Recent Insights Into Native Valve Infective Endocarditis: JACC Focus Seminar 4/4.

This focused review highlights the latest issues in native valve infective endocarditis. Native valve disease moderately increases the risk of developing infective endocarditis. In 2023, new diagnostic criteria were published by the Duke-International Society of Cardiovascular Infectious Diseases group. New pathogens were designated as typical, and findings on computed tomography imaging were included as diagnostic criteria. It is now recognized that a multidisciplinary approach to care is vital, and the role of an "endocarditis team" is highlighted. Recent studies have suggested that a transition from intravenous to oral antibiotics in selected patients may be reasonable, and the role of long-acting antibiotics is discussed. It is also now clear that an aggressive surgical approach can be life-saving in some patients. Finally, results of several recent studies have suggested there is an association between dental and other invasive procedures and an increased risk of developing infective endocarditis. Moreover, data indicate that antibiotic prophylaxis may be effective in some scenarios.

Nondental Invasive Procedures and Risk of Infective Endocarditis: Time for a Revisit: A Science Advisory From the American Heart Association.

There have been no published prospective randomized clinical trials that have: (1) established an association between invasive dental and nondental invasive procedures and risk of infective endocarditis; or (2) defined the efficacy and safety of antibiotic prophylaxis administered in the setting of invasive procedures in the prevention of infective endocarditis in high-risk patients. Moreover, previous observational studies that examined the association of nondental invasive procedures with the risk of infective endocarditis have been limited by inadequate sample size. They have typically focused on a few potential at-risk surgical and nonsurgical invasive procedures. However, recent investigations from Sweden and England that used nationwide databases and demonstrated an association between nondental invasive procedures, and the subsequent development of infective endocarditis (in particular, in high-risk patients with infective endocarditis) prompted the development of the current science advisory.

Antibiotic prophylaxis for patients at risk of infective endocarditis: an increasing evidence base?

Around 100 years ago, the first link between infective endocarditis (IE) and dental procedures was hypothesised; shortly after, physicians began to use antibiotics in an effort to reduce the risk of developing IE. Whether invasive dental procedures are linked to the development of IE, and antibiotic prophylaxis (AP) is effective, have since remained topics of controversy. This controversy, in large part, has been due to the lack of prospective randomised clinical trial data. From this suboptimal position, guideline committees representing different societies and countries have struggled to reach an optimal position on whether AP use is needed for invasive dental procedures (or other procedures) and in whom. We present the findings from an investigation involving a large US patient database, published earlier this year, by Thornhill and colleagues. The work featured the use of both a cohort and case-crossover design and demonstrated there was a significant temporal association between invasive dental procedures and development of IE in high-IE-risk patients. Furthermore, the study showed that AP use was associated with a reduced risk of IE. Additional data, also published this year, from a separate study using nationwide hospital admissions data from England by Thornhill's group, showed that certain dental and non-dental procedures were significantly associated with the subsequent development of IE. Two other investigations have reported similar concerns for non-dental invasive procedures and risk of IE. Collectively, the results of this work support a re-evaluation of the current position taken by the National Institute for Health and Care Excellence (NICE) and other organisations that are responsible for publishing practice guidelines.

Endocarditis, invasive dental procedures, and antibiotic prophylaxis efficacy in US Medicaid patients.

OBJECTIVE: Antibiotic prophylaxis is recommended before invasive dental procedures to prevent endocarditis in those at high risk, but supporting data are sparse. We therefore investigated any association between invasive dental procedures and endocarditis, and any antibiotic prophylaxis effect on endocarditis incidence. SUBJECTS AND METHODS: Cohort and case-crossover studies were performed on 1,678,190 Medicaid patients with linked medical, dental, and prescription data. RESULTS: The cohort study identified increased endocarditis incidence within 30 days of invasive dental procedures in those at high risk, particularly after extractions (OR 14.17, 95% CI 5.40-52.11, p < 0.0001) or oral surgery (OR 29.98, 95% CI 9.62-119.34, p < 0.0001). Furthermore, antibiotic prophylaxis significantly reduced endocarditis incidence following invasive dental procedures (OR 0.20, 95% CI 0.06-0.53, p < 0.0001). Case-crossover analysis confirmed the association between invasive dental procedures and endocarditis in those at high risk, particularly following extractions (OR 3.74, 95% CI 2.65-5.27, p < 0.005) and oral surgery (OR 10.66, 95% CI 5.18-21.92, p < 0.0001). The number of invasive procedures, extractions, or surgical procedures needing antibiotic prophylaxis to prevent one endocarditis case was 244, 143 and 71, respectively. CONCLUSIONS: Invasive dental procedures (particularly extractions and oral surgery) were significantly associated with endocarditis in high-risk individuals, but AP significantly reduced endocarditis incidence following these procedures, thereby supporting current guideline recommendations.

Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures.

BACKGROUND: Antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) is recommended to prevent infective endocarditis (IE) in those at high IE risk, but there are sparse data supporting a link between IDPs and IE or AP efficacy in IE prevention. OBJECTIVES: The purpose of this study was to investigate any association between IDPs and IE, and the effectiveness of AP in reducing this. METHODS: We performed a case-crossover analysis and cohort study of the association between IDPs and IE, and AP efficacy, in 7,951,972 U.S. subjects with employer-provided Commercial/Medicare-Supplemental coverage. RESULTS: Time course studies showed that IE was most likely to occur within 4 weeks of an IDP. For those at high IE risk, case-crossover analysis demonstrated a significant temporal association between IE and IDPs in the preceding 4 weeks (OR: 2.00; 95% CI: 1.59-2.52; P = 0.002). This relationship was strongest for dental extractions (OR: 11.08; 95% CI: 7.34-16.74; P < 0.0001) and oral-surgical procedures (OR: 50.77; 95% CI: 20.79-123.98; P < 0.0001). AP was associated with a significant reduction in IE incidence following IDP (OR: 0.49; 95% CI: 0.29-0.85; P = 0.01). The cohort study confirmed the associations between IE and extractions or oral surgical procedures in those at high IE risk and the effect of AP in reducing these associations (extractions: OR: 0.13; 95% CI: 0.03-0.34; P < 0.0001; oral surgical procedures: OR: 0.09; 95% CI: 0.01-0.35; P = 0.002). CONCLUSIONS: We demonstrated a significant temporal association between IDPs (particularly extractions and oral-surgical procedures) and subsequent IE in high-IE-risk individuals, and a significant association between AP use and reduced IE incidence following these procedures. These data support the American Heart Association, and other, recommendations that those at high IE risk should receive AP before IDP.

Infective endocarditis following invasive dental procedures: IDEA case-crossover study.

BACKGROUND: Infective endocarditis is a heart infection with a first-year mortality rate of ≈ 30%. It has long been thought that infective endocarditis is causally associated with bloodstream seeding with oral bacteria in ≈ 40-45% of cases. This theorem led guideline committees to recommend that individuals at increased risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. However, to the best of our knowledge, there has never been a clinical trial to prove the efficacy of antibiotic prophylaxis and there is no good-quality evidence to link invasive dental procedures with infective endocarditis. Many contend that oral bacteria-related infective endocarditis is more likely to result from daily activities (e.g. tooth brushing, flossing and chewing), particularly in those with poor oral hygiene. OBJECTIVE: The aim of this study was to determine if there is a temporal association between invasive dental procedures and subsequent infective endocarditis, particularly in those at high risk of infective endocarditis. DESIGN: This was a self-controlled, case-crossover design study comparing the number of invasive dental procedures in the 3 months immediately before an infective endocarditis-related hospital admission with that in the preceding 12-month control period. SETTING: The study took place in the English NHS. PARTICIPANTS: All individuals admitted to hospital with infective endocarditis between 1 April 2010 and 31 March 2016 were eligible to participate. INTERVENTIONS: This was an observational study; therefore, there was no intervention. MAIN OUTCOME MEASURE: The outcome measure was the number of invasive and non-invasive dental procedures in the months before infective endocarditis-related hospital admission. DATA SOURCES: NHS Digital provided infective endocarditis-related hospital admissions data and dental procedure data were obtained from the NHS Business Services Authority. RESULTS: The incidence rate of invasive dental procedures decreased in the 3 months before infective endocarditis-related hospital admission (incidence rate ratio 1.34, 95% confidence interval 1.13 to 1.58). Further analysis showed that this was due to loss of dental procedure data in the 2-3 weeks before any infective endocarditis-related hospital admission. LIMITATIONS: We found that urgent hospital admissions were a common cause of incomplete courses of dental treatment and, because there is no requirement to record dental procedure data for incomplete courses, this resulted in a significant loss of dental procedure data in the 2-3 weeks before infective endocarditis-related hospital admissions. The data set was also reduced because of the NHS Business Services Authority's 10-year data destruction policy, reducing the power of the study. The main consequence was a loss of dental procedure data in the critical 3-month case period of the case-crossover analysis (immediately before infective endocarditis-related hospital admission), which did not occur in earlier control periods. Part of the decline in the rate of invasive dental procedures may also be the result of the onset of illness prior to infective endocarditis-related hospital admission, and part may be due to other undefined causes. CONCLUSIONS: The loss of dental procedure data in the critical case period immediately before infective endocarditis-related hospital admission makes interpretation of the data difficult and raises uncertainty over any conclusions that can be drawn from this study. FUTURE WORK: We suggest repeating this study elsewhere using data that are unafflicted by loss of dental procedure data in the critical case period. TRIAL REGISTRATION: This trial is registered as ISRCTN11684416. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 28. See the NIHR Journals Library website for further project information.

Infective endocarditis is a life-threatening infection of the heart valves. Most people are at low risk of infective endocarditis. However, those with certain cardiac conditions are at moderate risk of infective endocarditis, and those with artificial or repaired heart valves, a history of infective endocarditis and certain congenital heart conditions are at high risk of infective endocarditis. In around 40­45% of cases, oral bacteria are the cause of infective endocarditis. For many years, those people at moderate or high risk of infective endocarditis were given antibiotics (antibiotic prophylaxis) before invasive dental procedures such as extractions to reduce the risk of infective endocarditis. There is no good-quality evidence, however, to support the effectiveness of antibiotic prophylaxis, or the link between invasive dental procedures and infective endocarditis. Many believe that the oral bacteria that cause infective endocarditis are more likely to enter the blood during daily activities (e.g. toothbrushing, flossing or chewing), particularly in those with poor oral hygiene, than on the rare occasions when invasive dental procedures are performed. The aim of this study was to link English NHS data on infective endocarditis-related hospital admissions and dental treatments to determine if infective endocarditis is more likely in the weeks immediately after an invasive dental procedure than at any other time. When we linked the data sets and plotted the occurrence of different dental treatments over the year before infective endocarditis-related hospital admission, we detected a problem in the way that dental data were recorded. Unfortunately, there was a failure to collect dental procedure data when courses of treatment were incomplete. As one of the most common reasons for not completing a course of treatment was emergency admission to hospital, this meant that the number of dental procedures recorded decreased in the weeks before any emergency hospital admission. We have attempted to correct for this, but the data loss has affected the data quality. Although the data suggest an association between invasive dental procedures and infective endocarditis in individuals at high risk of infective endocarditis, the certainty of this association has been weakened.

Escalating incidence of infective endocarditis in Europe in the 21st century.

AIM: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe. METHODS: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence. RESULTS: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%. CONCLUSION: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase. TRIAL REGISTERATION NUMBER: CRD42020191196.

Temporal Trends of Infective Endocarditis in North America From 2000 to 2017-A Systematic Review.

BACKGROUND: The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. METHODS: A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. RESULTS: Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. CONCLUSIONS: The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

Prescribing of antibiotic prophylaxis to prevent infective endocarditis.

BACKGROUND: In 2007, the American Heart Association recommended that antibiotic prophylaxis (AP) be restricted to those at high risk of developing complications due to infective endocarditis (IE) undergoing invasive dental procedures. The authors aimed to estimate the appropriateness of AP prescribing according to type of dental procedure performed in patients at high risk, moderate risk, or low or unknown risk of developing IE complications. METHODS: Eighty patients at high risk, 40 patients at moderate risk, and 40 patients at low or unknown risk of developing IE complications were randomly selected from patients with linked dental care, health care, and prescription benefits data in the IBM MarketScan Databases, one of the largest US health care convenience data samples. Two clinicians independently analyzed prescription and dental procedure data to determine whether AP prescribing was likely, possible, or unlikely for each dental visit. RESULTS: In patients at high risk of developing IE complications, 64% were unlikely to have received AP for invasive dental procedures, and in 32 of 80 high-risk patients (40%) there was no evidence of AP for any dental visit. When AP was prescribed, several different strategies were used to provide coverage for multiple dental visits, including multiday courses, multidose prescriptions, and refills, which sometimes led to an oversupply of antibiotics. CONCLUSIONS: AP prescribing practices were inconsistent, did not always meet the highest antibiotic stewardship standards, and made retrospective evaluation difficult. For those at high risk of developing IE complications, there appears to be a concerning level of underprescribing of AP for invasive dental procedures. PRACTICAL IMPLICATIONS: Some dentists might be failing to fully comply with American Heart Association recommendations to provide AP cover for all invasive dental procedures in those at high risk of developing IE complications.

Why are we seeing an increasing incidence of infective endocarditis in the UK?

The increasing incidence of infective endocarditis in England is real, and education is critical to ensure swift diagnosis and best clinical outcomes. Factors responsible remain speculative, but multiple explanations are likely.

Oral antibiotic prescribing by NHS dentists in England 2010-2017.

Introduction Dentists prescribe a significant proportion of all antibiotics, while antimicrobial stewardship aims to minimise antibiotic-prescribing to reduce the risk of developing antibiotic-resistance and adverse drug reactions.Aims To evaluate NHS antibiotic-prescribing practices of dentists in England between 2010-2017.Methods NHS Digital 2010-2017 data for England were analysed to quantify dental and general primary-care oral antibiotic prescribing.Results Dental prescribing accounted for 10.8% of all oral antibiotic prescribing, 18.4% of amoxicillin and 57.0% of metronidazole prescribing in primary care. Amoxicillin accounted for 64.8% of all oral antibiotic prescribing by dentists, followed by metronidazole (28.0%), erythromycin (4.4%), phenoxymethylpenicillin (0.9%), clindamycin (0.6%), co-amoxiclav (0.5%), cephalosporins (0.4%) and tetracyclines (0.3%). Prescriptions by dentists declined during the study period for all antibiotics except for co-amoxiclav. This increase is of concern given the need to restrict co-amoxiclav use to infections where there is no alternative. Dental prescribing of clindamycin, which accounted for 43.9% of primary care prescribing in 2010, accounted for only 14.6% in 2017. Overall oral antibiotic prescribing by dentists fell 24.4% as compared to 14.8% in all of primary care.Conclusions These data suggest dentists have reduced antibiotic prescribing, possibly more than in other areas of primary-care. Nonetheless, opportunities remain for further reduction.

Adverse drug reactions due to oral antibiotics prescribed in the community setting - England.

Background: Prescribing of oral antibiotics in the community setting is commonplace with ongoing efforts to optimize this practice. There are several concerns related to such prescriptions including antibiotic cost, development of bacterial resistance, and associated adverse drug reactions. We therefore performed an analysis of adverse drug reactions associated with oral antibiotics prescribed in community care (non-hospital) in England to determine adverse drug reaction reporting rates and severity of adverse reactions. Methods: Data for all oral antibiotic use in the primary care settings in England and the National Yellow Card Interactive Drug Analysis Profile was extracted for 2010 through 2017. Results: There were 320,599,292 prescriptions issued for oral antibiotics during the eight-year survey. Although the overall adverse drug reaction rate was relatively low at 58/1,000,000 prescriptions, the reported rates of serious (63.6%) and fatal (1.21%) reactions were striking and probably due to reporting bias as minor adverse drug reactions are less likely to be reported. Conclusions: Continued monitoring of adverse drug reactions rates for oral antibiotics prescribed in the community is warranted, considering the prevalence of serious and fatal reactions identified during the eight-year study period in the Yellow Card profile. These data should be useful in developing strategies to secure optimal prescribing practices.

Antibiotic Prophylaxis and Incidence of Endocarditis Before and After the 2007 AHA Recommendations.

BACKGROUND: The American Heart Association updated its recommendations for antibiotic prophylaxis (AP) to prevent infective endocarditis (IE) in 2007, advising that AP cease for those at moderate risk of IE, but continue for those at high risk. OBJECTIVES: The authors sought to quantify any change in AP prescribing and IE incidence. METHODS: High-risk, moderate-risk, and unknown/low-risk individuals with linked prescription and Medicare or commercial health care data were identified in the Truven Health MarketScan databases from May 2003 through August 2015 (198,522,665 enrollee-years of data). AP prescribing and IE incidence were evaluated by Poisson model analysis. RESULTS: By August 2015, the 2007 recommendation change was associated with a significant 64% (95% confidence interval [CI]: 59% to 68%) estimated fall in AP prescribing for moderate-risk individuals and a 20% (95% CI: 4% to 32%) estimated fall for those at high risk. Over the same period, there was a barely significant 75% (95% CI: 3% to 200%) estimated increase in IE incidence among moderate-risk individuals and a significant 177% estimated increase (95% CI: 66% to 361%) among those at high risk. In unknown/low-risk individuals, there was a significant 52% (95% CI: 46% to 58%) estimated fall in AP prescribing, but no significant increase in IE incidence. CONCLUSIONS: AP prescribing fell among all IE risk groups, particularly those at moderate risk. Concurrently, there was a significant increase in IE incidence among high-risk individuals, a borderline significant increase in moderate-risk individuals, and no change for those at low/unknown risk. Although these data do not establish a cause-effect relationship between AP reduction and IE increase, the fall in AP prescribing in those at high risk is of concern and, coupled with the borderline increase in IE incidence among those at moderate risk, warrants further investigation.