Antibacterial Agents
The antibiotic class of drugs has proliferated immensely since the first clinical use of sulfonamide in 1936 and the mass production of penicillin in 1941. In general, harmful effects have resulted from allergic reactions or inadvertent intravenous overdose. Serious toxicity from a single acute ingestion is rare. Table II–4 lists common and newer antibacterial agents that have been associated with significant toxic effects.
Drug | Half-lifea | Toxic Dose or Serum Level | Toxicity |
|---|---|---|---|
Aminoglycosides | |||
Amikacin | 2–3 h | >35 mg/L | Ototoxicity to vestibular and cochlear cells; nephrotoxicity causing proximal tubular damage and acute tubular necrosis; competitive neuromuscular blockade if given rapidly IV with other neuromuscular-blocking drugs. Threshold for toxic effects varies with the drug and dosage schedule. |
Gentamicin | 2 h | >12 mg/L | |
Kanamycin | 2–3 h | >30 mg/L | |
Neomycin | 0.5–1 g/d | ||
Streptomycin | 2.5 h | >40–50 mg/L | |
Tobramycin | 2–2.5 h | >10 mg/L | |
Bacitracin | Unknown | Ototoxicity and nephrotoxicity | |
Carbapenems | Chronic; >1 g every 6 h | Hypersensitivity reactions; seizures associated with renal dysfunction and high doses. | |
Doripenem | 1 h | ||
Ertapenem | 4 h (2.5 h in ages 3 mo–12 y) | ||
Imipenems/cilastatin | 1 h | ||
Meropenem | 1 h | ||
Cephalosporins | |||
Cefazolin Cephalothin | 90–120 min | Unknown | Convulsions reported in patients with renal insufficiency; coagulopathy associated with cefazolin. |
Cephaloridine | 6 g/d | Proximal tubular necrosis | |
Cefaclor | 0.6–0.9 h | Neutropenia | |
Cefoperazone | 102–156 min | 3–4 mg/L | One case of symptomatic hepatitis. All these antibiotics have the N-methyltetra-zolethiol side chain, which may inhibit aldehyde dehydrogenase to cause a disulfiram-like interaction with ethanol (See Disulfiram) and coagulopathy (inhibition of vitamin K production). |
Cefamandole | 30–60 min | ||
Cefotetan | 3–4.6 h | ||
Moxalactam | 114–150 min | ||
Cefmetazole | 72 min | ||
Ceftriaxone | 4.3–4.6 h; extensive excretion in bile | IV bolus over <3–5 min | Pseudolithiasis (“gallbladder sludge”). Should be administered IV over 30 minutes. |
Chloramphenicol | 4 h | >40 mg/L | Leukopenia, reticulocytopenia, circulatory collapse (“gray baby” syndrome) |
Dapsone | 10–50 h | As little as 100 mg in an 18-month-old | Methemoglobinemia, sulfhemoglobinemia, hemolysis; metabolic acidosis; hallucinations, confusion; hepatitis (See Dapsone) |
Daptomycin | 8–9 h | Chronic | A cyclic lipopeptide. Available only as an injection. May cause muscle pain, weakness, or asymptomatic elevation of the CK level. |
Ethambutol | 15 mg/kg/d | Optic neuritis, red-green color blindness, peripheral neuropathy | |
Ethionamide | 1.92 ± 0.27 h | Chronic | Hypothyroid, hypoglycemia, photosensitivity, neurotoxic effects |
Gramicidin | Unknown | Hemolysis | |
Isoniazid (INH) | 0.5–4 h | 1–2 g orally | Convulsions, metabolic acidosis (See Anion gap metabolic acidosis); hepatotoxicity and peripheral neuropathy with chronic use |
