Antimicrobials, including antibacterials, antifungals, and antivirals, have significantly improved the clinical care of infected patients since the introduction of penicillin in the 1940s. The development of antimicrobial-resistant strains of these pathogens has continually expanded the number of antimicrobials necessary, and this has increased the overall potential for toxicity after use. Fortunately, toxicity due to acute overdose is limited and chronic therapeutic doses are safe in the majority of patients.
Most adverse effects related to antimicrobials occur as a result of iatrogenic complications rather than intentional overdose. The diverse origins of these complications include dose, route and decision errors, allergic reactions, adverse effects, and interactions. Prevention, in the form of process improvements and information regarding populations at risk for adverse effects, is continually required to minimize these untoward events. Dosing errors are prominent in neonates and infants, necessitating care and constant diligence on the part of health care professionals.
Antimicrobials are more commonly associated with allergic reactions than are other xenobiotics. The reason for this is unclear, but it may be a result of their high frequency of use, repeated intermittent prescriptive use, or environmental contamination. A complete allergy history is essential to minimize these adverse events in patients being considered for antimicrobial therapy.
Many adverse effects attributed to antimicrobials are difficult to predict even when given patient and population specific parameters. In some cases, an excipient is responsible for the adverse effect, as recognized with the adverse effects found in patients after the use of procaine penicillin G. Antimicrobials are involved in many common and severe xenobiotic interactions, primarily through the inhibition of metabolic enzymes. Patients being considered for antimicrobial therapy should be carefully assessed for the use of concomitant therapies, both prescription and nonprescription which may 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 57–1 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 the therapeutic mechanisms.
TABLE 57–1.Antimicrobial Pharmacology and Adverse Effects ||Download (.pdf) TABLE 57–1. Antimicrobial Pharmacology and Adverse Effects
|Antimicrobial ||Antimicrobial Mechanism of Action ||Acute Overdose ||Chronic Administration |
|Antibacterial || || || |
|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 antagonism ||Hypersensitivity—immune |
|Chloramphenicol ||Inhibits 50s ribosomal subunit and inhibits protein synthesis in rapidly dividing cells ||Cardiovascular collapse ||“Gray baby syndrome” Same as mechanism of action |
|Fluoroquinolones ||Inhibit DNA topoisomerase and ...|