Dosing strategies to optimize currently available anti-MRSA treatment options (Part 2: PO options).

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen in both outpatient and inpatient settings. Research to optimize the dosing of these agents is needed to slow the development of antimicrobial resistance and to decrease the likelihood of clinical failure. Areas covered: This review summarizes the available data for orally administered antimicrobials routinely used as monotherapy for MRSA infections. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 - Present) search was performed to identify relevant literature for this review. Expert commentary: There is a vast divide in the amount of pharmacokinetic/pharmacodynamic data to guide dosing decisions for older MRSA agents compared with the oxazolidenones. Five-year view: Additional retrospective data will become available for the older MRSA agents in severe MRSA infections.

Dosing strategies to optimize currently available anti-MRSA treatment options (Part 1: IV options).

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a predominant pathogen resulting in significant morbidity and mortality. Optimal dosing of anti-MRSA agents is needed to help prevent the development of antimicrobial resistance and to increase the likelihood of a favorable clinical outcome. Areas covered: This review summarizes the available data for antimicrobials routinely used for MRSA infections that are not administered orally or topically. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 - Present) search was performed to identify relevant literature for this review. Expert commentary: Improvements in MIC determination and therapeutic drug monitoring are needed to fully implement individualized dosing that optimizes antimicrobial pharmacodynamics.Additional data will become available for these agents in regards to effectiveness for severe MRSA infections and pharmacokinetic data for special patient populations.

Dosing of antifungal agents in obese people.

Obesity is a worldwide epidemic associated with multiple comorbidities that increase the risk of hospitalization. Very little pharmacokinetic data are available for antifungal agents in obesity, as this population is often excluded from drug development studies and these agents are less commonly used than other antimicrobials. Systemic antifungal therapy for invasive candidiasis continues to have a high failure rate, and dose optimization in obesity provides an opportunity for improvement. Based on currently available data, some antifungals should be dosed based on total body weight (i.e. fluconazole), while others should not be adjusted for increased body weight (i.e. posaconazole). More studies are needed to determine if and when dosing changes are needed for many of the antifungal agents. Therefore, drug therapy regimens should be individually evaluated for dose optimization due to body weight.

Dosing of antibacterial agents in obese adults: does one size fit all?

Obesity is a global pandemic affecting 33% of adults in the United States. Obese persons receiving cefazolin or fluconazole have been shown to have worse outcomes with suboptimal dosing. Studies evaluating the safety of colistin, daptomycin, and vancomycin have shown increased weight or obesity may potentially increase toxicity. Many antimicrobials lack pharmacokinetic data to support dose individuation in obese persons, due in part to the lack of obese patients in drug development studies. A one size fits all approach to dose optimization for obese patients is not likely. Current expert opinion suggests some antimicrobials (i.e. vancomycin) be dosed according to total body weight, whereas others (i.e. aminoglycosides) require adjusted body weight for dose calculations. Yet other antimicrobials are reported to need no dose adjustment, largely based on studies using body mass index groups. Therefore, each drug should be individually evaluated to determine the proper dose for obese persons.

A standardized patient counseling rubric for a pharmaceutical care and communications course.

OBJECTIVE: To restructure a required pharmaceutical care and communications course to place greater emphasis on communication skills and include a high-stakes assessment. DESIGN: A standardized counseling rubric was developed for use throughout the pharmacy curriculum and the counseling laboratory practicals were changed to high-stakes assessments. ASSESSMENT: An annual mid-semester and end-of-semester high-stakes patient-counseling objective structured clinical examination (OSCE) conducted prior to and after revision of the course and counseling rubric documented improvements in students' scores. Performance on the post-course annual assessment patient counseling OSCE improved compared to that on the pre-course (p<0.001). CONCLUSION: The 2010 course revision improved students' medication counseling abilities and readiness to practice. Major course revisions should be undertaken only after input from all stakeholders and with data to support the need for change.

Safety and efficacy of simvastatin for the treatment of dyslipidemia in human immunodeficiency virus-infected patients receiving efavirenz-based highly active antiretroviral therapy.

STUDY OBJECTIVES: To evaluate the safety and efficacy of simvastatin for treatment of dyslipidemia in patients with the human immunodeficiency virus (HIV) who were receiving efavirenz-based highly active antiretroviral therapy (HAART), and to evaluate the effect of simvastatin when added to efavirenz on CD4(+) count, HIV viral load, and frequency of attainment of patient-specific National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III lipid goals. DESIGN: Retrospective medical record review. SETTING: Veterans Affairs health care system in Dallas, Texas. PATIENTS: Thirteen HIV-infected men who received a stable efavirenz-based HAART regimen concurrently with simvastatin 20 mg/day, and 19 HIV negative men who received simvastatin 20 mg/day (controls). MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were collected before and after starting simvastatin. Reductions in lipid profile values in the HIV-infected group versus HIV-negative group were as follows: total cholesterol -20% versus -28% (p=0.15), low-density lipoprotein cholesterol (LDL) -36% versus -41% (p=0.06), non-high-density lipoprotein cholesterol (non-HDL) -22% versus -33% (p=0.212), and total cholesterol:HDL ratio -33% versus -30% (p=0.26). These effects were seen without any documented adverse drug reactions or changes in viral and immunologic control. However, 28% fewer HIV-infected patients were able to achieve NCEP ATP III LDL goals compared with HIV-negative subjects. CONCLUSION: These preliminary comparative data suggest that simvastatin can be safely and effectively used to treat dyslipidemia in HIV-infected patients receiving efavirenz-based HAART without compromising viral or immunologic control. However, our results are suggestive of slight lessening of the LDL-lowering effects, which might be explained by the known reduction in simvastatin levels with efavirenz. Furthermore, fewer HIV-infected patients were able to meet their NCEP ATP III goals compared with HIV-negative controls, highlighting the difficulty in treating this population to current standards of care.

Multicenter evaluation of vancomycin dosing: emphasis on obesity.

BACKGROUND: There is a paucity of data available regarding the dosing of antimicrobials in obesity. However, data are available demonstrating that vancomycin should be dosed on the basis of actual body weight. METHODS: This study was conducted at 2 tertiary care medical centers that did not have pharmacy-guided vancomycin dosing programs or other institutional vancomycin dosing policies or protocols. Patients who received vancomycin between July 1, 2003, and June 30, 2006, were stratified by body mass index and randomly selected from the computer-generated queries. Patients >or=18 years of age with a creatinine clearance of at least 60 mL/min who received vancomycin for at least 36 hours were included. RESULTS: Data were collected on a random sampling of 421 patients, stratified by body mass index, who met the inclusion criteria. Most patients in each body mass index category received a fixed dose of vancomycin 2 g daily divided into 2 doses (underweight 82%, normal weight 90%, overweight 86%, and obese 91%). Adequate initial dosing (>or=10 mg/kg/dose) was achieved for 100% of underweight, 99% of normal weight, 93.9% of overweight, and 27.7% of obese patients (P < .0001). Ninety-seven percent of underweight, 46% of normal weight, 1% of overweight, and 0.6% of obese patients received >or=15 mg/kg/dose recommended by several Infectious Diseases Society of America guidelines. Pharmacists also failed to correct inadequate dosing because only 3.3% of patients receiving less than 10 mg/kg/dose had their regimen changed in the first 24 hours of therapy. CONCLUSION: In this multicenter pilot study, obese patients routinely received inadequate empiric vancomycin using a lenient assessment of dosing. Greater efforts should be undertaken to ensure patients receive weight-based dosing because inadequate dosing can lead to subtherapeutic concentrations and potentially worse clinical outcomes.

Lipid-lowering efficacy and safety after switching to atazanavir-ritonavir-based highly active antiretroviral therapy in patients with human immunodeficiency virus.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and lipid-lowering effects after switching from a non-atazanavir-containing, protease inhibitor-based highly active antiretroviral therapy (HAART) to atazanavir-ritonavir-based HAART in patients infected with human immunodeficiency virus (HIV). DESIGN: Multicenter, noncontrolled, retrospective study. SETTING: Three tertiary teaching hospitals. PATIENTS: Thirty-six patients with HIV infection, aged 18 years or older, who were receiving non-atazanavir-containing, protease inhibitor-based HAART that was switched to atazanavir 300 mg-ritonavir 100 mg-based HAART without changes in nucleoside reverse transcriptase inhibitors and confounders known to alter serum lipid levels. MEASUREMENTS AND MAIN RESULTS: Lipid profiles measured 4 weeks-6 months before the switch, as well as follow-up lipid profiles measured 4 weeks-6 months after receiving the new HAART regimen, were evaluated. The switch resulted in the following changes in lipid levels: total cholesterol -9% (p=0.002), low-density lipoprotein cholesterol -13% (p<0.001), high-density lipoprotein cholesterol (HDL) -2% (p=0.431), triglycerides -23% (p=0.007), non-HDL -11% (p=0.002), total cholesterol:HDL ratio -10% (p=0.004), and triglyceride:HDL ratio -24% (p=0.019). A subgroup analysis was conducted on the lipid profiles of nine patients who still met the strict inclusion and exclusion criteria up to 9 months after the switch; it showed that the reductions in their lipid profiles were sustained. In addition, 33% more patients achieved their National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III cholesterol goals. No significant changes were noted in median (interquartile range) CD4+ counts (372 [236-551] and 361 [217-464] cells/mm(3), p=0.118) or in number of patients with undetectable HIV viral loads ([defined as < 50 copies/ml] 32/36 and 31/36 patients, p>0.05) between baseline and after the switch, respectively. CONCLUSION: Switching to an atazanavir-ritonavir-based HAART regimen was associated with significant improvement in lipid profiles, similar to those seen in clinical trials, without compromising safety or viral and immunologic control. In addition, more patients were able to achieve their NCEP ATP III goals.