Macrolides

The Macrolide Antibiotics typically have a large lactone ring in their structure and are much more effective against gram-positive than gram-negative bacteria. They are also active against mycoplasmas and some rickettsiae.

Macrolides fall into three classes, depending on the size of the macrocyclic lactone ring. None of the 12-membered ring group is used clinically. Erythromycin and the closely related oleandomycin and troleandomycin belong to the 14-membered ring group. Azithromycin (synthesized from erythromycin) and gamithromycin are 15-ring members, a subclass referred to as azalides. Of the 16-membered ring group, spiramycin, josamycin, tylosin, and tilmicosin (synthesized from tylosin), are used clinically. Tulathromycin contains three amine rings and is classified as a triamilide. Ketolides, which include tylosin and spiramycin, are closely related macrolides.

Macrolide antibiotics are:

• azithromycin (brand name Zithromax),
• clarithromycin (brand names Klacid and Klacid LA),
• erythromycin (brand names Erymax, Erythrocin, Erythroped and Erythroped A),
• spiramycin (no brand), and
• telithromycin (brand name Ketek).

Mode of Action:

The antimicrobial mechanism seems to be the same for all of the macrolides. They interfere with protein synthesis by reversibly binding to the 50S subunit of the ribosome. They appear to bind at the donor site, thus preventing the translocation necessary to keep the peptide chain growing. The effect is essentially confined to rapidly dividing bacteria and mycoplasmas. Macrolides are regarded as being bacteriostatic but demonstrate bactericidal activity at high concentrations. Macrolides are significantly more active at higher pH ranges (7.8–8). Macrolides are considered to be time dependent in terms of antimicrobial efficacy.

The macrolides appear to have immunomodulatory effects useful to treat respiratory infections, in particular, those associated with Pseudomonas aeruginosa, based on efficacy at doses (concentrations) considered ineffective against susceptible bacteria.

Lack of cell wall permeability renders most gram-negative organisms inherently resistant to macrolides. There are a few exceptions, and gram-negative forms without cell walls are usually susceptible. Resistance to macrolides in gram-positive organisms results from alterations in ribosomal structure (target site methylation or mutation) and loss of macrolide affinity. Post-translational methylation results in cross-resistance to lincosamides and streptogramins. Macrolide resistance may be intrinsic or plasmid-mediated and constitutive or inducible; it may develop rapidly (erythromycin) or slowly (tylosin) and generally results in cross-resistance between macrolides. Efflux from cells is a second important mechanism of resistance for some members of this class, as is, less frequently, drug inactivation.

Macrolide antibiotics are only effective in treating bacterial infections associated with the following conditions:

• Ear, nose and throat infections - such as otitis media (infection of the middle ear), labyrinthitis (infection of the inner ear), sinusitis (infection of the sinuses), tonsillitis (infection of the tonsils) and laryngitis (infection of the voice box).
• Chest infections - such as pneumonia (infection of the lining of the lung), bronchitis (infection of the airways of the lung) and whooping cough.
• Skin infections - such as eczema, psoriasis or acne that has become infected.
• Mouth and dental infections - such as gingivitis (infection of the gums) and a tooth abscess (infection in the root of a tooth).
• Sexually transmitted infections - such as chlamydia.