Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study.

BACKGROUND: Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data. OBJECTIVE: The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock. METHODS: A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety. RESULTS: There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01). CONCLUSION AND RELEVANCE: FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.

Epidemiology of Methicillin-Resistant Staphylococcus aureus Diabetic Foot Infections in a Large Academic Hospital: Implications for Antimicrobial Stewardship.

INTRODUCTION: Diabetic foot infections (DFIs) are the leading cause of non-traumatic lower extremity amputations in the United States. Antimicrobials active against methicillin-resistant Staphylococcus aureus (MRSA) are recommended in patients with associated risk factors; however, limited data exist to support these recommendations. Due to the changing epidemiology of MRSA, and the consequences of unnecessary antibiotic therapy, guidance regarding the necessity of empirical MRSA coverage in DFIs is needed. We sought to 1) describe the prevalence of MRSA DFIs at our institution and compare to the proportion of patients who receive MRSA antibiotic coverage and 2) identify risk factors for MRSA DFI. METHODS: This was a retrospective cohort study of all adult, culture-positive DFI patients managed at University Hospital, San Antonio, TX between January 1, 2010 and September 1, 2014. Patient eligibility included a principal ICD-9-CM discharge diagnosis code for foot infection and a secondary diagnosis of diabetes. The primary outcome was MRSA identified in the wound culture. Independent variables assessed included patient demographics, comorbidities, prior hospitalization, DFI therapies, prior antibiotics, prior MRSA infection, and laboratory values. Multivariable logistic regression was used to identify risk factors for MRSA DFI. RESULTS: Overall, 318 patients met inclusion criteria. Patients were predominantly Hispanic (79%) and male (69%). Common comorbidities included hypertension (76%), dyslipidemia (52%), and obesity (49%). S. aureus was present in 46% of culture-positive DFIs (MRSA, 15%). A total of 273 patients (86%) received MRSA antibiotic coverage, resulting in 71% unnecessary use. Male gender (OR 3.09, 95% CI 1.37-7.99) and bone involvement (OR 1.93, 1.00-3.78) were found to be independent risk factors for MRSA DFI. CONCLUSIONS: Although MRSA was the causative pathogen in a small number of DFI, antibiotic coverage targeted against MRSA was unnecessarily high.

Retrospective cohort study evaluating the incidence of diabetic foot infections among hospitalized adults with diabetes in the United States from 1996-2010.

BACKGROUND: The prevalence of diabetes has increased over the last 2 decades; however, the national incidence of diabetic foot infections (DFIs) in the United States is unknown. We sought to determine national trends in DFIs among hospitalized adults in the United States over 15 years. METHODS: This was a retrospective cohort study of the U.S. National Hospital Discharge Survey from 1996-2010. Adult patients with a principal diagnosis of foot infection and a secondary diagnosis of diabetes were identified using ICD-9-CM codes. Incidence was defined as DFI discharges per 100 diabetes discharges. Independent risk factors for DFI among diabetics were identified using multivariable logistic regression. RESULTS: These data represent 1,059,552 DFI discharges over the study period. The incidence of DFI decreased from 1996 (2.3 DFIs/100 diabetes discharges) to 2010 (1.1 DFI/100 diabetes discharges). The proportion of patients experiencing lower-extremity amputation declined from 33.2% in 1996 to 17.1% in 2010. Peripheral vascular disease (odds ratio [OR], 2.89; 95% confidence interval [CI], 2.87-2.91), peripheral neuropathy (OR, 2.62; 95% CI, 2.60-2.64), and male sex (OR, 1.67; 95% CI, 1.66-1.68) were the leading risk factors for DFI. CONCLUSION: The incidence of DFI among hospitalized adults in the United States declined by more than half from 1996-2010.

Simeprevir and sofosbuvir for treatment of chronic hepatitis C infection.

PURPOSE: Chronic hepatitis C infection affects a large proportion of the world's population and can lead to significant morbidity and mortality. The standard of care for treatment of hepatitis C infection has been peginterferon and ribavirin, with or without a first-generation protease inhibitor. In late 2013 and early 2014, sofosbuvir and simeprevir obtained regulatory approval, offering the first possibility for all-oral treatment regimens. We provide a review of the clinical efficacy and safety of sofosbuvir- and simeprevir-containing regimens. METHODS: Studies were identified in PubMed using the terms sofosbuvir and simeprevir in combination with hepatitis C. Abstracts of additional studies presented at professional meetings but not yet published were also reviewed. All Phase 3 trials published by August 1, 2014, as well as Phase 2 studies for which there was not a corresponding Phase 3 trial, were included in the review. FINDINGS: Simeprevir was studied with peginterferon and ribavirin in 7 published Phase 3 trials, with overall efficacy rates of 59% to 100%. Sofosbuvir was studied with ribavirin and with or without peginterferon in 6 Phase 3 trials with overall efficacy rates of 50% to 93%. Patient groups with lower response rates tended to have cirrhosis and be older, men, and previous null responders. Simeprevir and sofosbuvir were studied in combination in 1 Phase 2a study with overall efficacy of 92%. Additional studies demonstrated the efficacy and safety of sofosbuvir regimens in patients before and after liver transplantation. Overall, the simeprevir- and sofosbuvir-containing regimens were tolerated better or as well as peginterferon and ribavirin regimens, with fatigue, headache, and nausea the most common adverse events. IMPLICATIONS: Results from numerous Phase 3 clinical trials indicate that sofosbuvir- and simeprevir-containing regimens are highly effective and safe for the treatment of chronic hepatitis C infection. The approval of these 2 agents has led to a complete overhaul of published guidelines, with sofosbuvir- and simeprevir-containing regimens included in preferred regimens.

Safety and tolerability of high-dose weekly liposomal amphotericin B antifungal prophylaxis.

Children with hematologic malignancies are at an increased risk of invasive fungal infections and a greater risk has been seen with exposure to building construction. Prophylaxis with high-dose (IV) liposomal amphotericin B (L-AmB) 10 mg/kg once weekly was initiated in our high risk children based on previous pharmacokinetic studies. This treatment regimen was associated with a 26% incidence of adverse infusion reactions.