The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14-and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.T he empirical antibiotic treatment of patients with potentially serious infections is a challenging task. Providing appropriate empirical coverage is proving more and more difficult as antibiotic resistance increases in both the hospital and the community (1). In such situations, physicians face a dilemma: to provide a very-broad-spectrum empirical coverage, accepting that on many occasions it will be excessive and might contribute to further resistance selection, or to use a narrower-spectrum empirical regimen, accepting that it may not cover the causative pathogen and might require correction once the susceptibility results are known (19).A key aspect of this decision-making process is the prognostic impact of empirical therapy. A meta-analysis recently showed reduced mortality rates for sepsis patients who received appropriate empirical therapy (22), although the studies analyzed were heterogeneous in terms of populations and types of infection covered. In both this study and another systematic review focusing on the methodological aspects of the topic (18), the need for new studies with improved methodologies was outlined. Bloodstream infection (BSI) has some advantages as a model for this kind of research. Although patients with bacteremia are only a subset of the pool of patients suffering ...

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Our objective was to evaluate the liver toxicity of antiretroviral regimens including fosamprenavir plus ritonavir (FPV/r) 1400/100 mg once daily (QD) in HIV/hepatitis C virus (HCV)-coinfected patients. This was a prospective cohort study that included 117 HIV/HCV-coinfected patients who started FPV/r 1400/100 mg QD-based antiretroviral therapy (ART) and who neither had received a previous antiretroviral regimen containing FPV nor had a past history of virologic failure while receiving protease inhibitors (PI). The primary end point of the study was the occurrence of grade 3-4 liver enzymes elevations (LEE) within 1 year after starting FPV/r QD. Factors potentially associated with grade 3-4 LEE, including baseline liver fibrosis, were analyzed. Eleven (9%) patients had a grade 3-4 LEE during the follow-up, resulting in an incidence of severe liver toxicity of 9% (95% confidence interval 4.1-14.6%). None of these cases led to FPV/r discontinuation. Baseline liver fibrosis could be assessed in 97 (83%) patients. Six of 71 patients (8%) with significant fibrosis had a grade 3-4 LEE versus 2 of 26 (8%) without significant fibrosis (p=1.0). Twenty (21%) patients had cirrhosis at baseline. There were no cases of LEE among cirrhotics. In conclusion, the incidence of severe liver toxicity after 1 year of therapy with FPV/r QD-based ART in HIV/HCV-coinfected patients is similar to what has been reported with other boosted PIs. In addition, the presence of significant fibrosis or cirrhosis was not associated with the emergence of liver toxicity. Thus, ART regimens containing FPV/r QD may be considered safe in HIV/HCV-coinfected patients, including those with cirrhosis.

Vitamin D insufficiency (D-INSUFF) has been associated with impaired immune response in human immunodeficiency virus (HIV) patients and with a worse prognosis in patients with liver fibrosis. Nevertheless, few studies have explored the influence of D-INSUFF in immunological response and liver parameters in HIV and hepatitis C virus co-infected patients (HIV/HCV) on long term highly active antiretroviral therapy (HAART) with successful immune and viral response. In this cross-sectional study, first we determined the prevalence of D-INSUFF in a cohort of HIV/HCV outpatients with liver fibrosis and second, we assessed whether the existence of D-INSUFF involves the appearance of relevant immunological data and/or particular clinical aspects related to liver disease.

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