Aran Singanayagam

C-Reactive Protein Is an Independent Predictor of Severity in Community-acquired Pneumonia

BACKGROUND C-reactive protein (CRP) is an acute phase protein synthesized by the liver primarily in response to interleukin-6. Initial studies have suggested that inflammatory markers may have a role in predicting severity. We investigated whether admission and day 4 CRP could predict severity in community-acquired pneumonia. METHODS A prospective study was carried out over a 2-year period in a large teaching hospital. CRP was measured on admission and on day 4. The outcomes of interest were: 30-day mortality; need for mechanical ventilation and/or inotropic support; development of complicated pneumonia (lung abscess, empyema, or complicated parapneumonic effusion); the value of predictive tests were assessed using multivariate logistic regression. RESULTS There were 570 patients included in the study; 30-day mortality was 9.6%. Low CRP levels showed a high negative predictive value for excluding 30-day mortality (CRP <10 mg/L=100%, CRP <50=99.1%, CRP <100=98.9%, CRP <200=94.9%). Low admission CRP levels <100 mg/L were independently associated with reduced 30-day mortality (odds ratio [OR] 0.18; 0.04-0.85), P=.03; need for mechanical ventilation and/or inotropic support (OR 0.21; 0.14-0.4), P=.002; and complicated pneumonia (OR 0.05; 0.01-0.35), P=.003. A CRP that fails to fall by 50% or more within 4 days of admission is independently associated with increased 30 day mortality (OR 24.5; 6.4-93.4), P <.0001; need for mechanical ventilation and/or inotropic support (OR 7.1; 2.8-17.8), P <.0001 and complicated pneumonia (OR 15.4; 6.32-37.6), P <.0001. CONCLUSIONS Admission CRP <100 mg/L has reduced risk for 30-day mortality, need for mechanical ventilation and/or inotropic support, and complicated pneumonia. Failure of CRP to fall by 50% or more at day 4 leads to an increased risk for 30-day mortality, need for mechanical ventilation and/or inotropic support, and complicated pneumonia. C-reactive protein is an independent marker of severity in community-acquired pneumonia.

Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis

Introduction International guidelines recommend a severity-based approach to management in community-acquired pneumonia. CURB65, CRB65 and the Pneumonia Severity Index (PSI) are the most widely recommended severity scores. The aim of this study was to compare the performance characteristics of these scores for predicting mortality in community-acquired pneumonia. Methods A systematic review and meta-analysis was conducted according to MOOSE (meta-analysis of observational studies in epidemiology) guidelines. PUBMED and EMBASE were searched (1980–2009). 40 studies reporting prognostic information for the PSI, CURB65 and CRB65 severity scores were identified. Performance characteristics were pooled using a random effects model. Relationships between sensitivity and specificity were plotted using summary receiver operator characteristic (sROC) curves. Results All three scores predicted 30 day mortality. The PSI had the highest area under the sROC curve, 0.81 (SE 0.008), compared with CURB65, 0.80 (SE 0.008), p=0.1, and CRB65, 0.79 (0.01), p=0.09. These differences were not statistically significant. Performance characteristics were similar across comparable cut-offs for low, intermediate and high risk for each score. In identifying low risk patients, PSI (groups I and II) had the best negative likelihood ratio 0.08 (0.06–0.12) compared with CURB65 (score 0–1) 0.21 (0.15–0.30) and CRB65 (score 0), 0.15 (0.10–0.22). Conclusion There were no significant differences in overall test performance between PSI, CURB65 and CRB65 for predicting mortality from community-acquired pneumonia.

Epidemiology, Antibiotic Therapy, and Clinical Outcomes in Health Care–Associated Pneumonia: A UK Cohort Study

BACKGROUND The recently introduced concept of health care-associated pneumonia (HCAP), referring to patients with frequent healthcare contacts and at higher risk of contracting resistant pathogens, is controversial. METHODS This prospective observational study recorded the clinical features, microbiology, and outcomes in a UK cohort of hospitalized patients with pneumonia. The primary outcome was 30-day mortality. Logistic regression was used to adjust for confounders when determining the impact of HCAP on clinical outcomes. RESULTS A total of 20.5% of patients met the HCAP criteria. HCAP patients were older than patients with community-acquired pneumonia (CAP) (median 76 y, IQR 65-83 vs 65 y, IQR 48-77; P < .0001) and more frequently had major comorbidities (62.1% vs 45.2%; P < .0001). Patients with HCAP had higher initial severity compared to CAP patients (Pneumonia Severity Index, mean 3.7 [SD 1.1] vs mean 3.1 [SD 1.3]; P < .0001) but also worse functional status using the Eastern Cooperative Oncology Group scale (mean 2.4 [SD 1.44] vs mean 1.4 [SD 1.13]; P < .0001) and more frequently had treatment restrictions such as do not resuscitate orders (59.9% vs 29.8%; P < .0001). Consequently mortality was increased (odds ratio [OR] 2.15 [1.44-3.22]; P = .002) in HCAP patients on univariate analysis. Multivariate analysis suggested this relationship was primarily due to confounders rather than a higher frequency of treatment failure due to resistant organisms (adjusted OR .97 [.61-1.55]; P = .9). The frequencies of Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Gram-negative Enterobacteriaceae were low in both cohorts. CONCLUSIONS HCAP is common in the United Kingdom and is associated with a high mortality. This increased mortality was primarily related to underlying patient-related factors rather than the presence of antibiotic-resistant pathogens. This study did not establish a clear indication to change prescribing practices in a UK cohort.

Prior statin use is associated with improved outcomes in community-acquired pneumonia.

BACKGROUND Statins have potent anti-inflammatory effects in laboratory studies of pulmonary inflammation. We investigated whether statin users had improved outcome when admitted with community-acquired pneumonia. METHODS We carried out a prospective observational study of patients admitted to the hospital with community-acquired pneumonia between January 2005 and November 2007. The use of statins, angiotensin-converting enzyme inhibitors, beta-blockers, and aspirin were recorded. The outcomes of interest were 30-day mortality, need for mechanical ventilation or inotropic support, and the development of complicated pneumonia. RESULTS On multivariate logistic regression, statin use was associated with significantly lower 30-day mortality (adjusted odds ratio [AOR] 0.46, 95% confidence interval [CI], 0.25-0.85, P=.01) and development of complicated pneumonia (AOR 0.44, 95% CI, 0.25-0.79, P=.006). There was no effect on requirement of mechanical ventilation or inotropic support (AOR 0.93, 95% CI, 0.49-1.76, P=.8). Patients prescribed statins had more severe pneumonia (median Pneumonia Severity Index 4, interquartile range [IQR] 3-4) compared with patients not prescribed cardiovascular drugs (median Pneumonia Severity Index 3, IQR 2-4, P < .0001). Despite this, C-reactive protein levels on admission were significantly lower in patients prescribed statins (median 119 mg/L, IQR 46-215) compared with patients prescribed no cardiovascular drugs (182 mg/L, IQR 66-326, P < .0001). On multivariate logistic regression, statin use was independently protective against a C-reactive protein that failed to fall by 50% or more at day 4 (AOR 0.50, 95% CI 0.27-0.92, P=.02). CONCLUSIONS Statin use is associated with reduced markers of systemic inflammation and improved outcomes in patients admitted with community-acquired pneumonia.

Predictors of Mortality in Hospitalized Adults with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis

RATIONALE There is a need to identify clinically meaningful predictors of mortality following hospitalized COPD exacerbation. OBJECTIVES The aim of this study was to systematically review the literature to identify clinically important factors that predict mortality after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS Eligible studies considered adults admitted to hospital with COPD exacerbation. Two authors independently abstracted data. Odds ratios were then calculated by comparing the prevalence of each predictor in survivors versus nonsurvivors. For continuous variables, mean differences were pooled by the inverse of their variance, using a random effects model. MEASUREMENTS AND MAIN RESULTS There were 37 studies included (189,772 study subjects) with risk of death ranging from 3.6% for studies considering short-term mortality, 31.0% for long-term mortality (up to 2 yr after hospitalization), and 29.0% for studies that considered solely intensive care unit (ICU)-admitted study subjects. Twelve prognostic factors (age, male sex, low body mass index, cardiac failure, chronic renal failure, confusion, long-term oxygen therapy, lower limb edema, Global Initiative for Chronic Lung Disease criteria stage 4, cor pulmonale, acidemia, and elevated plasma troponin level) were significantly associated with increased short-term mortality. Nine prognostic factors (age, low body mass index, cardiac failure, diabetes mellitus, ischemic heart disease, malignancy, FEV1, long-term oxygen therapy, and PaO2 on admission) were significantly associated with long-term mortality. Three factors (age, low Glasgow Coma Scale score, and pH) were significantly associated with increased risk of mortality in ICU-admitted study subjects. CONCLUSION Different factors correlate with mortality from COPD exacerbation in the short term, long term, and after ICU admission. These parameters may be useful to develop tools for prediction of outcome in clinical practice.

Risk factors for complicated parapneumonic effusion and empyema on presentation to hospital with community-acquired pneumonia.

Background: The aim of this study was to identify key factors on admission predicting the development of complicated parapneumonic effusion or empyema in patients admitted with community-acquired pneumonia. Methods: A prospective observational study of patients admitted with community-acquired pneumonia in NHS Lothian, UK, was conducted. Multivariate regression analyses were used to evaluate factors that could predict the development of complicated parapneumonic effusion or empyema, including admission demographics, clinical features, laboratory tests and pneumonia-specific (Pneumonia Severity Index (PSI), CURB65 (New onset confusion, urea >7 mmol/l, Respiratory rate ≥30 breaths/min, Systolic blood pressure < 90 mm Hg and/or diastolic blood pressure ≤60 mm Hg and age ≥65 years) and CRB65 (New onset confusion, Respiratory rate ≥30 breaths/min, Systolic blood pressure <90 mm Hg and/or diastolic blood pressure ≤60 mm Hg and age ≥65 years)) and generic sepsis scoring systems (APACHE II (Acute Physiology and Chronic Health Evaluation II), SEWS (standardised early warning score) and systemic inflammatory response syndrome (SIRS)). Results: 1269 patients were included in the study and 92 patients (7.2%) developed complicated parapneumonic effusion or empyema. The pneumonia-specific and generic sepsis scoring systems had no value in predicting complicated parapneumonic effusion or empyema. Multivariate logistic regression identified albumin <30 g/l adjusted odds ratio (AOR) 4.55 (95% CI 2.45 to 8.45, p<0.0001), sodium <130 mmol/l AOR 2.70 (1.55 to 4.70, p = 0.0005), platelet count >400×109/l AOR 4.09 (2.21 to 7.54, p<0.0001), C-reactive protein >100 mg/l AOR 15.7 (3.69 to 66.9, p<0.0001) and a history of alcohol abuse AOR 4.28 (1.87 to 9.82, p  =  0.0006) or intravenous drug use AOR 2.82 (1.09 to 7.30, p = 0.03) as independently associated with development of complicated parapneumonic effusion or empyema. A history of chronic obstructive pulmonary disease was associated with decreased risk, AOR 0.18 (0.06 to 0.53, p = 0.002). A 6-point scoring system using these combined variables had good discriminatory value: area under the receiver operator characteristic curve (AUC) 0.84 (95% CI 0.81 to 0.86, p<0.0001). Conclusion: This study has identified seven clinical factors predicting the development of complicated parapneumonic effusion or empyema. Independent validation is needed.

Validation of the Infectious Diseases Society of America/American Thoratic Society Minor Criteria for Intensive Care Unit Admission in Community-Acquired Pneumonia Patients Without Major Criteria or Contraindications to Intensive Care Unit Care

BACKGROUND The 2007 Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) guidelines for community-acquired pneumonia (CAP) recommended new criteria to guide admission to the intensive care unit (ICU) for patients with this condition. Although the major criteria (requirement for mechanical ventilation or septic shock requiring vasopressor support) are well established, the value of the minor criteria alone have not been fully validated. METHODS We performed a prospective observational study of consecutive adult patients with CAP admitted to NHS Lothian (Scotland, United Kingdom). Patients meeting the IDSA/ATS major criteria on admission were excluded, along with patients not suitable for ICU care owing to advanced directives or major comorbid illnesses. Performance characteristics for the IDSA/ATS minor criteria were calculated and compared with those for alternative scoring systems identified in the literature. Two definitions of severe CAP were used as primary end points: ICU admission, and subsequent requirement for mechanical ventilation or vasopressor support (MV/VS); 30-day mortality was a secondary outcome. RESULTS The study included 1062 patients with CAP potentially eligible for ICU admission. Each of the 9 minor criteria was associated with increased risk of MV/VS and 30-day mortality in univariate analysis. Two hundred seven patients had ≥ 3 minor criteria (19.5%). The IDSA/ATS 2007 criteria had an area under the receiver operating characteristic curve of 0.85 (0.82-0.88) for prediction of MV/VS, 0.85 (0.82-0.88) for prediction of ICU admission, and 0.78 (0.74-0.82) for prediction of 30-day mortality. The IDSA/ATS 2007 criteria were at least equivalent to more established scoring systems for prediction of MV/VS and ICU admission and equivalent to alternative scoring systems for predicting 30-day mortality in this patient population. CONCLUSIONS In a population of patients with CAP without contraindications to ICU care, the IDSA/ATS minor criteria predict subsequent requirement for MV/VS, ICU admission, and 30-day mortality.

Severity assessment tools to guide ICU admission in community-acquired pneumonia: systematic review and meta-analysis

BackgroundThe aim of this meta-analysis was to determine if severity assessment tools can be used to guide decisions regarding intensive care unit (ICU) admission of patients with community-acquired pneumonia.MethodsA search of PUBMED and EMBASE (1980–2009) was conducted to identify studies reporting pneumonia severity scores and prediction of ICU admission. Two reviewers independently collected data and assessed study quality. Performance characteristics were pooled using a random-effects model.ResultsSufficient data were collected to perform a meta-analysis on five current scoring systems: the Pneumonia Severity Index (PSI), the CURB65 score, the CRB65 score, the American Thoracic Society (ATS) 2001 criteria and the Infectious Disease Society of America/ATS (IDSA/ATS) 2007 criteria. The analysis was limited due to large variations in the ICU admission criteria, ICU admission rates and patient characteristics between different studies and different healthcare systems. In the pooled analysis, PSI, CURB65 and CRB65 performed similarly in terms of sensitivity and specificity across a range of cut-offs. Patients in CURB65 group 0 were at lowest risk of ICU admission (negative likelihood ratio 0.14; 95% confidence interval 0.06–0.34) while the ATS 2001 criteria had the highest positive likelihood ratio (7.05; 95% confidence interval 4.39–11.3).ConclusionLarge variations exist in the use of ICU resources between different studies and different healthcare systems. Scoring systems designed to predict 30-day mortality perform less well when ICU admission is taken into account. Further studies of dedicated ICU admission scores are required.

Systolic blood pressure is superior to other haemodynamic predictors of outcome in community acquired pneumonia

Introduction: Admission blood pressure (BP) assessment is a central component of severity assessment for community acquired pneumonia. The aim of this study was to establish which readily available haemodynamic measure on admission is most useful for predicting severity in patients admitted with community acquired pneumonia. Methods: A prospective observational study of patients admitted with community acquired pneumonia was conducted in Edinburgh, UK. The measurements compared were systolic and diastolic BP, mean arterial pressure and pulse pressure. The outcomes of interest were 30 day mortality and the requirement for mechanical ventilation and/or inotropic support. Results: Admission systolic BP <90 mm Hg, diastolic BP ⩽60 mm Hg, mean arterial pressure <70 mm Hg and pulse pressure ⩽40 mm Hg were all associated with increased 30 day mortality and the need for mechanical ventilation and/or inotropic support on multivariate logistic regression. The AUC values for each predictor of 30 day mortality were as follows: systolic BP <90 mm Hg 0.70; diastolic BP ⩽60 mm Hg 0.59; mean arterial pressure <70 mm Hg 0.64; and pulse pressure ⩽40 mm Hg 0.60. The AUC values for each predictor of need for mechanical ventilation and/or inotropic support were as follows: systolic BP <90 mm Hg 0.70; diastolic BP ⩽60 mm Hg 0.68; mean arterial pressure <70 mm Hg 0.69; and pulse pressure ⩽40 mm Hg 0.59. A simplified CRB65 score containing systolic blood pressure <90 mm Hg alone performed equally well to standard CRB65 score (AUC 0.76 vs 0.74) and to the standard CURB65 score (0.76 vs 0.76) for the prediction of 30 day mortality. The simplified CRB65 score was equivalent for prediction of mechanical ventilation and/or inotropic support to standard CRB65 (0.77 vs 0.77) and to CURB65 (0.77 vs 0.78). Conclusion: Systolic BP is superior to other haemodynamic predictors of 30 day mortality and need for mechanical ventilation and/or inotropic support in community acquired pneumonia. The CURB65 score can be simplified to a modified CRB65 score by omission of the diastolic BP criterion without compromising its accuracy.

Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies

Objective To study the association of clarithromycin with cardiovascular events in the setting of acute exacerbations of chronic obstructive pulmonary disease and community acquired pneumonia. Design Analysis of two prospectively collected datasets. Setting Chronic obstructive pulmonary disease dataset including patients admitted to one of 12 hospitals around the United Kingdom between 2009 and 2011; Edinburgh pneumonia study cohort including patients admitted to NHS Lothian Hospitals between 2005 and 2009. Population 1343 patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease and 1631 patients admitted with community acquired pneumonia. Main outcome measures Hazard ratios for cardiovascular events at one year (defined as hospital admissions with acute coronary syndrome, decompensated cardiac failure, serious arrhythmia, or sudden cardiac death) and admissions for acute coronary syndrome (acute ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina). Secondary outcomes were all cause and cardiovascular mortality at one year. Results 268 cardiovascular events occurred in the acute exacerbations of chronic obstructive pulmonary disease cohort and 171 in the community acquired pneumonia cohort over one year. After multivariable adjustment, clarithromycin use in acute exacerbations of chronic obstructive pulmonary disease was associated with an increased risk of cardiovascular events and acute coronary syndrome—hazard ratios 1.50 (95% confidence interval 1.13 to 1.97) and 1.67 (1.04 to 2.68). After multivariable adjustment, clarithromycin use in community acquired pneumonia was associated with increased risk of cardiovascular events (hazard ratio 1.68, 1.18 to 2.38) but not acute coronary syndrome (1.65, 0.97 to 2.80). The association between clarithromycin use and cardiovascular events persisted after matching for the propensity to receive clarithromycin. A significant association was found between clarithromycin use and cardiovascular mortality (adjusted hazard ratio 1.52, 1.02 to 2.26) but not all cause mortality (1.16, 0.90 to 1.51) in acute exacerbations of chronic obstructive pulmonary disease. No association was found between clarithromycin use in community acquired pneumonia and all cause mortality or cardiovascular mortality. Longer durations of clarithromycin use were associated with more cardiovascular events. Use of β lactam antibiotics or doxycycline was not associated with increased cardiovascular events in patients with acute exacerbations of chronic obstructive pulmonary disease, suggesting an effect specific to clarithromycin. Conclusions The use of clarithromycin in the setting of acute exacerbations of chronic obstructive pulmonary disease or community acquired pneumonia may be associated with increased cardiovascular events. These findings require confirmation in other datasets.