Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: a phase 1 open-label population pharmacokinetic study.

Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration. The safety, tolerability, and pharmacokinetics of subcutaneous infusions of high-dose BPG were assessed in 24 healthy adult volunteers assigned to receive either 3.6, 7.2, or 10.8 MU (three, six, and nine times the standard dose, respectively) as a single subcutaneous infusion. The delivery of the BPG to the subcutaneous tissue was confirmed with ultrasonography. Safety assessments, pain scores, and penicillin concentrations were measured for 16 weeks post-dose. Subcutaneous infusion of penicillin (SCIP) was generally well tolerated with all participants experiencing transient, mild infusion-site reactions. Prolonged elevated penicillin concentrations were described using a combined zero-order (44 days) and first-order (t1/2 = 12 days) absorption pharmacokinetic model. In simulations, time above the conventionally accepted target concentration of 20 ng/mL (0.02 µg/mL) was 57 days for 10.8 MU delivered by subcutaneous infusion every 13 weeks compared with 9 days of every 4-weekly dosing interval for the standard 1.2 MU intramuscular dose (i.e., 63% and 32% of the dosing interval, respectively). High-dose SCIP (BPG) is safe, has acceptable tolerability, and may be suitable for up to 3 monthly dosing intervals for secondary prophylaxis of RHD.

Investigating the effect of an education programme on diabetes and lipid lowering medication usage following coronary artery bypass graft surgery.

BACKGROUND: Guidelines advocate multifactorial cardiovascular risk management in patients with diabetes and atherosclerotic cardiovascular disease. AIM: In hospitalised patients with diabetes following coronary artery bypass graft (CABG), we aimed to evaluate the impacts of decision-support algorithms for optimising glycaemia and lipid-lowering. We also assessed the safety of initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors near time of hospital discharge. METHODS: This was a single-site, pre- and post-intervention analysis of glucose and lipid management in consecutive hospitalised patients with diabetes undergoing CABG surgery. The intervention involved education and decision-support algorithms designed by a multidisciplinary committee to guide cardiac surgery unit clinicians. RESULTS: A total of 200 patients were included in the study. The pre- and post-intervention groups had similar baseline characteristics (HbA1c 7.9 ± 1.9% vs 8.1 ± 1.8%). Of 4092 blood glucose measurements, the incidence of levels between 5 and 10 mmol/L was not different post-intervention (55.5% vs 57.0%; P = 0.441). Fewer endocrinology consultations occurred (59.0% vs 45.0%; P = 0.048) and rates of hypoglycaemia remained low. High-intensity statin was prescribed in >90% pre- and post-intervention, although non-statin lipid-lowering agents remained <10% despite patients not achieving LDL-C targets. No 30-day readmissions for diabetic ketoacidosis occurred in patients prescribed SGLT2 inhibitors. CONCLUSION: The intervention did not improve inpatient glycaemia or increase non-statin lipid-lowering prescriptions in patients with diabetes following CABG surgery but did reduce reliance on specialty input. Initiation of SGLT2 inhibitor therapy near time of hospital discharge was not associated with safety concerns. Alternative interventions or strategies are required to optimise glycaemia and non-statin lipid-lowering therapy prescribing in this setting.

Adherence to antimicrobial prophylaxis guidelines in cardiac implantable electronic device procedures in two Australian teaching hospitals.

Objective This study investigated antibiotic prophylaxis (AP) guideline adherence and the cardiac implantable electronic device (CIED) infection rate in two major Australian public teaching hospitals. Methods In a retrospective observational study, the medical records of patients who underwent CIED procedures between January and December 2017 were reviewed (Hospital A, n = 400 procedures; Hospital B, n = 198 procedures). Adherence to AP guidelines was assessed regarding drug, dose, timing, route and frequency. Infection was identified using follow-up documentation. Results AP was administered in 582 of 598 procedures (97.3%). Full guideline adherence was observed in 33.9% of procedures (203/598) and differed significantly between Hospitals A and B (47.3% vs 7.1%, respectively; P < 0.001). Common reasons for non-adherence were the timing of administration (42.3% vs 60.6% non-adherent in Hospitals A and B, respectively; P < 0.001) and repeat dosing (19.3% vs 78.8% non-adherent in Hospitals A and B, respectively; P < 0.001). Twenty infections were identified over 626.6 patient-years of follow-up (mean (±s.d.) follow-up 1.0 ± 0.3 years). The infection rate was 3.19 per 100 patient-years (P = 0.99 between hospitals). Two devices were removed due to infection; no patients died from CIED infection. Conclusions Although the rate of serious CIED infection was low, there was evidence of highly variable and suboptimal antibiotic use, and potential overuse of AP. What is known about the topic? Previous Australian studies have revealed high rates of inappropriate surgical AP. CIED infections are potentially life threatening, but can be avoided through effective use of AP. However, prolonged durations of AP in this setting may also result in complications, including Clostridioides difficile infection. What does this paper add? This study, the first to our knowledge to focus specifically on adherence to Australian guidelines for AP in CIED procedures, highlighted several common issues between AP in this setting and surgical and procedural AP more broadly. 'Early' and 'late' dose administration and extended post-procedural AP were common. Only 34% of prescriptions fully adhered to the guidelines; practices varied significantly between the two hospitals. What are the implications for practitioners? There is a clear need for institution-specific antimicrobial stewardship strategies to optimise AP in CIED procedures, aligned with the Antimicrobial Stewardship Clinical Care Standard. Patients are being placed at potentially avoidable risk of both complications of extended durations of AP and CIED infection, although the rate of serious CIED infection was low. A standardised approach to surveillance of CIED infections and prospective multisite audits of AP in CIED procedures using a validated tool, such as the Surgical National Antimicrobial Prescribing Survey, are recommended to better inform evidence-based practice. Potential strategies to optimise guideline adherence include prescribing support in patients with immediate penicillin hypersensitivity or methicillin-resistant Staphylococcus aureus colonisation, optimising the in-patient location of drug administration to promote timely dosing, limiting inappropriate post-procedural prophylaxis and routine S. aureus screening and decolonisation.

Managing inpatient hyperglycaemia and initiating sodium-glucose cotransporter 2 inhibitor therapy in the setting of diabetes and acute coronary syndrome.

We previously showed that implementing algorithms for managing diabetes in acute coronary syndrome was associated with improved inpatient glycaemic control and increased sodium-glucose cotransporter 2 (SGLT2) inhibitor prescriptions. The present study performed 1 year later found that inpatient hyperglycaemia had relapsed to pre-intervention rates, although SGLT2 inhibitor prescriptions remained increased. We discuss the challenges of improving inpatient glycaemic control.

Short-term outcomes following coronary artery bypass graft surgery in insulin treated and non-insulin treated diabetes: A tertiary hospital experience in Australia.

BACKGROUND AND AIMS: Outcomes after coronary artery bypass graft (CABG) surgery have improved due to advances in surgical technique and post-operative care. We aimed to describe contemporary clinical characteristics and short-term post-operative outcomes in diabetic patients undergoing CABG surgery. METHODS: A retrospective analysis of patients who underwent CABG surgery over a 4.5-year period in a Western Australian tertiary hospital was performed in September 2019. The cohort was stratified according to pre-operative diabetes status. RESULTS: A total of 1327 patients underwent CABG surgery, of which 572 (43.1%) had diabetes. Diabetic patients were more likely to be female (24.7% vs. 13.9%, p < 0.001) and have dyslipidaemia (83.0% vs. 68.1%, p < 0.001), hypertension (82.0% vs. 68.7%, p < 0.001), raised body mass index (29.8 ± 5.6 vs. 28.7 ± 5.1 kg/m2, p < 0.001), prior myocardial infarction (62.8% vs. 54.8%, p = 0.004), prior stroke (8.6% vs. 5.0%, p = 0.010), congestive cardiac failure (20.2% vs. 15.1%, p = 0.014), reduced estimated glomerular filtration rate (86.7 ± 36.1 vs. 90.8 ± 32.1 ml/min/1.73 m2, p = 0.036) and three-vessel coronary artery disease (74.8% vs. 67.3%, p = 0.003). Post-operative wound infections (3.1% vs. 1.5%, p = 0.022), new dialysis requirement (2.9% vs. 1.0%, p = 0.009) and 30-day hospital admission (13.1% vs. 8.5%, p = 0.007) was more likely in diabetic patients, but not myocardial infarction (3.0% vs. 2.0%, p = 0.247), stroke (1.4% vs. 0.8%, p = 0.286) or 30-day mortality (2.4% vs. 1.7%, p = 0.354). No significant differences were detected in short-term outcomes between patients with non-insulin (n = 398) versus insulin treated (n = 174) diabetes. CONCLUSIONS: Diabetic patients continue to represent a higher-risk cohort, highlighting the need for further strategies to reduce short-term adverse outcomes following CABG surgery.

The role of a Coronavirus disease 2019 pharmacist: an Australian perspective.

The coronavirus disease 2019 (COVID-19) pandemic has greatly impacted healthcare services around the world. Pharmacists are front-line healthcare professionals and integral members of the healthcare team. The deployment of a specialized 'COVID pharmacist' within our institution has demonstrated that the skills of the pharmacist can be adapted, expanded and utilized to alleviate the pressure of doctor shortages, reduce healthcare worker exposure to infected patients, contribute to therapeutic decisions and work collaboratively to tackle the challenges faced during this pandemic. This commentary details an Australian hospital pharmacy response to the COVID-19 pandemic, describing the unique clinical and practical contributions made by a specialized COVID pharmacist in our institution.

Is ward round participation by clinical pharmacists a valuable use of time and money? A time and motion study.

BACKGROUND: While the benefits of multidisciplinary ward round (WR) participation by clinical pharmacists have been demonstrated, it can be time-consuming. No previous studies have compared the specific benefits of WR participation and other clinical activities. OBJECTIVES: To assess the clinical impact of different clinical pharmacist activities and analyse patterns of practice based on WR involvement and timing and significance of clinical interventions. METHODS: In a prospective, observational time and motion study, clinical pharmacists servicing 6 unmatched specialty areas in a major quaternary public hospital were observed and their activities documented. Pharmacists' self-recorded interventions underwent expert panel assessment for significance and potential cost savings. Workflows and interventions were analysed for the 4 pharmacists involved in WRs ('WR pharmacists') during their time 'on' and 'off' rounds and for 2 pharmacists not involved in WRs ('non-WR pharmacists') using chi-square analyses. RESULTS: During 170 h of observation, 267 clinical interventions (53.9% minor, 40.1% moderate, 6.0% major) were recorded. WR pharmacists spent 24.3% of their time on rounds, and 64.8% of interventions were made during this time (intervention rates: 4.5/hour on WR vs. 0.8/hour off WR vs. 1.3/hour for non-WR pharmacists). Differences in WR and non-WR pharmacists' workflows were observed, although there was no difference in time spent on clinical/patient-centred activities (p = 0.70). WR involvement was associated with significantly quicker interventions (p < 0.001). All major interventions were made by WR pharmacists; 80% were made on rounds. Major interventions were estimated to have decreased lengths of stay, intensive care requirements and procedure costs. CONCLUSIONS: Clinical pharmacists focussed on patient-centred activities, regardless of WR involvement. Notwithstanding differences in the WR and non-WR specialty areas, WR participation was associated with more significant and timely interventions and potential cost savings. Coupled with the subjective benefits of WR participation observed, these findings support the potential value of clinical pharmacist WR participation.