A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients.

OBJECTIVES: To describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance. METHODS: Cirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model. RESULTS: We enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure-SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29-18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93-5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28-1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73-4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48-4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12-0.73; p 0.008). CONCLUSIONS: MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.

Risk factors associated with high linezolid trough plasma concentrations.

AIM: The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin. METHODS: Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High Cmin was considered when it was >8 mg/L. Univariate and multivariate analysis were performed. RESULTS: 34.6% patients had a Cmin >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD <40 mL/min. There were more patients co-treated with rifampin in the group with low Cmin. The only factor independently associated with Cmin >8 was the renal function. Patients with an eGF < 40 mL/min had significantly higher Cmin than those with eGF > 80 mL/min (OR: 4.273) and there was a trend towards a high Cmin in patients with eGF between 40-80 mL/min (OR: 2.109). CONCLUSIONS: High Cmin were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.

Staphylococcus aureus bacteremic pneumonia.

Staphylococcus aureus bacteremic pneumonia is an uncommon cause of hospitalization, with a high mortality rate. However, published reports are scarce and have included a small number of cases. All patients with S. aureus bacteremic pneumonia were prospectively collected in our institution from 2000 to 2014, and a retrospective revision was performed to identify risk factors associated with methicillin resistance and to update the mortality of this entity. A total of 98 patients were admitted: 57.1 % were due to methicillin-susceptible S. aureus (MSSA) and 42.8 % due to methicillin-resistant S. aureus (MRSA). In 40 patients (40.8 %), the infection was community acquired. Thirteen were ventilator-associated pneumonia episodes. The most frequent comorbidities were chronic lung disease (34.7 %), chronic renal failure (31.6 %), diabetes mellitus (29.6 %), and cardiovascular disease (31.6 %). Septic shock was present in 46 patients (46.9 %). The 30-day mortality was 46.9 %. MRSA infections occurred in older patients, more frequently with cardiovascular diseases, and they had received antibiotic treatment in the previous month more often than MSSA-infected patients. Patients with infection due to MSSA presented more frequently with septic shock, but they received more frequently appropriate empirical antibiotic therapy than patients with MRSA pneumonia (96 % vs. 38.1 %), and no differences in mortality were observed between both groups. In conclusion, S. aureus bacteremic pneumonia is a severe infection that, nowadays, affects people with comorbidities and the mortality is still high.

Community-onset bacteraemia of unknown origin: clinical characteristics, epidemiology and outcome.

Bacteraemia of unknown origin is prevalent and has a high mortality rate. However, there are no recent reports focusing on this issue. From 2005 to 2011, all episodes of community onset bacteraemia of unknown origin (CO-BSI), diagnosed at a 700-bed university hospital were prospectively included. Risk factors for Enterobactericeae resistant to third-generation cephalosporins (3GCR-E), Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus spp, and predictors of mortality were assessed by logistic regression. Out of 4,598 consecutive episodes of CO-BSI, 745 (16.2 %) were of unknown origin. Risk factors for S. aureus were male gender (OR 2.26; 1.33-3.83), diabetes mellitus (OR 1.71; 1.01-2.91) and intravenous drug addiction (OR 17.24; 1.47-202); for P. aeruginosa were male gender (OR 2.19; 1.10-4.37) and health-care associated origin (OR 9.13; 3.23-25.83); for 3GCR-E was recent antibiotic exposure (OR 2.53; 1.47-4.35), while for enterococci, it was recent hospital admission (OR 3.02; 1.64-5.55). Seven and 30-day mortality were 8.1 % and 13.4 %, respectively. Age over 65 years (OR 2.13; 1.28-3.55), an ultimately or rapidly fatal underlying disease (OR 4.15; 2.23-7.60), bone marrow transplantation (OR 4.07; 1.24-13.31), absence of fever (OR 4.45; 2.25-8.81), shock on presentation (OR 10.48; 6.05-18.15) and isolation of S. aureus (OR 2.01; 1.00-4.04) were independently associated with mortality. In patients with bacteraemia of unknown origin, a limited number of clinical characteristics may be useful to predict its aetiology and to choose the appropriate empirical treatment. Although no modifiable prognostic factors have been found, management optimization of S. aureus should be considered a priority in this setting.

Acquisition of resistant microorganisms and infections in HIV-infected patients admitted to the ICU.

Whether critically ill human immunodeficiency virus (HIV)-infected patients are at risk of acquiring nosocomial infections and resistant or potentially resistant microorganisms (RPRMs) remains to be clarified. The aim was to compare the acquisition of RPRMs, infections and mortality in critically ill HIV-infected and non-infected patients. An observational, prospective cohort study of patients admitted to a medical intensive care unit (ICU) was undertaken. Swabbing of nares, pharynx and rectum, and culture of respiratory secretions were obtained within 48 h of admission and thrice weekly thereafter. Clinical samples were obtained as deemed necessary by the attending physician. Clinical variables, severity scores on admission and exposures during ICU stay were collected. Logistic regression was used to evaluate ICU mortality. Out of the 969 included patients, 64 (6.6%) were HIV-infected. These patients had a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission (19.5 ± 6.6 vs. 21.1 ± 5.4, p = 0.02), stayed longer in the care unit and were more exposed to several invasive devices and antibiotics. There were no differences in the rate of acquisition of RPRMs and the only difference in ICU-acquired infections was a significantly higher incidence of catheter-related bacteraemia (3% vs. 9%, p = 0.03). The ICU-related mortality was similar in both groups (14% vs. 16%, p = 0.70) and in HIV-infected patients, it tended to be associated with a lower CD4 cell count (p = 0.06). Despite a longer ICU stay, critically ill HIV-infected patients did not show a higher rate of RPRMs acquisition. The rate of ICU-acquired infection was similar between HIV-infected and non-infected patients, except for catheter-related bacteraemia, which was higher in the HIV-infected population. Mortality was similar in both groups.

Comparison of acquisition of resistant microorganisms and infections in critically-ill patients with and without malignancies.

BACKGROUND: Patients with malignancies are often considered at risk of acquiring infections by resistant or potentially resistant microorganisms (RPRMs). However, data supporting this contention is scarce. We have compared critically ill patients with haematological malignancies (HM), solid tumours (ST) and without cancer (NC) in terms of acquisition of RPRMs, infections and mortality. METHODS: Observational, prospective cohort study of patients admitted to a medical intensive care unit (ICU). Swabbing of nares, pharynx and rectum, and culture of respiratory secretions were obtained within 48 h of admission and thrice weekly thereafter. Clinical samples were obtained as deemed necessary by the attending physician. Clinical variables, severity scores on admission and exposures during ICU stay were also collected. Multivariable logistic regression analysis was used to evaluate ICU mortality. RESULTS: Out of 969 included patients 127 (13.1%) had HM and 93 (9.6%) had ST. Patients with malignancies were more frequently exposed to central venous catheterization, methylprednisolone, and any antipseudomonal antibiotic whereas they were less commonly exposed to invasive mechanical ventilation. Patients with HM were more often admitted with an infection. There were no differences among groups in terms of RPRMs acquisition during ICU stay or prevalence of ICU-acquired infections due to any microorganism, including RPRMs. Having a HM was an independent predictor of mortality regardless of APACHE II score. CONCLUSION: Critically ill cancer patients did not show a higher rate of RPRMs acquisition nor ICU-acquired infections. Mortality was higher in the HM group and it was not accurately predicted on admission by APACHE II score.

Influence of empiric therapy with a beta-lactam alone or combined with an aminoglycoside on prognosis of bacteremia due to gram-negative microorganisms.

Evidence supporting the combination of aminoglycosides with beta-lactams for gram-negative bacteremia is inconclusive. We have explored the influence on survival of empirical therapy with a beta-lactam alone versus that with a beta-lactam-aminoglycoside combination by retrospectively analyzing a series of bacteremic episodes due to aerobic or facultative gram-negative microorganisms treated with single or combination therapy. The outcome variable was a 30-day mortality. Prognostic factors were selected by regression logistic analysis. A total of 4,863 episodes were assessed, of which 678 (14%) received combination therapy and 467 (10%) were fatal. Factors independently associated with mortality included age greater than 65 (odds ratio [OR], 2; 95% confidence interval [CI], 1.6 to 2.6), hospital acquisition (OR, 1.5; 95% CI, 1.2 to 1.9), a rapidly or ultimately fatal underlying disease (OR, 2.5; 95% CI, 2 to 3.2), cirrhosis (OR, 1.9; 95% CI, 1.4 to 2.6), prior corticosteroids (OR, 1.5; 95% CI, 1.1 to 2), shock on presentation (OR, 8.8; 95% CI, 7 to 11), pneumonia (OR, 2.8; 95% CI, 1.9 to 4), and inappropriate empirical therapy (OR, 1.8; 95% CI, 1.3 to 2.5). Subgroup analysis revealed that combination therapy was an independent protective factor in episodes presenting shock (OR, 0.6; 95% CI, 0.4 to 0.9) or neutropenia (OR, 0.5; 95% CI, 0.3 to 0.9). Combination therapy improved the appropriateness of empirical therapy in episodes due to extended-spectrum beta-lactamase (ESBL)- or AmpC-producing Enterobacteriaceae and Pseudomonas aeruginosa. In patients with gram-negative bacteremia, we could not find an overall association between empirical beta-lactam-aminoglycoside combination therapy and prognosis. However, a survival advantage cannot be discarded for episodes presenting shock or neutropenia, hence in these situations the use of combination therapy may still be justified. Combination therapy also should be considered for patients at risk of being infected with resistant organisms, if only to increase the appropriateness of empirical therapy.