Pallavi Mandal

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.

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.

Statins in community acquired pneumonia: Evidence from experimental and clinical studies

Statins are widely used to lower cholesterol and prevent complications of cardiovascular disease. The non-lipid lowering (pleiotropic) effects of statins may also have applications to the management of infections. These include effects on endothelial function, inflammation and coagulation pathways. Several observational studies have shown a significant reduction in 30-day mortality associated with prior statin therapy in hospitalised patients with sepsis and community acquired pneumonia. This article explores the evidence for statins as novel therapy in community acquired pneumonia. Experimental and animal studies suggest statins attenuate acute lung injury by modulating neutrophil function, reducing pro-inflammatory cytokine release and reducing vascular leak. Statins reduce endothelial dysfunction and have anti-thrombotic effects that improve outcome from pneumonia and sepsis in animal models. Clinical studies have provided conflicting results, but many suggest that statins may have a role in preventing pneumonia, or improving prognosis in hospitalised patients with community-acquired pneumonia.

Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled trial

BACKGROUND Bronchiectasis is characterised by chronic cough, sputum production, and recurrent chest infections. Pathogenesis is poorly understood, but excess neutrophilic airway inflammation is seen. Accumulating evidence suggests that statins have pleiotropic effects; therefore, these drugs could be a potential anti-inflammatory treatment for patients with bronchiectasis. We did a proof-of-concept randomised controlled trial to establish if atorvastatin could reduce cough in patients with bronchiectasis. METHODS Patients aged 18-79 years were recruited from a secondary-care clinic in Edinburgh, UK. Participants had clinically significant bronchiectasis (ie, cough and sputum production when clinically stable) confirmed by chest CT and two or more chest infections in the preceding year. Individuals were randomly allocated to receive either high-dose atorvastatin (80 mg) or a placebo, given orally once a day for 6 months. Sequence generation was done with a block randomisation of four. Random allocation was masked to study investigators and patients. The primary endpoint was reduction in cough from baseline to 6 months, measured by the Leicester Cough Questionnaire (LCQ) score, with a lower score indicating a more severe cough (minimum clinically important difference, 1·3 units). Analysis was done by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT01299181. FINDINGS Between June 23, 2011, and Jan 30, 2011, 82 patients were screened for inclusion in the study and 22 were excluded before randomisation. 30 individuals were assigned atorvastatin and 30 were allocated placebo. The change from baseline to 6 months in LCQ score differed between groups, with a mean change of 1·5 units in patients allocated atorvastatin versus -0·7 units in those assigned placebo (mean difference 2·2, 95% CI 0·5-3·9; p=0·01). 12 (40%) of 30 patients in the atorvastatin group improved by 1·3 units or more on the LCQ compared with five (17%) of 30 in the placebo group (difference 23%, 95% CI 1-45; p=0·04). Ten (33%) patients assigned atorvastatin had an adverse event versus three (10%) allocated placebo (difference 23%, 95% CI 3-43; p=0·02). No serious adverse events were recorded. INTERPRETATION 6 months of atorvastatin improved cough on a quality-of-life scale in patients with bronchiectasis. Multicentre studies are now needed to assess whether long-term statin treatment can reduce exacerbations. FUNDING Chief Scientists Office.

A pilot study of pulmonary rehabilitation and chest physiotherapy versus chest physiotherapy alone in bronchiectasis

AIM The aim of our study was to assess the efficacy of pulmonary rehabilitation in addition to regular chest physiotherapy in non cystic fibrosis bronchiectasis. METHODS Thirty patients with clinically significant bronchiectasis and limited exercise tolerance were randomized into either the control group receiving chest physiotherapy (8 weeks) or into the intervention group, receiving pulmonary rehabilitation in addition to chest physiotherapy (8 weeks). Both groups were encouraged to maintain their exercise program and or chest physiotherapy, following completion of the study. RESULTS End of training (8 weeks) No improvement in control group. In the intervention group, incremental shuttle walk test (ISWT) improved by 56.7 m (p = 0.03), endurance walk test (EWT) by 193.3 m (p = 0.01), Leicester Cough Questionnaire (LCQ) improved by 2.6 units (p < 0.001) and St. Georges Respiratory Questionnaire (SGRQ) by 8 units (p < 0.001). At 20 weeks (12 weeks post end of training) No improvement in control group. In the intervention group, ISWT improved by 80 m (p = 0.04) and EWT by 247.5 m (p = 0.003). LCQ improved by 4.4 units (p < 0.001) and SGRQ by 4 units (p < 0.001). CONCLUSION Pulmonary rehabilitation in addition to regular chest physiotherapy, improves exercise tolerance and health related quality of life in non cystic fibrosis bronchiectasis and the benefit was sustained at 12 weeks post end of pulmonary rehabilitation. Clinical trials regn no. NCT00868075.

Vascular complications are associated with poor outcome in community-acquired pneumonia

BACKGROUND Recognition of cardiovascular risk factors is important for primary and secondary prevention strategies. Recent evidence has linked lower respiratory tract infections with the development of acute myocardial infarction. AIM The aim of this study was to determine the frequency of cardiovascular and cerebrovascular events and the clinical outcomes, during hospitalization for community-acquired pneumonia (CAP). DESIGN We performed a retrospective study of 4408 patients with CAP presenting to five hospitals over a 2-year period. Clinical information, co-morbidities, cardiovascular events and 90-day mortality were collected from review of medical case notes. The relationship between cardiovascular events and outcomes were analysed using multivariable logistic regression. RESULTS From a total of 4408 patients, 2.2% developed stroke, 5% acute coronary syndrome or myocardial infarction and 9.3% new onset atrial fibrillation. These were associated with increased 90-day mortality [odds ratio (OR), 1.49 95% CI 1.18-1.87, P=0.0006]. Vascular events were independently associated with increased length of hospital stay-median 12 days (IQR 5-22), compared to patients with no vascular events 8 days (IQR 3-17 days, P<0.0001). CONCLUSION Cardiovascular and cerebrovascular events are common during hospitalization for CAP and are associated with increased 90-day mortality.

Incidence and Prognostic Implications of Acute Kidney Injury on Admission in Patients With Community-Acquired Pneumonia

BACKGROUND A consensus definition of acute kidney injury (AKI)-the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification-predicts mortality in general hospital and ICU populations. We aimed to assess its value on admission in patients with community-acquired pneumonia (CAP). METHODS A prospective observational study with CAP was carried out. We classified each patient according to his or her maximum RIFLE class using admission creatinine (risk, ≥ 1.5 × baseline creatinine; injury, ≥ 2 × baseline; failure, ≥ 3 × baseline; no-AKI, < 1.5 × baseline). Outcomes were 30-day mortality, requirement for mechanical ventilation and inotropic support (MV/IS), and requirement for renal replacement therapy (RRT). RESULTS A total of 1,241 patients were included (no-AKI, 1,018; risk, 130; injury, 63; failure, 30). On multivariate analysis, factors predicting development of AKI include severity of pneumonia (adjusted odds ratio [AOR], 1.74; 95% CI, 1.46-2.08; P < .0001), elevated C-reactive protein (AOR, 1.04; 95% CI, 1.03-1.06; P < .0001), and prior use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (AIIBs) (AOR, 1.77; 95% CI, 1.19-2.58; P = .005). Adjusting for severity of pneumonia, RIFLE criteria independently predicted 30-day mortality (AOR, 1.48; 95% CI, 1.15-1.91; P = .002), requirement for MV/IS (AOR, 2.22; 95% CI, 1.74-2.83; P < .0001), and RRT (AOR, 3.20; 95% CI, 2.01-5.11; P < .0001). Prior use of ACEIs or AIIBs was not associated with adverse outcome in either the entire cohort or patients without AKI. CONCLUSION The RIFLE classification is a simple tool to assess and classify AKI on admission and independently predicts 30-day mortality and the need for MV/IS and RRT in patients with CAP.

Safety and efficacy of CURB65-guided antibiotic therapy in community-acquired pneumonia

OBJECTIVES To determine whether the introduction of a community-acquired pneumonia (CAP) severity assessment tool to guide antibiotic selection could reduce broad-spectrum antibiotic prescribing without compromising patient safety. METHODS A prospective before and after evaluation study. Empirical antibiotic prescribing was studied for 18 months from June 2006 to January 2008 (pre-intervention) and then for 18 months following the implementation of a CURB65-guided antibiotic therapy guideline in June 2008. The primary outcome was the use of broad-spectrum antibiotics (cephalosporin, amoxicillin plus clavulanic acid and macrolides) in patients with CAP. Safety outcomes were 30 day mortality, requirement for mechanical ventilation and/or vasopressor support (MV/VS), development of complicated pneumonia, time to clinical stability (TCS) and length of hospital stay. RESULTS The introduction of CURB65-guided therapy resulted in an overall reduction in the prescription of cephalosporins (from 27.1% of patients receiving this agent in the overall pre-intervention cohort to 8.0% in the post-intervention cohort, P < 0.0001) and macrolides (72.8% to 58.7%, P < 0.0001), particularly among low-risk patients. There was a corresponding increase in the prescription of the narrower-spectrum agent amoxicillin (29.7% to 41.7%, P < 0.0001) and an increase in the use of amoxicillin monotherapy (10.4% to 29.9%, P < 0.0001). Co-amoxiclav use increased slightly as this agent replaced cephalosporins as first-line treatment for severe CAP. The guideline had no impact on 30 day mortality, MV/VS, complicated pneumonia, TCS or length of stay. Following the intervention, adherence to national guidelines increased from 25.4% of prescriptions to 61.9%, suggesting the potential for further improvements. CONCLUSIONS CURB65-guided antibiotic therapy was associated with a significant decrease in broad-spectrum antibiotic use. The intervention was safe with no impact on mortality, treatment failure or clinical response.