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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.

Purpose: To evaluate the stability of meropenem trihydrate in elastomeric infusion devices at a range of selected concentrations (6, 12, 20 and 25 mg/mL) at ambient, refrigeration and freezing temperatures., Methods: Meropenem Ranbaxy ® (meropenem trihydrate equivalent to anhydrous meropenem 1 g) vials for injection were reconstituted with 0.9% sodium chloride and adjusted to pH 6.5 using 1 M hydrochloric acid. Following preparation, solutions were stored for 7 days at either 6.7°C in elastomeric infusion devices or at -19°C in glass vials; samples of each concentration were removed from the infusion devices at specific time-points and stored for 24 hrs at 22.5°C. All solutions were assayed at specific time-points using high-performance liquid chromatography. Forced degradation in hydrochloric acid, sodium hydroxide and hydrogen peroxide was carried out at 40°C., Results: The lowest concentration of meropenem (6 mg/mL) displayed the highest stability. It maintained >90% of its initial concentration for up to 144 hrs when stored at 6.7°C and 72 hrs following 24 hrs storage at 22.5°C, having been initially refrigerated for 48 hrs. Meropenem 20 mg/mL required immediate administration following preparation under ambient temperatures, whilst meropenem 25 mg/mL did not remain stable following 24 hrs storage at ambient temperatures. Frozen meropenem solutions displayed good stability in all concentrations but were physically unstable due to the formation of a precipitate., Conclusion: At lower concentrations, meropenem showed suitable stability for storage and administration in elastomeric infusion devices, at refrigerated temperatures. To enhance the stability of lower concentration solutions when exposed to ambient temperatures by ambulatory patients, a more adept method of maintaining lower temperatures that reflect refrigerated conditions for elastomeric infusion devices should be devised., Competing Interests: The authors declare that they have no conflicts of interest to disclose in this work.

Background: Surgical site infections (SSIs) are a common complication following breast surgery procedures, despite being considered a clean surgery. The prevalence of SSIs can be minimised with the appropriate use of antibiotic prophylaxis as outlined in the Australian Therapeutic Guidelines (eTG). The aims of this study were to evaluate adherence to the eTG for antibiotic prophylaxis in breast surgery procedures at a Western Australian teaching hospital following an update of the guidelines in 2014 and examine the impact of prophylactic antibiotics on SSI incidence and length of hospital stay., Method: A retrospective cross-sectional study which reviewed medical records from a random sample of 250 patients selected from 973 patients who underwent breast surgical procedures between February 2015 and March 2017., Results: Overall adherence to current eTG occurred in 49.2% (123/250) of operations. Pre-operative and post-operative antibiotics were prescribed in 98.4% (246/250) and 11.2% (28/250) operations respectively. Adherence rates to three specific elements of the eTG (drug prescribed, drug dosage and timing of administration) were 91.6% (229/250), 53.6% (134/250) and 86.4% (216/250) respectively. For the 14.4% (36/250) patients with relevant drug allergies, there was zero adherence to the eTG. Overall recorded SSI prevalence was low at 5.2% (13/250). The mean length of stay in patients (2.3 ± 1.7 days) was not influenced by level of eTG adherence ( p  = 0.131) or SSIs ( p  = 0.306)., Conclusion: These data demonstrate a significant improvement in overall adherence to the eTG from 13.3% to 49.2% ( p  =  < 0.001). The level of detected SSIs in this study was low. Further improvement is necessary with respect to prescribing appropriate antibiotic dosages and for those with allergies., Competing Interests: The authors declare there are no competing interests.

Objective: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed., Data Sources: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals. Abstracts from conferences, article bibliographies, and product monographs were reviewed., Study Selection and Data Extraction: Relevant English-language studies or those conducted in humans were considered., Data Synthesis: Similar exposures of elvitegravir, darunavir, and atazanavir are achieved when combined with cobicistat or ritonavir. Cobicistat may not be as potent a CYP3A4 inhibitor as ritonavir in the presence of a concomitant inducer. Ritonavir induces CYP1A2, 2B6, 2C9, 2C19, and uridine 5'-diphospho-glucuronosyltransferase, whereas cobicistat does not. Therefore, recommendations for cobicistat with comedications that are extrapolated from studies using ritonavir may not be valid. Pharmacokinetic properties of the boosted antiretroviral can also affect interaction outcome with comedications. Problems can arise when switching patients from ritonavir to cobicistat regimens, particularly with medications that have a narrow therapeutic index such as warfarin., Conclusions: When assessing and managing potential interactions with ritonavir- or cobicistat-based regimens, clinicians need to be aware of important differences and distinctions between these agents. This is especially important for patients with multiple comorbidities and concomitant medications. Additional monitoring or medication dose adjustments may be needed when switching from one booster to another.

Background Guidelines for the appropriate use of antibiotic prophylaxis are provided in the Therapeutic Guidelines: Antibiotics (eTG) in Australia. Inappropriate use of antibiotics is problematic. Objective To examine adherence with therapeutic guidelines (eTG) in breast surgery and trends in non-adherence dependent on the type of breast surgery performed. Setting Major Western Australian teaching hospital. Method A retrospective cross-sectional study reviewed a random sample of 150 from 1049 eligible medical records of patients who underwent a breast surgical procedure in 2013 or 2014. Main outcome measure Adherence to the eTG. Results Antibiotic prophylaxis was prescribed for 139 (92.7%) operations. Adherence to the eTG occurred in 20 (13.3%) operations, whilst 11 (7.3%) did not adhere to any element of the eTG. Appropriate timing was the main factor not adhered to. Postoperative antibiotics were prescribed following 35 (23.3%) operations, with 32 (91.4%) administered beyond 24 h. Length of stay was significantly different (p = 0.0036) between surgical groups. There was a tendency for risk of an infection to be decreased with adherence (odds ratio: 0.23; 95% CI: 0.05, 1.07; p = 0.06). Conclusion Adherence to the eTG was low (13.3%), despite a decreased risk of SSI when guidelines were followed.

The evolution of human immunodeficiency virus (HIV) treatment has improved our understanding and management of complex pharmacological issues that have driven improved outcomes and quality of life of the HIV-infected patient. These issues include adherence, long- and short-term toxicities, pharmacoenhancement, pharmacogenomics, therapeutic drug monitoring, differential penetration of drugs into sanctuary sites, such as the central nervous system, genital tract and small bowel, and drug-drug and drug-food interactions related to cytochrome P450 drug-metabolizing enzymes, uridine diphosphate glucuronyltransferases and drug transporters, to name a few. There is future promise, as an increased understanding of the immunopathogenesis of HIV and global public health initiatives are driving novel treatment approaches with goals to prevent, control and, ultimately, eradicate HIV., (© 2014 The British Pharmacological Society.)