DESCRIPTION

The macrolide antimicrobials include erythromycin, azithromycin, clarithromycin, and other compounds with similar structure.

FORMS AND USES

• Macrolide antibiotics are used for the treatment of local or systemic infection with bacterial organisms.
• Macrolide antibiotics are available in a wide variety of forms, including azithromycin (Zithromax), erythromycin [base (E-Mycin), estolate, ethylsuccinate (EES), gluceptate, lactobionate, and stearate], clarithromycin (Biaxin), dirithromycin, and troleandomycin (Tao).

TOXIC DOSE

The macrolide antibiotics do not cause major toxicity in isolated acute overdose; they do, however, cause a number of adverse effects at therapeutic doses.

PATHOPHYSIOLOGY

• Toxic effects of the macrolides as a group include gastrointestinal irritation, cholestatic jaundice, ototoxicity, thrombophlebitis, and ventricular dysrhythmia; these effects are usually reversible upon discontinuation of the drug.
• Erythromycin may induce gastrointestinal symptoms, abdominal pain, thrombophlebitis, hearing loss, and exacerbation of weakness in myasthenia gravis.

DRUG AND DISEASE INTERACTIONS

Because they inhibit liver metabolism, macrolide antibiotics can increase the effects of benzodiazepines, calcium channel blockers, cyclic antidepressants, digoxin, ergotamine, estradiol, serotonin reuptake inhibitors, lovastatin (rhabdomyolysis), other macrolides, progesterone, theophylline, warfarin, and other agents.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects following exposure are typically mild.
• Death occurs only in conjunction with a coingestant.

CAUSES

• Macrolide antibiotic poisoning usually results from an accidental ingestion.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

PREGNANCY AND LACTATION

• Azithromycin and erythromycin. US FDA Pregnancy Category B. Studies indicate no fetal risk and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in pregnant women do not.
• Clarithromycin. US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• DRUG AND DISEASE INTERACTIONS
• EPIDEMIOLOGY
• CAUSES
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

Acute gastrointestinal effects can be caused by a wide variety of compounds, such as theophylline, salicylates, and caustic substances.

SIGNS AND SYMPTOMS

• Drug interactions are the primary cause of toxicity.
• Acute ingestion causes abdominal pain and other gastrointestinal effects.

HEENT

• Reversible ototoxicity characterized by a sensorineural hearing loss may occur.

Cardiovascular

• Ventricular dysrhythmias occur rarely in macrolide antibiotic toxicity.
• Erythromycin may produce thrombophlebitis.

Gastrointestinal

• Nausea, vomiting, abdominal pain, and diarrhea are common.
• Cholestatic jaundice, liver failure, and pseudomembranous colitis occur rarely.

Neurologic

• Erythromycin may exacerbate weakness in myasthenia gravis or cause sensorineural hearing loss.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No test may be needed in minimally symptomatic patients.

Recommended Tests

• Serum electrolytes, BUN, and creatinine should be obtained in severe cases to assess volume depletion and electrolyte abnormalities.
• ECG, serum acetaminophen, and aspirin levels should be obtained in overdose settings to detect occult ingestion.
• Audiologic testing should be performed for hearing complaints.

Not Recommended Tests

Serum drug levels are not clinically helpful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • HEENT
  • Cardiovascular
  • Gastrointestinal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Treatment should focus on general supportive care and expectant care of adverse effects.
• Dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• The patient or caregiver seems unreliable.
• Toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted for patients who develop persistent vomiting that is not controlled by antiemetic agents, or for other serious effects.

DECONTAMINATION

Out of Hospital

Emesis is not recommended because of the low toxic potential of macrolide antibiotics.

In Hospital

One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

There is no specific antidote available for macrolide antibiotic poisoning.

ADJUNCTIVE TREATMENT

• Hypotension is treated with isotonic fluid infusion, the Trendelenburg position, and vasopressors if needed; dopamine is preferred, and norepinephrine is used for refractory hypotension.
• Enhanced elimination by hemodialysis or hemoperfusion is not possible with macrolide antibiotics.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

ECG and cardiac monitoring is recommended for patients with cardiac complaints.

EXPECTED COURSE AND PROGNOSIS

• Acute overdose is usually benign and managed with supportive and conservative care.
• Ototoxicity is usually reversible.

DISCHARGE CRITERIA/INSTRUCTIONS

Patients may be discharged from the emergency department or hospital when acute effects remit and following psychiatric evaluation, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Macrolide antibiotic toxicity may be confused with ingestion of other agents or conditions that produce nonspecific CNS or respiratory depression, seizures, renal, bone marrow, or hepatic injury, or diarrheal illness.
• Patients often take over-the-counter medications and antibiotics on their own initiative, and occasionally fail to inform the health-care provider of these coingestants.

Poisoning by antibiotics: erythromycin and other macrolides.

See Also: SECTION II, Hypotension and Seizure chapters.

RECOMMENDED READING

Absher JR, Bale JF. Aggravation of myasthenia gravis by erythromycin. J Pediatr 1991;119:155-156.

Alcalay J, Halevy S, Theodor E, et al. Asymptomatic liver injury due to erythromycin stearate. Drug Intell Clin Pharm 1986;20:601-602.

Brandriss MW, Richardson WS, Barold SS. Erythromycin-induced QT prolongation and polymorphic ventricular tachycardia (torsades de pointes): case report and review. Clin Infect Dis 1994;18:995-998.

Author: Steven A. Seifert

Reviewer: Richard C. Dart