Antimicrobial stewardship in rural nursing homes: Impact of interprofessional education and clinical decision tool implementation on urinary tract infection treatment in a cluster randomized trial.

OBJECTIVES: To measure the impact of an antimicrobial stewardship initiative on the rate of urine culture testing and antimicrobial prescribing for urinary tract infections (UTIs) between control and intervention sites. Secondary objectives included evaluation of potential harms of the intervention and identifying characteristics of the population prescribed antimicrobials for UTI. DESIGN: Cluster randomized controlled trial. SETTING: Nursing homes in rural Alberta, Canada. PARTICIPANTS: The study included 42 nursing homes ranging from 8 to 112 beds.Methods/interventions:Intervention sites received on-site staff education, physician academic detailing, and integrated clinical decision-making tools. Control sites provided standard care. Data were collected for 6 months prior to and 12 months after the intervention. RESULTS: Resident age (83.0 vs 83.8 years) and sex distribution (female, 62.5% vs 64.5%) were similar between the groups. Statistically significant decreases in the rate of urine culture testing (-2.1 tests per 1,000 resident days [RD]; 95% confidence interval [CI], -2.5 to -1.7; P < .001) and antimicrobial prescribing for UTIs (-0.7 prescriptions per 1,000 RD; 95% CI, -1.0 to -0.4; P < .001) were observed in the intervention group. There was no difference in hospital admissions (0.00 admissions per 1,000 RD; 95% CI, -0.4 to 0.3; P = .76), and the mortality rate decreased by 0.2 per 1,000 RD in the intervention group (95% CI, -0.5 to -0.1; P = .002). Chart reviews indicated that UTI symptoms were charted in 16% of cases and that urine culture testing occurred in 64.5% of cases. CONCLUSION: A multimodal antimicrobial stewardship intervention in rural nursing homes significantly decreased the rate of urine culture testing and antimicrobial prescriptions for UTI, with no increase in hospital admissions or mortality.

Health Canada/BIOTECanada Summit on regulatory and clinical topics related to subsequent entry biologics (biosimilars), Ottawa, Canada, 14 May 2012.

In May 2012, Health Canada and other participants held a National Summit on Subsequent Entry Biologics (SEBs). Health Canada released a guidance document in March 2010 describing policy positions and data requirements for approval of SEBs. While Health Canada and health agencies in other regulatory jurisdictions are aligned on many scientific principles related to biosimilar drugs, Health Canada's specific requirements may not be widely understood by many Canadian stakeholders. The Summit provided an opportunity for education and dialog among physicians who prescribe biologics, provincial payers, and industry on the following topics: preclinical and clinical comparability studies; manufacturing and other product differences; extrapolation of indications; substitution and interchangeability of SEBs with reference biologic drugs in clinical practice; payers' current perspective; pharmacovigilance and naming. It is anticipated that the consensus reached at this meeting will further educate Canadian healthcare professionals, provincial payers, and insurers about the appropriate use of SEBs, and may be of general interest to others internationally.

Advantages of using tetrahydrofuran-water as mobile phases in the quantitation of cyclosporin A in monkey and rat plasma by liquid chromatography-tandem mass spectrometry.

A new analytical method is described here for the quantitation of anti-inflammatory drug cyclosporin A (CyA) in monkey and rat plasma. The method used tetrahydrofuran (THF)-water mobile phases to elute the analyte and internal standard, cyclosporin C (CyC). The gradient mobile phase program successfully eluted CyA into a sharp peak and therefore improved resolution between the analyte and possible interfering materials compared with previously reported analytical approaches, where CyA was eluted as a broad peak due to the rapid conversion between different conformers. The sharp peak resulted from this method facilitated the quantitative calculation as multiple smoothing and large number of bunching factors were not necessary. The chromatography in the new method was performed at 30 degrees C instead of 65-70 degrees C as reported previously. Other advantages of the method included simple and fast sample extraction-protein precipitation, direct injection of the extraction supernatant to column for analysis, and elimination of evaporation and reconstitution steps, which were needed in solid phase extraction or liquid-liquid extraction reported before. This method is amenable to high-throughput analysis with a total chromatographic run time of 3 min. This approach has been verified as sensitive, linear (0.977-4000 ng/mL), accurate and precise for the quantitation of CyA in monkey and rat plasma. However, compared with the usage of conventional mobile phases, the only drawback of this approach was the reduced detection response from the mass spectrometer that was possibly caused by poor desolvation in the ionization source. This is the first report to demonstrate the advantages of using THF-water mobile phases to elute CyA in liquid chromatography.

Disease-drug interaction: Reduced response to propranolol despite increased concentration in the rat with inflammation.

Inflammatory conditions reduce clearance, hence increase plasma concentration of drugs such as propranolol that are efficiently cleared by the liver. The therapeutic consequences of this increased plasma drug concentration is mainly unknown. However, for sotalol, another beta-adrenergic antagonist, inflammation causes reduced potency. Sotalol, however, is renally cleared; hence, its clearance is unaffected by inflammation. We examined if the inflammation-induced increased plasma propranolol concentration compensates for the reduced responsiveness. A modified lead I ECG was used to record PR interval and heart rate (HR). ECG was monitored following oral administration of 3, 5, 10, 15, 20, 25, and 30 mg/kg propranolol to both control and adjuvant arthritis (AA) rats. To confirm altered pharmacokinetics, single 25 mg/kg doses of propranolol were administered to both AA and control rats, with an inserted cannula in their right jugular vein for serial blood sampling. As expected, AA caused a significant reduction in the propranolol oral clearance and subsequently substantial increases in plasma total and unbound drug concentration. Interestingly, however, despite the elevated propranolol concentrations, the effect on HR remained unchanged and the prolongation of PR interval was significantly reduced in AA compared with control rats. The reduced sensitivity to propranolol in AA rats is suggestive of altered beta-adrenergic receptors function.