Macrolide

Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached.

Unlike penicillin, macrolides have been shown to be effective against Legionella pneumophila, Mycoplasma, Mycobacterium, some Rickettsia, and Chlamydia.

[10] The macrolide antibiotics erythromycin, clarithromycin, and roxithromycin have proven to be an effective long-term treatment for the idiopathic, Asian-prevalent lung disease diffuse panbronchiolitis (DPB).

[11][12] The successful results of macrolides in DPB stems from controlling symptoms through immunomodulation (adjusting the immune response),[12] with the added benefit of low-dose requirements.

[11] With macrolide therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil granulocyte proliferation but also lymphocyte activity and obstructive secretions in airways.

[13] This is evident, as the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of the macrolide-resistant bacterium Pseudomonas aeruginosa, macrolide therapy still produces substantial anti-inflammatory results.

This acquired resistance can be either plasmid-mediated or chromosomal, i.e., through mutation, and results in cross-resistance to macrolides, lincosamides, and streptogramins (an MLS-resistant phenotype).

[24] A 2008 British Medical Journal article highlights that the combination of some macrolides and statins (used for lowering cholesterol) is not advisable and can lead to debilitating myopathy.

[28] A study reported in 2019 found an association between erythromycin use during infancy and developing IHPS (Infantile hypertrophic pyloric stenosis) in infants.

Macrolides inhibit CYP3A4, which means they reduce its activity and increase the blood levels of the drugs that depend on it for elimination.

Clarithromycin and erythromycin have a 14-membered lactone ring, which is more prone to demethylation by CYP3A4 and subsequent formation of nitrosoalkenes, the reactive metabolites that cause MBI.

By inhibiting CYP3A4, macrolide antibitiotics, such as erythromycin and clarithromycin, but not azithromycin, can significantly increase the AUC of the drugs that depend on it for clearance, which can lead to higher risk of adverse effects or drug-drug interactions.

Azithromycin stands apart from other macrolide antibiotics because it is a weak inhibitor of CYP3A4, and does not significantly increase AUC value of co-administered drugs.

Co-administration of clarithromycin or erythromycin with statins can increase the risk of statin-induced myopathy, a condition that causes muscle pain and damage.

Symptoms of colchicine toxicity include gastrointestinal upset, fever, myalgia, pancytopenia, and organ failure.