Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections.

Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.

Implementation of Partnered Pharmacist Medication Charting in haematology and oncology inpatients.

AIM: Partnered Pharmacist Medication Charting (PPMC) in patients admitted under general medical units has been shown to reduce medication errors. The aim of this study is to evaluate the impact of the PPMC model on medication errors in patients admitted under cancer units in Victorian hospitals. METHODS: A prospective cohort study comparing cohorts before and after the introduction of PPMC was conducted. This included a 2-month pre-intervention phase and 3-month intervention phase. PPMC was implemented during the intervention phase as new model of care that enabled credentialed pharmacists to chart all admission medications, including pre-admission or new medications and cancer therapies, in collaboration with the admitting medical officer. The proportion of medication charts with at least one error was the primary outcome measure. RESULTS: Seven health services across Victoria were included in the study. The majority of health services were using paper-based prescribing systems for oncology. Of the 547 patients who received standard medical medication charting, 331 (60.5%) had at least one medication error identified compared to 18 out of 416 patients (4.3%) using the PPMC model (p < 0.001). The median (interquartile range) inpatient length of stay was 5 (2.9-10.6) days in pre-intervention and 4.9 (2.9-11) days in intervention (p = 0.88). In the intervention arm, 42 patients had cancer therapy charted by a pharmacist with no errors. CONCLUSIONS: PPMC was successfully scaled into cancer units as a collaborative medication safety strategy. The model was associated with significantly lower rates of medication errors, including cancer therapies. PPMC should be adopted more widely in cancer units in Australia.

Partnered pharmacist medication charting (PPMC) in regional and rural general medical patients.

OBJECTIVE: Errors in hospital medication charts are commonly encountered and have been associated with morbidity and mortality. This study evaluates the impact of the Partnered Pharmacist Medication Charting (PPMC) model on medication errors in general medical patients admitted to rural and regional hospitals. DESIGN/METHOD: A prospective cohort study, comparing before and after the introduction of PPMC was conducted in 13 rural and regional health services. This included a 1-month pre-intervention phase and 3-month intervention phase. In the intervention phase, PPMC was implemented as a new model of care in general medical units. SETTING: Victoria, Australia. PARTICIPANTS: Patients admitted to General Medical Units. OUTCOME MEASURE: The proportion of medication charts with at least one error was the primary outcome measure. Secondary outcome measures included inpatient length of stay (LOS), risk stratification of medication errors, Medical Emergency Team (MET) calls, transfers to ICU and hospital readmission. RESULTS: Of the 669 patients who received standard medical charting during the pre-intervention period, 446 (66.7%) had at least one medication error identified compared to 64 patients (9.5%) using PPMC model (p < 0.001). There were 1361 medication charting errors identified during pre-intervention and 80 in the post-intervention. The median (interquartile range) inpatient length of stay was 4.8 (2.7-10.8) in the pre-intervention and 3.7 days (2.0-7.0) among patients that received PPMC (p < 0.001). CONCLUSION: The PPMC model was successfully scaled across rural and regional Victoria as a medication safety strategy. The model was associated with significantly lower rates of medication errors, lower severity of errors and shorter inpatient length of stay.

Evaluation of medical emergency team medication management practices in acute hospitals: A multicentre study.

BACKGROUND: Medical emergency teams use medications to rescue deteriorating patients. Medication management is the system of steps and processes, including prescribing, distribution, administration, and monitoring, to achieve the best outcomes from medication use. Systems or standards for medication management by medical emergency teams have not been defined. OBJECTIVES: The aim of the study was to propose potential solutions to improve medical emergency team medication management by evaluating medication supply and related medication management practices during medical emergency team activations and understanding clinicians' perceptions about medical emergency team medication management in acute hospitals. METHODS: A prospective multicentre audit of intensive care unit-equipped hospitals in Victoria, Australia, was conducted. After advertisement and invitation via scheduled email newsletters to hospitals, a representative of the medical emergency team from each hospital self-administered an online audit tool during December 2019 and January 2020. Audit data were analysed descriptively, and perceptions were analysed using content analysis. RESULTS: Responses were received from 32 of the 44 (72.7%) eligible hospitals. At 17 of the 32 (53.1%) hospitals, arrest trolleys provided medications for medical emergency team activations, in addition to arrest calls. At 15 of the 32 (46.9%) hospitals, separate, dedicated medical emergency team medication supplies were used to care for deteriorating patients. Dedicated medical emergency team supplies contained a median of 20 (range = 8-37) medications, predominantly cardiovascular (median = 8, mode = 7, range = 4-16) and neurological medications (median and mode = 6, range = 0-11). Variation was observed in all storage and other supply-related medication management practices studied. The four most frequent categories of clinicians' perceptions described systematic challenges with availability of the right medication in the right place at the right time. CONCLUSIONS: Current supply and related medication management practices and clinicians' perceptions demonstrated further development is necessary for medication management to meet the needs of medical emergency team clinicians and their patients.

Multi-site evaluation of partnered pharmacist medication charting and in-hospital length of stay.

AIMS: To undertake a multicentre evaluation of translation of a partnered pharmacist medication charting (PPMC) model in patients admitted to general medical units in public hospitals in the state of Victoria, Australia. METHODS: Unblinded, prospective cohort study comparing patients before and after the intervention. Conducted in seven public hospitals in Victoria, Australia from 20 June 2016 to 30 June 2017. Patients admitted to general medical units were included in the study. Medication charting by pharmacists using a partnered pharmacist model was compared to traditional medication charting. The primary outcome variable was the length of inpatient hospital stay. Secondary outcome measures were medication errors detected within 24 h of the patients' admission, identified by an independent pharmacist assessor. RESULTS: A total of 8648 patients were included in the study. Patients who had PPMC had reduced median length of inpatient hospital stay from 4.7 (interquartile range 2.8-8.2) days to 4.2 (interquartile range 2.3-7.5) days (P < 0.001). PPMC was associated with a reduction in the proportion of patients with at least 1 medication error from 66% to 3.6% with a number needed to treat to prevent 1 error of 1.6 (95% confidence interval: 1.57-1.64). CONCLUSION: Expansion of the partnered pharmacist charting model across multiple organisations was effective and feasible and is recommended for adoption by health services.

Educating junior doctors and pharmacists to reduce discharge prescribing of opioids for surgical patients: a cluster randomised controlled trial.

OBJECTIVES: To evaluate whether educating junior doctors and hospital pharmacists about analgesic prescribing improved discharge prescribing of opioids for opioid-naïve patients after surgical admissions. DESIGN: Cluster randomised controlled trial, undertaken during the first half of 2019. SETTING: The Alfred Hospital, a major Melbourne teaching hospital with 13 surgical units. PARTICIPANTS: Opioid-naïve patients discharged from surgical units after a stay of at least 24 hours. INTERVENTION: Surgical units were randomised to the intervention or control arms. Interns, residents, and clinical pharmacists assigned to intervention arm units attended education sessions, presented by the hospital analgesic stewardship pharmacist, about appropriate analgesic prescribing for patients in hospital surgical units. MAIN OUTCOME MEASURES: The patients prescribed slow release opioids on discharge from hospital during the baseline (1 February - 30 April 2018) and post-intervention periods (17 February - 30 April 2019). RESULTS: During the baseline period, 1369 intervention unit and 1014 control unit admissions were included in our analysis; during the evaluation period, 973 intervention unit and 706 control unit episodes were included. After adjusting for age, length of stay, pain score, acute pain service involvement, and use of immediate release opioids prior to admission, patients in the intervention group were prescribed slow release opioids at discharge less frequently than patients in the control group (adjusted odds ratio [aOR], 0.52; 95% CI, 0.35-0.77) and were more frequently discharged without any prescribed opioids following the intervention (aOR, 1.69; 95% CI, 1.24-2.30). Providing de-escalation plans was more frequent for intervention than control group patients prescribed slow release opioids on discharge post-intervention (OR, 2.36; 95% CI, 1.25-4.45). CONCLUSIONS: Specific education for clinicians and pharmacists about appropriate analgesic prescribing for surgical patients is effective in reducing prescribing of opioids at discharge. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618000876291 (prospective).

Understanding how medications contribute to clinical deterioration and are used in rapid response systems: A comprehensive scoping review.

BACKGROUND: In hospitals, rapid response systems (RRSs) identify patients who deteriorate and provide critical care at their bedsides to stabilise and escalate care. Medications, including oral and parenteral pharmaceutical preparations, are the most common intervention for hospitalised patients and the most common cause of harm. This connection between clinical deterioration and medication safety is poorly understood. OBJECTIVES: To inform improvements in prevention and management of clinical deterioration, this review aimed to examine how medications contributed to clinical deterioration and how medications were used in RRSs. REVIEW METHODS: A scoping review was undertaken of medication data reported in studies of clinical deterioration or RRSs in diverse hospital settings between 2005 and 2017. Bibliographic database searches used permutations of "rapid response system," "medical emergency team," and keyword searching with medication-related terms. Independent selection, quality assessment, and data extraction informed mapping against four medication themes: causes of deterioration, predictors of deterioration, RRS use, and management. RESULTS: Thirty articles were reviewed. Quality was low: limited by small samples, observational, single-centre designs and few primary medication-related outcomes. Adverse drug reactions and potentially preventable medication errors, involving sedatives, analgesics, and cardiovascular agents, contributed to clinical deterioration. While sparsely reported, outcomes included death and escalation of care. In children, administration of antibiotics or nebulised medications appeared to predict subsequent deterioration. Cardiovascular medications, sedatives, and analgesics commonly were used to manage deterioration but further detail was lacking. Despite reported potential for patient harm, evaluation of medication management systems was limited. CONCLUSIONS: Medications contributed to potentially preventable clinical deterioration, with considerable harm, and were common interventions for its management. When assessing deteriorating patients or caring for patients who require escalation to critical care, clinicians should consider medication errors and adverse reactions. Studies with more specific medication-related, patient-centred end points could reduce medication-related deterioration and refine RRS medication use and management.

Reducing medication errors in hospital discharge summaries: a randomised controlled trial.

OBJECTIVES: To evaluate whether pharmacists completing the medication management plan in the medical discharge summary reduced the rate of medication errors in these summaries. DESIGN: Unblinded, cluster randomised, controlled investigation of medication management plans for patients discharged after an inpatient stay in a general medical unit. SETTING: The Alfred Hospital, an adult major referral hospital in metropolitan Melbourne, with an annual emergency department attendance of about 60000 patients. PARTICIPANTS: The evaluation included patients' discharge summaries for the period 16 March 2015 - 27 July 2015. INTERVENTIONS: Patients randomised to the intervention arm received medication management plans completed by a pharmacist (intervention); those in the control arm received standard medical discharge summaries (control). MAIN OUTCOME MEASURES: The primary outcome variable was a discharge summary including a medication error identified by an independent assessor. RESULTS: At least one medication error was identified in the summaries of 265 of 431 patients (61.5%) in the control arm, compared with 60 of 401 patients (15%) in the intervention arm (P<0.01). The absolute risk reduction was 46.5% (95% CI, 40.7-52.3%); the number needed to treat (NNT) to avoid one error was 2.2 (95% CI, 1.9-2.5). The absolute risk reduction for a high or extreme risk error was 9.6% (95% CI, 6.4-12.8%), with an NNT of 10.4 (95% CI, 7.8-15.5). CONCLUSIONS: Pharmacists completing medication management plans in the discharge summary significantly reduced the rate of medication errors (including errors of high and extreme risk) in medication summaries for general medical patients.Australia New Zealand Clinical Trials Registry number: ACTRN12616001034426.

The impact of a multidisciplinary antimicrobial stewardship team on the timeliness of antimicrobial therapy in patients with positive blood cultures: a randomized controlled trial.

BACKGROUND: Antimicrobial stewardship teams play an important role in assisting with the optimization of antimicrobial use in acute care settings. We aimed to determine whether a rapid review by a multidisciplinary antimicrobial stewardship team would improve the timeliness of optimal antimicrobial therapy for patients with positive blood cultures. METHODS: This prospective randomized controlled trial was undertaken in two Australian hospitals. Patients received either standard care (a clinical microbiologist, registrar or laboratory scientist communicating the positive blood culture by phone to the treating doctor) or intervention (standard care plus rapid review by a multidisciplinary antimicrobial stewardship team). Outcomes included time to appropriate and/or active antimicrobial therapy and in-hospital mortality. The trial was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12614000258651). RESULTS: A total of 160 patients were enrolled in this study: 81 in the standard care arm and 79 in the intervention arm. Patients in the intervention arm were commenced earlier on active (HR 8.02, 95% CI: 2.15-29.91) and appropriate antimicrobials (HR 1.95, 95% CI: 1.13-3.38), with a higher proportion of patients allocated to the intervention arm receiving active therapy at 48 h (96% versus 82%) and appropriate therapy at 72 h (70% versus 54%). The majority of patients where the blood culture was a contaminant were not started on antimicrobial therapy, and there were no significant differences in time to cessation of antimicrobial therapy. CONCLUSIONS: Antimicrobial stewardship team review of patients with pathogenic positive blood cultures improved the time to both active and appropriate antimicrobial therapy.

Recommendations and Low-Technology Safety Solutions Following Neuromuscular Blocking Agent Incidents.

BACKGROUND: Neuromuscular blocking agents (NMBs) are high-risk medications used to facilitate endotracheal intubation and artificial ventilation. In an incident at a metropolitan tertiary referral and teaching public hospital in Australia, a neurosurgical patient became unresponsive at the start of surgery. It was determined that cisatracurium was administered in error in place of midazolam; the patient was ventilated and the emergency surgery continued. Two additional non-operating room (OR) drug-swap cases involving cisatracurium were reported within 12 months of this event, resulting in a comprehensive review of NMB safety. METHODS: A root cause analysis (RCA) resulted in multiple interventions to decrease the risk of selection and administration errors: (1) review of NMB packaging and introduction of in-house NMB labeling by pharmacy procurement staff before distribution; (2) implementation of a medication administration in anesthetics guideline with ongoing education; (3) audit of storage with removal of NMBs; (4) review of new products by medication safety pharmacists and a senior anesthetist before distribution; and (5) use of red-barrel syringes for administering NMBs was expanded to all areas using NMBs to minimize syringe-swap incidents. RESULTS: In the four years since full implementation of interventions, there have been no reports of cisatracurum selection errors. An incident of atracurium administration resulted in further recommendations for review of OR cart storage. Ongoing monitoring via medication safety walkrounds, by OR staff, by the perioperative pharmacist, and through the hospital's medication incident monitoring system has not detected any further NMB incidents. CONCLUSIONS: Technological solutions have been shown to decrease the risk of NMB errors, yet multifaceted low-technology solutions may be an effective, cheaper alternative.

Use of anticoagulation in thyroid disease.

BACKGROUND: Hyperthyroidism and atrial fibrillation (AF) are both common in the Australian community, and often encountered in general practice. OBJECTIVE: This article discusses the risk of AF and thromboembolism in hyperthyroidism, the role of antithrombotic therapy in this setting, and appropriateness and safety of various antithrombotic agents in thyroid disease. DISCUSSION: Prevention of thromboembolism is an important consideration in the care of patients with AF and hyperthyroidism. However, the evaluation of thromboembolic risk and management in this setting is challenging. Thyroid disease results in a pro-coagulant state via disruption of coagulation pathways and alters the pharmacodynamics of anticoagulants. Currently, guidelines regarding anticoagulation in AF do not incorporate hyperthyroidism as an additional risk factor. Until further evidence becomes available, we recommend warfarin as the oral anticoagulant of choice in thyroid disease because of ease of monitoring and reversibility.

The prevalence and impact of antimicrobial allergies and adverse drug reactions at an Australian tertiary centre.

BACKGROUND: The prevalence and impact of antimicrobial "allergy" labels and Adverse Drug Reactions (ADRs) on antibiotic usage and antimicrobial stewardship initiatives is ill defined. We sought to examine the rate of antimicrobial "allergy labels" at our tertiary referral centre and impacts on antimicrobial usage and appropriateness. METHODS: Two inpatient antimicrobial prevalence surveys were conducted over a 1-week period in November 2013 and 2014 as part of the prospective National Antimicrobial Prescribing Survey (NAPS). Post survey, patients recorded in the NAPS database were assigned to two groups based upon recorded antimicrobial "allergy label" and ADR: (i) Antimicrobial Allergy/ADR (AA) or (ii) No Antimicrobial Allergy/ADR (NAA). Antimicrobial usage and antimicrobial appropriateness were compared between AA and NAA groups. RESULTS: From 509 identified patients the prevalence of an antimicrobial allergy or ADR was 25 %. The prevalence of "allergy labels"/ADR was 10 % (51/509) for penicillin V/G, 5 % (24/509) cephalosporins, 4 % (22/509) trimethroprim-sulfamethoxazole and 3 % (17/509) aminopenicillins. One thousand and seventy antimicrobials were prescribed during the study periods, the median antimicrobial duration was longer in the AA versus NAA group (6 days vs. 4 days; p = 0.018), and proportion of inappropriate antimicrobial prescribing higher in the AA group compared with NAA (29 %; 35/120 vs. 23 %; 86/367, p = 0.22). Oral antimicrobial administration was higher in the NAA than AA group (60 %; 177/297 vs. 46 %; 356/793, p = 0.0001). The proportion of patients that received a ß-lactam was lower in the AA versus NAA group (60 % vs. 79 %, p = 0.0001). CONCLUSIONS: In an Australian tertiary referral centre an antimicrobial "allergy" or ADR label was found to significantly impacted on rate of oral antimicrobial administration, beta-lactam usage, antimicrobial duration and antimicrobial appropriateness.

Pulmonary and systemic pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration.

The purpose of this study was to define the pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following intravenous (i.v.) and inhaled administration in cystic fibrosis (CF) patients. Six CF subjects were administered nebulized CMS doses of 2 and 4 million IU and an i.v. CMS infusion of 150 mg of colistin base activity. Blood plasma, sputum, and urine samples were collected for 12 to 24 h postdose. To assess the tolerability of the drug, lung function tests, blood serum creatinine concentrations, and adverse effect reports were recorded. All doses were well tolerated in the subjects. The pharmacokinetic parameters for CMS following i.v. delivery were consistent with previously reported values. Sputum concentrations of formed colistin were maintained at <1.0 mg/liter for 12 h postdose. Nebulization of CMS resulted in relatively high sputum concentrations of CMS and formed colistin compared to those resulting from i.v. administration. The systemic availability of CMS was low following nebulization of 2 and 4 million IU (7.93% ± 4.26% and 5.37% ± 1.36%, respectively), and the plasma colistin concentrations were below the limit of quantification. Less than 2 to 3% of the nebulized CMS dose was recovered in the urine samples in 24 h. The therapeutic availability and drug targeting index for CMS and colistin following inhalation compared to i.v. delivery were significantly greater than 1. Inhalation of CMS is an effective means of targeting CMS and formed colistin for delivery to the lungs, as high lung exposure and minimal systemic exposure were achieved in CF subjects.

Improving the transition of highly complex patients into the community: impact of a pharmacist in an allogeneic stem cell transplant (SCT) outpatient clinic.

PURPOSE: Patients having undergone allogeneic stem cell transplantation (SCT) require complex medication regimens. To ensure the safe and effective management of this patient group, specialised care in a centre with a dedicated and experienced healthcare team is essential. The aim of this study was to evaluate the effectiveness of a specialty clinical pharmacist working in an ambulatory SCT clinic. METHODS: A prospective cohort study was conducted on patients post SCT and discharged to the ambulatory setting. Patients were reviewed by a clinical pharmacist weekly for six visits. At these visits a medication review was undertaken. Interventions from these reviews were recorded. Interventions were then assigned a risk rating by a multidisciplinary panel. Adherence was also assessed by a Morisky questionnaire and review of dose administration aids. Comparison of data over the six-visit period was undertaken. RESULTS: In total 23 patients were enrolled in the study. All six visits were completed in 17 patients and 161 interventions were recorded at an average of 1.4 interventions per patient visit. The panel rated 40 % of interventions as high risk, 46 % as medium risk and 14 % as low risk. At all visit points high- and medium-risk interventions constituted >80 % of the total. Morisky scores improved by an average of 1.53 (p < 0.0001) between visits 1 and 6. All patients were scored as highly adherent by visit 6. CONCLUSIONS: A specialist clinical pharmacist in the SCT outpatient clinic resulted in regular and effective intervention contributing to improved medication management and adherence.

The impact of daptomycin therapeutic drug monitoring on clinical outcomes: a systematic review.

AIM: Daptomycin therapeutic drug monitoring (TDM) is a potentially valuable intervention for a relatively new drug. The aim of this study was to determine whether daptomycin TDM, including dose adjustment where necessary, improves the clinical outcomes of adult patients with Gram-positive infections. METHODS: A systematic review of English-language studies in MEDLINE (Ovid MEDLINE and Epub Ahead of Print, In-process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions), EMBASE via OVID, Cochrane Central Register of Controlled Trials via the OVID platform, Scopus and Web of Science online databases was performed and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There was no discrimination on study type or time of publication. STUDY SELECTION: Adults (age ≥18 years) with a Gram-positive infection requiring treatment with daptomycin who received TDM, with subsequent reporting of serum concentrations and dose adjustment where necessary, were included. RESULTS: In total, 2869 studies were identified, of which nine met the inclusion criteria. No studies of daptomycin TDM including a relevant control arm have been published to date. All of the included studies were single-arm observational cohort studies. Broad heterogeneity was observed between the studies in terms of included pathogens, infection types, daptomycin TDM practices, reported clinical outcomes, and reporting of potential confounders. CONCLUSIONS: No studies exploring the efficacy of routine daptomycin TDM on patient-centred outcomes in comparison with fixed dosing regimens have been published to date. This represents a key knowledge gap as opposed to an inherent lack of efficacy. Further well-designed, comparative studies are required to determine the role of daptomycin TDM in patients with Gram-positive infections.

Evaluation of the accuracy of a pharmacokinetic dosing program in predicting serum vancomycin concentrations in critically ill patients.

BACKGROUND: Optimization of the timing of appropriate antibiotics is crucial to improve the management of patients in severe sepsis and septic shock. Vancomycin is commonly used empirically in cases of nosocomial infections in critically ill patients. Therefore, early optimization of vancomycin pharmacokinetics is likely to improve outcomes. OBJECTIVE: To evaluate a pharmacokinetic program to predict serum vancomycin concentrations in accordance with administered dose, weight, height, and creatinine clearance in a critically ill population. METHODS: We conducted a prospective observational single-center study in a 45-bed intensive care unit (ICU). All patients hospitalized in the ICU requiring intravenous treatment with vancomycin for a suspected infection were enrolled. The modalities of vancomycin therapy and the monitoring of serum concentrations were left to the discretion of the treating clinician. We compared the measured serum vancomycin concentrations with those predicted by the MM-USCPACK program and analyzed the factors influencing the prediction. RESULTS: Fifty-four intravenous vancomycin courses were administered in 48 critically ill patients over the 3-month study. The precision was considered acceptable, based on a relative precision equal to 8.9% (interquartile range 3.5-18.9%) and the relative bias for all predictions was equal to -1.3%. Overall, 77.3% of predictions were within 20% of observed concentrations; factors correlating with a poorer prediction were a change in renal function, obesity, and the magnitude of organ dysfunction on initiation of vancomycin (expressed by a Systemic Organ Failure Assessment score >11). CONCLUSIONS: The MM-USCPACK program is a useful and reliable tool for prediction of serum vancomycin concentrations in patients hospitalized in ICU and likely reflects the close monitoring of renal function in this setting. For some patients (more severely ill, obese, or significant change in renal function during vancomycin therapy), predictions were less precise.

Vancomycin dosing: assessment of time to therapeutic concentration and predictive accuracy of pharmacokinetic modeling software.

BACKGROUND: Therapeutic drug monitoring is usually required for safe and effective administration of vancomycin. However, dosing recommendations from published guidelines are not suitable in achieving therapeutic vancomycin concentrations in a timely manner in patients with normal renal function. OBJECTIVE: To audit vancomycin dosing and concentrations at our institution and evaluate the predictive accuracy of a pharmacokinetic simulation program, with a view to implementing a pharmacy-based pharmacokinetic service for vancomycin monitoring. METHODS: Patients receiving vancomycin were identified prospectively through the therapeutic drug monitoring archives. Patient information was obtained from medication charts and medical records that were located on wards. Data were entered into the MM-USC*Pack program (Jelliffe R, University of Southern California, 2008, version 12.10). This software was used to predict initial and subsequent concentrations of vancomycin based on patient parameters. The predictive accuracy of this software was evaluated by comparing the predicted concentrations to the observed concentrations. RESULTS: During a 6-week period, 204 concentrations were measured in 77 patients. The most common dosing regimen was 1 g every 12 hours. Overall, initial trough concentrations were subtherapeutic (<10 mg/L) in 58% of patients and trough concentrations did not become therapeutic at any stage throughout therapy in 25% of patients. The pharmacokinetic modeling software demonstrated little systematic bias (-3.1%), but the precision (median prediction error) was 23% (interquartile range, 11-45%). Predictions were poorer in obese patients (body mass index >35 kg/m(2)) and in patients with unstable renal function. CONCLUSIONS: A delay in attaining target trough concentrations was observed in a significant proportion of patients. Pharmacokinetic modeling software is a potential tool to improve the timeliness of achieving adequate dosing by allowing concentrations to be determined prior to steady-state. The program was able to predict vancomycin concentrations across a heterogeneous patient population with little systematic bias, but only moderate precision.

Introduction of a modified analgesic ladder in the emergency depart-ment: Effect on oxycodone use for back pain.

OBJECTIVE: The aim of this study was to assess the introduction of an analgesic ladder and targeted education on oxycodone use for patients presenting to the emergency department (ED). DESIGN: A retrospective pre-post implementation study was conducted. Data were extracted for patients presenting from June to July 2016 (preintervention) and June to July 2017 (post-intervention). SETTING: The EDs of a major metropolitan health service and an affiliated community-based hospital. PARTICIPANTS: Patients with back pain where nonpharmacological interventions such as mobilization and physiotherapy are recommended as the mainstay of treatment. INTERVENTIONS: A modified analgesic ladder introduced in May 2017. The ladder promoted the use of simple analgesics such as paracetamol and nonsteroidal anti-inflammatory drug (NSAIDs) prior to opioids and tramadol in preference to oxycodone in selected patients. MAIN OUTCOME MEASURE(S): The proportion of patients prescribed oxycodone and total doses administered. RESULTS: There were 107 patients pre and 107 post-intervention included in this study. After implementation of the analgesic ladder, 78 (72.9 percent) preintervention patients and 55 (51.4 percent) post-intervention patients received oxycodone in ED (p = 0.001). The median oxycodone doses administered in the ED was 14 mg (interquartile range: 5-20 mg) and 5 mg (interquartile range: 5-10 mg; p < 0.001), respectively. On discharge from hospital, a prescription for oxycodone was issued for 36 (33.6 percent) patients preintervention and 26 (24.3 percent) patients post-intervention (p = 0.13). CONCLUSIONS: Among patients with back pain, implementation of a modified analgesic ladder was associated with a statistically significant but modest reduction in oxycodone prescription. Consideration of multifaceted interventions to produce major and sustained changes in opioid prescribing is required.

Early antimicrobial stewardship team intervention on appropriateness of antimicrobial therapy in suspected sepsis: a randomized controlled trial.

OBJECTIVES: There has been concern that the imperative to administer rapid antimicrobials in septic patients may result in inappropriate antimicrobial use. We aimed to determine the impact of early antimicrobial stewardship (AMS) team intervention in patients with Medical Emergency Team (MET) calls for suspected sepsis. METHODS: We performed a randomized controlled trial of non-ICU inpatients who had a MET call for suspected sepsis. Patients were randomized to standard care (management of antimicrobial therapy by the treating team) or early targeted intervention (AMS review 48 h post-MET call). The primary outcome was appropriateness of antimicrobial therapy 72 h post-MET call, as determined by a panel of blinded infectious diseases physicians. RESULTS: In total, 90 patients were enrolled; 45 were randomly allocated to the intervention group, and 45 to the control group. More patients in the AMS intervention group were receiving appropriate antimicrobials 72 h following the MET call (67% versus 44%, P = 0.03). In the intervention group, 27 recommendations were made by the AMS team; 74% of recommendations were accepted, including 30% of cases where antimicrobials were discontinued or de-escalated. There were non-significant differences in total duration of antimicrobial therapy (8.7 versus 10.7 days, P = 0.39), sepsis-related ICU-admission rates (13% versus 18%, P = 0.56) and sepsis-related in-hospital mortality (7% versus 9%, P = 0.71) between intervention and control groups, respectively. CONCLUSIONS: AMS team intervention resulted in significant improvement in appropriateness of antimicrobial therapy following MET calls due to suspected sepsis. Targeted AMS review should be implemented to support early antimicrobial de-escalation and optimization in patients with suspected sepsis.