Not Found

Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.


By Hans P. Schlecht, MD, MSc, Assistant Professor of Medicine, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Drexel University College of Medicine
Christopher Bruno, MD, Assistant Professor of Medicine, Division of infectious Diseases & HIV Medicine, Drexel University College of Medicine

Click here for
Patient Education

Macrolides (see Table: Macrolides) are antibiotics that are primarily bacteriostatic; by binding to the 50S subunit of the ribosome, they inhibit bacterial protein synthesis.





Oral or parenteral




Oral or parenteral






Except for telithromycin (see Telithromycin), macrolides are relatively poorly absorbed orally. Fidaxomicin is minimally absorbed and active only locally in the GI tract. Food has the following effects on macrolide absorption:

  • For extended-release clarithromycin, increased absorption

  • For immediate-release clarithromycin tablet or suspension, no effect

  • For azithromycin capsules and erythromycin (including base and stearate formulations), decreased absorption

  • For fidaxomicin, minimal effects

Once absorbed macrolides diffuse well into body fluids, except CSF, and are concentrated in phagocytes. Excretion is mainly in bile.


Macrolides are active against

  • Aerobic and anaerobic gram-positive cocci, except for most enterococci, many Staphylococcus aureus strains (especially methicillin-resistant strains), and some Streptococcus pneumoniae and S. pyogenes strains

  • Mycoplasma pneumoniae

  • Chlamydia trachomatis

  • Chlamydophila pneumoniae

  • Legionella sp

  • Corynebacterium diphtheriae

  • Campylobacter sp

  • Treponema pallidum

  • Propionibacterium acnes

  • Borrelia burgdorferi

Bacteroides fragilis is resistant. Clarithromycin and azithromycin have enhanced activity against Haemophilus influenzae and activity against Mycobacterium avium complex.

Macrolides have been considered the drug of choice for group A streptococcal and pneumococcal infections when penicillin cannot be used. However, pneumococci with reduced penicillin sensitivity are often resistant to macrolides, and in some communities, up to 20% of S. pyogenes are macrolide-resistant. Because they are active against atypical respiratory pathogens, they are often used empirically for lower respiratory tract infections, but another drug is often necessary to cover macrolide-resistant pneumococci. Macrolides have other clinical uses (see Table: Some Clinical Uses of Macrolides). Macrolides are not used to treat meningitis.

Fidaxomicin has minimal to no activity against gram-negative bacteria but is bactericidal against Clostridium difficile.

Some Clinical Uses of Macrolides





Infection due to Mycoplasma pneumoniae, Legionella sp, or Bordetella pertussis

Eradication of Corynebacterium diphtheriae in carriers

Drugs of choice

Symptomatic cat-scratch disease (Bartonella henselae)

Bacillary angiomatosis and peliosis hepatis in patients with AIDS (involving B. henselae or B. quintana)


Cerebral toxoplasmosis

Used with other drugs


Used with other drugs

Chlamydia trachomatis urethritis and cervicitis

Clarithromycin and azithromycin

Mycobacterium avium complex

Part of a multidrug regimen


Uncomplicated skin infections


Topical use

Bowel preparation before GI tract surgery

Taken orally and used with an oral aminoglycoside


Clostridium difficile


Macrolides are contraindicated in patients who have had an allergic reaction to them.

Concomitant administration of macrolides with astemizole, cisapride, pimozide, or terfenadine is contraindicated because potentially fatal cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, torsades de pointes) may occur when clarithromycin or erythromycin is given with these drugs. This effect is most likely due to inhibition of metabolism of these drugs by erythromycin and clarithromycin.

Use During Pregnancy and Breastfeeding

Erythromycin and azithromycin are in pregnancy category B (animal studies show no risk and human evidence is incomplete, or animal studies show risk but human studies do not). Erythromycin is considered safer because clinical use has been much more extensive.

Clarithromycin is in category C (animal studies show some risk, evidence in human studies is inadequate, but clinical benefit sometimes outweighs risk).

Erythromycin is considered compatible with breastfeeding. Safety of other macrolides during breastfeeding is unknown.

Adverse Effects

Main concerns include

  • GI disturbances (mainly with erythromycin)

  • QT-interval prolongation by erythromycin

  • Inhibition of hepatic metabolism, leading to numerous drug interactions

Erythromycin commonly causes dose-related GI disturbances, including nausea, vomiting, abdominal cramps, and diarrhea; disturbances are less common with clarithromycin and azithromycin. Taking the drug with food may help decrease GI disturbances. Erythromycin may cause dose-related tinnitus, dizziness, and reversible hearing loss. Cholestatic jaundice occurs most commonly with erythromycin estolate. Jaundice usually appears after 10 days of use, primarily in adults but can occur earlier if the drug has been given previously. Erythromycin is not given IM because it causes severe pain; when given IV, it may cause phlebitis or pain. Hypersensitivity reactions are rare.

Erythromycin causes QT-interval prolongation and predisposes to ventricular tachyarrhythmia, especially in women, in patients who have QT-interval prolongation or electrolyte abnormalities, and in patients taking another drug that may prolong the QT interval.

Dosing Considerations

For azithromycin, no dosage adjustment is required for renal insufficiency.

Erythromycin and, to some extent, clarithromycin interact with numerous drugs because they inhibit hepatic metabolism via the cytochrome P-450 (CYP450) system. Azithromycin is the least likely to interact with other drugs. Interactions may occur when erythromycin or clarithromycin is taken with the following:

  • Warfarin: Further elevation of the PT/INR

  • Lovastatin and simvastatin: Rhabdomyolysis

  • Midazolam and triazolam: Somnolence

  • Theophylline: Nausea, vomiting, and seizures

  • Tacrolimus, cyclosporine, and ergot alkaloids: Elevated serum levels of these drugs

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • ORAP
  • No US brand name