The antibacterial group 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.
TABLE II-4. ANTIBACTERIAL DRUGS| Drug | Toxicity |
|---|---|
Aminoglycosides Amikacin Gentamicin Kanamycin Neomycin Streptomycin Tobramycin | 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 | |
| Bedaquiline | QT prolongation, hepatotoxicity |
| Ethambutol | 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 | Severe nausea/vomiting, hepatitis, hypothyroidism, hypoglycemia, photosensitivity, neurotoxic effects |
| Isoniazid (INH) | Convulsions, metabolic acidosis, hypotension, acute hepatic failure; hepatotoxicity, peripheral neuropathy, and psychosis with chronic use |
| Pretomanid | Peripheral neuropathy, hepatotoxicity (with linezolid and bedaquiline) |
| Pyrazinamide | Hepatotoxicity, hyperuricemia |
| Rifampin, rifabutin, rifapentine | 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 | Minimal enteric systemic absorption; if administered parenterally or absorbed via breaks in skin, ototoxicity and nephrotoxicity |
Carbapenems Doripenem Ertapenem Imipenem/cilastatin Meropenem | Hypersensitivity reactions; seizures associated with renal dysfunction and high doses. Highest seizure risk with imipenem. |
| Cephalosporins | Hypersensitivity reactions; convulsions reported in patients with renal insufficiency and excessive doses |
Cefazolin Cephalothin | Coagulopathy associated with cefazolin |
| Cefaclor | Neutropenia |
Cefoperazone Cefamandole Cefotetan Moxalactam Cefmetazole | 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 and coagulopathy (inhibition of vitamin K production). |
| Ceftriaxone | Pseudolithiasis (“gallbladder sludge”). IV dose should be given over at least 30 min |
| Cefepime | Encephalopathy, myoclonic and nonconvulsive status epilepticus associated with high doses, renal dysfunction. |
| Cefiderocol | Transaminase elevation, hypokalemia, nausea, vomiting, diarrhea |
| Chloramphenicol | Leukopenia, reticulocytopenia, circulatory collapse (“gray baby” syndrome) |
| Clindamycin, lincomycin | Hypotension and cardiopulmonary arrest after rapid intravenous administration |
| Daptomycin | May cause muscle pain, weakness, or asymptomatic elevation of the CK level. Rare cases of rhabdomyolysis, dosage-related. |
| Fidaxomicin | Minimal systemic absorption; nausea/vomiting/abdominal pain possible |
| Folate antagonists | Bone marrow suppression |
| Pyrimethamine | Seizures, hypersensitivity reactions, folic acid deficiency |
| Trimethoprim | Methemoglobinemia, hyperkalemia |
| Fosfomycin | Low serum concentrations with oral administration; nausea, vomiting. Ototoxicity and taste disturbances in overdoses |
| Glycopeptides | |
| Dalbavancin | Highly protein bound; administered once weekly. Possible hepatotoxicity, bleeding risk; accidental double dose (3,000 mg) caused mild diarrhea. |
| Oritavancin | Highly protein bound; administered once weekly. P450 drug interactions. Interferes with coagulation lab tests (aPTT, INR). |
| Telavancin | Nephrotoxic; may cause QTc prolongation, foamy urine, “red man” syndrome; interferes with coagulation tests. |
| Vancomycin | Nephrotoxic at high doses. Hypotension, skin rash/flushing (“red man” syndrome) associated with rapid IV administration. Possible ototoxicity. |
| Gramicidin | Topical/ophthalmic agent. Hemolysis if systemically absorbed. |
| Lefamulin | QT prolongation, transaminase elevation; fetal harm in animals. |
| Linezolid, tedizolid | 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 | Least likely of the macrolides to induce torsade in animal studies and least potent P450 inhibitor. |
| Clarithromycin | Fatal hepatotoxicity reported (rare) |
| Dirithromycin | Hepatotoxicity |
| Erythromycin | Abdominal pain; idiosyncratic hepatotoxicity with estolate salt. Administration of more than 4 g/d may cause tinnitus, ototoxicity. |
| Tilmicosin (veterinary drug) | Cardiotoxic: tachycardia, decreased contractility, cardiac arrest |
| Nitrofurantoin | 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 |
| Metronidazole | |
| Tinidazole | |
| Penicillins | Hypersensitivity reactions; seizures with single high dose or chronic excessive doses in patients with renal dysfunction |
| Ampicillin, amoxicillin | High doses can cause acute kidney injury by crystal deposition; amoxicillin-clavulanate can cause liver injury. |
| Methicillin | Interstitial nephritis, leukopenia |
| Nafcillin | Neutropenia |
| Penicillin G | 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 | May interfere with platelet function; hypokalemia due to renal loss. Most formulations contain 2-5 mEq of sodium per gram of drug. Risk for toxicity higher in patients with renal insufficiency. |
Polymyxins Polymyxin B Polymyxin E (colistin) | Nephrotoxicity and noncompetitive neuromuscular blockade |
| 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 | Crystalluria associated with doses above daily maximum and with alkaline urine. Inhibits CYP1A2 - interactions with theophylline and caffeine. |
| Gatifloxacin | Case reports of induced cholestatic hepatitis and hallucinations. Hypoglycemia or hyperglycemia. Oral and parenteral products withdrawn from US market. |
| Gemifloxacin | Encephalopathy. |
| Levofloxacin | Hepatotoxicity, vision impairment, pseudotumor cerebri, autoimmune hemolytic anemia; interactions with herbal and natural supplements may cause cardiotoxicity. |
| Lomefloxacin | Phototoxicity, seizures. |
| Moxifloxacin | Highest QT prolongation of quinolones available in the United States. |
| Nalidixic acid | Metabolic acidosis; intracranial hypertension |
| Norfloxacin | Crystalluria associated with doses above daily maximum and with alkaline urine |
| Ofloxacin | Neuropsychiatric symptoms: agitation, confusion, hallucination, psychosis. |
| Sparfloxacin | 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 | Methemoglobinemia (see), sulfhemoglobinemia, hemolysis; metabolic acidosis; hallucinations, confusion; hepatotoxicity |
| Sulfamethoxazole | 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 | Nephrogenic diabetes insipidus |
| Doxycycline | Rare esophageal ulceration |
| Minocycline | Vestibular symptoms |
| Tetracycline | Benign intracranial hypertension. Degradation products (eg, expired prescriptions) are nephrotoxic, may cause Fanconi-like syndrome. Some products contain sulfites. Doses >4 g/d can cause acute fatty liver in pregnant women. |
| Tigecycline | Nausea and vomiting common; coagulopathy (rare). |
The precise mechanisms underlying toxic effects vary with the agent and are not well understood.
After acute oral overdose, most agents cause only nausea, vomiting, and diarrhea. Specific features of toxicity are described in Table II-4.
Is usually based on the history of exposure.