Incidence, Predictors, and Outcomes of Endocarditis After Transcatheter Aortic Valve Replacement in the United States.

OBJECTIVES: This study sought to evaluate the incidence and outcomes of endocarditis after transcatheter aortic valve replacement (TAVR). BACKGROUND: Data about endocarditis after TAVR are limited. METHODS: The study investigated Medicare patients who underwent TAVR from 2012 to 2017 and identified patients admitted with endocarditis during follow-up using a validated algorithm. The main study outcome was all-cause mortality. RESULTS: Of 134,717 patients who underwent TAVR, 1868 patients developed endocarditis during follow-up (incidence 0.87%/year), with majority of infections (65.0%) occurring within 1 year. Incidence of endocarditis declined in recent years. The most common organisms were Staphylococcus (22.0%), Streptococcus (20.0%), and Enterococcus (15.5%). Important predictors for endocarditis were younger age at TAVR, male sex, prior endocarditis, end-stage renal disease, repeat TAVR procedures, liver and lung disease, and post-TAVR acute kidney injury. Thirty-day and 1-year mortality were 18.5% and 45.6%, respectively. After adjusting for comorbidities and procedural complications, endocarditis after TAVR was associated with 3-fold higher risk of mortality (44.9 vs. 16.2 deaths per 100 person-years; adjusted hazard ratio [aHR]: 2.94; 95% confidence interval [CI]: 2.77 to 3.12; p < 0.0001). End-stage renal disease (aHR: 2.12; 95% CI: 1.72 to 2.60), endocarditis complicated by cardiogenic shock (aHR: 2.50, 95% CI: 1.56 to 4.02), ischemic stroke (aHR: 1.56; 95% CI: 1.07 to 2.28), intracerebral hemorrhage (aHR: 1.67; 95% CI: 1.01 to 2.76), acute kidney injury (aHR: 1.44; 95% CI: 1.27 to 1.63), blood transfusion (aHR: 1.28; 95% CI: 1.09 to 1.50), staphylococcal (aHR: 1.71; 95% CI: 1.49 to 1.97), and fungal endocarditis (aHR: 1.72; 95% CI: 1.23 to 2.39) (p < 0.05 for all) portended higher mortality following endocarditis. CONCLUSIONS: The incidence of endocarditis after TAVR is low and declining. However, it is associated with poor prognosis with one-half the patients dying within 1 year.

National Public Health Burden Estimates of Endocarditis and Skin and Soft-Tissue Infections Related to Injection Drug Use: A Review.

BACKGROUND: Despite concerns about the burden of the bacterial and fungal infection syndromes related to injection drug use (IDU), robust estimates of the public health burden of these conditions are lacking. The current article reviews and compares data sources and national burden estimates for infective endocarditis (IE) and skin and soft-tissue infections related to IDU in the United States. METHODS: A literature review was conducted for estimates of skin and soft-tissue infection and endocarditis disease burden with related IDU or substance use disorder terms since 2011. A range of the burden is presented, based on different methods of obtaining national projections from available data sources or published data. RESULTS: Estimates using available data suggest the number of hospital admissions for IE related to IDU ranged from 2900 admissions in 2013 to more than 20 000 in 2017. The only source of data available to estimate the annual number of hospitalizations and emergency department visits for skin and soft-tissue infections related to IDU yielded a crude estimate of 98 000 such visits. Including people who are not hospitalized, a crude calculation suggests that 155 000-540 000 skin infections related to IDU occur annually. DISCUSSION: These estimates carry significant limitations. However, regardless of the source or method, the burden of disease appears substantial, with estimates of thousands of episodes of IE among persons with IDU and at least 100 000 persons who inject drugs (PWID) with skin and soft-tissue infections annually in the United States. Given the importance of these types of infections, more robust and reliable estimates are needed to better quantitate the occurrence and understand the impact of interventions.

Reevaluation of the impact of methicillin-resistance on outcomes in patients with Staphylococcus aureus bacteremia and endocarditis.

BACKGROUND/AIMS: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals, and has recently emerged in the community. The impact of methicillin-resistance on mortality and medical costs for patients with S. aureus bacteremia (SAB) requires reevaluation. METHODS: We searched studies with SAB or endocarditis using electronic databases including Ovid-Medline, Embase-Medline, and Cochrane Library, as well as five local databases for published studies during the period January 2000 to September 2011. RESULTS: A total of 2,841 studies were identified, 62 of which involved 17,563 adult subjects and were selected as eligible. A significant increase in overall mortality associated with MRSA, compared to that with methicillin-susceptible S. aureus (MSSA), was evidenced by an odds ratio (OR) of 1.95 (95% confidence interval [CI], 1.73 to 2.21; p < 0.01). In 13 endocarditis studies, MRSA increased the risk of mortality, with an OR of 2.65 (95% CI, 1.46 to 4.80). When three studies, which compared mortality rates between CA-MRSA and CA-MSSA, were combined, the risk of methicillin-resistance increased 3.23-fold compared to MSSA (95% CI, 1.25 to 8.34). The length of hospital stay in the MRSA group was 10 days longer than that in the MSSA group (95% CI, 3.36 to 16.70). Of six studies that reported medical costs, two were included in the analysis, which estimated medical costs to be $9,954.58 (95% CI, 8,951.99 to 10,957.17). CONCLUSION: MRSA is still associated with increased mortality, longer hospital stays and medical costs, compared with MSSA in SAB in studies published since the year 2000.

Long-term outcome for the surgical treatment of infective endocarditis with a focus on intravenous drug users.

BACKGROUND: We reviewed our experience with surgical procedures for infective endocarditis (IE) in order to evaluate modern outcomes and objectively examine our institutional preferences, including the use of bioprostheses in intravenous drug users (IVDUs) regardless of age and prompt surgical intervention in patients with either septic cerebral emboli or active infection. METHODS: Review of medical records was conducted from February 1999 to November 2010. The Social Security Death Index was used to determine death from any cause in the postoperative period. Hospital records were used to identify infectious complications, recurrent endocarditis, and reoperation. RESULTS: Sixty-four patients were identified as IVDUs and 133 patients as non-IVDUs. Survival at 30 days, 1 year, 5 years, and 10 years for IVDUs and non-IVDUs was 91.2% versus 93.6%, 77.5% versus 83.0%, 46.7% versus 71.1%, and 41.1% versus 52.0%, respectively. Cox regression analysis identified intravenous drug use as an independent risk factor for diminished survival (p=0.03), although not for reoperation (p=0.95) despite 95.3% of IVDUs receiving bioprostheses versus 73.7% of non-IVDUs (p=0.0002, Fisher's exact test). Forty-three patients were identified as having preoperative septic cerebral emboli; none had a perioperative hemorrhagic event. Active infection approached significance as an independent risk factor for the composite end point of recurrent IE and perioperative infection (odds ratio 2.8; 95% confidence interval, 0.777 to 10.9; p=0.12, Fisher's exact test). CONCLUSIONS: Bioprostheses are reasonable for IVDUs undergoing valve replacement for IE regardless of age. Prompt surgical intervention in the setting of septic cerebral emboli is justified; in the setting of active infection it is less clear.

Outcomes and costs associated with a history of vancomycin exposure in patients with MRSA-related complicated bacteremia and infective endocarditis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the primary cause of complicated bacteremia (CB) and infective endocarditis (IE). Studies have compared the costs of treatment with vancomycin to those of other agents, as well as the efficacy and tolerability of these treatments. However, a literature search found no published studies of the effects of vancomycin exposure on outcomes and hospital costs in patients with CB or IE due to MRSA. OBJECTIVE: The aim of this study was to determine whether there is a quantitative relationship between the duration of vancomycin treatment or cumulative vancomycin exposure and outcomes or costs in patient with CB or IE due to MRSA. METHODS: Electronic medical records of confirmed cases of MRSA-related CB or IE from July 1, 2006, to June 30, 2008, were retrospectively reviewed to identify patients with a history of vancomycin exposure or no vancomycin exposure. Those who received vancomycin were stratified by the amount of drug administered or the duration of treatment to determine the relationship between treatment and outcomes. Data collected included demographic information, treatment information, attributable mortality, MIC data, and hospital costs. Classification and regression tree analysis (CART) was used to determine whether a history of vancomycin exposure was associated with treatment failure, attributable mortality, or both. The Mann-Whitney U test and the Fisher exact test were used for univariate analyses, and logistic regression was used for multivariate modeling. RESULTS: Data from 50 patients were evaluated (CB, 32; IE, 18). Overall rates of failure and attributable mortality were 32% and 16%, respectively. No significant differences were observed between the variables and costs. The CART break points for failure were ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years; for attributable mortality, the CART break points were ≥45 g and ≥31 days. In the final multivariate model for failure, ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years were predictors of failure (both, P = 0.002). Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.04), ≥45 g (P = 0.002), and ≥31 days of treatment (P = 0.002) in the previous 3 years were predictors of attributable mortality after adjustment for all covariates. CONCLUSIONS: Using the present model, cumulative vancomycin amount and duration were associated with attributable mortality and clinical failure but not with costs.

Epidemiologic features of infective endocarditis in Taiwanese adults involving native valves.

Little is known about the incidence and clinical outcomes of infective endocarditis (IE) involving native valves in Asian countries. This nationwide study investigated epidemiologic features and in-hospital mortality associated with IE in adults (age > or =18 years) based on Taiwan's National Health Insurance database from 1997 through 2002. Of 7,240 enrolled patients with IE involving native valves, the mean age was 53 +/- 19 years and 70% were men. The mean annual crude incidence was 7.6 per 100,000 inhabitants. The incidence was significantly higher in men than in women (10.4 vs 4.6 per 100,000; p <0.001). The incidence of IE increased steadily with age, ranging from 3.8 per 100,000 persons in patients <30 years of age to 33 per 100,000 persons in patients > or =80 years of age (p <0.001). Staphylococcal (32%) and streptococcal species (61%) were the most common causative pathogens. The mean in-hospital mortality rate was 18%. Multivariate analysis showed that male gender, older age (> or =50 years), diabetes mellitus, heart failure, neurologic complications, renal insufficiency, respiratory failure, shock, and Staphylococcus species as the causative microorganism were independent predictors of in-hospital mortality. In conclusion, this Taiwanese study revealed a high incidence of IE in men and elderly subjects. The in-hospital mortality rate remained high. Patients with IE who also developed shock and respiratory failure were the most likely to have a poor outcome.

Surgical management of infective endocarditis: early predictors of short-term morbidity and mortality.

BACKGROUND: Infective endocarditis is a diagnostic and therapeutic challenge that ultimately requires surgical intervention in 20% of all cases. Early determinants of morbidity and mortality in this high risk population are not well described. METHODS: The aim of this study was to determine preoperative clinical, microbiological, electrocardiographic, and echocardiographic variables that predicted the need for permanent pacemaker implantation and in-hospital death in a surgical cohort of patients with active infective endocarditis. RESULTS: We identified 91 patients (61 males and 30 females, mean age 58 +/- 16 years) who underwent surgical intervention for active culture-positive infective endocarditis as defined by the Duke criteria. Native valve infective endocarditis was present in 78 (85.7%) and prosthetic valve endocarditis in 13 (14.3%) of cases. The aortic valve was infected in 61 (67.0%), the mitral in 35 (38.5%), and multiple valves in 8 patients (8.8%). The most common indication for surgical intervention was intractable heart failure. Twenty-two patients (24.2%) required pacemakers, while there were 14 (15.4%) in-hospital deaths. In age-adjusted and gender-adjusted analyses, the presence of left bundle branch block on preoperative electrocardiogram (ECG) and presence of depressed left ventricular systolic function (ejection fraction [EF] < 50%) predicted the need for a permanent pacemaker implantation, while the presence of depressed left ventricular function predicted in-hospital mortality. CONCLUSIONS: Preoperative ECG findings of left bundle branch block and reduced left ventricular function may allow for early risk stratification of this high risk population.

Is antibiotic prophylaxis for bacterial endocarditis cost-effective?

BACKGROUND: Antibiotic prophylaxis for bacterial endocarditis is recommended by the American Heart Association (AHA) before undergoing certain dental procedures. Whether such antibiotic prophylaxis is cost-effective is not clear. The authors' objective is to estimate the cost-effectiveness of predental antibiotic prophylaxis in patients with underlying heart disease. METHODS: The authors conducted a cost-effectiveness analysis using a Markov model to compare cost-effectiveness of 7 antibiotic regimens per AHA guidelines and a no prophylaxis strategy. The study population consisted of a hypothetical cohort of 10 million patients with either a high or moderate risk for developing endocarditis. RESULTS: Prophylaxis for patients with moderate or high risk for endocarditis cost $88,007/quality-adjusted life years saved if clarithromycin was used. Prophylaxis with amoxicillin and ampicillin resulted in a net loss of lives. All other regimens were less cost-effective than clarithromycin. For 10 million persons, clarithromycin prophylaxis prevented 119 endocarditis cases and saved 19 lives. CONCLUSION: Predental antibiotic prophylaxis is cost-effective only for persons with moderate or high risk of developing endocarditis. Contrary to current recommendations, our data demonstrate that amoxicillin and ampicillin are not cost-effective and should not be considered the agents of choice. Clarithromycin should be considered the drug of choice and cephalexin as an alternative drug of choice. The current published guidelines and recommendations should be revised.

[Infective endocarditis in patients with chronic liver disease: clinical and prognostic assessment]. / Endocarditis infecciosa en pacientes con hepatopatía crónica: valoración clínica y pronóstica.

INTRODUCTION AND OBJECTIVES: Chronic liver disease increases the susceptibility to bacterial infections and infective endocarditis. Our aim was to determine the clinical and microbiological features and the prognosis in patients with chronic liver disease who also had infective endocarditis. PATIENTS AND METHOD: One hundred and seventy-four consecutive inpatients at our institution were recruited and followed. Thirty of them had chronic liver disease. Clinical, microbiological and echocardiographic variables were analyzed and, in some cases, histological variables were also recorded. RESULTS: Patients with chronic liver disease were younger (36 11 vs 54 18 years; p < 0.01) and had a larger proportion of intravenous drug users (73 vs 16%; p < 0.01), HIV infection (47 vs 10%; p < 0.01), right valve involvement and spleen enlargement, but heart failure appeared less often (7 vs 34%; p = 0.003). Thirty percent of the patients with and 51% of patients without chronic liver disease underwent surgery for infective endocarditis. Total mortality among patients with and without chronic liver disease was 40% and 31%, respectively. After adjustment for age and for the incidence of congestive heart failure, chronic liver disease doubled mid-term mortality with a RR = 2.45 (p = 0.015). CONCLUSIONS: Chronic liver disease has a significant impact on the prognosis in patients with infective endocarditis, and these patients should therefore be considered a high risk group.

Is there a role for surgery in the acute management of infective endocarditis? A decision analysis and medical claims database approach.

In the absence of good clinical evidence from a randomized trial, the authors performed a decision analysis to determine the potential value of early elective surgery (OPNOW) for patients with left-sided Staphylococcus aureus infective endocarditis. Initial impressions (before performance of decision analysis) and initial runs at the formal models using probability estimates derived from clinicians suggested that OPNOW (i.e., within a few days of starting antibiotics) offered no advantage over attempted medical cure (WAIT) (life expectancy: WAIT = 325 weeks; OPNOW = 255 weeks). Extensive sensitivity analyses identified critical variables that needed further empirical estimation. The Manitoba Health Services Commission database identified 127 incident cases of endocarditis between April 1, 1979, and March 31, 1985, enabling estimation of values for these critical variables. With these estimates, the early surgery strategy appeared much better than the previous analyses had suggested (life expectancy: WAIT = 208 weeks, OPNOW = 256 weeks). The authors believe that this approach of combining decision analysis with medical claims databases is useful as an alternative or precursor to randomized trials, especially where the resource requirements and logistic difficulties of performing randomized trials are great.

The impact of a policy of collaborative management on mortality and morbidity from infective endocarditis.

The present study represents a comprehensive retrospective review of endocarditis in a large district general hospital since the inception of a formalized policy involving collaborative management a decade ago. The principle was to involve a recognised team of cardiologists, specialists in infectious disease and microbiologists in the treatment of the disease from the moment of its diagnosis. The pattern of infection has not altered in terms of prevalent organisms and valves infected since the change in management policy. There has, however, been a significant decline in the mortality, from 34 to 24% for all patients with endocarditis. Amongst those referred for collaborative management, the mortality has fallen to 6%. The single greatest improvement is a reduction in the number of patients dying of heart failure, the number of patients developing systemic emboli or requiring prosthetic valve replacement remaining unchanged. The results indicate that early referral to, and treatment by, a multidisciplinary team can significantly reduce the mortality from bacterial endocarditis.

Indications for cardiac surgery in patients with active infective endocarditis.

Currently, absolute indications for valve replacement during active infective endocarditis include severe heart failure, the presence of an infecting microorganism that is not susceptible to available antimicrobial agents, and, in patients with an infected prosthetic valve, an unstable device. Relative indications include an etiologic microorganism other than a susceptible Streptococcus, relapse after presumed effective therapy, evidence of intracardiac extension of the infection, two or more systemic emboli, vegetations large enough to be demonstrated by echocardiography, and, in patients with an infected prosthetic device, early disease and periprosthetic leak. With use of data from the medical literature, a study generated by the cardiovascular surgical group at the University of Alabama School of Medicine, and a brief cost analysis, a point system was constructed to assist in decision-making concerning surgery in patients with active infective endocarditis. The usefulness of this system will depend on experience generated from its utilization in a larger number of patients as well as new data relative to a more complete understanding of the risks and benefits of surgery in this condition.

Current issues in prevention of infective endocarditis.

Prevention of infective endocarditis continues to concern health care providers in many specialties. The well-known lack of primary clinical trials in this area is not expected to change. Therefore, the evolution of recommendations and practice must be based on theoretic considerations and continuing assessment of secondary sources of information. Recent developments include a report of 52 cases in which antibiotic prophylaxis for infective endocarditis was attempted but appeared to fail. Most of these patients had undergone dental procedures after oral penicillin prophylaxis, with subsequent development of streptococcal endocarditis. In two thirds, the organism was sensitive to the antibiotic used. Notably, the most common underlying cardiac lesion among these patients was mitral valve prolapse. However, two recent independent analyses have concluded that providing endocarditis prophylaxis for all patients with mitral valve prolapse during procedures that might cause bacteremia would not be cost-effective. This is primarily because mitral valve prolapse is common and endocarditis is relatively rare, resulting in an adverse risk-benefit ratio. Parenteral prophylaxis for mitral valve prolapse might even cause a net loss of life from anaphylaxis. On the other hand, for the individual patient or physician, the reassurance provided by attempted prophylaxis with oral penicillin can be purchased at low cost and low risk. Very few cases of infective endocarditis have been reported after gastrointestinal and other endoscopic procedures; most of these do not need antibiotic coverage. Prophylactic antibiotics should be restricted to those situations in which both the procedure and the underlying cardiac condition seem to pose significant risk, for example, endoscopic sclerotherapy of esophageal varices in patients with prosthetic heart valves. Newly revised recommendations have been issued by the Medical Letter, the American Heart Association, and the American Dental Association. These regimens are shorter and simpler than earlier versions.

[Infectious endocarditis of the heart valves and valvular prostheses. report of 21 cases]. / Endocarditis infecciosa de válvulas cardíacas y prótesis valvulares. reporte de 21 casos.

During 1978, and 1979, the Surgery Division of The Cardiology and Pneumology Hospital of The National Medical Center (Mexican Institute for Social Security), studied and treated surgically twenty one cases -- in twenty patients -- of infectious endocarditis. Nine patients had an active infection in the heart valves and twelve in the prosthesis. The survival rate of the first group was 88.88% and of the second group 58.33%. The causes of death were due to the hemodynamic damage that the valvular or prosthetic dysfunction leads to, when there is a delay in the arrival of the patient to a medical unit of third level. The conventional medical treatment applicable to a reduced number of cases whose characteristics are discussed do not operate when dealing with patients with infected prosthesis or valve infections caused by non-gram positive bacteria. We conclude that this problem demands a better approach, principally surgical, to improve the prognosis of these patients.