Reasons Against Prophylaxis

Since IE is potentially fatal, prophylaxis seems reasonable. The benefit of giving antibiotic prophylaxis to otherwise healthy people, however, should outweigh its risks. The major complications associated with administration of prophylaxis include allergic reactions, toxic side effects of antimicrobials, adverse interactions with other drugs, and development of resistant organisms.

The most significant adverse event associated with the penicillins is hypersensitivity reactions, which can range from a troublesome rash to life-threatening anaphylaxis. Previous studies that have compared the rates of IE-associated deaths to the rates of deaths from antibiotic-induced anaphylaxis have questioned the benefit of prophylaxis. In a quantitative analysis of published data on prophylaxis in patients with mitral valve prolapse (MVP), Bor and Himmelstein [113] calculate that among 10 million patients with MVP undergoing a dental procedure, an estimated 47 nonfatal cases and 2 fatal cases of IE would occur if no prophylaxis were given, compared to 5 cases of IE and 175 deaths due to drug reactions if all patients were given prophylaxis with a penicillin. Similarly, Tzukert and colleagues [114] demonstrated that patients receiving penicillin/amoxi-cillin propylaxis to prevent IE are five times more likely to die from anaphylaxis to the drug than from IE, with estimated rates of 1.36 deaths versus 0.26 deaths per million population, respectively. These studies were conducted in the mid-1980s, and national guidelines have since been revised to tailor prophylaxis to at-risk patients. No study has since demonstrated whether the risk-benefit ratio has been modified by the latest recommendations. Nonetheless, the potential for adverse drug reactions must always be borne in mind. Such a consideration should also include non-allergic toxicities (e.g., amino-glycoside-induced nephrotoxicity), as well as potential drug-drug interactions.

An emerging problem resulting from inappropriate use of antimicrobial agents is the development of C. difficile-associated disease (CDAD). C. difficile is the most common cause of infectious diarrhea among hospitalized patients. It is well-documented that recent antibiotic use (e.g., within 42 days [115]) predisposes to acquisition of C. difficile. Essentially all antibiotics have been associated with risk for CDAD, including those recommended for IE prophylaxis. In a metaanalysis by Bignardi [116], use of ampicillin or amoxicillin was associated with a pooled odds ratio of 3.7 for acquiring disease (95% CI: 2.6-5.5), while the rates for clindamycin, regeneration cephalosporins, and vancomycin were 9 (6.3-12.9), 2.6 (1.8-3.7), 3.1 (1.8-5.2), respectively. Development of CDAD leads to prolonged hospitalizations [117,118]. It can also be associated with severe disease (i.e., megacolon, perforation, colectomy, shock requiring vasopressor therapy, or death within 30 days after diagnosis) [119]. In certain geographic areas, CDAD is associated with increased mortality rates, with a one-year cumulative attributable mortality of 17% [117]. Development of CDAD following antibiotic prophylaxis for dental procedures has been reported [120], as it has after single doses of antibiotics for other procedures [121,122]. Emergence of CDAD emphasizes the need to weigh the risks versus the benefits of antibiotic prophylaxis.

An additional concern from the large-scale use of IE prophylaxis is the development of antimicrobial resistance. In healthy human volunteers, administration of repeated doses of amoxicillin was followed by emergence of resistant VGS from the oral flora [123]. A case of S. mitis IE developing despite seemingly-appropriate prophylaxis has been reported in a patient who received two recent courses of amoxicillin for dental procedures [124]. In the neutropenic cancer patients, exposure to previous P-lactams was associated with an increased risk of bloodstream infection (non-endocarditis) with

P-lactam-resistant VGS [125,126]. Previous exposure to antibiotics has also permitted the emergence of resistant enterococci [127] and S. aureus [128,129]. Consequently, judicious use of antibiotics, in general, is advocated, and administration of antimicrobial prophylaxis should not be done indiscriminately, but tailored to those specifically at-risk for disease.

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