The introduction of penicillin in the 1940s revolutionized the care of patients with infectious diseases. Antimicrobials, including all categories of antibacterials, antifungals, and antivirals, significantly improve the clinical care and outcome of infected patients. Since early in their introduction, the development of antimicrobial-resistant strains of these pathogens has driven an increase in the number of antimicrobials necessary. This, in turn, continues to increase the overall potential for toxicity after use. Fortunately, with most antimicrobials, toxicity due to acute overdose is limited and chronic therapeutic doses are safe.
Most adverse drug events related to antimicrobials occur as a result of iatrogenic complications rather than intentional overdose. The diverse origins of these complications include dosing errors, route administration errors, allergic reactions, adverse drug events, and drug–drug-related interactions. Prevention, in the form of process improvements and information regarding populations at risk for adverse drug events, is continually required to minimize these untoward events. Dosing errors are prominent, particularly in neonates and infants, and those patients with compromised kidney or liver function necessitating care and constant diligence on the part of health care professionals.
Antimicrobials are more commonly associated with allergic reactions than are other pharmaceuticals. The reason is hypothesized to be either a result of their high frequency of use, repeated intermittent prescriptions, or environmental contamination. A complete allergy history is essential to minimize these adverse drug reactions in patients being considered for antimicrobial therapy.
Many adverse drug reactions attributed to antimicrobials are difficult to predict even when given patient and population specific parameters. In some cases, an excipient is found responsible for the adverse event, as is seen after the use of procaine penicillin G (Chap. 46). Antimicrobials are involved in many common and severe drug–drug interactions, primarily through the inhibition of cytochrome and other metabolic enzymes. Patients considered for antimicrobial therapy should be carefully assessed for the use of prescription and nonprescription therapies that are known to be pharmacokinetically or pharmacodynamically affected by the chosen antimicrobial.
PHARMACOLOGY AND TOXICOLOGY
Antimicrobial pharmacology is aimed at the destruction of microorganisms through the inhibition of cell cycle reproduction or the altering of a critical function within a microorganism. Table 54–1 lists antimicrobials and their associated mechanisms of activity, toxicologic effects, and related toxicologic mechanisms. Often the mechanisms for toxicologic effects following acute overdose differ from their therapeutic mechanisms.
TABLE 54–1Antimicrobial Pharmacology and Adverse Effects ||Download (.pdf) TABLE 54–1 Antimicrobial Pharmacology and Adverse Effects
|Antimicrobial ||Antimicrobial Mechanism of Action ||Acute Overdose ||Chronic Administration |
|Aminoglycosides ||Inhibit 30s ribosomal subunit ||Neuromuscular blockade—inhibit the release of acetylcholine from presynaptic nerve terminals and acts as an antagonist at acetylcholine receptors ||Nephrotoxicity/ototoxicity—form an iron complex that inhibits mitochondrial respiration and causes lipid peroxidation |
|Penicillins, cephalosporins, and other β-lactams ||Inhibit cell wall mucopeptide synthesis ||Seizures—agonist at picrotoxin-binding site, causing GABA ...|