**3.2. Alternative drugs to amoxicillin**

The three guidelines incorporate cephalosporins for parenteral administration as an alternative to amoxicillin. The cephalosporins are also recommended in patients with penicillin allergy, though this proposal is accompanied by a warning that the use of cephalosporins is contraindicated in individuals with a history of anaphylaxis.

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 progress to an episode of acute (fulminant) anaphylaxis.

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 case [14].

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].


*Abbreviations*: AIEPEG, Australian Infective Endocarditis Prophylaxis Expert Group; ESC, European Society of Cardiology; AHA, American Heart Association.

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

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 cardiac conditions [11].

Azithromycin and clarithromycin are macrolides with similar activity to erythromycin on the oral streptococci, but they show better gastrointestinal tolerance and a more favourable pharmacokinetic profile. Erythromycin is unstable under acidic gastric conditions, shows poor absorption and has a limited spectrum of activity. Azithromycin, on the other hand, causes fewer gastrointestinal side-effects, rapidly reaches high tissue concentrations and displays a better antibacterial spectrum, making it a good candidate for IE prophylaxis [16].

The Australian guideline includes a parenteral regimen of lincomycin, vancomycin or teicoplanin for patients with penicillin hypersensitivity and for those on long-term penicillin therapy or who have taken penicillin or related β-lactam antibiotics more than once in the previous month [12].

Finally, the ESC guideline is the most restrictive, recommending clindamycin as the only alternative antibiotic. In contrast to the proposal of the Australian expert committee, the European guideline states that the glycopeptides, such as vancomycin and teicoplanin, are not recommended because their efficacy has not been fully demonstrated and there is a potential for the induction of resistance [13].
