Part of polypeptide group of natural products.
Erythromycin, azithromycin and clarithromycin are available in the U.S.
Have immunomodulatory, anti-inflammatory, and anti-bacterial affects.
The immunomodulatory properties are related to the lactose ring.
Inhibit the production of many proinflammatory cytokines, such as IL-1, IL-6, IL-8, and TNF-alpha.
Azithromycin and clarithromycin are more chemically stable and better tolerated than erythromycin, and they have a broader antimicrobial spectrum than erythromycin against Mycobacterium avium complex (MAC), Haemophilus influenzae, nontuberculous mycobacteria, and Chlamydia trachomatis.
Have excellent activity against the atypical respiratory pathogens (C. pneumoniae and Mycoplasma species) and the Legionella species.
Azithromycin and clarithromycin have pharmacokinetics that allow shorter dosing schedules because of prolonged tissue levels.
Azithromycin and clarithromycin are active agents for MAC prophylaxis.
Clarithromycin is the most active MAC antimicrobial agent and should be part of any drug regimen for treating active MAC disease.
Both azithromycin and clarithromycin are well tolerated by children, azithromycin has the advantage of shorter treatment regimens and improved tolerance.
Intravenously administered azithromycin has been approved for treatment of adults with mild to moderate community-acquired pneumonia or pelvic inflammatory diseases.
Increasing macrolide resistance that is being reported with some of the common pathogens, particularly Streptococcus pneumoniae and group A streptococci.
All 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 diphtheria,Campylobacter sp ,Treponema pallidum,Propionibacterium acnes and Borrelia burgdorferi.
Bacteroides fragilis is resistant.
Have limited gram-negative activity.
Considered the drug of choice for group A streptococcal and pneumococcal infections when penicillin cannot be used.
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 are not used to treat meningitis.
Drugs of choice for cat-scratch disease.
Clinically important inhibitors of cytochrome P450 3A4 enzyme, especially erythromycin and clarithromycin.
Concomitant administration of macrolides with astemizole, or terfenadine is contraindicated. as reported cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, torsades de pointes) may occur.
In older adults erythromycin, and clarithromycin coadministration with a CYP3A4 metabolized statin -atorvastatin, simvastatin, and lovastatin, associated with increased risk of rhabdomyolysis, acute kidney injury and all cause mortality.
In a randomized trial azithromycin taking daily for one year among selected patients with COPD, when added to usual treatment, decreased the frequency of exacerbations and improve quality of life but caused hearing decrements in a small percentage of patients (Albert RK et al).
Among older adults taking a calcium channel blocker concurrent use with clarithromycin compared with azithromycin is associated with a greater 30 day risk of hospitalization for acute kidney injury Gandhi S et al).
Use of macrolides in patients with bronchiectasis as a maintenance therapy, reduces the rate of pulmonary exacerbations, but has increased rate of macrolide resistance.
Erythromycin may cause dose-related tinnitus, dizziness, and reversible hearing loss.
Cholestatic jaundice occurs most commonly with erythromycin.
Erythromycin not given IM because of pain.
Diarrhea, nausea, vomiting, and dizziness are the most common adverse effects.
Prolongation of the QT interval, hyperbilirubinemia, elevation of liver enzymes, transient loss of consciousness (sometimes associated with vagal syndrome), and visual disturbances (particularly a slowed ability to accommodate and to release accommodation) are less common.
Severe hepatotoxicity, which may be fatal and may require liver transplantation, may occur.
Cross-sensitivity with macrolides can occur.