Comparison of Nafcillin and Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia.

BACKGROUND: Traditionally, the antibiotic of choice for Methicillin-susceptible Staphylococcus aureus related blood stream infections (MSSA-BSI) are the antistaphylococcal penicillins. Cefazolin is considered an alternative agent, with recent evidence showing similar clinical efficacy. This study further evaluates the utility of nafcillin versus cefazolin in MSSA bacteremia including high disease burden sources of infection and its impact on treatment failure. METHODS: This retrospective study included patients admitted to Methodist LeBonheur Healthcare adult hospitals from 2011 to 2016. Patients were included if they received at least 3 days of either nafcillin or cefazolin and had a positive blood culture for MSSA. The primary objective was to evaluate rates of treatment failure between groups. Secondary outcomes included clinical and microbiological cure, MSSA-BSI associated readmissions, identification of risk factors for treatment failure including disease burden, in-hospital and 90 day mortality. RESULTS: A total of 277 patients were included (nafcillin n = 126; cefazolin n = 151). Treatment failure and microbiologic cure were similar between nafcillin and cefazolin (20.6% vs. 16.6%; 91.2% vs. 87.2%, respectively). Clinical cure was significantly higher in the cefazolin treatment arm (93.4 vs. 83.3%; P = 0.012). However, the total number of patients with high disease burden was greater in the nafcillin group (54.8% vs. 39.1%; P = 0.011). Higher rates of in-hospital mortality were observed in the nafcillin group (15.1% vs. 6%; P = 0.016). CONCLUSIONS: Our study observed significantly higher rates of clinical cure and reduced in-hospital mortality in patients who received cefazolin. Further analysis is warranted to evaluate the effectiveness of these agents and identifying predictors of treatment failure.

Transplantation of kidneys from hepatitis C-infected donors to hepatitis C-negative recipients: Single center experience.

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.

Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic Therapies.

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

ß-Blockade in Heart Failure With Reduced Ejection Fraction: Does Heart Rate Control Influence Readmissions?

BACKGROUND: Raised resting heart rate (HR), >70 beats per minute (bpm), has been shown to be a risk factor for adverse cardiovascular outcomes and hospital readmissions, specifically in patients with heart failure with reduced ejection fraction (HF rEF). Given their mortality benefit, ß-blockers are recommended in HF rEF, with a goal to titrate to a maximum tolerated dose rather than a specific HR target. OBJECTIVE: To determine the impact of optimal HR control achievement prior to hospital discharge on hospital readmissions in patients with HF rEF receiving ß-blockade. METHODS: A retrospective study of patients admitted to 5 adult hospitals within a large urban health-care system, between 2013 and 2015, was conducted. Patients were identified via International Classification of Diseases, Ninth Revision ( ICD-9) coding for acute on chronic HF rEF. RESULTS: Of the 225 patients included, 20% achieved optimal HR control (n = 46, HR <70 bpm; n = 179, HR ≥70 bpm) and only 15% received ß-blocker titration during hospital admission. Of note, 25% of patients receiving ≥50% target dose (n = 79) and 28% receiving 100% target dose (n = 39) achieved optimal HR control. At 30 days, patients with an HR <70 bpm versus HR ≥70 bpm exhibited similar readmission rates (9% vs 11%, respectively; P > .99) and ED visits (11% vs 8%, respectively; P = .57). CONCLUSIONS: Readmission rates were similar among patients with HF rEF despite the majority failing to achieve optimal HR control from ß-blockade. However, ß-blocker dosing remains suboptimal relative to guideline-recommended target doses. Opportunities exist for inpatient clinicians to optimize ß-blockade in an attempt to achieve HR control.

Evaluation of warfarin dose requirements in patients with chronic kidney disease and end-stage renal disease.

STUDY OBJECTIVES: The effect of chronic kidney disease (CKD) on warfarin has gained attention because of an increased risk of thromboembolism and an increased risk of bleeding associated with warfarin treatment in these patients. Data suggest that patients with reduced kidney function require lower warfarin doses; however, relatively few patients with end-stage renal disease (ESRD) were included in previous studies. The goal of this study was to evaluate warfarin dosing requirements and time to reach therapeutic international normalized ratio (INR) in patients with CKD stages 3-5 and ESRD compared with patients with normal kidney function (NKF). METHODS: A historical cohort was identified to evaluate warfarin response in 210 hospitalized adults with varying degrees of kidney function initiated or maintained on warfarin for 4 or more consecutive days including 49 patients with NKF (glomerular filtration rate [GFR] higher than 60 ml/min/1.73 m(2) ), 44 with CKD stage 3, 27 with CKD stage 4/5, and 90 with ESRD. The average daily dose (ADD), time to achieve a therapeutic INR, and adverse effects were compared. MEASUREMENTS AND MAIN RESULTS: The ADD to maintain a therapeutic INR was 5.6 ± 1.7 mg in the NKF group, 4.3 ± 1.6 mg in CKD stage 3, 4.6 ± 1.9 mg in CKD stage 4/5, and 4.8 ± 1.9 mg in ESRD. The ADD was lower in CKD/ESRD patients compared with NKF patients (p=0.001), especially among whites. The time to reach a therapeutic INR in patients newly initiated on warfarin was significantly lower in the CKD/ESRD group when compared with the NKF group (p=0.02). No differences in bleeding episodes were observed during hospitalization or within 30 days of discharge in patients with CKD stage 3 or higher compared with patients with NKF. CONCLUSIONS: Our findings suggest that CKD and ESRD patients require ~20% lower warfarin doses to maintain a therapeutic INR and may require less time to achieve a therapeutic INR compared with patients with NKF.