Aminoglycosides Amikacin Gentamicin Kanamycin Neomycin Streptomycin Tobramycin | 2–3 h 2 h 2–3 h 2.5 h 2–2.5 h | Varies Varies >30 mg/L 0.5–1 g/d >40–50 mg/L Varies | Toxic 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, dosage schedule, treatment duration, and sampling time. |
| Antimycobacterials | | | Used for treatment of tuberculosis and other mycobacterial infections |
| Bedaquiline | 4–5 mo | Unknown | QT prolongation, hepatotoxicity |
| Ethambutol | 4 h | Chronic; 15 mg/kg/d and up | Optic neuritis, red-green color blindness, peripheral neuropathy. Risk of ocular adverse effects increases with dose: 1% at 15 mg/kg/d, 5% at 25 mg/kg/d, 18% at 35 mg/kg/d. |
| Ethionamide | 1.92 ± 0.27 h | GI intolerance acute; other effects chronic | Severe nausea/vomiting, hepatitis, hypothyroidism, hypoglycemia, photosensitivity, neurotoxic effects |
| Isoniazid (INH) | 0.5–4 h | 1–2 g orally | Convulsions, metabolic acidosis, hypotension, acute hepatic failure; hepatotoxicity and peripheral neuropathy with chronic use |
| Pyrazinamide | 9–10 h | 40–50 mg/kg/d for prolonged period | Hepatotoxicity, hyperuricemia |
| Rifampin, rifabutin, rifapentine | 1.5–5 h, 36 h, 13 h | 100 mg/kg/d (fatal exposures at 14–60 g) | All patients will develop harmless red discoloration of urine, sweat, and tears. With acute exposure, abdominal pain, vomiting and diarrhea (may be red), facial edema, pruritus. Severe toxicity includes acute hepatic failure, seizures, cardiac arrest. Antibiotics of rifamycin class are inducers of hepatic cytochrome P450 enzymes, especially CYP3A4. |
| Bacitracin | | Unknown | Minimal enteric systemic absorption; if administered parenterally or absorbed via breaks in skin, ototoxicity and nephrotoxicity |
| Carbapenems | | | Hypersensitivity reactions; seizures associated with renal dysfunction and high doses |
| Doripenem | 1 h | Chronic | |
| Ertapenem | 4 h (2.5 h in ages 3 mo–12 y) | Chronic | |
| Imipenems/cilastatin | 1 h | Acute: >1 g every 6 h; Chronic | Highest seizure risk for imipenem |
| Meropenem | 1 h | Chronic | |
| Cephalosporins | | | Hypersensitivity reactions; convulsions reported in patients with renal insufficiency and excessive doses |
Cefazolin Cephalothin | 90–120 min | Unknown | Coagulopathy associated with cefazolin |
| Cefaclor | 0.6–0.9 h | Chronic | Neutropenia |
Cefoperazone Cefamandole Cefotetan Moxalactam Cefmetazole | 102–156 min 30–60 min 3–4.6 h 114–150 min 72 min | 3–4 mg/L | One case of symptomatic hepatitis. All these antibiotics have the N-methylthiotetrazole side chain, which may inhibit aldehyde dehydrogenase to cause a disulfiram-like interaction with ethanol (Disulfiram) and coagulopathy (inhibition of vitamin K production). |
| 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 min |
| Cefepime | 2 h | Chronic | Encephalopathy, nonconvulsive status epilepticus associated with high doses, renal dysfunction. |
| Chloramphenicol | 4 h | >40 mg/L | Leukopenia, reticulocytopenia, circulatory collapse ("gray baby" syndrome) |
| Clindamycin, lincomycin, | 2.4–3 h, 4.4–6.4 h | Unknown | Hypotension and cardiopulmonary arrest after rapid intravenous administration |
| Daptomycin | 8–9 h | Chronic | May cause muscle pain, weakness, or asymptomatic elevation of the CK level. Rare cases of rhabdomyolysis, dosage-related. |
| Fidaxomicin | 12 h | Unknown | Minimal systemic absorption; nausea/vomiting/abdominal pain possible |
| Folate antagonists | | | Bone marrow suppression |
| Pyrimethamine | 2–6 h | Acute ≥300 mg; Chronic | Seizures, hypersensitivity reactions, folic acid deficiency |
| Trimethoprim | 8–11 h | Unknown | Methemoglobinemia, hyperkalemia |
| Fosfomycin | 12 h | Unknown | Low serum concentrations with oral administration; nausea, vomiting. Ototoxicity and taste disturbances in overdoses |
Glycopeptides |
Dalbavancin | 346 h | Unknown | Highly protein bound; administered once weekly. No experience in overdose; possible hepatotoxicity, bleeding risk. |
| Oritavancin | 245 h | Unknown | Highly protein bound; administered once weekly. P450 drug interactions. Interferes with coagulation lab tests (aPTT, INR). |
| Telavancin | 8 ± 1.5 h | Chronic | Nephrotoxic; may cause QTc prolongation, foamy urine, "red man" syndrome; interferes with coagulation tests. |
| Vancomycin | 4–6 h | >80 mg/L acute; >25 mg/L chronic | Nephrotoxic at high doses. Hypotension, skin rash/flushing ("red man" syndrome) associated with rapid IV administration. Possible ototoxicity. |
| Gramicidin | | Unknown | Topical/ophthalmic agent. Hemolysis if systemically absorbed. |
| Linezolid, tedizolid | 4.5–5.5 h, 12 h | Duration-related (>2 wk) | Thrombocytopenia, anemia; lactic acidosis (rare); peripheral neuropathy and optic neuritis with prolonged use. Linezolid is an inhibitor of monoamine oxidase; serotonin syndrome reported when combined with antidepressants. |
| Macrolides | | | Can prolong the QT interval and lead to torsade de pointes (atypical ventricular tachycardia). Inhibitors of CYP enzymes. |
| Azithromycin | 68 h | Chronic | Least likely of the macrolides to induce torsade in animal studies and least potent P450 inhibitor. |
| 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 h | Minimum toxic dose unknown, but 1–1.5 mL (300–450 mg) caused serious symptoms | Cardiotoxic: tachycardia, decreased contractility, cardiac arrest |
| Nitrofurantoin | 20 min | Unknown | Nausea/vomiting with acute overdose; hemolysis in G6PD-deficient patients is possible. Pulmonary hypersensitivity reactions with long-term use. |
| Nitroimidazoles | | | Seizures with acute overdose; peripheral neuropathy with chronic use; disulfiram-like reactions with ethanol (Disulfiram) |
| Metronidazole | 6–14 h | 5 g/d | |
| Tinidazole | 12–14 h | Chronic | |
| Penicillins | | | Hypersensitivity reactions; seizures with single high dose or chronic excessive doses in patients with renal dysfunction |
Ampicillin, | 1.5 h | Unknown | Acute renal failure caused by crystal deposition |
amoxicillin | 1.3 h | | |
| Methicillin | 30 min | Unknown | Interstitial nephritis, leukopenia |
| Nafcillin | 1.0 h | Unknown | Neutropenia |
| Penicillin G | 30 min | 10 million units/d IV (6 g), or CSF >5 mg/L | Administration of long-acting IM salt formulations (benzathine, procaine) via IV route associated with cardiovascular collapse and death. |
Penicillins, anti-pseudomonal |
Carbenicillin Mezlocillin Piperacillin/tazobactam Ticarcillin | 1.0–1.5 h 0.8–1.1 h 0.6–1.2 h 1.0–1.2 h | >300 mg/kg/d or >250 mg/L >300 mg/kg/d >300 mg/kg/d >275 mg/kg/d | Bleeding disorders due to impaired platelet function; hypokalemia (formulations have high sodium content). Risk for toxicity higher in patients with renal insufficiency. |
Polymyxins |
Polymyxin B | 4.3–6 h | 30,000 units/kg/d | Nephrotoxicity and noncompetitive neuromuscular blockade |
| Polymyxin E (colistin) | 2–3 h | 250 mg IM in a 10-month-old caused acute renal failure | |
| Quinolones | | | Tendonitis and tendon rupture (higher risk with increased age, corticosteroid use, renal dysfunction) Potentially irreversible peripheral neuropathy. Some agents can prolong the QT interval. Headache, dizzinesss, seizures. Acute liver injury. Dysglycemia in susceptible populations. |
| Ciprofloxacin | 4 h | Acute 7.5 g | Crystalluria associated with doses above daily maximum and with alkaline urine. Inhibits CYP1A2 – interactions with theophylline and caffeine. |
| 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. |
| Gemifloxacin | 7 h | Chronic | Encephalopathy |
| Levofloxacin | 6–8 h | Chronic | Hepatotoxicity, vision impairment, pseudotumor cerebri, autoimmune hemolytic anemia; interactions with herbal and natural supplements may cause cardiotoxicity. |
| Lomefloxacin | 8 h | Chronic | Phototoxicity, seizures |
| Moxifloxacin | 12 h | Chronic | Highest QT prolongation of quinolones available in the United States. |
| Nalidixic acid | 1.1–2.5 h | 50 mg/kg/d | Metabolic acidosis; intracranial hypertension |
| Norfloxacin | 3–4 h | Chronic | 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). |
| Sulfonamides and Sulfones | | | Hypersensitivity reactions, including severe rash; frequently co-administered with folate antagonists |
| Dapsone | 10–50 h | As little as 100 mg in an 18-month-old | Methemoglobinemia (see Dapsone), sulfhemoglobinemia, hemolysis; metabolic acidosis; hallucinations, confusion; hepatitis |
| Sulfamethoxazole | | Unknown | Acute renal failure caused by crystal deposition |
| Tetracyclines | | | Use of tetracyclines may discolor/damage developing teeth, avoid in pregnancy and children <8 y. Risk of fetal harm in pregnancy. |
| Demeclocycline | 10–17 h | Chronic | Nephrogenic diabetes insipidus |
| Doxycycline | 12–20 h | Chronic | Rare esophageal ulceration |
| Minocycline | 11–26 h | Chronic | Vestibular symptoms |
| Tetracycline | 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 |
| >4 g/d in pregnancy or >15 mg/L | Acute fatty liver |
| Tigecycline | 37–67 h | Chronic | Nausea and vomiting common. |