intervention, involving a face-to-face meeting (a medication review and a consumer-centred video) and health coaching every two weeks. Thirty-six were randomised to receive usual care. All participants were followed for nine months post-intervention. There were no differences in adherence between groups measured by Medication Event Monitoring System (MEMS), however, it was underutilised by 42% of participants. Based on the self-reported Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©) score, the percentage of adherent participants decreased significantly between baseline and 3 to 12 months in the control group (p-values < 0.001) whilst the percentage of adherent participants in the intervention group remained constant over time. No group differences were detected in other outcomes. Due to the complex medication regimen, developing and testing a medication adherence intervention is difficult in kidney transplantation.

Vancomycin dosing in chronic high-flux haemodialysis: a systematic review.

The aim of this study was to systematically evaluate whether non-weight-based dosing (non-WBD) or weight-based dosing (WBD) of vancomycin leads to a higher proportion of patients achieving the pharmacokinetic/pharmacodynamic target. Studies from January 1985 to February 2017 were identified through Cochrane, MEDLINE and Embase databases. Those conducted in adults with end-stage renal disease receiving high-flux haemodialysis (HD) and intravenous vancomycin were included. The primary outcome was the proportion of patients with a pre-HD vancomycin concentration of 15-20 mg/L and/or an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio ≥400. Of the 3948 studies screened, 5 met the inclusion criteria. The proportion of patients with pre-HD concentrations between 15-20 mg/L were 35% (non-WBD) and 13% (WBD) post-loading dose. During maintenance dosing, the proportion of patients with pre-HD concentrations between 15-20 mg/L were 37% (non-WBD) and 50-67% (WBD). The proportion of pre-HD concentrations <15 mg/L was greater in the non-WBD group post-loading dose but was similar between the non-WBD and WBD group during maintenance dosing. One study reported that all patients had an AUC/MIC ≥ 400 for micro-organisms with an MIC ≤ 1 mg/L for weight-based maintenance dosing. The limited data suggest that WBD may be preferential as there was a smaller proportion of pre-HD concentrations falling below 15 mg/L. However, larger well-designed studies of higher quality are required to provide guidance for vancomycin dosing in the high-flux HD setting. Future research should focus on reporting AUC/MIC ratios and exploring clinical outcomes in this patient population.