Paula Peyrani

SMART-COP: A Tool for Predicting the Need for Intensive Respiratory or Vasopressor Support in Community-Acquired Pneumonia

BACKGROUND Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study.

BACKGROUND The American Thoracic Society and Infectious Diseases Society of America provide guidelines for management of hospital-acquired, ventilator-associated, and health-care-associated pneumonias, consisting of empirical antibiotic regimens for patients at risk for multidrug-resistant pathogens. We aimed to improve compliance with these guidelines and assess outcomes. METHODS We implemented a performance-improvement initiative in four academic medical centres in the USA with protocol-based education and prospective observation of outcomes. Patients were assessed for severity of illness and followed up until death, hospital discharge, or day 28. We included patients in intensive-care units who were at risk for multidrug-resistant pneumonia and were treated empirically. FINDINGS 303 patients at risk for multidrug-resistant pneumonia were treated empirically, and prescribed treatment was guideline compliant in 129 patients and non-compliant in 174 patients. 44 (34%) patients died before 28 days in the compliance group and 35 (20%) died in the non-compliance group. Five patients in the compliance group and seven in the non-compliance group were lost to follow-up after day 14. Kaplan-Meier estimated survival to 28 days was 65% in the compliance group and 79% in the non-compliance group (p=0·0042). This difference persisted after adjustment for severity of illness. Median length of stay and duration of mechanical ventilation did not differ between groups. Compliance failures included non-use of dual treatment for Gram-negative pathogens in 154 patients and absence of meticillin-resistant Staphylococcus aureus coverage in 24 patients. For patients in whom pathogens were subsequently identified, empirical treatment was active in 79 (81%) of 97 of patients receiving compliant therapy compared with 109 (85%) of 128 of patients receiving non-compliant therapy. INTERPRETATION Because adherence with empirical treatment was associated with increased mortality, we recommend a randomised trial be done before further implementation of these guidelines. FUNDING Pfizer, US Medical.

Acute Myocardial Infarction in Hospitalized Patients with Community-Acquired Pneumonia

BACKGROUND An epidemiological link between respiratory infection and acute myocardial infarction (AMI) has been suggested, and recent data indicate that there is an association between AMI and pneumococcal community-acquired pneumonia (CAP) in hospitalized patients. The objective of this study was to investigate the association of AMI with the severity of pneumonia at hospitalization and clinical failure during hospitalization among patients with CAP. METHODS An observational, retrospective study involving consecutive patients hospitalized with CAP was performed at the Veterans Hospital of Louisville, Kentucky. Patients admitted to the intensive care unit were defined as having severe CAP. Clinical failure was defined as the development of respiratory failure or shock. AMI was diagnosed on the basis of abnormal troponin levels and electrocardiogram findings. Propensity-adjusted models that controlled for clinical and nonclinical factors were used to investigate the association between AMI and pneumonia severity index and between AMI and clinical failure. RESULTS Data for a total of 500 patients were studied. At hospital admission, AMI was present in 13 (15%) of 86 patients with severe CAP. During hospitalization, AMI was present in 13 (20%) of 65 patients who experienced clinical failure. Following risk adjustment, significant associations were discovered between AMI and the pneumonia severity index score (modeled with a restricted cubic spline) (P = .05) and between AMI and clinical failure (P = .04). CONCLUSIONS A combined diagnosis of CAP and AMI is common among hospitalized patients with severe CAP. In cases in which the clinical course of a hospitalized patient with CAP is complicated by clinical failure, AMI should be considered as a possible etiology.

Relationship of Vancomycin Minimum Inhibitory Concentration to Mortality in Patients With Methicillin-Resistant Staphylococcus aureus Hospital-Acquired, Ventilator-Associated, or Health-care-Associated Pneumonia

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined. METHODS Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables. RESULTS The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality. CONCLUSIONS Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.

Incidence, Etiology, Timing, and Risk Factors for Clinical Failure in Hospitalized Patients With Community-Acquired Pneumonia

BACKGROUND The etiology of clinical failure in hospitalized patients with community-acquired pneumonia (CAP) may be related or unrelated to pulmonary infection. The objective of this study was to define the incidence, etiology, timing, and risk factors associated with clinical failures related to CAP vs those unrelated to CAP. METHODS Observational retrospective study of consecutive CAP patients. All patients who experienced clinical failure were identified. Cases were presented to a review committee that defined, by consensus, etiology, timing, and risk factors for clinical failures related to CAP. RESULTS Among 500 patients who were enrolled in the study, clinical failure was identified in 67 (13%). Clinical failure was related to CAP in 54 patients (81%). The most common etiologies for clinical failure related to CAP were severe sepsis (33%), acute myocardial infarction (28%), and progressive pneumonia (19%). All cases of severe sepsis occurred in the first 72 h of hospitalization. The most common etiology for clinical failure unrelated to CAP was the development of hospital-acquired pneumonia (45%). At the time of hospital admission, factors associated with clinical failure related to CAP were advanced age, congestive heart failure, hypotension, abnormal gas exchange, acidosis, hypothermia, thrombocytopenia, and pleural effusion. CONCLUSIONS The development of severe sepsis early during hospitalization is the primary etiology for clinical failure related to CAP. To achieve early treatment intervention, physicians should maintain a high index of suspicion for severe sepsis in hospitalized patients with CAP. To decrease the number of clinical failures unrelated to CAP, interventions need to be developed at the local level to improve the processes of care for patients with pneumonia.

Thrombocytopenia and Thrombocytosis at Time of Hospitalization Predict Mortality in Patients With Community-Acquired Pneumonia

BACKGROUND Platelets are inflammatory cells with an important role in antimicrobial host defenses. We speculate that an abnormal platelet count may be a marker of severity in patients with community-acquired pneumonia (CAP). The objectives of this study were to evaluate if abnormal platelet count in hospitalized patients with CAP was associated with 30-day mortality and to compare platelet count and leukocyte count as predictors of 30-day mortality. METHODS We performed a retrospective cohort study of 500 consecutive patients hospitalized with CAP at the Veterans Hospital of Louisville, Kentucky, between June 2001 and March 2006 to investigate the association of platelet count and leukocyte count with 30-day mortality. Predictor variables were platelet count and leukocyte count. Abnormal platelet count was < 100,000/L (thrombocytopenia) and > 400,000/L (thrombocytosis). The outcome variable was 30-day mortality. To control for potential confounding, a propensity score that incorporated 33 variables was used. RESULTS Platelet count was strongly associated (P = .0009) with 30-day mortality, whereas no association was observed for leukocyte count (P = .5114). High platelet counts resulted in a significantly increased risk of mortality. CONCLUSIONS Thrombocytopenia and thrombocytosis are associated with mortality in patients hospitalized with CAP. When evaluating an initial CBC test in patients with CAP, an abnormal platelet count is a better predictor of outcome than an abnormal leukocyte count.

Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia: Retrospective Analysis of the IMPACT-HAP Database

BACKGROUND The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. OBJECTIVE The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. METHODS This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. RESULTS Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, P = 0.0003). CONCLUSIONS Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

The Presence of Pneumococcal Bacteremia Does Not Influence Clinical Outcomes in Patients With Community-Acquired Pneumonia: Results From the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

BACKGROUND It remains unknown whether pneumococcal bacteremia increases the risk of poor outcomes in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to investigate whether the presence of pneumococcal bacteremia influences the clinical outcomes of hospitalized patients with CAP. METHODS We performed secondary analyses of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP and pneumococcal bacteremia, and patients with CAP and negative blood culture findings. To identify the effect of pneumococcal bacteremia on patient outcomes, we modeled all-cause mortality and CAP-related mortality using logistic regression analysis, and time to clinical stability and length of hospital stay using Cox proportional hazards models. RESULTS We studied 125 subjects with pneumococcal bacteremic CAP and 1,847 subjects with nonbacteremic CAP. The multivariable regression analysis revealed a lack of association of pneumococcal bacteremic CAP and time to clinical stability (hazard ratio, 0.87; 95% confidence interval [CI], 0.7 to 1.1; p = 0.25), length of hospital stay (hazard ratio, 1.14; 95% CI, 0.91 to 1.43; p = 0.25), all-cause mortality (odds ratio [OR], 0.68; 95% CI, 0.36 to 1.3; p = 0.25), and CAP-related mortality (OR, 0.86; 95% CI, 0.35 to 2.06; p = 0.73). CONCLUSIONS Pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP. Factors related to severity of disease are confounders of the association between pneumococcal bacteremia and poor outcomes. This study indicates that the presence of pneumococcal bacteremia by itself should not be a contraindication for deescalation of therapy in clinically stable hospitalized patients with CAP.

Decrease in Long-term Survival for Hospitalized Patients With Community-Acquired Pneumonia

BACKGROUND The association of hospitalization because of community-acquired pneumonia (CAP) and long-term survival has not been fully examined. We measured the long-term survival of hospitalized patients with CAP adjusted for the effects of comorbidities. METHODS A cohort of adult patients admitted to the medical services of the Veterans Affairs Medical Center, Louisville, Kentucky, was retrospectively examined. A Kaplan-Meier survival curve was constructed to assess the effect of CAP admission status on patient survival. A Cox proportional hazards regression model included comorbidities as predictors and time to death as the outcome in the construction of a modified Charlson Comorbidity Index (mCCI). The mCCI was internally validated to evaluate the predictability of patient survival. The mCCI and age > 65 years were included as potential confounders in a final Cox proportional hazards regression model with CAP admission status as the main predictor and time to death as the outcome. RESULTS CAP was identified in 624 (9%) out of 6,971 patients. The Kaplan-Meier survival curve showed a significantly shorter survival among patients with CAP than those without CAP (P < .0001). The internal validation of the mCCI showed that patients were more likely to die as the mCCI increased (P < .0001). The Cox proportional hazards regression modeling the association between time to death and CAP admission after adjusting for elderly age and the mCCI showed that hospitalization due to CAP was a statistically significant predictor of decreased survival (hazard ratio, 1.4; 95% CI, 1.2-1.5; P < .0001). CONCLUSION There is a decreased long-term survival among hospitalized patients with CAP after adjusting for comorbidities and aging. Future research to understand the pathophysiology of the long-term CAP outcomes is necessary to develop treatment strategies.

ORIGINAL RESEARCHPNEUMONIAThe Presence of Pneumococcal Bacteremia Does Not Influence Clinical Outcomes in Patients With Community-Acquired Pneumonia: Results From the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

BACKGROUND It remains unknown whether pneumococcal bacteremia increases the risk of poor outcomes in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to investigate whether the presence of pneumococcal bacteremia influences the clinical outcomes of hospitalized patients with CAP. METHODS We performed secondary analyses of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP and pneumococcal bacteremia, and patients with CAP and negative blood culture findings. To identify the effect of pneumococcal bacteremia on patient outcomes, we modeled all-cause mortality and CAP-related mortality using logistic regression analysis, and time to clinical stability and length of hospital stay using Cox proportional hazards models. RESULTS We studied 125 subjects with pneumococcal bacteremic CAP and 1,847 subjects with nonbacteremic CAP. The multivariable regression analysis revealed a lack of association of pneumococcal bacteremic CAP and time to clinical stability (hazard ratio, 0.87; 95% confidence interval [CI], 0.7 to 1.1; p = 0.25), length of hospital stay (hazard ratio, 1.14; 95% CI, 0.91 to 1.43; p = 0.25), all-cause mortality (odds ratio [OR], 0.68; 95% CI, 0.36 to 1.3; p = 0.25), and CAP-related mortality (OR, 0.86; 95% CI, 0.35 to 2.06; p = 0.73). CONCLUSIONS Pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP. Factors related to severity of disease are confounders of the association between pneumococcal bacteremia and poor outcomes. This study indicates that the presence of pneumococcal bacteremia by itself should not be a contraindication for deescalation of therapy in clinically stable hospitalized patients with CAP.