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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.

Copyright 2018 Lavers et al. 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.

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.

© 2017, Springer International Publishing.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.

Background Patients frequently report antibiotic allergies; however, only 10% of labelled patients have a true allergy. Aim We investigated the documentation of antibiotic ‘allergy’ labels (AAL) and the effect of labelling on clinical outcomes, in a West Australian adult tertiary hospital. Methods Retrospective cross-sectional analysis of patients captured in the 2013 and 2014 National Antimicrobial Prescribing Surveys was carried out. Data were collected on documented antibiotic adverse drug reactions, antibiotic cost, prescribing appropriateness, prevalence of multi-drug resistant organisms, length of stay, intensive care admission and readmissions. Results Of the 687 patients surveyed, 278 (40%) were aged 70 or above, 365 (53%) were male and 279 (41%) were prescribed antibiotics. AAL were recorded in 122 (18%) patients and the majority were penicillin labels (n = 87; 71%). Details of AAL were documented for 80 of 141 (57%) individual allergy labels, with 61 describing allergic symptoms. Patients with beta-lactam allergy labels received fewer penicillins (P = 0.0002) and more aminoglycosides (P = 0.043) and metronidazole (P = 0.021) than patients without beta-lactam labels. Five patients received an antibiotic that was contraindicated according to their allergy status. Patients with AAL had significantly more hospital readmissions within 4 weeks (P = 0.001) and 6 months (P = 0.025) of discharge, compared with unlabelled patients. The majority (81%) of readmitted labelled patients had major infections. Conclusions AAL are common, but poorly documented in hospital records. Patients with AAL are significantly more likely to require alternative antibiotics and hospital readmissions. There may be a role for antibiotic allergy delabelling to mitigate the clinical and economic burdens for patients with invalid allergy labels.

The evolution of 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 include adherence, long and short-term toxicities, pharmacoenhancement, pharmacogenomics, therapeutic drug monitoring (TDM), differential penetration of drugs into sanctuary sites such as the central nervous system (CNS), genital tract and small bowel and drug-drug and drug-food interactions related to cytochrome P450 drug metabolizing enzymes, UGT1A1 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.