Objective: To evaluate whether one antibiotic achieves equal outcomes compared with combination antibiotic therapy in patients with Pseudomonas aeruginosa ventilator-associated pneumonia. Design: A retrospective, multicenter, observational, cohort study. Setting: Five intensive care units in Spanish university hospitals. Patients: Adult patients identified to have monomicrobial episodes of ventilator-associated pneumonia with significant quantitative respiratory cultures for P. aeruginosa. Interventions: None. Measurement and Main Results: A total of 183 episodes of monomicrobial P. aeruginosa ventilator-associated pneumonia were analyzed. Monotherapy alone was used empirically in 67 episodes, being significantly associated with inappropriate therapy (56.7% vs. 90.5%, p < .001). Hospital mortality was significantly higher in the 40 patients with inappropriate therapy compared with those at least on antibiotic with activity in vitro (72.5% vs. 23.1%, p < .05). Excess mortality associated with monotherapy was estimated to be 13.6% (95% confidence interval −2.6 to 29.9). The use of monotherapy or combination therapy in the definitive regimen did not influence mortality, length of stay, development of resistance to the definitive treatment, or appearance of recurrences. Inappropriate empirical therapy was associated with increased mortality (adjusted hazard ratio 1.85; 95% confidence interval 1.07–3.10; p = .02) in a Cox proportional hazard regression analysis, after adjustment for disease severity, but not effective monotherapy (adjusted hazard ratio 0.90; 95% confidence interval 0.50–1.63; p = .73) compared with effective combination therapy (adjusted hazard ratio 1). The other two variables also independently associated with mortality were age (adjusted hazard ratio 1.02; 95% confidence interval 1.01–1.04; p = .005) and chronic cardiac insufficiency (adjusted hazard ratio 1.90; 95% confidence interval 1.04–3.47; p = .035). Conclusions: Initial use of combination therapy significantly reduces the likelihood of inappropriate therapy, which is associated with higher risk of death. However, administration of only one effective antimicrobial or combination therapy provides similar outcomes, suggesting that switching to monotherapy once the susceptibility is documented is feasible and safe.

Background and Purpose—: Bone marrow mononuclear cell (BM-MNC) intra-arterial transplantation improves recovery in experimental models of ischemic stroke. We aimed to assess the safety, feasibility, and biological effects of autologous BM-MNC transplantation in patients with stroke. Methods—: A single-blind (outcomes assessor) controlled Phase I/II trial was conducted in patients with middle cerebral artery stroke. Autologous BM-MNCs were injected intra-arterially between 5 and 9 days after stroke. Follow-up was done for up to 6 months and blood samples were collected for biological markers. The primary outcome was safety and feasibility of the procedure. The secondary outcome was improvement in neurological function. Results—: Ten cases (BM-MNC-treated) and 10 control subjects (BM-MNC-nontreated) were consecutively included. Mean National Institutes of Health Stroke Scale before the procedure was 15.6. Mean BM-MNCs injected were 1.59×10 ⁸ . There was no death, stroke recurrence, or tumor formation during follow-up, although 2 cases had an isolate partial seizure at 3 months. After transplantation, higher plasma levels of beta nerve growth factor (β-nerve growth factor) were found compared with control subjects ( P =0.02). There were no significant differences in neurological function at 180 days. A trend to positive correlation between number of CD34+ cells injected and Barthel Index was found ( r =0.56, P =0.09). Conclusions—: Intra-arterial BM-MNC transplantation in subacute ischemic stroke is feasible and seems to be safe. Larger randomized trials are needed to confirm the safety and elucidate the efficacy of BM-MNC transplantation. Clinical Trial Registration-URL—: www.clinicaltrials.gov . Unique identifier: NCT00761982.

Introduction: Genetic variations may influence clinical outcomes in patients with sepsis. The present study was conducted to evaluate the impact on mortality of three polymorphisms after adjusting for confounding variables, and to assess the factors involved in progression of the inflammatory response in septic patients. Method: The inception cohort study included all Caucasian adults admitted to the hospital with sepsis. Sepsis severity, microbiological information and clinical variables were recorded. Three polymorphisms were identified in all patients by PCR: the tumour necrosis factor (TNF)-α 308 promoter polymorphism; the polymorphism in the first intron of the TNF-β gene; and the IL-10-1082 promoter polymorphism. Patients included in the study were followed up for 90 days after hospital admission. Results: A group of 224 patients was enrolled in the present study. We did not find a significant association among any of the three polymorphisms and mortality or worsening inflammatory response. By multivariate logistic regression analysis, only two factors were independently associated with mortality, namely Acute Physiology and Chronic Health Evaluation (APACHE) II score and delayed initiation of adequate antibiotic therapy. In septic shock patients (n = 114), the delay in initiation of adequate antibiotic therapy was the only independent predictor of mortality. Risk factors for impairment in inflammatory response were APACHE II score, positive blood culture and delayed initiation of adequate antibiotic therapy. Conclusion: This study emphasizes that prompt and adequate antibiotic therapy is the cornerstone of therapy in sepsis. The three polymorphisms evaluated in the present study appear not to influence the outcome of patients admitted to the hospital with sepsis.