Carlos A. Alvarez

Association of Azithromycin With Mortality and Cardiovascular Events Among Older Patients Hospitalized With Pneumonia

IMPORTANCE Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. OBJECTIVE To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. DESIGN Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy. SETTING This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines. MAIN OUTCOMES AND MEASURES Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. RESULTS Of 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 patients exposed to azithromycin and 31,863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04). CONCLUSIONS AND RELEVANCE Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use.

Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study

BackgroundPrevious studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB).MethodsAdults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model.ResultsOverall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08).ConclusionsOver one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.

Empiric guideline-recommended weight-based vancomycin dosing and mortality in methicillin-resistant Staphylococcus aureus bacteremia: A retrospective cohort study

BackgroundNo studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia.MethodsThis was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature.ResultsA total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39]) or multivariable (OR 0.71, 95%CI 0.33-1.55) analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity.ConclusionsEmpiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.

Cardiovascular Risk in Diabetes Mellitus: Complication of the Disease or of Antihyperglycemic Medications

Cardiovascular disease is the principal complication and the leading cause of death for patients with diabetes (DM). The efficacy of antihyperglycemic treatments on cardiovascular disease risk remains uncertain. Cardiovascular risk factors are affected by antihyperglycemic medications, as are many intermediate markers of cardiovascular disease. Here we summarize the evidence assessing the cardiovascular effects of antihyperglycemic medications with regard to risk factors, intermediate markers of disease, and clinical outcomes.

State-of-the-Art: Hypo-responsiveness to Oral Antiplatelet Therapy in Patients with Type 2 Diabetes Mellitus

Diabetes mellitus is a global pandemic, associated with a high burden of cardiovascular disease. There are multiple platelet derangements in patients with diabetes, and antiplatelet drugs remain the first-line agents for secondary prevention as well as for high-risk primary prevention among patients with diabetes. This review provides a summary of oral antiplatelet drug hypo-responsiveness in patients with diabetes, specifically aspirin and clopidogrel resistance. Topics discussed include antiplatelet testing, definitions used to define hypo-response and resistance, its prevalence, association with clinical outcomes, and strategies to mitigate resistance. The role of prasugrel and ticagrelor, as well as investigational agents, is also discussed.

Ranolazine for the treatment of refractory angina in a veterans population.

BACKGROUND Pivotal ranolazine trials did not require optimization of conventional medical therapy including coronary revascularization and antianginal drug therapy prior to ranolazine use. This case series describes the use of ranolazine for the treatment of chronic stable angina refractory to maximal medical treatment in a veterans population. RESULTS A total of 18 patients with a median age of 66 years were identified. All patients had prior percutaneous coronary intervention and/or coronary artery bypass graft surgery; 83% had three-vessel coronary artery disease, with left main disease present in 39% of patients. Prior to initiating ranolazine, antianginal use consisted of beta blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%). Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were controlled. Median preranolazine angina episodes and sublingual nitroglycerin (SLNTG) doses per week were 14 and 10, respectively, with a Canadian Cardiovascular Society (CCS) angina grade of III-IV in 67% of patients. After initiation of ranolazine, median angina episodes per week and SLNTG doses used per week decreased to 0.7 and 0, respectively, with CCS grade of III-IV declining to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina episodes. CONCLUSION The addition of ranolazine to maximally tolerated conventional antianginal drug therapy post coronary revascularization was associated with decreases in angina episodes and SLNTG utilization and improvement in CCS angina grades. Ranolazine may provide an effective treatment option for revascularized patients with refractory angina.

Reliability of a seminar grading rubric in a grand rounds course.

Purpose: Formal presentations are a common requirement for students in health professional programs, and evaluations are often viewed as subjective. To date, literature describing the reliability or validity of seminar grading rubrics is lacking. The objectives of this study were to characterize inter-rater agreement and internal consistency of a grading rubric used in a grand rounds seminar course. Methods: Retrospective study of 252 student presentations given from fall 2007 to fall 2008. Data including student and faculty demographics, overall content score, overall communication scores, subcomponents of content and communication, and total presentation scores were collected. Statistical analyses were performed using SPSS, 16.0. Results: The rubric demonstrated internal consistency (Cronbach’s alpha = 0.826). Mean grade difference between faculty graders was 4.54 percentage points (SD = 3.614), with ≤ 10-point difference for 92.5% of faculty evaluations. Student self evaluations correlated with faculty scores for content, communication, and overall presentation (r = 0.513, r = 0.455, and r = 0.539; P < 0.001 for all respectively). When comparing mean faculty scores to student’s self-evaluations between quintiles, students with lower faculty evaluations overestimated their performance, and those with high faculty evaluations underestimated their performance (P < 0.001). Conclusion: The seminar evaluation rubric demonstrated inter-rater agreement and internal consistency.

Challenges with Diagnosing and Managing Sepsis in Older Adults

ABSTRACT Sepsis in older adults has many challenges that affect rate of septic diagnosis, treatment, and monitoring parameters. Numerous age-related changes and comorbidities contribute to increased risk of infections in older adults, but also atypical symptomatology that delays diagnosis. Due to various pharmacokinetic/pharmacodynamic changes in the older adult, medications are absorbed, metabolized, and eliminated at different rates as compared to younger adults, which increases risk of adverse drug reactions due to use of drug therapy needed for sepsis management. This review provides information to aid in diagnosis and offers recommendations for monitoring and treating sepsis in the older adult population.

Exposure to high-risk medications is associated with worse outcomes in older veterans with chronic pain

Background:Chronic pain is common, costly and leads to significant morbidity in older adults, yet there are limited data on medication safety. The authors sought to evaluate the association of incident high-risk medication in the elderly (HRME) with mortality, emergency department (ED) or hospital care among older adults with chronic pain. Methods:A retrospective Veterans Health Administration cohort study was conducted examining older veterans with chronic pain diagnoses and use of incident HRME (opioids, skeletal muscle relaxants, antihistamines and psychotropics). Outcomes evaluated included all-cause mortality, ED visits or inpatient hospital care. Descriptive statistics summarized variables for the overall cohort, the chronic pain cohort and those with and without HRME. Separate generalized linear mixed-effect regression models were used to examine the association of incident HRME on each outcome, controlling for potential confounders. Results:Among 1,807,404 veterans who received Department of Veterans Affairs care in 2005 to 2006, 584,066 (32.3%) had chronic pain; 45,945 veterans with chronic pain (7.9%) had incident HRME exposure. The strongest significant associations of incident HRME were for high-risk opioids with all-cause hospitalizations (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.95–2.23), skeletal muscle relaxants with all-cause ED visits (OR 2.62, 95% CI 2.52–2.73) and mortality (OR 0.80, 95% CI 0.74–0.86), antihistamines with all-cause ED visits (OR 2.82 95% CI 2.72–2.95) and psychotropics with all-cause hospitalizations (OR 2.15, 95% CI 1.96–2.35). Conclusions:Our data indicate that incident HRME is associated with clinically important adverse outcomes in older veterans with chronic pain and highlight the importance of being judicious with prescribing certain classes of drugs in this vulnerable population.

Empiric weight-based vancomycin in intensive care unit patients with methicillin-resistant Staphylococcus aureus bacteremia

Background:Previous studies were conducted in all hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia to determine safety and effectiveness of guideline-recommended, weight-based dosing of vancomycin. In these studies, it was observed that severely ill patients (Pitt bacteremia score ≥4 or intensive care unit [ICU] patients) were at an increased risk of mortality and/or nephrotoxicity. Therefore, a subanalysis of the effect of guideline-recommended vancomycin dosing on in-hospital mortality and nephrotoxicity in ICU patients with MRSA bacteremia was conducted. Methods:This multicenter, retrospective, cohort study was conducted in a subset of ICU patients from a previous MRSA bacteremia study. Patients were ≥18 years old and received ≥48 hours of empiric vancomycin from July 1, 2002, to June 30, 2008. The incidence of nephrotoxicity and in-hospital mortality was compared in patients who received guideline-recommended dosing (at least 15 mg/kg per dose) to patients who received non–guideline-recommended dosing of vancomycin. Multivariable generalized linear mixed-effects models were constructed to determine independent risk factors for in-hospital mortality and nephrotoxicity. Results:Guideline-recommended dosing was received by 34% of patients (n = 137). Nephrotoxicity occurred in 35% of patients receiving guideline-recommended dosing and 39% receiving non–guideline-recommended dosing (P = 0.67). In-hospital mortality rate was 24% among patients who received guideline-recommended dosing compared with 31% for non–guideline-recommended dosing (P = 0.40). Guideline-recommended dosing was not associated with nephrotoxicity (odds ratio: 1.10; 95% confidence interval: 0.43–2.79) or in-hospital mortality (odds ratio: 0.54; 95% confidence interval: 0.22–1.36) in the multivariable analysis. Conclusions:Guideline-recommended dosing of vancomycin in ICU patients with MRSA bacteremia is not significantly associated with nephrotoxicity or in-hospital mortality. However, the 7% absolute difference for in-hospital mortality suggests that larger studies are needed.