chapter  6
20 Pages

Cardiovascular Toxicity of Antimicrobials

ByDaniel P. Healy

Despite the rapid proliferation of novel anti-infective agents beginning in the

1960s and continuing through the 1980s, infectious diseases remain the third

leading cause of death in the United States and the second leading cause of death

worldwide (1). Community-acquired pneumonia alone affects approximately

4.5 million adults annually in the United States (2). Therefore, it is not surprising

that antimicrobial agents continue to be among the most commonly prescribed

drug classes. Fortunately, with the exception of life-threatening immediate

hypersensitivity reactions, the toxicity profile of most antimicrobial compounds

is relatively unremarkable. This may be attributed, at least in part, to the rela-

tively short courses (e.g., 2 weeks) of antibiotics given for most common infections. Indeed, with longer courses of antibiotics required for infrequently

encountered chronic infections or in critically ill patients, the risk of renal,

hepatic, hematologic, and other types of serious toxicity significantly increases.

Overall, the incidence of direct cardiovascular toxicity associated with anti-

microbial therapy is very low. While certain antimicrobial compounds may

possess direct cardiodepressant activity, generally this has only been demon-

strated when using supraphysiologic concentrations in vitro or in anesthetized

animals (3). Clinically, such cardiovascular toxicity associated with anti-

microbial administration would not be expected to manifest unless one or more

risk factors or conditions are present such as, but not limited to, diminished

cardiac reserve (e.g., congestive heart failure, circulatory shock), the presence of

cardiac arrhythmias, administration in an immunocompromised host, use of

general anesthesia, presence of sepsis or septic shock, drug overdose, pharma-

cokinetic drug interactions resulting in elevated plasma levels of the antibiotic,

and additive or synergistic pharmacodynamic effects when used in combination

with other drugs possessing inherent depressant activity on the heart or vascu-

lature (4-6). It is due to these many potential clinical factors that have not been

thoroughly studied in the context of cardiovascular drug toxicity that warrants

discussion of the mechanisms underlying the cardiotoxicity of antimicrobials.