Candida infective endocarditis: an observational cohort study with a focus on therapy.

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.

High-dose daptomycin therapy for left-sided infective endocarditis: a prospective study from the international collaboration on endocarditis.

The use of daptomycin in Gram-positive left-sided infective endocarditis (IE) has significantly increased. The purpose of this study was to assess the influence of high-dose daptomycin on the outcome of left-sided IE due to Gram-positive pathogens. This was a prospective cohort study based on 1,112 cases from the International Collaboration on Endocarditis (ICE)-Plus database and the ICE-Daptomycin Substudy database from 2008 to 2010. Among patients with left-sided IE due to Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecalis, we compared those treated with daptomycin (cohort A) to those treated with standard-of-care (SOC) antibiotics (cohort B). The primary outcome was in-hospital mortality. Time to clearance of bacteremia, 6-month mortality, and adverse events (AEs) ascribable to daptomycin were also assessed. There were 29 and 149 patients included in cohort A and cohort B, respectively. Baseline comorbidities did not differ between the two cohorts, except for a significantly higher prevalence of diabetes and previous episodes of IE among patients treated with daptomycin. The median daptomycin dose was 9.2 mg/kg of body weight/day. Two-thirds of the patients treated with daptomycin had failed a previous antibiotic regimen. In-hospital and 6-month mortalities were similar in the two cohorts. In cohort A, median time to clearance of methicillin-resistant S. aureus (MRSA) bacteremia was 1.0 day, irrespective of daptomycin dose, representing a significantly faster bacteremia clearance compared to SOC (1.0 versus 5.0 days; P < 0.01). Regimens with higher daptomycin doses were not associated with increased incidence of AEs. In conclusion, higher-dose daptomycin may be an effective and safe alternative to SOC in the treatment of left-sided IE due to common Gram-positive pathogens.

Emergence of coagulase-negative staphylococci as a cause of native valve endocarditis.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are an infrequent cause of native valve endocarditis (NVE), and our understanding of NVE caused by CoNS is incomplete. METHOD: The International Collaboration on Endocarditis-Prospective Cohort Study includes patients with endocarditis from 61 centers in 28 countries. Patients with definite cases of NVE caused by CoNS who were enrolled during the period June 2000-August 2006 were compared with patients with definite cases of NVE caused by Staphylococcus aureus and patients with NVE caused by viridans group streptococci. Multivariable logistic regression was used to determine factors associated with death in patients with NVE caused by CoNS. RESULTS: Of 1635 patients with definite NVE and no history of injection drug use, 128 (7.8%) had NVE due to CoNS. Health care-associated infection occurred in 63 patients (49%) with NVE caused by CoNS. Comorbidities, long-term intravascular catheter use, and history of recent invasive procedures were similar among patients with NVE caused by CoNS and among patients with NVE caused by S. aureus. Surgical treatment for endocarditis occurred more frequently in patients with NVE due to CoNS (76 patients [60%]) than in patients with NVE due to S. aureus (150 [33%]; P=.01) or in patients with NVE due to viridans group streptococci (149 [44%]; P=.01). Despite the high rate of surgical procedures among patients with NVE due to CoNS, the mortality rates among patients with NVE due to CoNS and among patients with NVE due to S. aureus were similar (32 patients [25%] and 124 patients [27%], respectively; P=.44); the mortality rate among patients with NVE due to CoNS was higher than that among patients with NVE due to viridans group streptococci (24 [7.0%]; P=.01). Persistent bacteremia (odds ratio, 2.65; 95% confidence interval, 1.08-6.51), congestive heart failure (odds ratio, 3.35; 95% confidence interval, 1.57-7.12), and chronic illness (odds ratio, 2.86; 95% confidence interval, 1.34-6.06) were independently associated with death in patients with NVE due to CoNS (c index, 0.73). CONCLUSIONS: CoNS have emerged as an important cause of NVE in both community and health care settings. Despite high rates of surgical therapy, NVE caused by CoNS is associated with poor outcomes.

The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: an analysis from the ICE Prospective Cohort Study (ICE-PCS).

BACKGROUND: Embolic events to the central nervous system are a major cause of morbidity and mortality in patients with infective endocarditis (IE). The appropriate role of valvular surgery in reducing such embolic events is unclear. The purpose of this study was to determine the relationship between the initiation of antimicrobial therapy and the temporal incidence of stroke in patients with IE and to determine if this time course differs from that shown for embolic events in previous studies. METHODS: Prospective incidence cohort study involving 61 tertiary referral centers in 28 countries. Case report forms were analyzed from 1437 consecutive patients with left-sided endocarditis admitted directly to participating centers. RESULTS: The crude incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days in the first week of therapy and fell to 1.71/1000 patient days in the second week. This rate continued to decline with further therapy. Stroke rates fell similarly regardless of the valve or organism involved. After 1 week of antimicrobial therapy, only 3.1% of the cohort experienced a stroke. CONCLUSIONS: The risk of stroke in IE falls dramatically after the initiation of effective antimicrobial therapy. The falling risk of stroke in patients with IE as a whole precludes stroke prevention as the sole indication for valvular surgery after 1 week of therapy.

Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus.

BACKGROUND: Phenol-soluble modulins (PSM) are amphipathic proteins produced by Staphylococcus aureus that promote virulence, inflammatory response, and biofilm formation. We previously showed that MRSA isolates from soft tissue infection (SSTI) produced significantly higher levels of PSM than MRSA isolates from hospital-acquired pneumonia (HAP) or infective endocarditis (IE). In this investigation, we sought to validate this finding in methicillin-susceptible S. aureus (MSSA) isolates. METHODS: MSSA isolates (n = 162) from patients with SSTI, HAP, and IE were matched 1:1:1 based on geographic origin of the infection to form 54 triplets (North America n = 27, Europe n = 25, Australia n = 2). All isolates underwent spa typing and were classified using eGenomics. In vitro PSM production was quantified by high-performance liquid chromatography/mass spectrometry. Fischer's Exact Test and the Kruskal-Wallis test were used for statistical analysis. RESULTS: Spa1 was more common in SSTI (14.81% SSTI, 3.70% HAP, 1.85% IE) (p < 0.03). Spa2 was more common in HAP (0% SSTI, 12.96% HAP, 3.70% IE) (p < 0.01). Levels of PSMα1-4 all differed significantly among the three clinical groups, with SSTI isolates producing the highest levels and IE producing the lowest levels of PSMα1-4. Spa1 isolates produced significantly more delta-toxin (p < 0.03) than non-Spa1 isolates. No associations between PSM levels and clinical outcome of SSTI, HAP, or IE were identified. CONCLUSION: Production of PSMα1-4 is highest in SSTI MSSA isolates, supporting the hypothesis that these peptides are important for SSTI pathogenesis. These findings are similar to those described in MRSA, and demonstrate that associations between PSM levels and type of infection are independent of the methicillin-resistance status of the isolate.

Staphylococcus aureus endocarditis: a consequence of medical progress.

CONTEXT: The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown. OBJECTIVES: To document the international emergence of health care-associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care-associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons). CONCLUSIONS: S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.