**4. At-risk patients**

About 10% of patients attending dental consultations are allergic to penicillin and its derivatives, although a large majority of these reported allergic reactions are no more than minor side-effects or late hypersensitivity reactions presenting as pruritus or rash, but not IgEmediated. Urticaria (hives) is IgE-mediated; it only accounts for 10% of all exanthematous drug reactions, but may be interpreted as a clinical sign of immediate hypersensitivity that could

The main antigenic determinant of the anaphylactic reaction to penicillins is the β-lactam ring, a part of the molecule that is essential for its bactericidal activity and that also forms part of the chemical structure of the cephalosporins and clavulanates (clavulanic acid), among others. Drug-related anaphylaxis is a life-threatening medical emergency and, as a result, the administration of β-lactam drugs is contraindicated in patients who give a history of penicillin allergy until such time as allergy testing establishes the true risk of anaphylaxis in each individual

The three main guidelines coincide on the oral or intravenous administration of 600 mg of clindamycin as the antibiotic of choice in patients allergic to penicillins (**Table 2**). Clindamycin has intrinsic in vitro activity against streptococci, staphylococci and anaerobes, it rarely causes allergic reactions and it has a low incidence of side-effects, making it an ideal alternative antibiotic based on its antimicrobial spectrum and biosafety. However, some authors have demonstrated that it is ineffective in preventing bacteraemia following dental procedures [15].

Clindamycin Clindamycin

Azithromycin Clarithromycin

**Australia (AIEPEG) Europe (ESC) USA (AHA)**

*Abbreviations*: AIEPEG, Australian Infective Endocarditis Prophylaxis Expert Group; ESC, European Society of

**Table 2.** Alternative antibiotics for prophylaxis against infective endocarditis in patients allergic to penicillins and their

The 2007 AHA guideline describes in great detail specific situations that could require changes to the application of the prophylactic regimens in clinical practice. For example, intramuscular injections should be avoided in patients receiving anticoagulants. In patients attending the dental clinic whilst on treatment with penicillins for other causes, it is preferable to delay dental therapy for at least 10 days; it is accepted that viridans group streptococci in the oral cavity of patients on long-term antibiotic therapy could be relatively resistant to penicillin or amoxicillin, and the cessation of antibiotic therapy allows the usual oral flora to be re-established. When the dental intervention cannot be postponed, the health professional should select a different class of antibiotic rather than increase the dose of the current antibiotic; options include clindamycin, azithromycin and clarithromycin, though only for patients with the highest-risk

progress to an episode of acute (fulminant) anaphylaxis.

20 Contemporary Challenges in Endocarditis

case [14].

Clindamycin Lincomycin Vancomycin Teicoplanin

derivatives.

cardiac conditions [11].

Cardiology; AHA, American Heart Association.

In its conclusions, the 2007 AHA guideline states that IE prophylaxis for dental procedures is a reasonable practice only for patients with underlying heart conditions associated with the highest risk of an adverse outcome [11]. New pathophysiological concepts and risk-benefit analyses justify the current tendency of the scientific community towards more limited indications for antibiotic prophylaxis in IE (**Table 3**).


**Table 3.** Arguments for the restriction of the indication for prophylaxis against infective endocarditis [13].

Epidemiological evidence also supports this restrictive policy, as the incidence of IE and its associated mortality have not varied in recent decades despite the use of antibiotic prophylaxis. At the present time, we are seeing an increase in the number of cases of IE due to *Staphylococcus* *aureus* and of unknown aetiology and a fall in the incidence of cases of IE of streptococcal aetiology [17]. This has occurred despite the evident, considerable increase in the number of dental interventions and in the ratio of dentists to population in recent years.

In this context and awaiting relevant new data, NICE in the UK continues its recommendation to universally cease antibiotic prophylaxis for medical interventions, although the majority of cardiologists and cardiac surgeons consider antibiotic prophylaxis necessary for patients at highest risk of adverse outcomes from endocarditis [9].


**Table 4.** Patients in whom prophylaxis against infective endocarditis is not recommended [18].

The 1997 AHA guideline was the first to stratify cardiac conditions into high, moderate and low risk for IE [18]. AHA experts stated that the risk of suffering IE assumed by low-risk patients undergoing dental treatment could be considered negligible, no higher than in the general population, and, as a result, they recommended abolishing antibiotic prophylaxis for routine dental treatment in these patients. This 1997 recommendation was particularly helpful in clinical practice because heart murmurs, pacemakers and minor congenital defects were frequently reported by dental patients in their medical records. The establishment of a restrictive position on the part of the health authorities regarding antibiotic prophylaxis created a framework of medico-legal protection in dental practice. The 1997 AHA guideline thus provided dentists with a certain capacity to evaluate the prescription of prophylaxis in patients with a history of cardiac disease and moderate their natural tendency to prescribe universal antibiotic cover derived from a fear of missing one of the numerous indications (**Table 4**). This conceptual change was further strengthened 10 years later when the 2007 AHA committee eliminated antibiotic prophylaxis for patients considered to be in the moderate risk category in the 1997 guideline (**Table 5**), on the basis that "*previously published AHA guidelines for the prevention of IE contained ambiguities and inconsistencies and were often based on minimal published data or expert opinion, they were subject to conflicting interpretations among patients, healthcare providers, and the legal system about patient eligibility for prophylaxis and whether there was strict adherence by healthcare providers to AHA recommendations for prophylaxis*" [11].

The current result of this policy limiting the indications for antibiotic prophylaxis to the highest risk cardiac conditions is stated even more restrictively in the 2015 ESC guideline (**Table 6**). In their recommendation, the ESC excludes prophylaxis even in heart transplant recipients who develop heart valve disease; this is considered a true high-risk condition in the AHA and Australian guidelines. The Australian recommendations also include rheumatic heart disease in indigenous Australians, a population in which unusually high prevalence and mortality related to this disease have been detected [19].

	- ✓ Ductus arteriosus

*aureus* and of unknown aetiology and a fall in the incidence of cases of IE of streptococcal aetiology [17]. This has occurred despite the evident, considerable increase in the number of

In this context and awaiting relevant new data, NICE in the UK continues its recommendation to universally cease antibiotic prophylaxis for medical interventions, although the majority of cardiologists and cardiac surgeons consider antibiotic prophylaxis necessary for patients at

**•** Surgical repair of atrial septal defect, ventricular septal defect, or patent ductus arteriosus (without residua beyond 6

The 1997 AHA guideline was the first to stratify cardiac conditions into high, moderate and low risk for IE [18]. AHA experts stated that the risk of suffering IE assumed by low-risk patients undergoing dental treatment could be considered negligible, no higher than in the general population, and, as a result, they recommended abolishing antibiotic prophylaxis for routine dental treatment in these patients. This 1997 recommendation was particularly helpful in clinical practice because heart murmurs, pacemakers and minor congenital defects were frequently reported by dental patients in their medical records. The establishment of a restrictive position on the part of the health authorities regarding antibiotic prophylaxis created a framework of medico-legal protection in dental practice. The 1997 AHA guideline thus provided dentists with a certain capacity to evaluate the prescription of prophylaxis in patients with a history of cardiac disease and moderate their natural tendency to prescribe universal antibiotic cover derived from a fear of missing one of the numerous indications (**Table 4**). This conceptual change was further strengthened 10 years later when the 2007 AHA committee eliminated antibiotic prophylaxis for patients considered to be in the moderate risk category in the 1997 guideline (**Table 5**), on the basis that "*previously published AHA guidelines for the prevention of IE contained ambiguities and inconsistencies and were often based on minimal published data or expert opinion, they were subject to conflicting interpretations among patients, healthcare providers, and the legal system about patient eligibility for prophylaxis and whether there*

*was strict adherence by healthcare providers to AHA recommendations for prophylaxis*" [11].

The current result of this policy limiting the indications for antibiotic prophylaxis to the highest risk cardiac conditions is stated even more restrictively in the 2015 ESC guideline (**Table 6**). In

dental interventions and in the ratio of dentists to population in recent years.

highest risk of adverse outcomes from endocarditis [9].

**•** Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators.

**Table 4.** Patients in whom prophylaxis against infective endocarditis is not recommended [18].

**•** Isolated secundum atrial septal defect.

22 Contemporary Challenges in Endocarditis

**•** Previous coronary artery bypass graft surgery. **•** Mitral valve prolapse without valvar regurgitation. **•** Physiologic, functional or innocent heart murmurs. **•** Previous Kawasaki disease without valvar dysfunction. **•** Previous rheumatic fever without valvar dysfunction.

months).

	- ✓ Rheumatic
	- ✓ Collagen vascular disease
	- ✓ Others

**Table 5.** Cardiac conditions that carry a moderate risk of infective endocarditis [18].

Finally, dental surgeons show a degree of concern over the need for prophylaxis when performing dental procedures on patients with implanted cardiac devices such as pacemakers, stents and implantable defibrillators. In 2007, Lockhart et al. published an interesting literature review on this subject, revealing widely differing opinions, a situation that usually leads dentists to contact physicians for advice on management. Interestingly, most physicians, surgeons and medical specialists want their patients to receive antibiotic prophylaxis for all invasive dental procedures to prevent distant site infection of organs, tissues or prosthetic materials, and a number of them do so for medico-legal rather than scientific reasons. The majority of the literature sources agree that there is no indication for prophylaxis in patients with cardiac devices. Bacterial seeding of a graft site via a haematogenous route is an uncommon event and most of infections occurring in the first 2 months are due to *Staph‐ ylococcus* spp. and non-oral bacteria, probably as result of the manoeuvres of graft placement [20].

Based on these premises, it could be stated that patients with implantable cardiac devices may be cautiously covered with antibiotic prophylaxis exclusively during the early post-implantation period, though this is mainly for medico-legal reasons. Considering the current IE prophylaxis guidelines, there is no reason for antibiotic use during routine dental treatment in patients with implantable cardiac devices, unless individual cases present concomitant diseases that could justify such a decision.

	- **a.** Any type of cyanotic CHD.
	- **b.** Any type of CHD repaired with a prosthetic material, whether placed surgically or by percutaneous techniques, up to 6 months after the procedure or lifelong if residual shunt or valvular regurgitation remains.

**Table 6.** Cardiac conditions associated with the highest risk of adverse outcomes of endocarditis according to the European Society of Cardiology guideline [13].
