Epidemiology, risk factors, and clinical effect of infections by multiresistant bacteria in cirrhosis are poorly known. This work was a prospective evaluation in two series of patients with cirrhosis admitted with infection or developing infection during hospitalization. The first series was studied between 2005 and 2007 (507 bacterial infections in 223 patients) and the second between 2010 and 2011 (162 bacterial infections in 110 patients). In the first series, 32% of infections were community acquired (CA), 32% healthcare associated (HCA), and 36% nosocomial. Multiresistant bacteria (92 infections; 18%) were isolated in 4%, 14%, and 35% of these infections, respectively (P < 0.001). Extended-spectrum b-lactamaseproducing Enterobacteriaceae (ESBL-E; n 5 43) was the main multiresistant organism identified, followed by Pseudomonas aeruginosa (n 5 17), methicillin-resistant Staphylococcus aureus (n 5 14), and Enterococcus faecium (n 5 14). The efficacy of currently recommended empirical antibiotic therapy was very low in nosocomial infections (40%), compared to HCA and CA episodes (73% and 83%, respectively; P < 0.0001), particularly in spontaneous bacterial peritonitis, urinary tract infection, and pneumonia (26%, 29%, and 44%, respectively). Septic shock (26% versus 10%; P < 0.0001) and mortality rate (25% versus 12%; P 5 0.001) were significantly higher in infections caused by multiresistant strains. Nosocomial origin of infection (hazard ratio [HR], 4.43), long-term norfloxacin prophylaxis (HR, 2.69), recent infection by multiresistant bacteria (HR, 2.45), and recent use of b-lactams (HR, 2.39) were independently associated with the development of multiresistant infections. Results in the second series were similar to those observed in the first series. Conclusions: Multiresistant bacteria, especially ESBL-producing Enterobacteriaceae, are frequently isolated in nosocomial and, to a lesser extent, HCA infections in cirrhosis, rendering third-generation cephalosporins clinically ineffective. New antibiotic strategies tailored according to the local epidemiological patterns are needed for the empirical treatment of nosocomial infections in cirrhosis. (HEPATOLOGY 2012;55:1551-1561

We conducted population-based surveillance for Candida bloodstream infections in Spain to determine its incidence, the extent of antifungal resistance, and risk factors for mortality. A case was defined as the first positive blood culture for any Candida spp. in a resident of Barcelona, from 1 January 2002 to 31 December 2003. We defined early mortality as occurring between days 3 to 7 after candidemia and late mortality as occurring between days 8 to 30. We detected 345 cases of candidemia, for an average annual incidence of 4.3 cases/100,000 population, 0.53 cases/1,000 hospital discharges, and 0.73 cases/10,000 patient-days. Outpatients comprised 11% of the cases, and 89% had a central venous catheter (CVC) at diagnosis. Overall mortality was 44%. Candida albicans was the most frequent species (51% of cases), followed by Candida parapsilosis (23%), Candida tropicalis (10%), Candida glabrata (8%), Candida krusei (4%), and other species (3%). Twenty-four isolates (7%) had decreased susceptibility to fluconazole (MIC > 16 g/ml). On multivariable analysis, early death was independently associated with hematological malignancy (odds ratio [

Background: A study was undertaken to validate the modified American Thoracic Society (ATS) rule and two British Thoracic Society (BTS) rules for the prediction of ICU admission and mortality of community acquired pneumonia and to provide a validation of these predictions on the basis of the pneumonia severity index (PSI). Method: Six hundred and ninety six consecutive patients (457 men (66%), mean (SD) age 67.8 (17.1) years, range 18-101) admitted to a tertiary care hospital were studied prospectively. Of these, 116 (16.7%) were admitted to the ICU. Results: The modified ATS rule achieved a sensitivity of 69% (95% CI 50.7 to 77.2), specificity of 97% (95% CI 96.4 to 98.9), positive predictive value of 87% (95% CI 78.3 to 93.1), and negative predictive value of 94% (95% CI 91.8 to 95.8) in predicting admission to the ICU. The corresponding predictive indices for mortality were 94% (95% CI 82.5 to 98.7), 93% (95% CI 90.6 to 94.7), 49% (95% CI 38.2 to 59.7), and 99.5% (95% CI 98.5 to 99.9), respectively. These figures compared favourably with both the BTS rules. The BTS-CURB criteria achieved predictions of pneumonia severity and mortality comparable to the PSI. Conclusions: This study confirms the power of the modified ATS rule to predict severe pneumonia in individual patients. It may be incorporated into current guidelines for the assessment of pneumonia severity. The CURB criteria may be used as an alternative tool to PSI for the detection of low risk patients.

Background: Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. Methods: The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor a (TNFa) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, >65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, >65 years of age) scales. A total of 453 hospitalised CAP patients were included. Results: The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. Conclusions: Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.

To assess whether methicillin resistance is a microbial characteristic associated with deleterious clinical outcome, we performed a cohort study on 908 consecutive episodes of Staphylococcus aureus bacteremia and a case-control study involving 163 pairs of patients matched for preexisting comorbidities, prognosis of the underlying disease, length of hospitalization, and age. Of 908 bacteremic episodes, 225 (24.8%) were due to methicillin-resistant S. aureus (MRSA). Multivariate analysis did not reveal that methicillin resistance was an independent predictor for mortality when shock, source of bacteremia, presence of an ultimately or rapidly fatal underlying disease, acquisition of the infection in an intensive care unit (ICU), inappropriate empirical therapy, female sex, and age were taken into account. Nonetheless, methicillin resistance was an independent predictor for shock. The case-control study could not confirm that shock was linked to MRSA when prior antimicrobial therapy, inappropriate treatment, ICU residence, and female sex were considered. Our data suggest that cohort studies tend to magnify the relationship of MRSA with clinical markers of microbial pathogenicity and that this effect is a shortcoming of these kind of studies that is caused by inadequate control for underlying diseases.

Patients with cirrhosis, particularly those with decompensated cirrhosis, are at increased risk of bacterial infections that may further precipitate other liver decompensations including acute‐on‐chronic liver failure. Infections constitute the main cause of death in patients with advanced cirrhosis, and strategies to prevent them are essential. The main current strategy is the use of prophylactic antibiotics targeted at specific subpopulations at high risk of infection: prior episode of spontaneous bacterial peritonitis, upper gastrointestinal bleeding, and low‐protein ascites with associated poor liver function. Antibiotic prophylaxis effectively prevents not only the development of bacterial infections in all these indications but also further decompensation (variceal bleeding, hepatorenal syndrome) and improves survival. However, antibiotic prophylaxis is also associated with a clinically relevant and increasing drawback, the development of infections due to multidrug‐resistant organisms. Several strategies have been suggested to balance the risks and benefits of antibiotic prophylaxis. Conclusion: Antibiotic stewardship principles such as the restriction of antibiotic prophylaxis to subpopulations at a very high risk for infection, the avoidance of antibiotic overuse, and early deescalation policies are key to achieve this balance; nonantibiotic prophylactic measures such as probiotics, prokinetics, bile acids, statins, and hematopoietic growth factors could also contribute to ameliorate the development and spread of multidrug‐resistant bacteria in cirrhosis. (Hepatology 2016;63:2019‐2031)

The predictive rule to identify severe CAP is accurate for ICU admission and improved the prediction of mortality, compared with the previous American Thoracic Society guidelines. The need for ICU admission derived from minor severity criteria alone is uncertain and deserves further investigation.

To analyze the interaction between empirical therapy and MDR, a variable combining both was introduced in the multivariate analysis. Inappropriate therapy was significantly associated with higher mortality regardless of the susceptibility pattern, and there was a trend toward higher mortality in patients receiving appropriate therapy for MDR than in those appropriately treated for non-MDR strains (OR, 2.2; 95% CI, 0.9 to 5.4). In 47.9% of MDR PAB episodes, appropriate therapy consisted of monotherapy with amikacin. In conclusion, MDR PAB is associated with a higher mortality than non-MDR PAB. This may be related to a higher rate of inappropriate empirical therapy and probably also to amikacin as frequently the only appropriate empirical therapy given to patients with MDR PAB.