Jordi Carratalà

Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patients individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panels recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data

BACKGROUND Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each days delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each days delay). INTERPRETATION We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING F Hoffmann-La Roche.

Community-acquired pneumonia in very elderly patients: causative organisms, clinical characteristics, and outcomes.

We performed an observational analysis of pro-spectively collected data on 1,474 adult patients who were hospitalized for community-acquired pneumonia; 1,169 patients were under 80 years of age and 305 (21%) patients were over 80 years (“very elderly”). Mean patient ages were 60 years in the former group and 85 years in the latter group. Severely immunosuppressed patients and nursing-home residents were not included. Comorbidities significantly associated with older age were chronic obstructive pulmonary disease, chronic heart disease, and dementia. The most common causative organism was Streptococcus pneumoniae (23% in both groups). Aspiration pneumonia was more frequent in the very elderly (5% in younger patients versus 10% in the very elderly);Legionella pneumophila (8% in younger patients versus 1% in the very elderly) and atypical agents (7% in younger patients versus 1% in the very elderly) were rarely recorded in the very elderly. While very elderly patients complained less frequently of pleuritic chest pain, headache, and myalgias, they were more likely to have absence of fever and altered mental status on admission. No significant differences were observed between groups as regards incidence of classic bacterial pneumonia syndrome (60% versus 59%) in 343 patients with pneumococcal pneumonia. The development of inhospital complications (26% in younger versus 32% in very elderly patients) as well as early mortality (2% in younger versus 7% in very elderly patients) and overall mortality (6% in younger versus 15% very elderly patients) were significantly higher in very elderly patients. Acute respiratory failure and shock/multiorgan failure were the most frequent causes of death, especially of early mortality. Factors independently associated with 30-day mortality in the very elderly were altered mental status on admission (odds ratio, 3.69), shock (odds ratio, 10.69), respiratory failure (odds ratio, 3.50), renal insufficiency (odds ratio, 5.83), and Gram-negative pneumonia (odds ratio, 20.27).

Contribution of a Urinary Antigen Assay (Binax NOW) to the Early Diagnosis of Pneumococcal Pneumonia

We evaluated the usefulness of a rapid urinary antigen test (Binax NOW; Binax) to detect Streptococcus pneumoniae for the early diagnosis of community-acquired pneumococcal pneumonia (PP) in 220 nonseverely immunosuppressed adults. We compared results of this test with those of sputum Gram staining. The rapid urinary antigen test showed limited sensitivity (65.9%; 95% confidence interval [CI], 51.4-80.4) but high specificity (100%; 95% CI, 99.7-100) for diagnosing PP. The test was more sensitive for patients with versus those without high-risk pneumonia (94% vs. 63%; P<.001) and for patients without versus those with demonstrative results of a sputum Gram stain (97% vs. 55%; P<.001), and it tended to be more sensitive for patients with versus those without bacteremic PP (92% vs. 74%; P=NS). Rapid urinary antigen testing permitted early diagnosis of PP in 26% more patients than did Gram staining but missed 22% of the rapid diagnoses initially identified by Gram staining. On the basis of our results, a sequential approach is proposed, with reservation of urinary antigen testing for high-risk patients for whom demonstrative results of a sputum Gram stain are unavailable.

Prospective Study of the Usefulness of Sputum Gram Stain in the Initial Approach to Community-Acquired Pneumonia Requiring Hospitalization

From February 1995 through May 1997, we prospectively studied 533 patients with community-acquired pneumonia requiring hospitalization in order to assess the current usefulness of sputum Gram stain in guiding the etiologic diagnosis and initial antibiotic therapy when applied routinely. Sputum samples of good quality were obtained in 210 (39%) patients, 175 of whom showed a predominant morphotype. Sensitivity and specificity of Gram stain for the diagnosis of pneumococcal pneumonia were 57% and 97%, respectively; the corresponding values for Haemophilus influenzae pneumonia were 82% and 99%. Patients with a predominant morphotype were more frequently treated with monotherapy than were patients without a demonstrative sputum sample (89% vs. 75%; P<.001). Analysis of our data shows that a good-quality sputum sample can be obtained from a substantial number of patients with community-acquired pneumonia. Gram stain was highly specific for the diagnosis of pneumococcal and H. influenzae pneumonia and may be useful in guiding pathogen-oriented antimicrobial therapy.

Etiology, Reasons for Hospitalization, Risk Classes, and Outcomes of Community-Acquired Pneumonia in Patients Hospitalized on the Basis of Conventional Admission Criteria

We performed an observational analysis of prospectively collected data on 533 nonseverely immunosuppressed adult patients who were hospitalized for community-acquired pneumonia on the basis of conventional admission criteria. For this population, we correlated etiology, reasons for admission, and outcomes using the Pneumonia Severity Index (PSI), to identify major discrepancies between the PSI risk class and the conventional criteria for deciding the site of care. PSI classes and corresponding mortality rates were as follows: class I, 51 patients (0%); class II, 62 (2%); class III, 117 (3%); class IV, 198 (10%); and class V, 105 (29%). We identified significant discrepancies between both methods. Overall, 230 patients (40%) who were hospitalized according to conventional criteria were assigned to low-risk classes. Of these 230 patients, 137 (60%) needed supplementary oxygen or had pleural complications; for the remaining patients, there were no irrefutable reasons for admission. This latter group deserves prospective evaluation in randomized studies that compare ambulatory and in-hospital management.

Tuberculosis after Solid-Organ Transplant: Incidence, Risk Factors, and Clinical Characteristics in the RESITRA (Spanish Network of Infection in Transplantation) Cohort

BACKGROUND It is necessary to clarify the incidence of and risk factors for tuberculosis (TB) among solid-organ transplant (SOT) recipients as well as changes in the chronology, clinical presentation, and prognosis of the disease. METHODS A total of 4388 SOT recipients were monitored prospectively at 16 transplant centers included in the Spanish Network for Research in Infectious Diseases (REIPI). TB episodes were studied, and the incidence rate was calculated. Certain variables were analyzed, by Cox regression analysis, as potential risk factors for TB. RESULTS Among the 4388 SOT recipients, 21 cases of TB were reported (0.48%). The median duration of follow-up was 360 days (range, 0-720 days). The global incidence of TB was 512 cases per 10(5) patients per year (95% confidence interval [CI], 317-783), which was higher than that in the general population in Spain (18.9 cases per 10(5) inhabitants per year; relative risk [RR], 26.6). The highest incidence (2072 cases per 10(5) patients per year; 95% CI, 565-5306) was observed among lung transplant recipients (RR, 73.3). Of the TB cases, 95% occurred within the first year after transplant, and 76% were pulmonary forms. Crude mortality was 19.0%, and attributable mortality was 9.5%. Multivariate analysis identified recipient age (RR, 1.05; 95% CI, 1.0-1.1) and receipt of a lung transplant (RR, 5.6; 95%, 1.9-16.9) as independent risk factors. CONCLUSIONS TB incidence is increased among SOT recipients. The risk factors identified were age and receipt of a lung transplant. TB-attributable mortality (9.5%) is still high.

Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes

OBJECTIVES To assess the risk factors, antibiotic therapy and outcomes of multidrug-resistant Gram-negative bacilli (MDRGNB) bacteraemia in hospitalized patients with cancer. METHODS Episodes of MDRGNB bacteraemia were compared with a susceptible control group in a 4 year prospective study. RESULTS Of 747 bacteraemias, 372 (49.7%) were caused by a Gram-negative bacilli (GNB). Fifty-one of these (13.7%) were caused by a multidrug-resistant (MDR) strain. Previous antibiotics [odds ratio (OR) 3.57; 95% confidence interval (CI) 1.63-7.80] and urinary catheter (OR 2.41; 95% CI 1.01-5.74) were identified as independent risk factors for MDRGNB acquisition. The most frequent mechanism of resistance was extended-spectrum β-lactamase (ESBL) production (45%), mainly by Escherichia coli, followed by Amp-C cephalosporinase hyperproduction (24%). Patients with MDRGNB bacteraemia more frequently received inadequate initial antibiotic therapy (69% versus 9%; P < 0.001) and time to adequate therapy was longer in this group (41% versus 4%; P < 0.001). Patients in the resistant group more frequently required intensive care unit (ICU) admission (14% versus 5%; P = 0.023), had greater need for mechanical ventilation (14% versus 3%; P = 0.005) and had a higher overall case-fatality rate (41% versus 21%; P = 0.003). Risk factors for mortality were solid tumour (OR 5.04; 95% CI 2.49-10.19), current corticosteroid use (OR 4.38; 95% CI 2.39-8.05), ICU admission (OR 11.40; 95% CI 3.19-40.74) and MDRGNB bacteraemia (OR 3.52; 95% CI 1.36-9.09). CONCLUSIONS MDRGNB bacteraemia was common among cancer patients, especially in those exposed to antibiotics and urinary catheter. The most frequent mechanism of resistance was ESBL production. Patients with MDRGNB more frequently received inadequate empirical antibiotic therapy and presented poorer outcomes with a higher overall case-fatality rate (within 30 days).

Bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome

OBJECTIVES To assess the clinical features, risk factors, molecular epidemiology and outcome of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteraemia in hospitalized cancer patients. METHODS Episodes of ESBL-EC bacteraemia were compared with a susceptible control group in a 3 year prospective study. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by PFGE. RESULTS Out of 531 episodes of bacteraemia, 135 were caused by E. coli. Seventeen of these cases involved ESBL-EC-producing strains (12.6%). In the multivariate analysis, female gender [odds ratio (OR) 3.43; 95% confidence interval (CI) 1.03-11.4] and previous antibiotic therapy (OR 3.22; 95% CI 1.00-10.3) were found to be independent risk factors for ESBL acquisition. An analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (59%). Patients with ESBL-EC bacteraemia were more likely to have received an inadequate empirical antibiotic therapy (65% versus 6%; P = 0.000), and the time to adequate therapy was longer in this group (0 versus 1.50 days; P = 0.000). The overall mortality rate was 22%, ranging from 20% to 35% (P = 0.20). Risk factors for mortality were solid tumour (OR 19.41; 95% CI 4.66-80.83), corticosteroid therapy (OR 3.04 95% CI 1.05-8.81) and intensive care unit admission (OR 248.24, 95% CI 18.49-3332.14). In neutropenic patients, ESBL-EC bacteraemia was associated with poorer outcome and a higher overall mortality rate (37.5% versus 6.5%; P = 0.01). CONCLUSIONS In our centre, ESBL-EC bacteraemia is frequent among cancer patients, especially in those exposed to antibiotic pressure. All ESBL-EC strains were unrelated and most of them carried a CTX-M group enzyme. Patients with ESBL-EC bacteraemia received inadequate empirical antibiotic therapy more frequently than patients carrying a susceptible strain, but significant differences in mortality could not be demonstrated.

Factors Associated with Complications and Mortality in Adult Patients Hospitalized for Infectious Cellulitis

The aim of this study was to analyze medical outcomes, including risks for complications and mortality, in 332 adult patients hospitalized for cellulitis. The infection was documented microbiologically in 128 cases (39%). Staphylococcus aureus (46 cases) and Streptococcus pyogenes (22 cases) were the most frequent causative pathogens. Overall, 63 patients (19%) were discharged early (≤4 days) and 166 patients (50%) were hospitalized for more than 4 days without developing any complications. One hundred three patients (31%) had one or more complications or died. Of these, 78 required surgical debridement, 10 required plastic surgery, 7 underwent amputation, and 15 had shock on presentation. When comparing the three study groups (patients discharged early, patients hospitalized for ≤4 days without complications, and patients who developed 1 or more complication or who died), patients who were discharged early (low risk) were more frequently female and were less likely to have multiple comorbid conditions, hypoalbuminemia, renal insufficiency, and/or cutaneous necrosis at presentation. Overall mortality (<30 days) was 5% (16/332 patients). Factors associated with death were male sex, presence of multiple comorbid conditions, congestive heart failure, morbid obesity, hypoalbuminemia, renal insufficiency, shock, and Pseudomonas aeruginosa cellulitis. These findings can be used to stratify patients with acute cellulitis according to risks for complications and mortality and may be helpful when deciding the most appropriate means of care, i.e. outpatient treatment or hospitalization.