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 |
Lincomycin, clindamycin | 4.4–6.4 h 2.4–3 h | Unknown | Hypotension and cardiopulmonary arrest after rapid intravenous administration |
Linezolid | 4.5–5.5 h | Duration-related (>2 wk) | Thrombocytopenia, anemia; peripheral neuropathy. Linezolid is an inhibitor of monoamine oxidase (See Monoamine Oxidase Inhibitors). |
Macrolides | | | Can prolong the QT interval and lead to torsade de pointes (atypical ventricular tachycardia). |
Azithromycin | 68 h | Chronic | Least likely of the macrolides to induce torsade in animal studies. |
Clarithromycin | 3–4 h | Chronic | |
Dirithromycin | 44 (16–55) h | Chronic | Hepatotoxicity |
Erythromycin | 1.4 h | Unknown | Abdominal pain; idiosyncratic hepatotoxicity with estolate salt. Administration of more than 4 g/d may cause tinnitus, ototoxicity. |
Tilmicosin (veterinary drug) | Death may occur within 1 hour | Minimum toxic dose unknown, but 1–1.5 mL (300–450 mg) caused serious symptoms | Cardiotoxic: tachycardia, decreased contractility, cardiac arrest |
Metronidazole | 6–14 h | 5 g/d | Seizures; at therapeutic doses may cause disulfiram-like interaction with ethanol (See Disulfiram). |
Tinidazole | 12–14 h | Chronic | Seizures, peripheral neuropathy |
Nalidixic acid | 1.1–2.5 h | 50 mg/kg/d | Seizures, hallucinations, confusion; visual disturbances; metabolic acidosis; intracranial hypertension |
Nitrofurantoin | 20 min | Unknown | Hemolysis in G6PD-deficient patients |
Penicillins | | | |
Penicillin | 30 min | 10 million units/d IV (6 g), or CSF >5 mg/L | Seizures with single high dose or chronic excessive doses in patients with renal dysfunction |
Methicillin | 30 min | Unknown | Interstitial nephritis, leukopenia |
Nafcillin | 1.0 h | Unknown | Neutropenia |
Ampicillin, amoxicillin | 1.5 h 1.3 h | Unknown | Acute renal failure caused by crystal deposition |
Penicillins, antipseudomonal | | | |
Carbenicillin | 1.0–1.5 | >300 mg/kg/d or >250 mg/L | Bleeding disorders due to impaired platelet function; hypokalemia. Risk for toxicity higher in patients with renal insufficiency. |
Mezlocillin | 0.8–1.1 | >300 mg/kg/d |
Piperacillin | 0.6–1.2 | >300 mg/kg/d |
Ticarcillin | 1.0–1.2 | >275 mg/kg/d |
Polymyxins | | | Nephrotoxicity and noncompetitive neuromuscular blockade |
Polymyxin B | 4.3–6 h | 30,000 units/kg/d | |
Polymyxin E | | 250 mg IM in a 10-month-old | |
Pyrazinamide | 9–10 h | 40–50 mg/kg/d for prolonged period | Hepatotoxicity, hyperuricemia |
Pyrimethamine | 2–6 h | Acute ≥300 mg Chronic | Seizures Folic acid deficiency, hematologic effects, hypersensitivity reactions |
Quinolones | | | May damage growing cartilage, tendonitis, tendon rupture; hemolysis in patients with G6PD deficiency; exacerbation of myasthenia gravis; acute renal failure, hepatotoxicity. Some agents can prolong the QT interval. Seizures and dysglycemia in susceptible populations. |
Ciprofloxacin | 4 h | | Crystalluria associated with doses above daily maximum and with alkaline urine. Inhibits CYP1A2. |
Gatifloxacin | 7–14 h | Hypoglycemia or hyperglycemia within 6 and 5 days of therapy, respectively | Case reports of induced cholestatic hepatitis and hallucinations. Hypoglycemia or hyperglycemia. Oral and parenteral products withdrawn from US market. |
Levofloxacin | 6–8 h | Chronic | Irreversible peripheral neuropathy, hepatotoxicity, vision impairment, pseudotumor cerebri, autoimmune hemolytic anemia; interactions with herbal and natural supplements may cause cardiotoxicity. |
Lomefloxacin | 8 h | | Phototoxicity, seizures |
Norfloxacin | 3–4 h | | Crystalluria associated with doses above daily maximum and with alkaline urine |
Ofloxacin | 7.86 ± 1.81 h | Chronic | Psychotoxicity |
Sparfloxacin | 16–30 h | Chronic | Associated with prolonged QT interval and torsade de pointes. Photosensitivity (use at least SPF 15 in sun-exposed areas). |
Trovafloxacin | 9.1–12.2 h | | Pancreatitis and acute hepatitis (deaths reported). Alatrofloxacin is the IV form of trovafloxacin. Withdrawn from market. |
Rifampin | 1.5–5 h | 100 mg/kg/d | Facial edema, pruritus; headache, vomiting, diarrhea; red urine and tears. Antibiotics of rifamycin class are inducers of hepatic cytochrome P-450 enzymes, especially CYP3 A. |
Spectinomycin | 1.2–2.8 h | | Acute toxicity not reported |
Sulfonamides | | Unknown | Acute renal failure caused by crystal deposition |
Tetracyclines | 6–12 h | >1 g/d in infants | Benign intracranial hypertension. Degradation products (eg, expired prescriptions) are nephrotoxic, may cause Fanconi-like syndrome. Some products contain sulfites. May discolor/damage developing teeth. |
| | >4 g/d in pregnancy or >15 mg/L | Acute fatty liver |
Demeclocycline | 10–17 h | Chronic | Nephrogenic diabetes insipidus |
Minocycline | 11–26 h | Chronic | Vestibular symptoms |
Tigecycline | 37–67 h | Chronic | A glycylcycline (analog of minocycline). May cause fetal harm. Available only as an IV injection. |
Telavancin | 8 ± 1.5 h | Chronic | Nephrotoxic; may cause QTc prolongation, foamy urine, “red man” syndrome; interferes with coagulation tests. |
Trimethoprim | 8–11 h | Unknown | Bone marrow depression, methemoglobinemia, hyperkalemia |
Vancomycin | 4–6 h | >80 mg/L | Ototoxic and nephrotoxic. Hypertension, skin rash/flushing (“red man” syndrome) associated with rapid IV administration. |