Ane Uranga

Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial

IMPORTANCE The optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) has not been well established. OBJECTIVE To validate Infectious Diseases Society of America/American Thoracic Society guidelines for duration of antibiotic treatment in hospitalized patients with CAP. DESIGN, SETTING, AND PARTICIPANTS This study was a multicenter, noninferiority randomized clinical trial performed at 4 teaching hospitals in Spain from January 1, 2012, through August 31, 2013. A total of 312 hospitalized patients diagnosed as having CAP were studied. Data analysis was performed from January 1, 2014, through February 28, 2015. INTERVENTIONS Patients were randomized at day 5 to an intervention or control group. Those in the intervention group were treated with antibiotics for a minimum of 5 days, and the antibiotic treatment was stopped at this point if their body temperature was 37.8°C or less for 48 hours and they had no more than 1 CAP-associated sign of clinical instability. Duration of antibiotic treatment in the control group was determined by physicians. MAIN OUTCOMES AND MEASURES Clinical success rate at days 10 and 30 since admission and CAP-related symptoms at days 5 and 10 measured with the 18-item CAP symptom questionnaire score range, 0-90; higher scores indicate more severe symptoms. RESULTS Of the 312 patients included, 150 and 162 were randomized to the control and intervention groups, respectively. The mean (SD) age of the patients was 66.2 (17.9) years and 64.7 (18.7) years in the control and intervention groups, respectively. There were 95 men (63.3%) and 55 women (36.7%) in the control group and 101 men (62.3%) and 61 women (37.7%) in the intervention group. In the intent-to-treat analysis, clinical success was 48.6% (71 of 150) in the control group and 56.3% (90 of 162) in the intervention group at day 10 (P = .18) and 88.6% (132 of 150) in the control group and 91.9% (147 of 162) in the intervention group at day 30 (P = .33). The mean (SD) CAP symptom questionnaire scores were 24.7 (11.4) vs 27.2 (12.5) at day 5 (P = .10) and 18.6 (9.0) vs 17.9 (7.6) at day 10 (P = .69). In the per-protocol analysis, clinical success was 50.4% (67 of 137) in the control group and 59.7% (86 of 146) in the intervention group at day 10 (P = .12) and 92.7% (126 of 137) in the control group and 94.4% (136 of 146) in the intervention group at day 30 (P = .54). The mean (SD) CAP symptom questionnaire scores were 24.3 (11.4) vs 26.6 (12.1) at day 5 (P = .16) and 18.1 (8.5) vs 17.6 (7.4) at day 10 (P = .81). CONCLUSIONS AND RELEVANCE The Infectious Diseases Society of America/American Thoracic Society recommendations for duration of antibiotic treatment based on clinical stability criteria can be safely implemented in hospitalized patients with CAP. TRIAL REGISTRATION clinicaltrialsregister.eu Identifier: 2011-001067-51.

Bacteremic Pneumococcal Pneumonia in Elderly and Very Elderly Patients Host- and Pathogen-Related Factors, Process of Care, and Outcome

BACKGROUND Hospitalizations due to pneumonia increase steadily with age. The purpose of this study is to explore differences in host- and pathogen-related factors, process of care, and outcome as a function of age in elderly patients with bacteremic pneumococcal pneumonia and identify factors related to mortality. METHODS This was a prospective observational study of a cohort of elderly (65-79 years) and very elderly patients (≥ 80 years old) diagnosed with bacteremic pneumococcal pneumonia. The serotypes of the strains isolated and their resistance were also analyzed. RESULTS During the study period, 399 patients were identified, of whom 225 patients (140 elderly and 85 very elderly patients) were included. Despite the groups having similar characteristics on admission, very elderly patients had higher rates of both hospital (16.47% vs 7.14%, p = .028) and 30-day (20% vs 6.43%, p = .002) mortality. Factors found to be predictors of mortality were: altered mental status (odds ratio [OR]: 13.18; 95% confidence interval [CI]: 3.68-47.23), respiratory rate more than or equal to 30/min (OR: 5.82; 95% CI: 1.82-18.64), systolic blood pressure less than 90 mmHg (OR: 10.90; 95% CI: 1.45-81.93), blood urea nitrogen more than 30 mg/dL (OR: 5.41; 95% CI: 1.03-28.42), bilateral or multilobar lung involvement (OR: 5.24; 95% CI: 1.55-17.76), and age (OR: 1.19; 95% CI: 1.09-1.30). CONCLUSIONS Very elderly patients have poorer outcomes with no significant differences in host- and pathogen-related factors or process of care. Mortality rates in these patients are associated with age and the severity of their clinical condition.

Streptococcus pneumoniae antigen in urine: Diagnostic usefulness and impact on outcome of bacteraemic pneumococcal pneumonia in a large series of adult patients

Urinary pneumococcal antigen detection provides good results in the diagnosis of pneumococcal pneumonia but has rarely been used in bacteraemic pneumococcal pneumonia and it is not known whether it is associated with outcome in this type of pneumonia. Our objectives were to assess the usefulness of an immunochromatographic technique for detecting the pneumococcal antigen in urine in a large prospective study of patients with bacteraemic pneumococcal pneumonia and explore any potential association with outcomes.

Chronic Obstructive Pulmonary Disease Subtypes. Transitions over Time.

Background Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time. Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year. Methods Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics. Results Four subtypes were identified. Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity. Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C. Subtype D had higher rates of hospitalization the previous year, and comorbidities. After 1 year, all clusters remained stable. Generally, patients continued in the same subtype but 28% migrated to another cluster. Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to. Conclusions Chronic obstructive pulmonary disease clusters remained stable over 1 year. Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes.

Predicting 1-year mortality after hospitalization for community-acquired pneumonia

Background Community-acquired pneumonia (CAP) is a major public health problem with high short- and long-term mortality. The main aim of this study was to develop and validate a specific prognostic index for one-year mortality in patients admitted for CAP. Methods This was an observational, prospective study of adults aged ≥18 years admitted to Galdakao-Usansolo Hospital (Bizkaia, Spain) from January 2001 to July 2009 with a diagnosis of CAP surviving the first 15 days. The entire cohort was divided into two parts, in order to develop a one-year mortality predictive model in the derivation cohort, before validation using the second cohort. Results A total of 2351 patients were included and divided into a derivation and a validation cohort. After deaths within 15 days were excluded, one-year mortality was 10.63%. A predictive model was created in order to predict one-year mortality, with a weighted score that included: aged over 80 years (4 points), congestive heart failure (2 points), dementia (6 points), respiratory rate ≥30 breaths per minute (2 points) and blood urea nitrogen >30 mg/dL (3 points) as predictors of higher risk with C-index of 0.76. This new model showed better predictive ability than current risk scores, PSI, CURB65 and SCAP with C-index of 0.73, 0.69 and 0.70, respectively. Conclusions An easy-to-use score, called the one-year CAPSI, may be useful for identifying patients with a high probability of dying after an episode of CAP.

The burden of PCV13 serotypes in hospitalized pneumococcal pneumonia in Spain using a novel urinary antigen detection test. CAPA study

BACKGROUND Streptococcus pneumoniae serotypes distribution in community-acquired pneumonia (CAP) requiring hospitalization in adults after introduction of PCV13 in children is not well known. Our aim was to evaluate the distribution of serotypes in pneumococcal pneumonia according to risk factors and comorbidity conditions after the introduction of PCV13 in children in 2010. METHODS A prospective study from 2011 to 2014 was performed in immunocompetent adults hospitalized with CAP in 3 Spanish hospitals. Microbiological confirmation was obtained using a serotype specific urinary antigen detection test (UAD test), Binax Now and conventional cultures. RESULTS 1258 adults were enrolled and pneumococcal pneumonia (invasive disease in 17.7%) was confirmed in 368 (29.3%) and 17.6% of the any-cause CAP were caused by PVC13 serotypes (3.5% PCV7 serotypes). Around 60% of pneumococcal CAP were caused by PCV13 serotypes (74.6% in invasive episodes vs 57.4% in non-invasive ones). The most prevalent serotypes in invasive disease were 1, 3, 7F, 19A and 14. No significant differences were observed in the distribution of PCV13 serotypes across the study periods. Regarding comorbidity, the rate of PCV13 serotypes was similar among them, and it was slightly higher in those with no underlying conditions. CONCLUSIONS Serotypes included in PCV13 caused a significant proportion of CAP in adults with underlying conditions and in healthy adults, with no significant changes in cases due to PCV7 or PCV13 from 2011 to 2014, suggesting an insufficient indirect protection from childhood vaccination. Strategies for implementing pneumococcal vaccination of adults are encouraged to reduce the incidence of pneumococcal episodes.

Long-term Mortality in Community-acquired Pneumonia

Community acquired pneumonia (CAP) is considered a major problem of public health due to its high morbimortality.1 To a large extent, mortality depends on the place where the patients are treated. In outpatients, the rate is less than 3%, in patients admitted to a conventional unit, the rate ranges from 5 to 10%, whereas in those patients who require admission to an intensive care unit amounts to 25% if they require orotracheal intubation and up to 50% if they require vasopressors.2 Most studies published to date have studied the relationship between pneumonia and short-term mortality. However, there are data indicating that patients who survive a pneumonia episode have a high mortality rate, even in the medium and long term, with figures of 8, 21, and 36% after 90 days, one year, and five years, respectively.3 Often, an acute condition in older adults that requires hospitalization implies a subsequent clinical worsening. This issue seems to be particularly frequent in patients suffering from pneumonia. Kaplan et al.4 assessed patients admitted for pneumonia and found that in-hospital mortality rate was the half in the control group compared with the CAP group. One-year mortality after hospital discharge and adjusted for comorbidities was 33.6% among those patients who had been discharged with a diagnosis of CAP versus 24.9% in the control group without CAP (p = 0.001). There are several predictive factors of long-term mortality. Numerous articles highlight age as one of the main predictors of mortality. Indeed, inflammation among elderly people should be assessed independently as it probably has a distinctive role. What still remains to be clarified is the cut-off point at which age begins to be a risk factor. The number of individuals aged over 65 years has increased in recent years and that number is expected to rise from 12% in 2000 to 20% in 2030, and even reaching the double in 2050.5 In general, the older adult population suffers from a greater number of comorbidities and the functional status is often poor. In addition, most studies point out that the male sex is associated with higher mortality rates.4 Similarly, some authors found an alarming difference regarding race, with increased 2-year mortality rate in black individuals compared with white individuals6. Healthcare-

Validation of IDSA/ATS Algorithm for Duration of Pneumonia Therapy—Reply

In Reply We thank Fralick and colleagues and Novack and colleagues for their thoughtful response to our Invited Commentary.1 The Choosing Wisely campaign is an important movement in medicine in the United States, and we applaud the authors of the Choosing Wisely campaign for its success. The campaign’s effects clearly extend beyond mere conversation to promote value as a central tenet of the medical profession. Respectfully, however, we suggest that having established a strong foundation, we must expand Choosing Wisely to address the complex and persistent problem of low-value care. With regard to the Choosing Wisely video modules, we support the goal of tying them to maintenance of certification and continuing medical education. Our comments were meant to highlight further opportunities for development. This includes more closely linking recommendations to practical decision-making tools. More pressing, we should use Choosing Wisely’s popularity to promote greater emphasis on communication skills in the training and certification of physicians at all levels. Whether it is termed shared decisionmaking or otherwise, this includes an ability to explain the best evidence on risks and benefits with facility, as well as to elicit patient goals with empathy. There remain many unanswered questions on how to achieve this goal most effectively. We hope that together, using Choosing Wisely as a platform, we can spur further investigation into how these essential skills can be imparted to ensure the best care for patients.

Predisposing factors for bacteremia in patients with community-acquired pneumonia and positive pneumococcal urinary antigen

Objective: The presence of bacteremia in pneumococcal community-acquired pneumonia (P-CAP) is associated with more morbidity and poorer outcome. Our aim was to identify factors associated with bacteremia in patients with P-CAP diagnosed by positive urinary antigen (+UA). Methods: Prospective observational study, including all immunocompetent patients hospitalized for P-CAP (diagnosed by +UA on admission) in the pneumology service of 2 hospitals for a 15-year period. Blood cultures (BC) were taken from all patients. Patients were divided in 2 groups according to the BC results. Univariate and multivariate analysis were performed. Results: We included 957 patients with P-CAP; 342 (35.7%) with positive BC. Figure1: main characteristics of both groups. Figure2: multivariate analysis of factors associated with bacteriemia. Conclusions : - Neoplastic disease, BUN ≥ 30, Na - Pneumococcal vaccine, previous antibiotic treatment and COPD were protective factors for bacteremia in our patients.

Lung asbestos content in patients with lung cancer in different Spanish regions. The AMCANES study

Aim: To study a representative sample of patients with lung cancer in Spain in order to assess the involvement of asbestos as a causal factor. Methods: We present data from the first 60 patients diagnosed with lung cancer and undergoing lung resection surgery at five hospitals in Spain: Terrassa (Barcelona) (n = 22), Alicante (n = 12), Biscay (n = 15, two hospitals) and Navarre (n = 11). All patients were administered a specific questionnaire regarding their exposure to asbestos. In all individuals, lung tissue samples of 2 cm 3 were collected. For analysis of the asbestos bodies (AB), lung samples underwent chemical digestion with sodium hypochlorite. AB count was performed by light microscopy. Results: Fifty-one men (85%) and nine women, mean age (SD) 64 (11) years, were studied. Fifty-eight patients (97%) were smokers. Nineteen patients (32%) reported occupational exposure to asbestos. Asbestos bodies were found in 41 patients (68%), but their numbers exceeded 1000 AB/g dry tissue (range: 1008-129880) in only four (three of them with a history of occupational exposure). The median (range) of AB/g dry tissue was 53 (0-436) and 208 (0-129880) for exposed and unexposed individuals respectively (p Conclusions: The preliminary results of this questionnaire point to a high rate of asbestos exposure in Spanish lung cancer patients. Most cases presented asbestos in the lung, while levels with diagnostic value were observed in 7% of lung cancer patients. Study funded by SEPAR and FUCAP and presented on behalf of the AMCANES project research team.