A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections.

BACKGROUND: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy. METHODS: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression. RESULTS: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-ß-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result. CONCLUSIONS: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC. CLINICAL TRIALS REGISTRATION: NCT01122368.

Jávea consensus guidelines for the treatment of Candida peritonitis and other intra-abdominal fungal infections in non-neutropenic critically ill adult patients.

BACKGROUND: Although the management of the invasive candidiasis has improved in the last decade, controversial issues yet remain, especially in the diagnostic and therapeutic approaches to Candida peritonitis and other forms of intra-abdominal fungal infections. AIMS: We sought to identify core clinical knowledge about intra-abdominal fungal infections and to achieve high-agreement recommendations required to care for critically ill adult patients with Candida peritonitis and other forms of intra-abdominal fungal infection. METHODS: A biregional Spanish survey, to elucidate the consensus about the already mentioned fungal infections by means of the Delphi technique, was conducted anonymously by e-mail with 29 multidisciplinary experts in invasive fungal infections from 14 hospitals in the Valencia and Murcia communities during 2014. Respondents included intensivists, anesthesiologists, microbiologists, pharmacologists, and infectious disease specialists, who answered 31 questions prepared by a coordination group after a strict review of the literature from the 5 previous years. The educational objectives spanned 6 categories: epidemiology, microbiological diagnosis, clinical diagnosis, antifungal treatment, de-escalation therapy, and special situations. The agreement required among the panelists for each item to be selected had to be higher than 70%. After extracting the recommendations from the selected items, a meeting at which the experts were asked to validate the previously selected recommendations in a second round of scoring took place. RESULTS: After the second round, 36 recommendations were validated according to the following distribution: epidemiology (5), microbiological diagnosis (4), clinical diagnosis (4), antifungal treatment (3), de-escalation therapy (4), and special situations (16). CONCLUSIONS: Treatment of Candida peritonitis and other forms of intra-abdominal fungal infections in ICU patients requires a broad range of knowledge application and skills that our recommendations address. Based on the DELPHI methodology, these recommendations might help to optimize the therapeutic management of these patients in special situations and in various scenarios to improve their outcome.

Palliative treatment of dyspnea with epidural methadone in advanced emphysema.

STUDY OBJECTIVES: This study investigated whether epidural methadone perfusion at the thoracic level can mitigate dyspnea in patients with advanced emphysema. DESIGN: Open-label clinical trial without a control group. SETTING: University hospital. PATIENTS: The inclusion criteria were a diagnosis of emphysema, basal dyspnea index (Mahler scale) < or = 3, FEV(1) < or = 35%, and no indication for pneumoreduction or lung transplantation surgery. INTERVENTIONS: An epidural catheter was inserted at the thoracic level connected to a perfusion pump for administering methadone (6 mg/24 h). Assessments were made at baseline, 1 week, and 1 month after catheter insertion. MEASUREMENTS: Pulmonary function tests were performed, and determinations were made of arterial blood gas levels, respiratory control data, dyspnea quantification by Mahler transitional dyspnea index (TDI), and the Borg scale change with inspiratory resistive loading, 6-min walk (6MW) distance, and health-related quality of life using the Chronic Respiratory Disease Questionnaire. RESULTS: Of the nine patients studied, infection and catheter migration lead to suspension of treatment before the end of the study in two cases. A significant improvement in dyspnea occurred by 1 week: mean TDI, 3.77 (SD, 1.98) [p < 0.01]. After 1 month of treatment, there were significant improvements in the 6MW distance (mean, 35.33 m; SD, 17.03; p < 0.05), health-related quality of life (mean, 1.63; SD, 0.36; p < 0.05), and dyspnea (mean TDI, 5.33; SD, 2.16; p < 0.05). In addition, after 1 month, Paco(2) fell by 6.67 mm Hg (p < 0.05) and rapid shallow breathing index decreased from 38 to 27 (p < 0.05). These changes occurred without any alteration in the subject's ability to perceive or respond to inspiratory loading. CONCLUSION: Epidural methadone perfusion at chest level can effectively palliate dyspnea and improve exercise capacity and quality of life in patients with advanced emphysema, without deterioration in respiratory control or lung function. These data suggest that modulation of spinal cord afferent signaling is an appropriate novel target for dyspnea control in chronic respiratory disease.

Bugs, hosts and ICU environment: countering pan-resistance in nosocomial microbiota and treating bacterial infections in the critical care setting.

ICUs are areas where resistance problems are the largest, and these constitute a major problem for the intensivist's clinical practice. Main resistance phenotypes among nosocomial microbiota are (i) vancomycin-resistance/heteroresistance and tolerance in grampositives (MRSA, enterococci) and (ii) efflux pumps/enzymatic resistance mechanisms (ESBLs, AmpC, metallo-betalactamases) in gramnegatives. These phenotypes are found at different rates in pathogens causing respiratory (nosocomial pneumonia/ventilator-associated pneumonia), bloodstream (primary bacteremia/catheter-associated bacteremia), urinary, intraabdominal and surgical wound infections and endocarditis in the ICU. New antibiotics are available to overcome non-susceptibility in grampositives; however, accumulation of resistance traits in gramnegatives has led to multidrug resistance, a worrisome problem nowadays. This article reviews microorganism/infection risk factors for multidrug resistance, suggesting adequate empirical treatments. Drugs, patient and environmental factors all play a role in the decision to prescribe/recommend antibiotic regimens in the specific ICU patient, implying that intensivists should be familiar with available drugs, environmental epidemiology and patient factors.

Bugs, hosts and ICU environment: countering pan-resistance in nosocomial microbiota and treating bacterial infections in the critical care setting.

ICUs are areas where resistance problems are the largest, and they constitutes a major problem for the intensivist's clinical practice. Main resistance phenotypes among nosocomial microbiota are: i) vancomycin-resistance/heteroresistance and tolerance in grampositives (MRSA, enterococci) and ii) efflux pumps/enzymatic resistance mechanisms (ESBLs, AmpC, metallobetalactamases) in gramnegatives. These phenotypes are found at different rates in pathogens causing respiratory (nosocomial pneumonia/ventilator-associated pneumonia), bloodstream (primary bacteremia/catheter-associated bacteremia), urinary, intraabdominal and surgical wound infections and endocarditis in the ICU. New antibiotics are available to overcome non-susceptibility in grampositives; however, accumulation of resistance traits in gramnegatives has lead to multidrug resistance, a worrisome problem nowadays. This article reviews by microorganism/infection risk factors for multidrug resistance, suggesting adequate empirical treatments. Drugs, patient and environmental factors all play a role in the decision to prescribe/recommend antibiotic regimens in the specific ICU patient, implying that intensivists should be familiar with available drugs, environmental epidemiology and patient factors.

Magnetic resonance imaging in patients with spinal neurostimulation systems.

BACKGROUND: The safety of performing magnetic resonance imaging (MRI) in patients with spinal cord stimulation (SCS) systems needs to be documented. A prospective in vivo study in patients with SCS, exploring the changes produced by MRI and the associated side effects, was performed. METHODS: After ethics committee approval and patient consent, 31 consecutive patients with SCS at different spinal levels requiring a scheduled MRI evaluation were studied during an 18-month period. All MRIs were performed with a 1.5-T clinical use magnet and a specific absorption rate of no more than 0.9 W/kg. Frequency tables were used for the descriptive study, whereas comparative evaluations were made with the chi-square test for qualitative variables and single-factor analysis of variance for quantitative variables. RESULTS: The mean patient age was 49 +/- 9.5 yr; 67.7% were women (n = 21), and 32.3% were men (n = 10). None of the patients experienced hemodynamic, respiratory, or neurologic alterations. Reported changes were as follows: increased temperature in the generator's area (n = 2, 6.5%); increased in the intensity of the stimulation (n = 1, 3.2%); impedance greater than 4,000 Omega on several of the electrodes in the leads (n = 1, 3.2%); telemetry not possible (n = 2, 6.5%). Radiologic evaluation after MRI revealed no spatial displacements of the SCS leads in any case. CONCLUSION: Under the conditions of the described protocol, MRI in patients with SCS systems resulted in few complications. None of the recorded problems were serious, and in no case were patients harmed or the systems reprogrammed. Maximum patient satisfaction was reported in all cases.