Eyal Braun

National Multicenter Study of Predictors and Outcomes of Bacteremia upon Hospital Admission Caused by Enterobacteriaceae Producing Extended-Spectrum β-Lactamases

ABSTRACT Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia

IntroductionCommunity acquired pneumonia (CAP) is a major cause of morbidity and mortality. While there is much data about risk factors for severe outcome in the general population, there is less focus on younger group of patients. Therefore, we aimed to detect simple prognostic factors for severe morbidity and mortality in young patients with CAP.MethodsPatients of 60 years old or younger, who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between March 1, 2005 and December 31, 2008 were retrospectively analyzed for risk factors for complicated hospitalization and 90-day mortality.ResultsThe cohort included 637 patients. 90-day mortality rate was 6.6% and the median length of stay was 5 days. In univariate analysis, male patients and those with co-morbid conditions tended to have complicated disease. In multivariate analysis, variables associated with complicated hospitalization included post chest radiation state, prior neurologic damage, blood urea nitrogen (BUN) > 10.7 mmol/L and red cell distribution width (RDW) > 14.5%; whereas, variables associated with an increased risk of 90-day mortality included age ≥ 51 years, prior neurologic damage, immunosuppression, and the combination of abnormal white blood cells (WBC) and elevated RDW. Complicated hospitalization and mortality rate were significantly higher among patients with increased RDW regardless of the white blood cell count. Elevated RDW was associated with a significant increase in complicated hospitalization and 90-day mortality rates irrespective to hemoglobin levels.ConclusionsIn young patients with CAP, elevated RDW levels are associated with significantly higher rates of mortality and severe morbidity. RDW as a prognostic marker was unrelated with hemoglobin levels.Trial registrationClinicalTrials.Gov NCT00845312

Telephone follow-up improves patients satisfaction following hospital discharge

BACKGROUND Many patients encounter problems in the first weeks after discharge from hospital. Telephone follow-up (TFU) is reputed to be a good tool for providing medical advice, managing symptoms, identifying complications and giving reassurance after discharge. Therefore, we aimed to study whether tight TFU would increase patient satisfaction, improve compliance and reduce re-hospitalization rate. METHODS The study population included 400 patients, hospitalized in an Internal Medicine Department, randomly divided into two groups; TFU and control. TFU took place one week and one month after discharge. Three months later, members of both groups were contacted by telephone. RESULTS Satisfaction was increased in the TFU group compared with control group by 6-12% in most fields. Notably, 87% of patients in the TFU group indicated that earlier telephone contact increased their satisfaction. In addition, 78.2% of the patients in the control group reported that they performed the tests that were recommended at discharge and 86.5% reported that they received explanations regarding their medications. In the TFU group, this percentage was increased significantly to 86.9% (P=0.02) and 96.7% (P<0.0001), respectively. As to treatment results, 93% of the patients in the TFU group as compared to 84% in the control group reported improvement in their symptoms. A non-significant trend towards fewer readmission was observed in the TFU group (26% vs. 35% P=0.062). CONCLUSIONS TFU can improve medical treatment by increasing satisfaction and compliance. A trend towards decreased readmission rates was observed, which may lead to a reduction in the burden on the medical system.

Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump

Widespread vascular endothelial injury is the major mechanism for multiorgan dysfunction in sepsis. Following this process, the permeability of the alveolar capillaries is augmented with subsequent increase in water content and acute respiratory distress syndrome (ARDS). Nevertheless, the role of alveolar epithelium is less known. Therefore, we examined alveolar fluid clearance (AFC) using isolated perfused rat lung model in septic rats without ARDS. Sepsis was induced by ligating and puncturing the cecum with a 21-gauge needle. AFC was examined 24 and 48 h later. The expression of Na-K-ATPase proteins was examined in type II alveolar epithelial cells (ATII) and basolateral membrane (BLM). The rate of AFC in control rats was 0.51 ± 0.02 ml/h (means ± SE) and decreased to 0.3 ± 0.02 and 0.33 ± 0.03 ml/h in 24 and 48 h after sepsis induction, respectively (P < 0.0001). Amiloride, significantly decreased AFC in sepsis; conversely, isoproterenol reversed the inhibitory effect of sepsis. The alveolar-capillary barrier in septic rats was intact; therefore the finding of increased extravascular lung water in early sepsis could be attributed to accumulation of protein-poor fluid. The expression of epithelial sodium channel and Na-K-ATPase proteins in whole ATII cells was not different in both cecal ligation and puncture and control groups; however, the abundance of Na-K-ATPase proteins was significantly decreased in BLMs of ATII cells in sepsis. Early decrease in AFC in remote sepsis is probably related to endocytosis of the Na-K-ATPase proteins from the cell plasma membrane into intracellular pools, with resultant inhibition of active sodium transport in ATII cells.

Natural history and decolonization strategies for ESBL/carbapenem-resistant Enterobacteriaceae carriage: systematic review and meta-analysis

BACKGROUND ESBL-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading worldwide. Their natural reservoir is intestinal. METHODS We carried out a systematic review and meta-analysis to estimate CRE and ESBL carriage duration and to evaluate the effect of decolonization therapy. We included cohort and comparative studies examining the natural history of CRE/ESBL colonization, examining rates of carriage following decolonization or comparing decolonization and no decolonization conducted in the healthcare setting or in the community. A comprehensive search was conducted until November 2015. We compiled carriage rates at 1, 3, 6 and 12 months with and without decolonization therapy and assessed the effect of decolonization. RESULTS Thirty-seven studies fulfilled inclusion criteria. In healthcare settings, pooled ESBL/CRE colonization rates decreased without intervention from 76.7% (95% CI = 69.3%-82.8%) at 1 month to 35.2% (95% CI = 28.2%-42.9%) at 12 months of follow-up. Following decolonization, the rate was 37.1% (95% CI = 27.5%-47.7%) at end of therapy and 57.9% (95% CI = 43.1%-71.4%) at 1 month. In two randomized trials, carriage was significantly reduced at end of therapy (risk ratio = 0.42, 95% CI = 0.25-0.65), but the effect was not significant after 1 month (risk ratio = 0.72, 95% CI = 0.48-1.05), with no longer follow-up. Heterogeneity was explained by surveillance methodology, with no differences observed between ESBLs and CREs. Among community dwellers, ESBL colonization decreased from 52.3% (95% CI = 29.5%-74.2%) at 1 month to 19.2% (95% CI = 9.7%-34.4%) at 6 months. CONCLUSIONS A significant proportion of ESBL and CRE carriers remain colonized up to 1 year in the healthcare setting. While short-term decolonization therapy reduces carriage during therapy, its longer-term effects are unclear.

Clinical and experimental pain perception is attenuated in patients with painless myocardial infarction

Abstract Background. The lack of pain alarm in painless myocardial infarction (MI) leads to increased morbidity and mortality, since patients do not seek medical treatment in a timely manner. We aimed to explore whether reduced systemic pain perception in response to experimental stimuli and pain related personality variables characterizes painless MI patients. Methods. Level of chest pain intensity was assessed by numerical scale, range from 0 (no pain) to 100 (maximal pain). Heat pain threshold, magnitude estimation of supra‐threshold phasic and tonic painful stimuli as well as anxiety and pain catastrophizing scores were assessed in 92 acute MI patients; 67 with and 25 without chest pain, respectively. All experimental stimuli were performed by Thermal Sensory Analysis (TSA) and applied to the right forearm. Results. Greater intensity of chest pain scores was inversely correlated with lower pain threshold (r = −0.417, p < 0.001), and directly associated with higher pain scores in response to the heat pain (r = 0.354, p = 0.002). Patients with painful MI demonstrated lower pain threshold (41.9 ± 3.6 °C vs. 44.9 ± 3.8 °C, p = 0.001) and higher catastrophizing level (10.6 ± 12.0 vs. 5.4 ± 8.8, p = 0.032). Logistic regression analysis revealed that older age and lower pain scores in response to supra‐threshold painful stimuli were associated with greater risk for painless MI. The demographic variables, history of ischemic heart, risk factors for coronary artery disease, ST‐T segment changes on ECG and troponin levels were similar in both groups. Conclusions. This study suggests that reduced systemic pain perception as well as cognitive personality variables play an important role in the etiology of painless MI.

Incidence and risk factors for endocarditis among patients with health care-associated Staphylococcus aureus bacteraemia.

Abstract Background: Staphylococcus aureus infective endocarditis (IE) is a characteristic community-acquired infection, however most cases are presently occurring in the health care setting. This study investigated the incidence and risk factors for S. aureus IE in patients with nosocomial and health care-associated S. aureus bacteraemia (SAB). Methods: Consecutive patients with health care-associated and hospital-acquired SAB were prospectively recruited over a 30-month period. Patients were followed up for at least 12 weeks after the initial positive blood culture result. The primary endpoint was the diagnosis of IE. Results: IE occurred in 11 of 303 patients (3.6%). Patient characteristics at diagnosis and that were associated with IE included the number of positive blood cultures obtained during hospitalization (p = 0.003), the duration of bacteraemia (p < 0.001), bacteraemia persisting for > 3 days (odds ratio (OR) 14.5, 95% confidence interval (CI) 4.0–52.8; p < 0.001), performance of echocardiography (OR 1.88, 95% CI 1.69–2.1; p = 0.001), presence of a well known predisposing risk for IE (OR 57.2, 95% CI 13.6–240.5; p < 0.001), a non-fatal McCabe score (OR 2.10, 95% CI 1.4–3.1; p = 0.02), and the duration of fever related to the infection (p = 0.026). On multivariable analysis, the presence of a predisposing risk for IE, prolonged bacteraemia, and non-fatal McCabe score remained significantly associated with IE. Conclusions: In this study the incidence of IE was lower than previously reported. Three clinical characteristics were identified as risk factors for IE among patients with SAB acquired in a health care setting.

Lymphangitis Carcinomatosis of Unknown Origin Presenting as Severe Pulmonary Hypertension

&NA; An apparently healthy 46‐year‐old woman was admitted because of progressive shortness of breath that had begun 2 months before her admission. Physical examination revealed a patient with respiratory distress, tachycardia, and mild jugular venous distention; otherwise, results were unremarkable. Our investigation revealed hypoxia and severe pulmonary hypertension with signs of right heart dysfunction, but no primary cause was found. The patient died 5 days after admission. Autopsy revealed pulmonary lymphangitis carcinomatosis caused by papillary carcinoma. No primary tumor was found.