G. R. Corey

Impact of the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study

Objective To quantify the change in prescribing of antibiotic prophylaxis before invasive dental procedures for patients at risk of infective endocarditis, and any concurrent change in the incidence of infective endocarditis, following introduction of a clinical guideline from the National Institute for Health and Clinical Excellence (NICE) in March 2008 recommending the cessation of antibiotic prophylaxis in the United Kingdom. Design Before and after study. Setting England. Population All patients admitted to hospital in England with a primary or secondary discharge diagnosis of acute or subacute infective endocarditis. Main outcome measures Monthly number of prescriptions for antibiotic prophylaxis consisting of a single 3 g oral dose of amoxicillin or a single 600 mg oral dose of clindamycin, and monthly number of cases of infective endocarditis, infective endocarditis related deaths in hospital, or cases of infective endocarditis with a possible oral origin for streptococci. Results After the introduction of the NICE guideline there was a highly significant 78.6% reduction (P<0.001) in prescribing of antibiotic prophylaxis, from a mean 10 277 (SD 1068) prescriptions per month to 2292 (SD 176). Evidence that the general upward trend in cases of infective endocarditis before the guideline was significantly altered after the guideline was lacking (P=0.61). Using a non-inferiority test, an increase in the number of cases of 9.3% or more could be excluded after the introduction of the guideline. Similarly an increase in infective endocarditis related deaths in hospital of 12.3% or more could also be excluded. Conclusion Despite a 78.6% reduction in prescribing of antibiotic prophylaxis after the introduction of the NICE guideline, this study excluded any large increase in the incidence of cases of or deaths from infective endocarditis in the two years after the guideline. Although this lends support to the guideline, ongoing data monitoring is needed to confirm this, and further clinical trials should determine if antibiotic prophylaxis still has a role in protecting some patients at particularly high risk.

Telavancin versus Standard Therapy for Treatment of Complicated Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: FAST 2 Study

ABSTRACT Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients ≥18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with Staphylococcus aureus at baseline (n = 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant S. aureus (MRSA) at baseline (n = 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with S. aureus infection was better with telavancin compared to standard therapy (92% versus 78%, P = 0.07) and significantly better in patients with MRSA (92% versus 68%; P = 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.

Stroke location, characterization, severity, and outcome in mitral vs aortic valve endocarditis

Objective: To characterize the incidence and clinical features of patients with infective endocarditis (IE) and stroke. Methods: The authors reviewed the records of 707 patients diagnosed with definite or possible IE between January 1984 and November 1999. Stroke was confirmed by application of strict definitions and classified by type, pathophysiology, vascular territory, and severity. The authors determined mortality rates for the initial hospitalization and 12 months after admission. Results: Strokes occurred in 68 (9.6%) of 707 patients with IE, 38 (17%) of 218 patients with mitral valve endocarditis (MVE), 14 (9%) of 149 patients with aortic valve endocarditis (AVE), and 16 (5%) of 340 patients with other forms of IE (OR for MVE vs AVE = 2.0, 95% CI 1.1 to 3.9). Among the patients with MVE or AVE and stroke, there were no significant relationships between site of vegetation and length of hospitalization, stroke severity, mortality during the initial hospitalization, or 12-month mortality. Fifty-two percent of patients with stroke and IE died within 1 year of admission. Conclusions: The overall incidence of stroke in patients with IE (9.6%) is lower than previous reports (21 to 39%). Patients with MVE had a greater risk of stroke than patients with AVE. Fifty-two percent of patients died within 1 year of admission for IE.

Prognostic Factors in 61 Cases of Staphylococcus aureus Prosthetic Valve Infective Endocarditis from the International Collaboration on Endocarditis Merged Database

Staphylococcus aureus prosthetic valve infective endocarditis (SA-PVIE) is associated with a high mortality rate, but prognostic factors have not been clearly elucidated. The International Collaboration on Endocarditis merged database (ICE-MD) contained 2212 cases of definite infective endocarditis (as defined using the Duke criteria), 61 of which were SA-PVIE. Overall mortality rate was 47.5%, stroke was associated with an increased risk of death, and early valve replacement was not associated with a significant survival benefit in the whole population; however, patients who developed cardiac complications and underwent early valve replacement had the lowest mortality rate (28.6%).

Emergence of endocarditis due to group D streptococci: findings derived from the merged database of the International Collaboration on Endocarditis

The aim of the present study was to compare the epidemiological and clinical characteristics of Streptococcus bovis endocarditis with those of endocarditis caused by oral streptococci, using data obtained from a large international database of uniformly defined cases of infective endocarditis. S. bovis, a well-known cause of infective endocarditis, remains the common name used to designate group D nonenterococcal streptococci. In some countries, the frequency of S. bovis endocarditis has increased significantly in recent years. Data from the International Collaboration on Endocarditis merged database was used to identify the main characteristics of S. bovis endocarditis and compared them with those of infective endocarditis (IE) due to oral streptococci. The database contained 136 cases of S. bovis IE and 511 cases of IE due to oral streptococci. Patients with S. bovis IE were significantly older those with IE due to oral streptococci (63±16 vs. 55±18 years, P<0.00001). The proportion of streptococcal IE due to S. bovis increased from 10.9% before 1989 to 23.3% after 1989 (P=0.0007) and was 56.7% in France as compared with 9.4% in the rest of Europe and 6.0% in the USA (P<0.00001). Patients with S. bovis IE had more comorbidity and never used intravenous drugs. Complication rates, rates of valve replacement, and mortality rates were similar in the two groups. In conclusion, this study confirmed that S. bovis IE has unique characteristics when compared to endocarditis due to oral streptococci and that it emerged in the 1990s, mainly in France, a finding that is yet unexplained.

Enterococcal prosthetic valve infective endocarditis: report of 45 episodes from the International Collaboration on Endocarditis-merged database

Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20% vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics, mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers in this study.

Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database

Infective endocarditis due to coagulase-negative staphylococci is increasingly recognized as a difficult-to-treat disease associated with poor outcome. The aim of this report is to describe the characteristics and outcome of patients with prosthetic valve endocarditis (PVE) due to coagulase-negative staphylococci versus those of patients with PVE due to Staphylococcus aureus and viridans streptococci. Patients were identified through the International Collaboration on Endocarditis Merged Database. A total of 54 cases of coagulase-negative staphylococci PVE, 58 cases of S. aureus PVE, and 63 cases of viridans-streptococci-related PVE were available for analysis. There was no difference between the three groups with respect to the type of valve involved or the rate of embolization. However, heart failure was encountered more frequently with coagulase-negative staphylococci (54%) than with either S. aureus (33%; p=0.03) or viridans streptococci (32%; p=0.02). In addition, valvular abscesses complicated 39% of infections due to coagulase-negative staphylococci compared with 22% of those due to S. aureus (p=0.06) and 6% of those due to viridans streptococci (p<0.001). Mortality was highest in patients with S. aureus and coagulase-negative staphylococcal endocarditis (47 and 36%, respectively; p=0.22) and was considerably lower in patients with viridans streptococcal endocarditis (p=0.002 compared to patients with coagulase-negative staphylococcal endocarditis). The results of this analysis demonstrate the aggressive nature of coagulase-negative staphylococcal PVE and the substantially greater morbidity and mortality associated with this infection compared to PVE caused by other pathogens.

Risk Factors for Infective Endocarditis in Patients with Enterococcal Bacteremia: A Case-Control Study

Abstract.Background:Based on previous studies, enterococcal infective endocarditis (IE) is considered a unimicrobial, community-acquired disease of older Caucasian men.Patients and Methods:We evaluated the relationship between enterococcal bacteremia and IE by comparing clinical and demographic characteristics of all cases of enterococcal IE within an 8-year period (n = 41) with controls randomly chosen from patients with enterococcal bacteremia without IE.Results:By univariate and multivariable analyses, the presence of a prosthetic valve (PV) and infection with Enterococcus faecalis were significantly associated with IE, while age, gender, race, polymicrobial infection and community-acquired infection were not. Almost an equal number of women and men had enterococcal IE. Cases of enterococcal IE were commonly nosocomial (39%) and polymicrobial (17%).Conclusions:Enterococcal endocarditis can no longer be considered exclusively a unimicrobial, community-acquired disease of Caucasian men. Instead, our data suggest that the presence of a PV and infection by E. faecalis are associated with an increased risk for IE.

Coagulase-negative staphylococcal prosthetic valve endocarditis—a contemporary update based on the International Collaboration on Endocarditis: prospective cohort study

Objective: To describe the contemporary features of coagulase-negative staphylococcal (CoNS) prosthetic valve endocarditis (PVE). Design: Observational study of prospectively collected data from a multinational cohort of patients with infective endocarditis. Patients with CoNS PVE were compared to patients with Staphylococcus aureus and viridans streptococcal (VGS) PVE. Setting: The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) is a contemporary cohort of patients with infective endocarditis from 61 centres in 28 countries. Patients: Adult patients in the ICE-PCS with definite PVE and no history of injecting drug use from June 2000 to August 2005 were included. Interventions: None. Main outcome measures: Heart failure, intracardiac abscess, death. Results: CoNS caused 16% (n = 86) of 537 cases of definite non-injecting drug use-associated PVE. Nearly one-half (n = 33/69, 48%) of patients with CoNS PVE presented between 60 days and 365 days of valve implantation. The rate of intracardiac abscess was significantly higher in patients with CoNS PVE (38%) than in patients with either S aureus (23%, p = 0.03) or VGS (20%, p = 0.05) PVE. The rate of abscess was particularly high in early (50%) and intermediate (52%) CoNS PVE. In-hospital mortality was 24% for CoNS PVE, 36% for S aureus PVE (p = 0.09) and 9.1% for VGS PVE (p = 0.08). Meticillin resistance was present in 68% of CoNS strains. Conclusions: Nearly one-half of CoNS PVE cases occur between 60 days and 365 days of prosthetic valve implantation. CoNS PVE is associated with a high rate of meticillin resistance and significant valvular complications.

Staphylococcus aureus bacteremia in the surgical patient: a prospective analysis of 73 postoperative patients who developed Staphylococcus aureus bacteremia at a tertiary care facility

BACKGROUND Staphylococcus aureus is a frequent cause of infection and bacteremia in the postoperative patient. Unfortunately, there have been no prospective studies evaluating these patients, so the incidence of complications, subsequent treatment algorithms, and prognosis remain undefined. The objectives of this prospective study of postoperative Staphylococcus aureus bacteremia (SAB) were to define the primary sources of bacteremia and to identify the common complications of SAB in the postoperative setting. METHODS A registry was developed into which 309 consecutive adult patients with SAB were prospectively enrolled between September 1994 and December 1996. Seventy-three of these patients (23.6%) developed SAB in the postoperative setting. RESULTS Analysis of the clinical features of these 73 postoperative patients revealed three important results. First, infective endocarditis is surprisingly common in postoperative patients with SAB and the classical stigmata of endocarditis are often absent. Transesophageal echocardiography was performed in 31 of 73 patients; 10 of these patients (32.3%) met Duke Criteria for definite endocarditis, but only 3 of these patients had vegetations detected by transthoracic echocardiography, and only 2 patients had peripheral stigmata of infective endocarditis. Second, the development of SAB after cardiothoracic surgery was strongly associated with underlying S. aureus mediastinitis. Twenty-one of the 23 patients who developed SAB after median sternotomy had mediastinitis (positive predictive value 91.3%). In many cases, the diagnosis of mediastinitis was not apparent when SAB was detected. Third, complications, relapses, and mortality were high in postoperative patients with SAB. Fourteen of 73 patients (19.2%) developed multiple noncardiac metastatic complications, including metastatic abscesses (5), septic emboli (3), pneumonia or empyema (2), septic arthritis (1), epidural abscess (1), and other metastatic foci (7). Twelve of 73 patients (16.4%) had recurrent staphylococcal infection after treatment of their first episode of SAB, including 8 patients (11.0%) with recurrent bacteremia. Of patients who survived, those with recurrent staphylococcal infection were more likely to have an infected surgical wound than were patients who were cured of infection (p = 0.05). Finally, mortality attributable to SAB (11.0%), and all-cause mortality (21.9%), was high. CONCLUSIONS SAB in the postoperative setting is often a severe disease with high morbidity and mortality. A thorough diagnostic evaluation is indicated in surgical patients with S. aureus bacteremia to ensure the early detection of metastatic infections such as infective endocarditis and to define foci such as mediastinitis re quiring surgical intervention.