Adverse effects associated with antimicrobials occur primarily in three circumstances: side effects with therapeutic dosing, acute toxicity resulting from excessive dosing, and subacute to chronic effects from sustained therapeutic use. Side effects can be immunologic (allergic) or nonimmunologic (pharmacologic or idiosyncratic) in nature. Antibiotics cause more reported allergic reactions than other drugs, possibly due to their high frequency of use that is often in a repeated and interrupted fashion. Sometimes a diluent or other chemical constituent in the formulation of a drug causes the adverse effect.
Most patients who sustain an acute antimicrobial overdose remain asymptomatic, and observation is generally all that is required. Measurement of drug levels is not helpful for management but may be confirmatory. Levels are available for several antibiotics such as chloroquine, isoniazid, and quinine. Ancillary testing should be based on the substance ingested and the clinical condition of the patient, such as methemoglobin concentrations for patients with dapsone or chloroquine toxicity.1 Some antimicrobials are associated with specific, significant toxicities following an acute ingestion and may require particular therapy (Table 206-1).
TABLE 206-1Select Antimicrobial Toxicities and Their Specific Treatments |Favorite Table|Download (.pdf) TABLE 206-1 Select Antimicrobial Toxicities and Their Specific Treatments
|Drug ||Acute Toxicity ||Special Therapy for Symptomatic Overdose |
|Penicillin ||Seizures (50 million units or more IV) ||Benzodiazepines |
|Amoxicillin ||Crystalluria, hematuria, acute renal failure ||IV fluid |
|Cephalosporins ||Encephalopathy, seizures ||Benzodiazepines |
|Chloramphenicol ||Cardiovascular collapse ||Hemodialysis |
|Fluoroquinolones ||Seizures ||Benzodiazepines |
|Macrolides ||Prolonged QT interval, torsades de pointes arrhythmia ||Magnesium sulfate |
|Sulfonamides ||Methemoglobinemia ||Methylene blue |
|Vancomycin ||"Red man syndrome" (anaphylactoid response) ||Slow or stop infusion, antihistamines |
|Chloroquine ||Seizures, QRS-complex and QT-interval prolongation, hypotension, hypokalemia ||Epinephrine, diazepam |
|Quinine (quinidine) ||Sodium-potassium channel blockade, α-adrenergic antagonism, hypoglycemia, ototoxicity, ophthalmic toxicity ||Multidose activated charcoal, sodium bicarbonate, dextrose, octreotide |
|Primaquine ||Methemoglobinemia, hemolysis ||Methylene blue |
|Antituberculous medications |
|Isoniazid ||Inhibition of γ-aminobutyric acid synthesis and functional deficiency pyridoxine, seizures ||Benzodiazepines, high-dose pyridoxine |
Consider GI decontamination for patients suspected of ingesting a toxic amount of a potentially dangerous antimicrobial agent. Single-dose activated charcoal without sorbitol given orally or via nasogastric tube is most beneficial within 1 hour of the ingestion.2,3 Multidose activated charcoal is indicated in symptomatic patients who have ingested dapsone or quinine.4 Hemodialysis or hemoperfusion is effective at reducing concentrations of dapsone,5,6 chloramphenicol, cefepime,7,8 and possibly pentamidine.9
PENICILLINS, CEPHALOSPORINS, AND OTHER β-LACTAM AGENTS
Acute overdoses of penicillins and cephalosporins mainly produce nausea, vomiting, and diarrhea but are rarely life threatening. Large doses of penicillins or cephalosporins may produce seizures through γ-aminobutyric acid inhibition, and seizures are managed by administration of benzodiazepines or barbiturates. Seizures resulting from intrathecal doses of penicillins or cephalosporins may require cerebral spinal fluid exchange for treatment. Imipenem may cause seizures in overdose or at therapeutic doses, and these ...