Macrolides and Ketolides

Agents: clarithromycin, azithromycin,  erythromycin, telithromycin (a ketolide)

Macrolides are among the antibiotics used most frequently in the outpatient setting because of their broad coverage of respiratory pathogens.  Though their coverage is broad, it is not particularly deep, because there is increasing resistance to these agents (especially in  Streptococcus pneumoniae). To combat this resistance, the ketolide derivatives (including telithromycin) have been introduced with better coverage of resistant S. pneumoniae. Unfortunately, telithromycin appears to have a significant risk of hepatotoxicity. Although erythromycin is the class patriarch, because of its adverse effects, drug interactions, and frequent dosing, it has little use except as a GI stimulant.

Spectrum

Good: atypicals,  Haemophilus influenzae,  Moraxella catarrhalis,  Helicobacter pylori,  Mycobacterium avium

Moderate: S. pneumoniae (telithromycin < macrolides), S. pyogenes

Poor : staphylococci, enteric GNRs (azithromycin < clarithromycin), anaerobes, enterococci .

Adverse Effects

Gastrointestinal: Significant GI adverse effects  (nausea, vomiting, diarrhea) have been associated with the macrolides. Erythromycin is the worst offender—it is employed as a pro-kinetic agent for patients with impaired GI motility.

Hepatic: Rare but serious adverse hepatic events have been associated with the macrolides.  Telithromycin has been associated with hepatic failure leading to death or the need for transplantation.

Cardiac: Prolongation of the QT interval has been seen with the macrolides, again most commonly with erythromycin. Use with caution in patients with preexisting heart conditions,  those on antiarrhythmic drugs, or those taking interacting drugs (see below).

Important Facts

• Drug interaction alert! These drugs (with the exception of azithromycin) are potent inhibitors of drug-metabolizing cytochrome P450 enzymes. Be sure to screen your patient’s regimen with a computerized drug interaction checker or a drug information resource before starting these agents.

• Azithromycin has a prolonged half-life such that a 3- to 5-day course may be adequate for most infections, instead of 7–10 days with other drugs. This makes use of the Z-pak® and the newer Z-max® possible.

• Macrolides are bacteriostatic drugs and are not appropriate for infections in which cidal activity is usually required (meningitis, endocarditis, etc.).

• Prevpac® is a combination of drugs prescribed for eradication of H. pylori and the treatment of peptic ulcer disease. In addition to clarithromycin and lansoprazole, it contains amoxicillin. Be sure to screen patients for beta-lactam allergies and drug interactions before administering it.

What They’re Good For

Upper and lower respiratory tract infections,  chlamydia, atypical mycobacterial infections, and traveler’s diarrhea (azithromycin). Clarithromycin is a key component in the treatment of H. pylori–induced GI ulcer disease in combination with other drugs and acid-suppressive agents.

Don’t Forget!

Sure, macrolides are good respiratory tract drugs and are relatively benign, but do you really need to be treating your patient’s nonspecific (possibly viral)  cough and cold with any antibiotic? Besides causing possible adverse reactions and wallet toxicity, over-use of these drugs has contributed to increasing  resistance. How about some decongestants, acetaminophen, and chicken soup instead?

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.