Stuart Dickerman

Non-HACEK Gram-Negative Bacillus Endocarditis

Context Infective endocarditis due to non-HACEK organisms has been considered to be associated with injection drug use. Contribution Analysis of 2761 cases of patients with infective endocarditis from an international collaborative of 61 hospitals found that non-HACEK organisms account for fewer than 2% of the cases, and that most patients with non-HACEK endocarditis had infections associated with health care. Of patients with non-HACEK infections, 59% had implanted endovascular devices or prosthetic valves, but only 4% had injection drug use. More than one half of patients with non-HACEK infections required cardiac surgery and 24% died. Implication Infective endocarditis due to non-HACEK organisms is a rare but frequently fatal condition. It is much more frequently associated with implanted endovascular devices than with injection drug use. The Editors Infective endocarditis caused by non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species) gram-negative bacilli is a rare and poorly characterized disease. The literature describing non-HACEK gram-negative bacillus endocarditis primarily consists of several small case series from the 1970s and 1980s of outbreaks in injection drug users in large urban areas, such as Detroit (1, 2), Cleveland (3), and San Francisco (4, 5). As a result, endocarditis due to non-HACEK gram-negative bacilli has been considered to be almost exclusively associated with injection drug use (6, 7). In contrast to this reporting bias, however, non-HACEK gram-negative bacillus endocarditis has been occasionally reported to be a nosocomial problem, particularly in patients with early endocarditis after cardiac surgery (811). The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) database was created in 1999. From 1 January 2000 to 31 August 2005, 2761 patients with definite endocarditis from 61 centers in 28 countries were prospectively enrolled. This resource offers a unique opportunity to evaluate the epidemiology, characteristics, and outcome of endocarditis due to non-HACEK gram-negative bacilli in a large, contemporary, and international cohort of well-characterized patients with endocarditis. Methods The International Collaboration on Endocarditis Prospective Cohort Study Hospitalized patients with endocarditis (12) were identified prospectively by using site-specific procedures to ensure consecutive enrollment. Informed consent (oral or written) was obtained from all patients according to local institutional review board or ethics committee instructions. A standard case report form containing 275 variables was completed for each patient on enrollment at the participating site. The ICE-PCS database is maintained at the Duke Clinical Research Institute, Durham, North Carolina, which serves as the coordinating center for the ICE studies, with approval from the institutional review board. We included all patients with endocarditis from sites that met performance criteria for participation. These site criteria included 1) minimum enrollment of 12 cases per year in a center with access to cardiac surgery, 2) the presence of patient identification procedures to ensure consecutive enrollment and to minimize ascertainment bias (as described elsewhere) (13, 14), 3) high-quality data with query resolution, and 4) institutional review board or ethics committee approval or waiver based on local standards. All patients from sites that did not meet these criteria (totaling 494 case-patients from 14 sites) were excluded. Sample We included patients who had both definite endocarditis according to the modified Duke criteria (12) and isolation of a pure culture of an aerobic gram-negative bacillus from the bloodstream or valve. To ensure that the diagnosis of gram-negative endocarditis was accurate, the following additional criteria were applied when interpreting the blood culture results: 1) the patients bacteremia had to meet the definition for persistently positive blood cultures when applying the modified Duke criteria; 2) a single blood culture positive for a gram-negative organism was not considered to constitute a minor microbiological criterion when applying the modified Duke criteria; and 3) patients with endocarditis due to anaerobes, Brucella species, HACEK organisms, or other fastidious gram-negative pathogens (for example, Pasteurella species) or polymicrobial infections were excluded. Definitions We used published definitions of health carerelated variables (15, 16). Nonnosocomial health careassociated infection was defined as a health careassociated infection that was not acquired as a hospital inpatient (for example, hemodialysis, outpatient cancer chemotherapy, or receipt of intravenous antibiotics at home) (16). A nosocomial infection was defined as a health careassociated infection that was acquired after at least 48 hours as a hospital inpatient. Prosthetic endocarditis was defined as endocarditis involving a prosthetic heart valve or implanted endovascular device, such as a permanent cardiac pacemaker, cardioverter defibrillator, or aortic stent. Statistical Analysis Patients with definite non-HACEK gram-negative bacillus endocarditis were compared with all other patients with definite endocarditis in the ICE-PCS database. Continuous variables are presented as medians and 25th and 75th percentiles. Categorical variables are presented as frequencies and percentages of the specified group. Univariable comparisons were made by using the Wilcoxon rank-sum test or the chi-square test as appropriate. For all tests, a P value of 0.05 or less was considered statistically significant. Missing data for each variable were excluded from the denominator as indicated in Table 1. All statistical analyses were performed by using SAS software (version 8.2, SAS Institute, Cary, North Carolina). Table 1. Frequency of Individual Duke Criteria among 49 Patients with Non-HACEK Gram-Negative Bacillus Endocarditis* Role of the Funding Source The study did not receive funding. Results Of the 2761 patients with definite endocarditis, 49 (1.8%) had endocarditis due to non-HACEK gram-negative bacilli. Twenty-six of these patients (53%) were enrolled from Europe; 11 (22%) from North America; and the remainder from South America, New Zealand, Australia, the Middle East, and Asia. Patient enrollment was constant throughout the study period. Characteristics of Non-HACEK Gram-Negative Bacillus Endocarditis Patients with non-HACEK gram-negative bacillus endocarditis were more likely to have had symptoms for more than 1 month than were patients infected with other pathogens (90% [95% CI, 82% to 98%] vs. 77% [CI, 75% to 79%], respectively; P= 0.035) (Table 2). Injection drug use was uncommon in patients with non-HACEK gram-negative bacillus endocarditis and in patients with endocarditis due to other organisms (4% [CI, 0% to 9%] vs. 10% [CI, 9% to 11%]; P= 0.20). In contrast, health care contact was a statistically significant risk factor for non-HACEK gram-negative bacillus endocarditis (57% [CI, 43% to 71%] vs. 30% [CI, 28% to 32%]; P< 0.001), largely because the proportion of nosocomial infections was higher in the non-HACEK gram-negative bacillus endocarditis group (39% [CI, 25% to 53%] vs. 14% [CI, 13% to 15%]; P< 0.001). The Figure shows the routes of acquisition of non-HACEK gram-negative bacillus endocarditis compared with Staphylococcus aureus endocarditis (15) and all other causes of endocarditis in the ICE-PCS database. Table 2. Characteristics of Patients with Non-HACEK Gram-Negative Bacillus Infective Endocarditis and Those with Other Causes of Endocarditis* Figure. Routes of acquisition among patients with definite endocarditis due to non-HACEK gram-negative bacilli, Staphylococcus aureus , and other pathogens. HACEK = Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species. Implanted endovascular devices were more common in patients with non-HACEK gram-negative bacillus endocarditis than in patients with other pathogens (29% [CI, 16% to 42%] vs. 11% [CI, 10% to 12%]; P< 0.001). Patients with non-HACEK gram-negative bacillus endocarditis were also statistically significantly more likely than patients with other causes of endocarditis to have a presumed source of infection involving the genitourinary or nonoral gastrointestinal tract (35% [CI, 22% to 48%] vs. 12% [CI, 11% to 13%]; P< 0.001). A nondental invasive procedure within 60 days before symptom onset was more likely in patients with non-HACEK gram-negative bacillus endocarditis than in patients with other causes of endocarditis (38% [CI, 24% to 52%] vs. 19% [CI, 18% to 20%]; P= 0.002). Intracardiac abscesses were statistically significantly more common in patients with non-HACEK gram-negative bacillus endocarditis than in patients with endocarditis due to other organisms (25% [CI, 13% to 37%] vs. 14% [CI, 13% to 15%]; P= 0.034). The in-hospital mortality rate was 24% (CI, 12% to 36%) for patients with non-HACEK gram-negative bacillus endocarditis and 17% (CI, 16% to 18%) for patients with other causes of endocarditis (P= 0.190). Of the 49 patients with non-HACEK gram-negative bacillus endocarditis, 20 (41%) had native-valve endocarditis and 29 (59%) had prosthetic endocarditis. All 49 cases were confirmed as definite endocarditis by the modified Duke criteria: 22 (45%) were histopathologically (16 patients [33%]) or macroscopically (at surgery in 6 patients [12%]) confirmed (Table 1). Of the 16 patients with pathologic confirmation, 8 had valve cultures, 2 had device cultures, and 1 had an aortic aneurysm culture. Microbiology of Non-HACEK Gram-Negative Bacillus Endocarditis The most common pathogens in patients with non-HACEK gram-negative bacillus endocarditis were Escherichia coli (14 patients [29%]) and Pseudomonas aeruginosa (11 patients [22%]). Othe

Influence of the Timing of Cardiac Surgery on the Outcome of Patients With Infective Endocarditis and Stroke

BACKGROUND The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

Echocardiographic Findings Predict In-Hospital and 1-Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis Analysis From the International Collaboration on Endocarditis-Prospective Echo Cohort Study

Background— Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results— Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus . Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non- S aureus IE; P <0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non- S aureus IE; P <0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P <0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P =0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P =0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P =0.004) were the only independent predictors of 1-year mortality. Conclusions— S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.Background—Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results—Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P=0.004) were the only independent predictors of 1-year mortality. Conclusions—S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.

Echocardiographic Findings Predict In-Hospital and 1 Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis

Background— Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results— Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus . Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non- S aureus IE; P <0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non- S aureus IE; P <0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P <0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P =0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P =0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P =0.004) were the only independent predictors of 1-year mortality. Conclusions— S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.Background—Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results—Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P=0.004) were the only independent predictors of 1-year mortality. Conclusions—S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.

Echocardiographic agreement in the diagnostic evaluation for infective endocarditis

Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data. IE reproducibility was assessed on a subset of echocardiograms from subjects enrolled in the International Collaboration on Endocarditis registry. Specific echocardiographic case report forms were used. Intra-observer agreement was assessed from six site readers on ten randomly selected echocardiograms. Inter-observer agreement between sites and an echocardiography core laboratory was assessed on a separate random sample of 110 echocardiograms. Agreement was determined using intraclass correlation (ICC), coverage probability (CP), and limits of agreement for continuous variables and kappa statistics (κweighted) and CP for categorical variables. Intra-observer agreement for LVEF was excellent [ICC = 0.93 ± 0.1 and all pairwise differences for LVEF (CP) were within 10 %]. For IE categorical echocardiographic variables, intra-observer agreement was best for aortic abscess (κweighted = 1.0, CP = 1.0 for all readers). Highest inter-observer agreement for IE categorical echocardiographic variables was obtained for vegetation location (κweighted = 0.95; 95 % CI 0.92–0.99) and lowest agreement was found for vegetation mobility (κweighted = 0.69; 95 % CI 0.62–0.86). Moderate to excellent intra- and inter-observer agreement is observed for echocardiographic variables in the diagnostic assessment of IE. A pragmatic approach for determining echocardiographic data reproducibility in a large, multicentre, site interpreted observational cohort is feasible.

Echocardiographic Findings Predict In-Hospital and 1-Year Mortality in Left-Sided Native Valve Staphylococcus aureus EndocarditisCLINICAL PERSPECTIVE

Background— Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results— Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus . Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non- S aureus IE; P <0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non- S aureus IE; P <0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P <0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P =0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P =0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P =0.004) were the only independent predictors of 1-year mortality. Conclusions— S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.Background—Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results—Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P=0.004) were the only independent predictors of 1-year mortality. Conclusions—S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.

ECHOCARDIOGRAPHIC FINDINGS PREDICT IN-HOSPITAL AND 1-YEAR MORTALITY IN LEFT-SIDED NATIVE VALVE STAPHYLOCOCCUS AUREUS ENDOCARDITIS: AN ANALYSIS FROM THE INTERNATIONAL COLLABORATION ON ENDOCARDITIS- PROSPECTIVE ECHO COHORT STUDY

Staphylococcus aureus is the leading cause of infective endocarditis (IE) in industrialized countries. In fact, S aureus IE increased at a rate of 1.1% per quarter in the United States from 1999 to 2008. This is problematic because S aureus IE is associated with more complications and higher mortality compared with IE due to other pathogens. However, it remains unknown whether this finding persists when S aureus is compared with a non-S aureus cohort with similar baseline characteristics and if echocardiographic variables can identify patients with increased mortality in S aureus IE.