**2. Impact of the nice recommendations**

**1. Historical perspectives**

16 Contemporary Challenges in Endocarditis

manipulations that affect the gum.

recommended [2].

organisms.

In 1955, the American Heart Association (AHA) was the first medical society to establish the need for a prophylactic antibiotic regimen to prevent infective endocarditis (IE) in at-risk patients undergoing various surgical procedures, including tooth extractions and other dental

In the pre-antibiotic era, reports based on clinical observations described cases of IE of streptococcal aetiology in which there was a history of professional dental manipulation. This suggested the possibility that "transient bacteraemia during dental procedures may lead to

The 1955 AHA Committee on the Prevention of Rheumatic Fever and Bacterial Endocarditis concluded that patients undergoing dental procedures must be protected by high concentrations of antibiotic present in the blood at the time of the procedure. Penicillin administered parenterally was preferred, although oral penicillin V was introduced as second choice. In cases of sensitivity to penicillin, other antibiotics such erythromycin or tetracycline were

Since that time, the scientific community has universally accepted the need for antibiotic prophylaxis in patients susceptible to developing IE. Experimental models developed in the 1970s provided evidence of the efficacy of prophylaxis in animals and demonstrated the ability of antibiotics to prevent *Streptococcus sanguinis* endocarditis [3]. However, the different antibiotic regimens to prevent IE in dental patients were developed based on empirical criteria. In 1982, the British Society for Antimicrobial Chemotherapy included amoxicillin in the prophylactic antibiotic regimen against IE [4]. Amoxicillin has a broad antibacterial spectrum and a more favourable pharmacokinetic profile than penicillin V for oral administration; this has made it the drug of choice in all current guidelines on the use of antibiotics to prevent IE. The main inclusion criteria for the prophylactic regimens established by the first committees were the rheumatic heart disease and congenital malformations, but fundamental changes have been introduced since that time regarding "patients considered to be at risk of IE". The campaigns for the prevention of rheumatic fever, the increase in the prevalence of intravenous drug abuse and the growth in cardiovascular interventions have transformed the microbiological patterns of IE, with a relative decrease in the incidence of streptococcal endocarditis and a significant increase in endocarditis due to staphylococci and other less common

These changes make it difficult to draw reliable epidemiological conclusions on the efficacy of antibiotics for the prevention of IE. In general, the majority of studies indicate that, despite the universal implantation of antibiotic prophylaxis prior to the dental treatment, no global

This has been one of the main arguments put forward by the British health authorities to revoke the indications for antibiotic prophylaxis in patients undergoing dental, digestive tract or genitourinary interventions. A few years ago, the National Institute for Health and Clinical

reduction in the prevalence of IE has been achieved [5].

subacute endocarditis in subjects with abnormal heart valves" [1].

In the controversial document published in 2008, NICE brought about the complete cessation of antibiotic prophylaxis for all patients at risk of IE undergoing dental interventions [6]. The main premises on which the British experts based this decision was the quantifiable risk of antibiotic administration to the individual patient, the potential appearance of unnecessary antimicrobial resistance and the economic analysis of the cost-effectiveness of prophylaxis.

The recommendation was based on the limited available evidence on antibiotic prophylaxis as an effective method to reduce the incidence of IE when given before an interventional procedure. Furthermore, the existence of transient bacteraemia during activities of daily living, such as toothbrushing or chewing, diminishes the significance of dental procedures as a cause of IE, making antibiotic prophylaxis virtually ineffective for preventing the disease.

Consequently, NICE did not recommend antibiotic prophylaxis against IE in persons undergoing dental procedures or digestive, respiratory or genitourinary tract interventions, except for manipulations at an infected non-dental site.

The expert committees across the rest of the world, including the AHA and the European Society of Cardiology (ESC), have continued to recommend antibiotic prophylaxis in high-risk individuals, and these protocols are followed by most cardiologists and cardiac surgeons.

The first studies on the epidemiological repercussions of the implementation of the NICE guideline showed a substantial reduction in the prescription of antibiotics in its area of influence and the data gathered showed no significant changes in the general upward trend in cases of IE [7].

In 2013, a case of IE was reported in which aetiological analysis suggested a very strong association with a previous dental intervention performed without antibiotic cover. The affected patient had a metallic aortic valve and developed a fatal episode of *S. sanguinis* endocarditis 10 days after undergoing a dental procedure without antibiotic prophylaxis, following the NICE recommendations. The dental history of the patient showed that he had received antibiotic prophylaxis during dental sessions over the previous 10 years with no adverse outcomes [8].

The most recent epidemiological studies have identified a significant increase in the incidence of IE after implementation of the NICE guideline. A retrospective study was performed in England to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of IE [9]. The data collected and the subsequent analysis suggested that after March 2008—the year of publication of the NICE guideline—the number of cases of IE increased significantly above the expected historical trend.

According to some experts, these data are mainly observational and do not prove that the lower level of antibiotic prophylaxis was the cause of the increase in IE. However, no other satisfactory explanation for this increase in the incidence of IE has yet been put forward [10].

Despite this, NICE has reviewed all evidence relating to the effectiveness of IE prophylaxis as a precaution but, at present, they have found no need to change any of the existing 2008 guideline. They have, however, made an additional research recommendations on antibiotic prophylaxis against IE as summarised in **Table 1**.


*Note*: https://nice.org.uk/guidance/CG64/chapter/Recommendations-for-research#4-antibiotic-prophylaxis-againstinfective-endocarditis

**Table 1.** NICE recommendations for research. Antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures (updated in 2015).
