Erythromycin is a traditional drug of choice in corynebacterial infections (diphtheria, corynebacterial sepsis, erythrasma) and in respiratory, neonatal, ocular, or genital chlamydial infections. While it was used in treatment of community-acquired pneumonia because its spectrum of activity includes pneumococcus, M pneumoniae, and L pneumophila, newer macrolides are better tolerated and more commonly selected. Macrolide resistance is increasing in pneumococci and M pneumoniae. Erythromycin had also been useful as a penicillin substitute in penicillin-allergic individuals with infections caused by staphylococci and streptococci. Emergence of erythromycin resistance in staphylococci and in strains of group A streptococci has made macrolides less attractive as first-line agents for treatment of pharyngitis and skin and soft tissue infections. Erythromycin has been studied as prophylaxis against endocarditis during dental procedures in individuals with valvular heart disease, but clindamycin, which is better tolerated, has largely replaced it.
The oral dosage of erythromycin base or stearate is 0.25–0.5 g every 6 hours (for children, 40 mg/kg/d). The dosage of erythromycin ethylsuccinate is 0.4–0.8 g every 6 hours. Oral erythromycin base (1 g) is sometimes combined with oral neomycin or kanamycin for preoperative preparation of the colon. The intravenous dosage of erythromycin lactobionate is 0.5–1.0 g every 6 hours for adults and 15–20 mg/kg/d divided every 6 hours for children. The higher dosage is recommended when treating pneumonia caused by L pneumophila.
Anorexia, nausea, vomiting, and diarrhea are common. Gastrointestinal intolerance, which is due to a direct stimulation of gut motility, is the most common reason for selecting an alternative to erythromycin. This side effect may actually be desirable in some circumstances, leading to the off-label use of erythromycin to treat patients with gastroparesis.
Erythromycins, particularly the older estolate formulation, can produce acute cholestatic hepatitis (fever, jaundice, impaired liver function), probably as a hypersensitivity reaction. Most patients recover from this, but hepatitis recurs if the drug is readministered. Other allergic reactions include fever, eosinophilia, and rashes.
Erythromycin metabolites inhibit cytochrome P450 enzymes and, thus increase the serum concentrations of numerous drugs, including theophylline, warfarin, cyclosporine, and methylprednisolone. Erythromycin increases serum concentrations of oral digoxin by increasing its bioavailability.
Clarithromycin is derived from erythromycin by addition of a methyl group and has improved acid stability and oral absorption compared with erythromycin. Its mechanism of action is the same as that of erythromycin. Clarithromycin and erythromycin are similar with respect to antibacterial activity except that clarithromycin is more active against Mycobacterium avium complex (see Chapter 47). Clarithromycin also has activity against Mycobacterium leprae, Toxoplasma gondii, and H influenzae. Erythromycinresistant streptococci and staphylococci are also resistant to clarithromycin.