Time to sputum conversion in patients with pulmonary tuberculosis: A score to estimate the infectious period.

Introduction: Patients with pulmonary tuberculosis (PTB) disease and positive sputum cultures are the main source of infection. Culture conversion time is inconsistent and defining the length of respiratory isolation is challenging. The objective of this study is to develop a score to predict the length of isolation period. Methods: A retrospective study was carried out to evaluated risk factors associated with persistent positive sputum cultures after 4 weeks of treatment in 229 patients with PTB. A multivariable logistic regression model was used to determinate predictors for positive culture and a scoring system was created based on the coefficients of the final model. Results: Sputum culture was persistently positive in 40.6%. Fever at consultation (1.87, 95% CI:1.02-3.41), smoking (2.44, 95% CI:1.36-4.37), >2 affected lung lobes (1.95, 95% CI:1.08-3.54), and neutrophil-to-lymphocyte ratio > 3.5 (2.22, 95% CI:1.24-3.99), were significantly associated with delayed culture conversion. Therefore, we assembled a severity score that achieved an area under the curve of 0.71 (95% CI:0.64-0.78). Conclusions: In patients with smear positive PTB, a score with clinical, radiological and analytical parameters can be used as a supplemental tool to assist clinical decisions in isolation period.

Triggering receptor (TREM-1) expressed on myeloid cells predicts bacteremia better than clinical variables in community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Some clinical variables are associated with bacteremia in patients with community-acquired pneumonia (CAP). The aim of this study was to analyse the accuracy of the soluble form of triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict positive blood cultures in comparison with established clinical prognostic variables. METHODS: In addition to collecting clinical and laboratory information, a commercially available immunoassay kit was used to measure the serum sTREM-1 levels on the first day of admit ion in patients with CAP. Receiver operating characteristic (ROC) curves were used to compare the ability of sTREM-1 and commonly used clinical variables to identify bacteremia. RESULTS: Blood cultures yielded a pathogen in 13 (10.4%) out of 124 patient samples. The microorganisms isolated were Streptococcus pneumoniae (11 patients) and Klebsiella pneumoniae (2 patients). The presence of pleuritic chest pain, tachycardia and extreme white cell count (WCC) were associated with bacteremia. However, ROC curve analysis showed an accuracy of sTREM-1 (area under the receiver operating characteristic curve (AUC) 0.84, 95% CI: 0.72-0.95), which was higher than pleuritic chest pain (AUC 0.71, 95% CI: 0.57-0.84), tachycardia (AUC 0.73, 95% CI: 0.58-0.88) and extreme WCC (AUC 0.70, 95% CI: 0.55-0.85) for predicting positive blood cultures. Low admission sTREM-1 serum values had a high negative predictive value for excluding bacteremia (sTREM-1 <120 pg/mL = 98.8%). CONCLUSIONS: This preliminary study suggests that the determination of sTREM-1 serum levels on admission may be more accurate than clinical variables for identifying bacteremic patients.

A prediction rule for estimating the risk of bacteremia in patients with community-acquired pneumonia.

BACKGROUND: We endeavored to construct a simple score based entirely on epidemiological and clinical variables that would stratify patients who require hospital admission because of community-acquired pneumonia into groups with a low or high risk of developing bacteremia. METHODS: Derivation and internal validation cohorts were obtained by retrospective analysis of a database that included 3116 consecutive patients with community-acquired pneumonia from 2 university hospitals. Potential predictive factors were determined by means of a multivariate logistic regression equation applied to a cohort consisting of 60% of the patients. Points were assigned to significant parameters to generate the score. It was then internally validated with the remaining 40% of patients and was externally validated using an independent multicenter cohort of 1369 patients. RESULTS: The overall rates of bacteremia were 12%-16% in the cohorts. The clinical probability estimate of developing bacteremia was based on 6 variables: liver disease, pleuritic pain, tachycardia, tachypnea, systolic hypotension, and absence of prior antibiotic treatment. For the score, 1 point was assigned to each predictive factor. In the derivation cohort, a cutoff score of 2 best identified the risk of bacteremia. In the validation cohorts, rates of bacteremia were <8% for patients with a score 1 (43%-49% of patients), whereas blood culture results were positive in 14%-63% of cases for patients with a score 2. CONCLUSIONS: This clinical score, based on readily available and objective variables, provides a useful tool to predict bacteremia. The score has been internally and externally validated and may be useful to guide diagnostic decisions for community-acquired pneumonia.

Risk factors and outcome of community-acquired pneumonia due to Gram-negative bacilli.

BACKGROUND AND OBJECTIVE: Several sets of guidelines have advocated initial antibiotic treatment for community-acquired pneumonia due to Gram-negative bacilli in patients with specific risk factors. However, evidence to support this recommendation is scarce. We sought to identify risk factors for community-acquired pneumonia due to Gram-negative bacilli, including Pseudomonas aeruginosa, and to assess outcomes. METHODS: An observational analysis was carried out on prospectively collected data for immunocompetent adults hospitalized for community-acquired pneumonia in two acute-care hospitals. Cases of pneumonia due to Gram-negative bacilli were compared with those of non-Gram-negative bacilli causes. RESULTS: Sixty-one (2%) of 3272 episodes of community-acquired pneumonia were due to Gram-negative bacilli. COPD (odds ratio (OR) 2.4, 95% confidence interval (CI): 1.2-5.1), current use of corticosteroids (OR 2.8, 95% CI: 1.2-6.3), prior antibiotic therapy (OR 2.6, 95% CI: 1.4-4.8), tachypnoea >or=30 cycles/min (OR 2.1, 95% CI: 1.1-4.2) and septic shock at presentation (OR 6.1, 95% CI: 2.5-14.6) were independently associated with Gram-negative bacilli pneumonia. Initial antibiotic therapy in patients with pneumonia due to Gram-negative bacilli was often inappropriate. These patients were also more likely to require admission to the intensive care unit, had longer hospital stays, and higher early (<48 h) (21% vs 2%; P < 0.001) and overall mortality (36% vs 7%; P < 0.001). CONCLUSIONS: These results suggest that community-acquired pneumonia due to Gram-negative bacilli is uncommon, but is associated with a poor outcome. The risk factors identified in this study should be considered when selecting initial antibiotic therapy for patients with community-acquired pneumonia.

C-reactive protein and other predictors of poor outcome in patients hospitalized with exacerbations of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: CRP is elevated in patients with acute exacerbations of COPD (AECOPD), but there is little information on whether this biomarker can help to identify adverse short-term clinical outcomes. METHODS: A 6-month prospective study of all patients with AECOPD requiring hospital admission. Clinical, laboratory (including plasma CRP levels at admission) and functional data were recorded. The outcome variable (the adverse outcome) consisted of: (i) death in hospital or within 15 days of discharge, (ii) transfer to the intensive care unit, or (iii) development of acute heart failure during hospitalization. RESULTS: Data from 147 patients with a total of 160 admissions were recorded. During follow up, 38 (23.7%) adverse outcomes were observed, including 13 (8.8%) and 8 (5.4%) patients who died during hospitalization or within 15 days of discharge, respectively. CRP at a level of 50 mg/L was related to an adverse outcome (OR 4.9, 95% CI: 1.92-12.6, P < 0.01), although by itself it was neither sensitive nor specific (area under the receiver operating characteristic curve (AUC) 0.69, 95% CI: 0.60-0.77). However, a risk score derived from the combination of CRP with other variables, such as 'current smoker', 'at least two comorbidities' and 'confusion,' at admission showed good predictive ability to identify an adverse outcome (AUC of 0.80, 95% CI: 0.72-0.88). CONCLUSIONS: Plasma CRP in combination with other variables obtained at admission may assist identification of high-risk patients with AECOPD.

Pleural fluid interleukin-8 and C-reactive protein for discriminating complicated non-purulent from uncomplicated parapneumonic effusions.

BACKGROUND AND OBJECTIVE: This study was designed to test the hypothesis that measurement of IL-8 and CRP in pleural fluid could improve the identification of patients with non-purulent parapneumonic effusions that ultimately require chest tube drainage. METHODS: We assessed IL-8, CRP and three classical parameters (pH, glucose and LDH) in the pleural fluid of 100 patients with parapneumonic effusions. Forty-nine of these patients had non-purulent complicated effusions (complicated parapneumonic pleural effusion, CPPE), and 51 had uncomplicated parapneumonic pleural effusions (UPPE). Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid biochemical parameters for differentiating among the two patient groups. IL-8 production was determined using a commercially available ELISA kit, and CRP was measured by immunoassay. RESULTS: At a cutoff value of 1000 pg/mL, IL-8 differentiated CPPE from UPPE with a sensitivity of 84% and a specificity of 82%. Likewise, CRP levels were higher in CPPE than in UPPE, and showed 72% sensitivity and 71% specificity at a cutoff value of 80 mg/L. We found that all five pleural fluid tests showed similar diagnostic accuracies when evaluated by receiver-operating characteristic analysis. However, multivariate analysis indicated that the size of the effusion, as well as pleural fluid pH and IL-8 concentration, were the best discriminatory parameters, with likelihood ratios of 6.4, 4.4 and 3.9, respectively. CONCLUSIONS: Pleural fluid IL-8 is an accurate marker for the identification of non-purulent CPPE.

Contribution of a pleural antigen assay (Binax NOW) to the diagnosis of pneumococcal pneumonia.

STUDY OBJECTIVES: To determine whether the detection of pneumococcal antigen in pleural fluid augments conventional microbiological methods used for the etiologic diagnosis of pneumonia. METHODS: In this retrospective study, a rapid immunochromatographic test (ICT) [NOW Streptococcus pneumoniae assay; Binax; Scarborough, ME] was performed on pleural fluid samples from 34 patients with pneumonia due to S pneumoniae, 89 patients with effusions of nonpneumococcal origin, and 17 patients with pneumonia of unknown etiology. Data on blood cultures, pleural fluid cultures, and urinary antigen tests were recorded. RESULTS: The ICT test result was positive in 24 of 34 patients (70.6%) with pneumococcal pneumonia and negative in 83 of 89 patients (93.3%) without pneumococcal pneumonia. The sensitivity of the pleural ICT test was higher than that obtained for blood (37.5%) and pleural fluid cultures (32.3%), but lower than the detection of pneumococcal antigen in urine samples (82.1%). However, three patients with pneumococcal pneumonia and a negative ICT urine test result had a positive pleural fluid antigen detection result test. Previous antibiotic exposure did not influence pneumococcal antigen detection in either pleural fluid or urine specimens. Six additional patients with empyema due to anaerobes (three patients), Streptococcus viridans (two patients), and Enterococcus faecalis (one patient) had false-positive pleural ICT test results. Finally, the ICT assay finding was also positive in 5 of 17 patients (29.4%) with pneumonia without a definite microbiological cause. CONCLUSIONS: The ICT test performed on pleural fluid samples augments the standard diagnostic methods of blood and pleural fluid cultures, even in the case of prior antibiotic therapy, and enhances the ICT urinary antigen assay.

Characteristics of community-acquired pneumonia in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVES: Community-acquired pneumonia is a frequent event in the course of chronic obstructive pulmonary disease (COPD). The aim of the present study was to provide information on clinical and microbiological characteristics and outcome of community-acquired pneumonia in these patients, in a comparative study with the non-COPD population. DESIGN: Prospective study of cases. SETTING: A university hospital in Lleida, Spain. PATIENTS: During a 6 year-period, we prospectively studied the clinical and radiological manifestations, microbiological data and outcome of all patients with community-acquired pneumonia. A comparative analysis of characteristics of pneumonia between 132 patients with a definitive diagnosis of COPD and 575 patients who did not have this underlying disease was performed. MEASUREMENTS AND RESULTS: COPD was associated with an older and predominantly male population. These patients frequently had concomitant comorbidities such as diabetes mellitus or chronic heart failure. Clinical presentation was more severe, manifested by septic shock, tachypnea, lower values of pH, pO(2) and oxygen saturation, and greater values of pCO(2). Purulent expectoration was also more frequent in this subset of patients. Admission was usually required for patients with COPD, and length of hospitalization was significantly increased; however, difference in the mortality rate was not observed. Although the spectrum of responsible microorganisms was very similar, the incidence of Pseudomonas aeruginosa and other Gram-negative bacilli was increased in COPD, particularly among patients with advanced situation and/or oral corticosteroid treatment. CONCLUSIONS: Community-acquired pneumonia in patients with COPD was associated with epidemiological and clinical particularities mainly related to the underlying disease but showed only minor differences in outcome parameters. Gram-negative bacilli and P. aeruginosa are potential pathogens that need to be considered.

The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms.

Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p < 0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82-0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms.

Community-acquired pneumonia as the initial manifestation of serious underlying diseases.

PURPOSE: Community-acquired pneumonia is common among patients with coexisting illnesses and it can be the initial manifestation of these comorbid diseases. The objectives of our study were to evaluate the frequency of this association and to analyze whether certain characteristics could predict the presence of unknown comorbid conditions. SUBJECTS AND METHODS: Over a 5-year period, we prospectively studied 660 consecutive patients with community-acquired pneumonia seen at our institution. In a subgroup of these patients, diagnosis of previously unknown comorbid conditions was established during follow-up. Characteristics of these patients were compared with data from the remaining sample of patients. RESULTS: Prior underlying diseases were present in 298 (45%) patients. One or more new comorbid conditions were found in 41 (6%), of which diabetes (14 cases), malignancies (12 cases), chronic obstructive pulmonary disease (8 cases), and human immunodeficiency virus (HIV) infection (5 cases) were the most common. In the comparative study, a bacterial etiology, positive blood cultures, and hospitalization were more frequently found (P < 0.05) in patients with new comorbid conditions than atypical microorganisms or viruses, negative blood cultures, or outpatient care. CONCLUSION: In the initial diagnostic workup of patients with community-acquired pneumonia, the possibility of unknown comorbid conditions should be carefully evaluated.

Etiology and outcome of community-acquired pneumonia in patients with diabetes mellitus.

STUDY OBJECTIVES: It has been suggested that diabetes mellitus is associated with an increased susceptibility to infection, the risk of using more aggressive therapeutic agents, and increased morbidity and mortality; however, current evidence supporting these events in the field of pneumonia is scarce. The aim of the present study was to provide information on clinical and microbiological characteristics and the outcome of community-acquired pneumonia in patients with diabetes mellitus. DESIGN: Prospective study of cases. SETTING: A university hospital in Lleida, Spain. PATIENTS: During a 5-year period, we prospectively studied the clinical and radiologic characteristics, the spectrum of causative agents and other microbiological data, and the outcomes of 660 consecutive episodes of community-acquired pneumonia. Data derived from 106 patients with diabetes mellitus were analyzed and compared with data obtained from the remaining population. MEASUREMENTS AND RESULTS: Patients with diabetes mellitus were significantly older (p = 0.001) and more frequently had other concomitant comorbid conditions (p = 0.018). Diabetes was also significantly associated with the development of pleural effusion (p = 0.015) and mortality (p = 0.002); for both events, diabetes remained as an independent predictive factor in multivariate analyses. By contrast, the incidence of the main etiologic agents, and the bacteremia or empyema rates did not show significant differences in relation to the remaining patients. In the subgroup of patients with diabetes, mortality was associated with the presence of multilobar infiltrates (p = 0.004), concomitant underlying diseases (p = 0.004), and some diabetes-related complications (nephropathy, p = 0.040; and vasculopathy, p = 0.002), although only multilobar infiltrates and comorbidities were selected as prognostic factors in the multivariate analysis. CONCLUSIONS: In patients with community-acquired pneumonia, diabetes mellitus is associated with a poor prognosis, increasing the rate of pleural effusion and mortality. Our results suggest that this adverse outcome is more attributable to the underlying circumstances of patients than to uncommon microbiological findings.

Evaluation of the polymerase chain reaction method for detection of Streptococcus pneumoniae DNA in pleural fluid samples.

STUDY OBJECTIVE: Streptococcus pneumoniae is the most frequent causative agent of community-acquired pneumonia (CAP); however, an etiologic diagnosis by traditional techniques can be accomplished in only a small percentage of patients with CAP. Pleural fluid is present in approximately 40% of patients with CAP; therefore, we hypothesized that detection of S pneumoniae DNA in pleural fluid by polymerase chain reaction (PCR) may help to increase the rate of diagnosis of pneumococcal pneumonia. DESIGN: A prospective study of cases. SETTING: A university hospital in Lleida, Spain. PATIENTS AND METHODS: One hundred two samples of pleural fluid (51 samples from consecutive adult patients with pneumonia and 51 samples from unselected control subjects) were tested by the nested-PCR method to detect selected pneumolysin gene of S pneumoniae, and the results were compared with those provided by alternative diagnostic methods. RESULTS: PCR in pleural fluid had a diagnostic sensitivity of 78% in patients with pneumococcal pneumonia, with positive results in 2 of 2 patients (100%) and 5 of 7 patients (71%) who had positive or negative pleural fluid culture findings, respectively. PCR results were also positive in 3 of 24 patients (12%) with pneumonia of unknown etiology and negative in all patients with pneumonia due to microorganisms other than S pneumoniae. Thus, the calculated specificity was 93%. Among control subjects, PCR gave positive results in two cases (4%). CONCLUSION: The nested-PCR test, applied to pleural fluid samples from patients with CAP, showed a sensitivity of 78% and a specificity of 93% in the diagnosis of pneumococcal pneumonia.

[Community-acquired pneumonia: usefulness of clinical presentation in the selection of antibiotic treatment]. / Neumonía adquirida en la comunidad: utilidad de la presentación clínica para la elección del tratamiento antibiótico.

BACKGROUND: Our purpose was to assess the usefulness of a strategy based on the clinical presentation in order to choose antibiotics in patients with non-severe community-acquired pneumonia (CAP). PATIENTS AND METHOD: During one year, all patients admitted to the emergency department with a diagnosis of non-severe (Fine risk-classes I, II and III) CAP, were randomized and assigned into the following groups: GROUP 1: the clinical presentation was not taken into account and all patients were treated with levofloxacin; GROUP 2: patients with typical presentation were treated with amoxicillin and patients with atypical presentation were treated with clarithromycin. The following aspects were evaluated during the follow-up: presence of fever after 72 h of treatment, days of hospitalization and complications. RESULTS: The eventual population analyzed included 125 patients: 59 (47%) were assigned to Group 1 and 66 (53%) to Group 2. Patients assigned to Group 1 had a lower rate of fever after 72 h of treatment (7% vs 27%, p = 0.005); they were hospitalized for fewer days (4.8 vs 8.1 days, p = 0.01), and had less complications: changes in antibiotic treatment (10% vs 23% p = NS), admissions in ICU (0% vs 5%, p = NS), re-admissions in hospital (0% vs 5%, p = 0.05) and mortality (0% vs 2%, p = NS). CONCLUSIONS: A strategy of empiric treatment of non-severe CAP with levofloxacin as the antibiotic of choice is more useful than that of a treatment based on the clinical presentation.

A pilot study on the diagnostic accuracy of proadrenomedullin and proatrial natriuretic Peptide in lower respiratory tract infections.

BACKGROUND: Pneumonia is the leading cause of death among infectious diseases in developed countries. However, the severity of pneumonia requiring hospitalization often makes the initial diagnosis difficult because of an equivocal clinical picture or interpretation of the chest film. The objective of the present study was to assess the usefulness of the plasma levels of mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) in differentiating pneumonia from other lower respiratory tract infections (LRTIs). METHODS: A retrospective study was conducted. The plasma levels of MR-proADM and MR-proANP were measured in 85 patients hospitalized for LRTIs, 56 of whom with diagnosis of pneumonia and 29 with other LRTIs. RESULTS: The patients with pneumonia had increased MR-proADM levels (median 1.46 nmol/L [IQR 25-75, 0.82-2.02 nmol/L]) compared with the patients with other LRTIs (median 0.88 nmol/mL [0.71-1.39 nmol/L]) (p= 0.04). However, the MR-proANP levels did not show differences between the groups. The optimal threshold of MR-proADM to predict pneumonia was 1.5 nmol/L, which yielded a sensitivity of 51.7% (95% CI, 38.0-65.3), a 79.3% specificity (95% CI, 60.3-92.0), and an odds ratio of 6.64 (95% CI, 1.32-32.85). The combination of this parameter with C-reactive protein in an "and" rule increased the specificity for detecting pneumonia significantly. CONCLUSION: MR-proADM levels (but not MR-proANP levels) are increased in patients with pneumonia although its discriminatory power is moderate.

[Multidisciplinary guidelines for the management of community-acquired pneumonia]. / Guía multidisciplinar para la valoración pronóstica, diagnóstico y tratamiento de la neumonía adquirida en la comunidad.

Community-acquired pneumonia (CAP) is an infectious respiratory disease with an incidence that ranges from 3 to 8 cases per 1,000 inhabitants per year. This incidence increases with age and comorbidities. Forty per cent of CAP patients require hospitalization and around 10% of these patients are admitted in an Intensive Care Unit (ICU). Several studies have suggested that the implementation of clinical guidelines has a positive impact in the outcome of patients including mortality and length of stay. The more recent and used guidelines are those from Infectious Diseases Society of America/American Thoracic Society, published in 2007, the 2009 from the British Thoracic Society, and that from the European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases, published in 2010. In Spain, the most recently released guideline is the Sociedad Española de Neumología y Cirugía Torácica-2011 guideline. The present guidelines GNAC are designed to be used by the majority of health-care professionals that can participate in the care of CAP patients including diagnosis, decision of hospital and ICU admission, treatment and prevention. The Centro Cochrane Iberoamericano (CCIB) has participated in summarizing the previous guidelines and in the bibliography search. For each one of the following sections the panel of experts has developed a table with recommendations classified according to its evidence, strength and practical applicability using the Grading of Recommendations of Assessment Development and Evaluations (GRADE) system: 1. Epidemiology, microbiological etiology and antibiotic resistances.2. Clinical and microbiological diagnosis.3. Prognostic scales and decision of hospital admission.4. ICU admission criteria. 5. Empirical and definitive antibiotic treatment.6. Treatment failure. 7. Prevention.

[Contact investigation according to concentric circles in a case of laryngeal tuberculosis]. / Estudio de contactos según círculos concéntricos en un caso de tuberculosis laríngea.

OBJECTIVE: To describe the census and contact investigation in a case of laryngeal tuberculosis. METHODS: Based on a patient with laryngeal tuberculosis and through interviews and ocular inspection, we established three circles of contacts. The tuberculin test was performed (positive ≥5 mm). Persons testing positive were invited to undergo a chest x-ray. The association of the infection was calculated with the odds ratio. The exposure-response relationship was determined with the linear trend χ2 test. RESULTS: The overall prevalence of infection was 39.9% (67/168). The prevalence among coworkers was 60.0% (24/40), that among frequenters of the town bar was 43.3% (13/30) and the conversions rate was 12.9%. There was a relationship with the degree of exposure (p <0.0001). CONCLUSIONS: Laryngeal tuberculosis involved high transmission to coworkers and frequenters of the town bar. In-depth studies through concentric circles and good communication with exposed individuals should be carried out.

Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.

BACKGROUND: Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay. METHODS AND FINDINGS: We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults. CONCLUSIONS: Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

Pleural fluid C-reactive protein contributes to the diagnosis and assessment of severity of parapneumonic effusions.

BACKGROUND AND AIMS: Prompt identification of parapneumonic effusions has immediate therapeutic benefits. We aimed to assess whether C-reactive protein (CRP) and routine biochemistries in pleural fluid are accurate markers of parapneumonic effusions, and to evaluate their properties as indicators for drainage (complicated parapneumonic effusion). METHODS: A retrospective review of 340 non-purulent parapneumonic effusions and 1,659 non-parapneumonic exudates from a single center was performed and the discriminative properties of pleural fluid routine biochemistries and, when available, CRP were evaluated. CRP, along with classical fluid parameters, was also applied to classify patients as having complicated or uncomplicated parapneumonic effusions. ROC analysis established the threshold of CRP for discriminating between groups. RESULTS: Pleural fluids with neutrophilic predominance and CRP levels >45 mg/dL were most likely to be parapneumonic in origin (likelihood ratio=7.7). When attempting to differentiate non-purulent complicated from uncomplicated effusions, a CRP >100mg/L had the same performance characteristics (area under the curve=0.81) as the widely accepted biochemistries pH and glucose. Combinations of CRP with pH or glucose resulted in incrementally discriminating values, pertaining to either sensitivity (75-80%) or specificity (97%), for complicated effusions. CONCLUSION: Pleural fluid CRP may be a useful adjunctive test in pleural effusions, both as a marker of parapneumonics and, particularly, as a differentiator between complicated and uncomplicated effusions.