Evaluation of a trough-only extrapolated area under the curve vancomycin dosing method on clinical outcomes.

Background Vancomycin dosing strategies targeting trough concentrations of 15-20 mg/L are no longer supported due to lack of efficacy evidence and increased risk of nephrotoxicity. Area-under-the-curve (AUC24) nomograms have demonstrated adequate attainment of AUC24 goals ≥ 400 mg h/L with more conservative troughs (10-15 mg/L). Objective The purpose of this study is to clinically validate a vancomycin AUC24 dosing nomogram compared to conventional dosing methods with regards to therapeutic failure and rates of acute kidney injury. Setting This study was conducted at a tertiary, community, teaching hospital in the United States. Method This retrospective, cohort study compared the rates of therapeutic failures between AUC24-extrapolated dosing and conventional dosing methods. Main outcome measure Primary outcome was treatment failure, defined as all-cause mortality within 30 days, persistent positive methicillin-resistant Staphylococcus aureus blood culture, or clinical failure. Rates of acute kidney injury in non-dialysis patients was a secondary endpoint. Results There were 96 participants in the extrapolated-AUC24 cohort and 60 participants in the conventional cohort. Baseline characteristics were similar between cohorts. Failure rates were 11.5% (11/96) in the extrapolated-AUC24 group compared to 18.3% (11/60) in the conventional group (p = 0.245). Reasons for failure were 6 deaths and 5 clinical failures in the extrapolated-AUC24 cohort and 10 deaths and 1 clinical failure in the conventional group. Acute kidney injury rates were 2.7% (2/73) and 16.4% (9/55) in the extrapolated-AUC24 and conventional cohorts, respectively (p = 0.009). Conclusion Extrapolated-AUC24 dosing was associated with less nephrotoxicity without an increase in treatment failures for bloodstream infections compared to conventional dosing. Further investigation is warranted to determine the relationship between extrapolated-AUC24 dosing and clinical failures.

Non-occlusive ST-segment elevated myocardial infarction following the administration of liposomal amphotericin B in the treatment of cryptococcal meningitis.

WHAT IS KNOWN AND OBJECTIVE: Liposomal amphotericin B (L-AmB) is the cornerstone of many serious invasive fungal infections. Despite lower frequencies of commonly reported adverse events in clinical trials compared to conventional formulations, post-marketing complications continue to mount. CASE DESCRIPTION: We present a case of chest pain following the initial dose of L-AmB for cryptococcal meningitis. Electrocardiogram demonstrated no acute electrocardiogram findings. Upon rechallenge, the chest pain worsened was subsequently accompanied by ST-segment elevation. Emergent coronary angiography found no acute findings. WHAT IS NEW AND CONCLUSION: Providers should be aware of cardiac complications with L-AmB, including non-occlusive ST-segment elevation.

Gender differences in risk profile and outcome of Middle Eastern patients undergoing percutaneous coronary intervention.

OBJECTIVES: To determine the gender differences in cardiovascular risk profile and outcomes among patients undergoing percutaneous coronary intervention (PCI). Methods: In a prospective multicenter study of consecutive Middle Eastern patients managed with PCI from January 2013 to February 2014 in 12 tertiary care centers in Amman and Irbid, Jordan. Clinical and coronary angiographic features, and major cardiovascular events were assessed for both genders from hospital stay to 1 year. Results: Women comprised 20.6% of 2426 enrolled patients, were older (mean age 62.9 years versus 57.2 years), had higher prevalence of hypertension (81% versus 57%), diabetes (66% versus 44%), dyslipidemia (58% versus 46%), and obesity (44% versus 25%) compared with men, p less than 0.001. The PCI for ST-segment elevation myocardial infarction was indicated for fewer women than men (23% versus 33%; p=0.001). Prevalence of single or multi-vessel coronary artery disease was similar in women and men. More women than men had major bleeding during hospitalization (2.2% versus 0.6%; p=0.003) and at one year (2.5% versus 0.9%; p=0.007). There were no significant differences between women and men in mortality (3.1% versus 1.7%) or stent thrombosis (2.1% versus 1.8%) at 1 year. Conclusion: Middle Eastern women undergoing PCI had worse baseline risk profile compared with men.Except for major bleeding, no gender differences in the incidence of major adverse cardiovascular events were demonstrated.

Constipation-predominant irritable bowel syndrome: a review of current and emerging drug therapies.

Irritable bowel syndrome (IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS (IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.