Impact of Pharmacy Practice Model Expansion on Pharmacokinetic Services: Optimization of Vancomycin Dosing and Improved Patient Safety.

Background: The impact of pharmacy interventions on optimizing vancomycin therapy has been described, however interventions vary among studies and the most optimal pharmacy practice model (PPM) for pharmacokinetic (PK) services has not been established. Objective: The purpose of this study is to demonstrate the value of 24 hours a day, 7 days a week (24/7) PK services. Methods: New PK services were implemented in 2 phases with institutional PPM expansion. Phase 1 included universal monitoring by pharmacists with recommendations made to prescribers during business hours. Phase 2 expanded clinical pharmacists' coverage to 24/7 and provided an optional 24/7 pharmacist-managed PK consult service. We compared vancomycin therapeutic trough attainment, dosing, and clinical and safety outcomes between phases 1 and 2 in adult inpatients receiving therapeutic intravenous vancomycin. Results. One hundred and fifty patients were included in each phase. Phase 2 had a greater proportion of vancomycin courses with therapeutic initial trough concentrations (27.5% vs 46.1%; p = 0.002), higher initial trough concentrations (10.9 mcg/mL vs 16.4 mcg/mL; p < 0.001), and optimized initial vancomycin dosing (13.5 mg/kg vs 16.2 mg/kg; p < 0.001). Phase 2 also saw significant reduction in the incidence of vancomycin-associated nephrotoxicity (21.1% vs 11.7%; p = 0.038). Dose optimization and improvement in initial target trough attainment were most notable among intensive care unit (ICU) patients. Conclusions. Our study demonstrated that 24/7 PK services implemented with institutional PPM expansion optimized vancomycin target trough attainment and improved patient safety.

Early clinical experience with anidulafungin at a large tertiary care medical center.

STUDY OBJECTIVE: To evaluate early clinical experience with anidulafungin. DESIGN: Retrospective cohort study. SETTING: Large, university-affiliated, tertiary care medical center. PATIENTS: All patients receiving anidulafungin between July 15, 2006, and January 15, 2007. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients received at least one dose of anidulafungin. Safety and tolerability were evaluated in all patients; efficacy outcomes were assessed in 13 patients who had a documented fungal infection and received anidulafungin for a minimum of 5 days. Common conditions at baseline were hepatic dysfunction (25 patients [71%]), severe sepsis (17 patients [49%]), and solid organ or hematopoietic stem cell transplantation (10 patients [29%]). Eight patients (23%) were receiving drugs with the potential to interact with echinocandins other than anidulafungin. Seventeen (49%) of the 35 patients received anidulafungin as empiric antifungal therapy. Anidulafungin was used to treat invasive candidiasis in seven patients (20%) and candidemia in 10 patients (29%); Candida albicans or Candida glabrata was isolated most frequently in these two infections combined (7 isolates each [41%]/17 infections). A favorable efficacy outcome was noted in 10 (77%) of 13 evaluable patients. One patient developed breakthrough Candida parapsilosis fungemia while receiving anidulafungin. Overall, anidulafungin was well tolerated, with only one patient having an infusion- related reaction. Anidulafungin was also well tolerated among patients receiving concomitant metronidazole. CONCLUSION: Anidulafungin was well tolerated and produced favorable outcomes in the majority of the patients evaluated. The availability of anidulafungin makes it a feasible option for antifungal therapy, particularly in patients who have hepatic dysfunction and in those who are receiving drugs than can interact with other echinocandins.

Comparison of outcomes from daptomycin or linezolid treatment for vancomycin-resistant enterococcal bloodstream infection: A retrospective, multicenter, cohort study.

BACKGROUND: The optimal treatment for bloodstream infections (BSIs) with vancomycin-resistant enterococci (VRE) is unknown. OBJECTIVE: This study examined outcomes in patients treated with daptomycin or linezolid for VRE BSI. METHODS: A retrospective, multicenter, cohort study was performed via chart review. Hospitalized patients treated for VRE BSI with daptomycin or linezolid from September 1, 2003, to June 30, 2007, were identified via pharmacy and microbiology reports at each institution. Patients aged <18 years or with polymicrobial bacteremia were excluded from analysis. Linezolid and daptomycin were included because the participating institutions used either of the 2 agents as first-line treatment for VRE BSI. Univariate and multivariate analyses were performed to determine the effect of drug selection on mortality and duration of BSI. Duration of BSI was defined as the amount of time from the draw date of the first positive blood culture to the draw date of the first finalized negative blood culture. Adverse events were not assessed. RESULTS: One-hundred one patients from 3 participating US hospitals experiencing VRE BSI were identified. Sixty-seven patients were treated with daptomycin and 34 with linezolid. Baseline characteristics appeared comparable between the daptomycin- and linezolidtreated groups, with the exception of shock (P = 0.049), prior vancomycin treatment (P = 0.002), and prior linezolid treatment (P < 0.001), all of which occurred significantly more often in daptomycin-treated patients. Inpatient mortality occurred in 31 daptomycin- and 10 linezolid-treated patients (46.3% vs 29.4%; P = NS). Linear regression found that shock (P = 0.015), infective endocarditis (P = 0.021), and concurrent rifampin or gentamicin treatment (P = 0.01) were associated with prolonged duration of positive cultures. Logistic regression revealed that shock (odds ratio [OR] = 14.24; P = 0.008), infection with Enterococcus faecium (OR = 53.10; P = 0.024), previous linezolid treatment (OR = 6.63; P = 0.031), concurrent rifampin or gentamicin treatment (OR = 6.48; P = 0.046), and a nonline source of infection (OR = 6.67; P = 0.019) were associated with increased mortality. CONCLUSIONS: In this retrospective cohort analysis, there were no significant differences in mortality of VRE BSI between patients receiving daptomycin or linezolid. Underlying comorbidities appeared to best predict outcome; however, given the retrospective nature of this study, larger, prospective, randomized, comparative studies are needed to control for potential biases and determine definitive outcome differences between these 2 antimicrobials.

Micafungin for the prophylaxis and treatment of Candida infections.

Invasive fungal infection is a significant cause of morbidity and mortality worldwide. The incidence of these infections is steadily increasing. In addition, strains resistant to many commonly used antifungal agents are becoming more prevalent. Many new antifungals have become commercially available in recent years, which have vastly improved the ability to treat these infections effectively. Micafungin is one of three commercially available echinocandins available for use in the USA. This class of agents possess a unique mechanism of action that helps to reduce toxicity while maintaining potent antifungal activity. Micafungin is currently approved for the treatment of esophageal candidiasis in adults and is the only in its class approved for the prophylaxis of Candida infection in patients who have undergone hematopoietic stem cell transplantation. It was also recently approved in the USA for the treatment of candidemia and other forms of invasive candiaisis (acute disseminated candiaisis, Candida peritonitis and abscess). In general, micafungin is well tolerated and has favorable safety and drug-interaction profiles.

Eszopiclone (Lunesta): a new nonbenzodiazepine hypnotic agent.

Randomized, placebo-controlled trials have shown that eszopiclone, a newly available nonbenzodiazepine hypnotic, effectively treats the symptoms of insomnia. Its pharmacokinetic and pharmacodynamic parameters are similar to those of the other currently available nonbenzodiazepine hypnotics (i.e., zolpidem and zaleplon). The unique quality of eszopiclone lies in its product labeling. It is not restricted to short-term use, unlike both zolpidem and zaleplon. Dosing of eszopiclone should begin at 2 mg for nonelderly patients and may be initiated at or increased to 3 mg if clinically indicated. The 3-mg nightly dose is more effective at sleep maintenance. Eszopiclone is well tolerated, with the main treatment-emergent side effects being unpleasant taste, headache, and dizziness. No studies comparing eszopiclone with nonpharmacologic insomnia treatments or other hypnotic agents, including zolpidem and zaleplon, are currently available.