Incidence and nature of adverse reactions to antibiotics used as endocarditis prophylaxis

Abstract

Objectives: Antibiotic prophylaxis (AP) administration prior to invasive dental procedures has been a leading focus of infective endocarditis prevention. However, there have been long-standing concerns about the risk of adverse drug reactions as a result of this practice. The objective of this study was to identify the incidence and nature of adverse reactions to amoxicillin and clindamycin prophylaxis to prevent infective endocarditis.

Methods: We obtained AP prescribing data for England from January 2004 to March 2014 from the NHS Business Services Authority, and adverse drug reaction data from the Medicines and Healthcare Products Regulatory Agency's Yellow Card reporting scheme for prescriptions of the standard AP protocol of a single 3 g oral dose of amoxicillin or a single 600 mg oral dose of clindamycin for those allergic to penicillin.

Results: The reported adverse drug reaction rate for amoxicillin AP was 0 fatal reactions/million prescriptions (in fact 0 fatal reactions for nearly 3 million prescriptions) and 22.62 non-fatal reactions/million prescriptions. For clindamycin, it was 13 fatal and 149 non-fatal reactions/million prescriptions. Most clindamycin adverse drug reactions were Clostridium difficile infections.

Conclusions: AP adverse drug reaction reporting rates in England were low, particularly for amoxicillin, and lower than previous estimates. This suggests that amoxicillin AP is comparatively safe for patients without a history of amoxicillin allergy. The use of clindamycin AP was, however, associated with significant rates of fatal and non-fatal adverse drug reactions associated with C. difficile infections. These were higher than expected and similar to those for other doses, durations and routes of clindamycin administration.

Keywords: adverse drug reactions; amoxicillin; clindamycin; dental.

Figure 1.

Amoxicillin and clindamycin AP prescribing data. (a) Number of AP prescriptions dispensed each month (red, single 3 g oral dose of amoxicillin; blue, single 600 mg oral dose of clindamycin). Figure 1(a) is similar to a figure we recently had published in Lancet, but shows a further 10 months of data. (b) Number of amoxicillin AP prescriptions dispensed each month, by prescriber (red, dentists; blue, general practitioners; green, hospitals; purple, nurses). The numbers of hospital and nurse prescriptions are too small to see easily. (c) Number of clindamycin AP prescriptions dispensed each month, by prescriber (red, dentists; blue, general practitioners; green, hospitals; purple, nurses). The numbers of hospital and nurse prescriptions are too small to see easily. In each case, the grey bars indicate March 2008, when NICE recommended the cessation of AP for IE. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.