Macrolides

Macrolides are commonly used antibiotics in treatment of a variety of conditions including typical and atypical pneumonia. Macrolides work by binding to the 50s subunit of ribosomes, which prevents protein synthesis. Macrolides are bacteriostatic.  Resistance is common and is accomplished by efflux pumps, alterations of the 50s subunit, decreased uptake, and enzymatic degradation.  Macrolides can cause ototoxicity, hepatotoxicity, prolonged QT interval, and are metabolized by the cytochrome P450 system, which can result in medication interactions.  

Class Drugs

• Azithromycin

• Clarithromycin

• Erythromycin

• Telithromycin

Class Mechanism of Action

Binds to 50s subunit of bacterial ribosome, which prevents protein synthesis

Bacteriostatic

Class Applications

See individual drugs

Class Adverse Effects

Resistance

• Efflux pumps

Pumps decrease intracellular concentration of drug

• Change of 50s subunit, which decreases drugs affinity for binding and limits effectiveness

• Decreased uptake by organism

• Enzymatic resistance

Erythromycin esterase found in plasmids of gram-negatives (some cross resistance to azithromycin and clarithromycin)

Increased motility and stomach cramping

Hypersensitivity

Ototoxicity

Caution in patients with liver disease

• Accumulation in the liver

• Hepatotoxicity

Prolonged QT interval

Drug-drug interactions due to inhibition of CYP450 (Warfarin, statins, digoxin, etc.)

Drug Table

Drug Name	Application	Comments	Image
Azithromycin	Respiratory infections; H. influenzae; M. catarrhalis; S. pneumoniae (significant resistance developing); M. pneumonia (atypical pneumonia); Mycobacterium avium complex (MAC) (M avium and M intracellulare); Used in combination with rifampin and ethambutol for treatment of MAC; Solo treatment for MAC prophylaxis; Urethritis; Chlamydia		"Arizona" "Throw mice in"
Clarithromycin	Respiratory infections; H. influenzae; M. catarrhalis; S. pneumoniae (significant resistance developing); H. pylori		"Clarinet" "Throw mice in"
Erythromycin	Treatment of ileus; Respiratory infections; H. influenzae; M. catarrhalis; S. pneumoniae (significant resistance developing); M. pneumonia (atypical pneumonia)		"Red" "Throw mice in"
Telithromycin	Similar to azithromycin	Limited use due to severe hepatotoxicity	"Telephone" "Throw mice in"