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Purpose Recent data have not demonstrated improved outcomes when guideline-concordant (GC) antibiotics are given to patients with health care–associated pneumonia (HCAP). This study was designed to evaluate the relationship between health outcomes and GC therapy in patients admitted to an intensive care unit (ICU) with HCAP. Materials and methods We performed a population-based cohort study of patients admitted to greater than 150 hospitals in the US Veterans Health Administration system to compare baseline characteristics, bacterial pathogens, and health outcomes in ICU patients with HCAP receiving GC-HCAP therapy, GC community-acquired pneumonia (GC-CAP) therapy, or non-GC therapy. The primary outcome was 30-day patient mortality. Risk factors for the primary outcome were assessed in a multivariable logistic regression model. Results A total of 3593 patients met inclusion criteria and received GC-HCAP therapy (26%), GC-CAP therapy (23%), or non-GC therapy (51%). Patients receiving GC-HCAP had higher 30-day patient mortality compared to GC-CAP patients (34% vs 22%; P Conclusions Our data do not demonstrate improved outcomes among ICU patients with HCAP who received GC-HCAP therapy.

OBJECTIVE:The aim of this study was to compare the incidence of skin and soft tissue infections (SSTIs) across healthcare settings and analyze direct healthcare expenditures related to SSTIs in 2000 and 2012 in the United States. METHODS:We performed a retrospective, cross-sectional analysis of nationally representative data from the Medical Expenditure Panel Surveys. Population-based incidence rates were examined for all healthcare settings that include inpatient visits, emergency department visits and ambulatory visits for SSTIs. The direct costs of healthcare services utilization were reported. Population-based prescribing rates for each antimicrobial class during ambulatory visits were compared. RESULTS:A total of 2.4 million patients experienced an SSTI in 2000 compared to 3.3 million in 2012 (40% increase). From 2000 to 2012, the incidence of patients with at least one hospital visit for SSTIs increased 22%, ambulatory care visits increased 30%, and emergency department visits increased 40%. The incidence of SSTIs in children and adolescents declined 50% (from 150 to 76 per 10,000 person; RR = 0.51, 95% CI: 0.38-0.67; p 65 years of age) increased almost 2-fold (from 67 to 130 per 10,000 person; RR = 1.94, 95% CI: 1.44-2.61; p

The echinocandins target fungi by inhibiting the production of (1,3)-β-d-glucan, an essential component of the fungal cell wall. These agents have less toxicity to mammalian cells, as compared to other antifungals; however, they maintain potent activity against many pathogenic fungi, including polyene- and azole-resistant isolates. Members of this class are highly protein-bound, and the addition of serum or albumin to the growth medium has profound effects on their in vitro potency and pharmacodynamics. In addition, studies have demonstrated an association between in vitro activity, in the presence of serum, and outcomes in animal models of invasive fungal infections. Serum and albumin may also be useful to help detect echinocandin-resistant Candida isolates with point mutations in the gene that encodes for glucan synthase. Thus, in vitro studies evaluating echinocandins in the presence of protein can provide valuable insight regarding their potency and pharmacodynamics.

The annual incidence of skin and soft tissue infections (SSTIs) has nearly tripled in the US since the early 1990s. Many purulent SSTIs in the community setting are caused by methicillin-resistant Staphylococcus aureus (MRSA). Incision and drainage (ID) are indicated for most purulent MRSA infections; however, the use of adjunctive antibacterials is controversial. The objective of this study was to systematically evaluate studies that have investigated whether or not antibacterials provide added benefit to ID alone for purulent MRSA SSTIs. We included articles from MEDLINE and The Cochrane Library that fulfilled the following criteria: (i) original research; (ii) English language; (iii) compared ID alone versus ID plus antibacterials for purulent MRSA SSTIs; and (iv) compared patient outcomes. We also reviewed the references of these articles to identify other relevant studies. Studies that solely examined paediatric patients were excluded. To facilitate cross-study comparison, we systematically evaluated the following study characteristics: (i) study design; (ii) patient population; (iii) comparator groups; (iv) sample size; (v) outcome measures; (vi) outcome definitions; (vii) duration of follow-up; and (viii) measurement and adjustment of potential confounding variables. Eleven studies, spanning more than 30 years, met inclusion criteria. Two of these were conducted prior to the emergence of MRSA in the community; another evaluated cephalexin versus placebo for MRSA. None of these found added benefit of adjunctive antibacterials. Four studies compared health outcomes between patients who received 'active' or 'appropriate' therapy and those who received 'inactive' or 'inappropriate' therapy after ID for purulent MRSA SSTIs. Two of these studies found 'active' or 'appropriate' therapy to be beneficial, while two others did not. Four studies compared health outcomes between patients who received anti-MRSA antibacterials plus ID with those who received alternative antibacterials plus ID for purulent MRSA SSTIs. Three of these reported improved outcomes with anti-MRSA antibacterials, while another reported mixed findings. Presently, the bulk of the available evidence suggests anti-MRSA antibacterials provide added benefit to ID alone for purulent MRSA SSTIs; however, the current evidence is limited to small, case-control, observational studies.

Background Fenofibrate-associated nephrotoxicity has been described in two randomized controlled trials and several observational studies. However, little is known regarding its incidence and the population(s) at risk. Objective This study aims to quantify the incidence and identify potential risk factors for development of nephrotoxicity in patients receiving fenofibrate. Methods A retrospective, observational study was conducted in the South Texas Veterans Health Care System. Data were collected regarding baseline demographics, concurrent medical conditions, medications, laboratory results, and fenofibrate use. Results Within 6 months after initiation of fenofibrate in 428 patients, 115 (27%) experienced an increase in serum creatinine of ≥0.3 mg/dL. Any renal disease ( P = .001), chronic kidney disease ( P = .01), and diabetes ( P = .02) were significantly more prevalent in patients with fenofibrate-associated nephrotoxicity. Patients with nephrotoxicity had significantly greater serum creatinine (1.2 [SD 0.3] vs. 1.1 mg/dL [SD 0.3], P = .0002) and lower estimated glomerular filtration rate (72 [SD 20] vs 81 mL/min/1.73m 2 [SD 20], P P = .0003), furosemide ( P = .02), and angiotensin-converting enzyme inhibitors ( P = .02). The incidence of nephrotoxicity was significantly greater in patients initiated on high-dose versus those on low-dose fenofibrate ( P = .002). In a multivariable regression model, renal disease ( P = .02), high-dose fenofibrate ( P = .001), and dihydropyridine calcium channel blocker use ( P = .02) were determined to be independent predictors of development of increased serum creatinine on fenofibrate. Conclusion This observational study suggests fenofibrate-associated nephrotoxicity occurs more frequently than previously reported, particularly in patients with renal disease and in those receiving high-dose fenofibrate or concomitant calcium channel blockers.

Objectives The benefit of improved health outcomes for blacks receiving highly active antiretroviral therapy (HAART) lags behind that of whites. This project therefore sought to determine whether the reason for this discrepancy in health outcomes could be attributed to disparities in use of antiretroviral therapy between black and white patients with HIV. Materials and methods The 1996-2006 National Hospital Ambulatory Medical Care Surveys were used to identify hospital outpatient visits that documented antiretrovirals. Patients younger than 18 years, of nonblack or nonwhite race, and lacking documentation of antiretrovirals were excluded. A multivariable logistic regression model was constructed with race as the independent variable and use of HAART as the dependent variable. Results Approximately 3 million HIV/AIDS patient visits were evaluated. Blacks were less likely than whites to use HAART and protease inhibitors (odds ratio, 95% CI 0.81 [0.81-0.82] and 0.67 [0.67-0.68], respectively). More blacks than whites used non-nucleoside reverse transcriptase inhibitors (odds ratio, 95% CI 1.18 [1.17-1.18]). In 1996, the crude rates of HAART were relatively low for both black and white cohorts (5% vs 6%). The rise in HAART for blacks appeared to lag behind that of whites for several years, until 2002, when the proportion of blacks receiving HAART slightly exceeded the proportion of whites receiving HAART. In later years, the rates of HAART were similar for blacks and whites (81% vs 82% in 2006). Blacks appeared less likely than whites to use protease inhibitors and more likely than whites to use non-nucleoside reverse transcriptase inhibitors from 2000 to 2004. Conclusions Blacks experienced a lag in the use of antiretrovirals at the beginning of the study; this discrepancy dissipated in more recent years.

Objective To provide an overview of the regulation issues surrounding compounding pharmacy that allowed the United States fungal meningitis outbreak to occur and the changes in regulation that ensued. Summary In September 2012, a single case report sparked an investigation into a nationwide outbreak of fungal meningitis due to contaminated injectable drugs. The source of the contamination, New England Compounding Center (NECC), was in violation of several state and federal laws and had a history of such violations. The regulation of compounding pharmacies has historically been left to the states, while manufacturing fell under the jurisdiction of the Food and Drug Administration. However, as more compounders took part in large-scale interstate distribution of drugs, the current state-based regulatory system became less equipped to provide oversight. The lack of a clear definition of “compounding pharmacy” further obscures proper oversight and regulation. Congress and several states have taken steps to build safeguards against large-scale compounding by increasing inspections, adopting stricter licensing requirements, and enacting the Drug Quality and Security Act of 2013. Conclusion While the current compounding regulation changes are a necessary step forward, it remains to be seen how effective they will be in safeguarding the public.

Purpose The literature describing fenofibrate-associated nephrotoxicity was reviewed. Summary Fenofibrate-associated nephrotoxicity is an underrecognized adverse effect that is being reported with increasing frequency in the medical literature. A MEDLINE search identified articles describing fenofibrate-associated nephrotoxicity. Two retrospective chart reviews reported this adverse reaction in transplant recipients and patients with renal insufficiency. A case series of six patients noted that the adverse reaction also occurred in patients without a predisposition to renal injury. Two small prospective studies have examined fenofibrate-associated nephrotoxicity, with conflicting findings regarding the mechanism. Finally, a large retrospective review and a population-based cohort study found that patients with preexisting renal disease or taking high-dosage fenofibrate have a higher risk of developing fenofibrate-associated nephrotoxicity. Fenofibrate-associated nephrotoxicity was shown to be reversible with both discontinuation and continued use of fenofibrate, though one study found that the elevations in serum creatinine (SCr) levels were permanent in study participants. Some argue that SCr elevations described in these articles were not due to renal toxicity but may be attributed to reversible mechanisms. While several mechanisms may be biologically plausible, none of the theories have been tested in clinical trials. A possible mechanism for the increase in SCr levels may include changes in renal hemodynamics causing volume depletion and the impairment of generation of vasodilatory prostaglandins, leading to renal vasoconstriction. Conclusion Fenofibrate-associated nephrotoxicity is an underrecognized adverse drug reaction. Several published reports have detailed possible etiologies; however, data detailing the true incidence of fenofibrate-associated nephrotoxicity and its associated risk factors are limited.

Hyperglycemia, a common finding in critically ill patients, is linked to poor outcomes in multiple conditions. The Leuven I study published in 2001 was the first evaluation of intensive insulin therapy, and the 3.4% absolute reduction in mortality in a single-center surgical intensive care unit led to widespread endorsement of the therapy. In a subsequent study in a medical intensive care unit, reduction in mortality was not significant. Two multicenter studies were stopped early because of significantly higher rates of hypoglycemia in the patients receiving intensive insulin therapy. The episodes of hypoglycemia were linked to increased mortality. In the largest prospective study conducted to date, mortality was significantly higher (P = .02) in patients who had intensive therapy (27.5%) than in control patients (24.9%). Thus, after years of research, intensive insulin therapy does not appear to convey the original benefit in all critically ill patients. Several organizations have proposed alternative blood glucose targets, such as 140 to 180 mg/dL, to both provide glycemic control and reduce the opportunity for hypoglycemic episodes.

The purpose of this systematic review was to identify studies that evaluated HIV/AIDS disparities by examining differences in the receipt of antiretroviral therapy and differences in mortality between blacks and whites in the United States. The authors conducted 2 Web-based literature searches of the MEDLINE database for published peer reviewed scientific articles that analyzed black race as a predictor of antiretroviral therapy and mortality. Five reports met the criteria for the antiretroviral literature search, whereas seven reports met the criteria for the mortality literature search. After evaluating individual study results, it appears the evidence to identify racial differences in the receipt of antiretroviral therapy as well as the evidence to document disparities in mortality is either limited or mixed. Further research is needed to support or refute the hypothesis that there are inequalities for blacks with HIV/AIDS.

The health benefits for blacks on highly active antiretroviral therapy (HAART) lags behind that of whites. We therefore investigated whether this discrepancy in health outcomes is attributable to disparities in the receipt of appropriate HAART between black and white human immunodeficiency virus (HIV) patients.The 2000-2005 National Ambulatory Medical Care Surveys were used to identify patients receiving antiretrovirals. Regimens were evaluated for appropriateness according to national antiretroviral guideline recommendations. A multivariable logistic regression model was used to assess black race as a predictor for appropriate HAART.An estimated 4.1 million HIV-related visits with antiretroviral therapy were identified. Eighty-six percent of visits were associated with appropriate therapy; inappropriate therapy was often due to antiretroviral monotherapy. Interestingly, blacks were more likely to receive appropriate therapy in comparison to white patients (94% vs 83%, P.001). Multivariable analysis revealed black race as an independent predictor for an appropriate regimen (chi2 likelihood ratio, 12.3, P.001) when controlling for age, gender, insurance status, and geographic region.Health outcome disparities between black and white HIV patients do not appear to be attributable to differences in receipt of appropriate HAART. Further investigations are warranted to identify factors responsible for these outcome disparities.

Background In general, the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) population has begun to experience the benefits of highly active antiretroviral therapy (HAART); unfortunately, these benefits have not extended equally to Blacks in the United States, possibly due to differences in patient comorbidities and demographics. These differences include rates of hepatitis B and C infection, substance use, and socioeconomic status. To investigate the impact of these factors, we compared hospital mortality and length of stay (LOS) between Blacks and Whites with HIV/AIDS while adjusting for differences in these key characteristics. Methods The 1996–2006 National Hospital Discharge Surveys were used to identify HIV/AIDS patients admitted to US hospitals. Survey weights were incorporated to provide national estimates. Patients < 18 years of age, those who left against medical advice, those with an unknown discharge disposition and those with a LOS < 1 day were excluded. Patients were stratified into subgroups by race (Black or White). Two multivariable logistic regression models were constructed with race as the independent variable and outcomes (mortality and LOS > 10 days) as the dependent variables. Factors that were significantly different between Blacks and Whites at baseline via bivariable statistical tests were included as covariates. Results In the general US population, there are approximately 5 times fewer Blacks than Whites. In the present study, 1.5 million HIV/AIDS hospital discharges were identified and Blacks were 6 times more likely to be hospitalized than Whites. Notably, Blacks had higher rates of substance use (30% vs. 24%; P < 0.001), opportunistic infections (27% vs. 26%; P < 0.001) and cocaine use (13% vs. 5%; P < 0.001). Conversely, fewer Blacks were co-infected with hepatitis C virus (8% vs. 12%; P < 0.001). Hepatitis B virus was relatively infrequent (3% for both groups). Crude mortality rates were similar for both cohorts (5%); however, a greater proportion of Blacks had a LOS > 10 days (21% vs. 19%; P < 0.001). Black race, in the presence of comorbidities, was correlated with a higher odds of LOS > 10 days (OR, 95% CI = 1.20 [1.10–1.30]), but was not significantly correlated with a higher odds of mortality (OR, 95% CI = 1.07 [0.93–1.25]). Conclusion Black race is a predictor of LOS > 10 days, but not mortality, among HIV/AIDS patients admitted to US hospitals. It is possible that racial disparities in hospital outcomes may be closing with time.