Programs

Cempra Pharmaceuticals has exclusive rights to all uses and all indications for over 500 macrolides.

Macrolides are a group of antimicrobial drugs that are active against aerobic and anaerobic gram-positive cocci and are typically prescribed for the treatment of respiratory tract and soft tissue infections. Approximately 80% of current macrolide use is within pediatrics.

By reversibly binding to the 50S subunit of the bacterial ribosome, these drugs block protein synthesis, preventing bacterial growth and reproduction. This action is primarily bacteriostatic, meaning that these antibiotics inhibit growth without killing the bacteria. They must then work with the immune system to remove the microorganisms from the body. However, at higher concentrations, macrolides are also bactericidal (can kill bacteria). Macrolides are a common substitute for patients when penicillin cannot be used.

Some of the most commonly prescribed macrolides include erythromycin, azithromycin (Zithromax®), clarithromycin (Biaxin®), dirithromycin (Dynabac®), and roxithromycin (Rulid®, Surlid®).

 There is currently a great need for a new macrolide as 45% of pneumococci and Group A beta hemolytic streptococci are resistant to the current arsenal of macrolides

Beyond Antibiotics
Some macrolides have also demonstrated properties beyond antibiotics. Research on the use of macrolides to address multiple therapeutic needs in the areas of inflammation, diabetic gastroparesis and cancer is ongoing.

Structure Macrolides belong to the polyketide class of natural products. It is the macrolide ring – a large lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, are attached – that is responsible for the antimicrobial properties of this drug class. The lactone ring can be 14, 15 or 16-membered.

Resistance
Acquired bacterial resistance to macrolides primarily occurs through post-transcriptional methylation of the 23S bacterial ribosome. This results in cross-resistance to macrolides, lincosamides, and streptogramins.

Although rare, acquired resistance can also result from the production of drug-inactivating enzymes such as esterases or kinases, as well as the production of active ATP-dependent efflux proteins that transport macrolides outside of the cell.

Ketolides
Ketolides are antibiotics that are belong to the macrolide group and are also used to treat respiratory tract infections. These drugs are effective against macrolide-resistant bacteria due to their ability to bind to two sites on the bacterial ribosome. Examples include telithromycin (Ketek®) and cethromycin.