All-in-One Prophylaximagic!

I had my six-monthly checkup with my immunology insultant consultant last week (no infections to report, trough IgG of 7.5 g L^-1 which is double what it was a year ago). I have common variable immunodeficiency, a genetic condition which means I don’t produce antibodies, so untreated I can get frequent and repeat infections.

We were reviewing my treatment plan, and discussing that I’ve now been on prophylactic antibiotics for six months. The antibiotic of choice at my hospital is azithromycin, a member of a family of antibiotics called macrolides which also includes erithromycin and clarithromycin.

Molecular structure of azithromycin (C38H72N2O12)

Molecular structure of azithromycin. Note the large ring in the top left of the image. Thanks to Wikimedia

Molecularly, macrolides are characterised by having a ring of 14 or more (mainly carbon) atoms, making them quite large. As a comparison, benzylpenicillin has 16 carbon atoms in total and a molecular mass of 334.4, whilst azithromycin has 38 carbon atoms and a molecular mass of 749.0, more than twice the mass.

Pharmacologically, macrolides block protein synthesis in bacteria. All cells (and bacteria are just cells with a thick wall) depend on constant replacement of their proteins, so blocking their manufacture kills bacteria rapidly.

Macrolides also have a cunning trick of getting to the bacteria. Neutrophils, a type of white blood cell which is attracted to infections sites, transport as much of the macrolide molecules as possible in the cell. Once neutrophils find the infection, they release bomblets of anti-bacterial chemicals along with the antibiotic. The net effect is they get to the bacteria very quickly and if the chemical warfare from the neutrophils doesn’t kill them off, the macrolides soon do.

However, macrolides are not a one trick pony. In addition to being efficient killers, they also have other beneficial effects, in particular being potent anti-inflammatories. Unlike common anti-inflammatories like ibuprofen, which have a single mode of action, macrolides are multi-modal and suppress inflammation in multiple ways.

One trick they have is protecting the body from the damage caused by the neutrophil attack chemicals. Another trick, also associated with neutrophils, is that they may promote the migration of the chemical warfare specialists to the infection sites, meaning more of them get to the infection, and they get there faster.

They have also been implicated in suppressing expression of endothelin-1. ET1, as it’s known, is a powerful vasodilator which promotes blood flow in the area around an infection, and is what causes infected wounds to go characteristically red and inflamed. In addition, macrolides have been associated with reduction of other signalling chemicals, cytokines and interleukins, which promote inflammation.

These effects have been shown to be beneficial, particularly in a range of respiratory conditions. This includes asthma, particularly where the patient is sensitive to environmental irritants such as dust, and a condition called diffuse panbronchiolitis (DPB). DPB is characterised by extensive bacterial infection in the lungs, and constriction of the airways in response. Treatment with macrolides has increased survival rates from around 50% to better than 96%, with it’s effects exceeding that of an antibiotic alone.

Whilst macrolides become concentrated in normal cells, they aren’t transported into the space in the lungs where air exchange occurs, the bronchial tree. However, they have been shown to have benefit on the lung function tests of patients with bronchiectasis and cystic fibrosis, not by directly affecting the flora, but by decreasing inflammation and promoting the migration of neutrophils. In addition, macrolides may have benefits in atheroma (fatty arteries, which have a strong association with serious and fatal heart disease), arthritis and some forms of cancer.

For those of us who do have poor immune systems, just reducing the bacterial infections is great, but reducing the inflammatory response is a buy-one-get-one-free bonus. So, here’s to an amazing group of drugs that’s making my life more liveable.


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About David Waldock

Open University graduate, health and life science at undergraduate level, science and society at post-graduate. Interested in how the Internet is transforming the ways in which the public(s) engage with science(s). Also interested in "the skeptical movement" as a form of science activism and it's effectiveness in achieving its goals. Interested in the representation of LGB types in science and in the periscience communities. Work for a well known and loved public institution. Views are mine and not necessarily my employers.

6 responses to “All-in-One Prophylaximagic!”

  1. Ruby Finnis says :

    Thanks David
    Yes I too was told about this from my Consultant Immunologist.
    Also – if you take an ACE Inhibitor with the Azithromycin, the anti inflammatory properties are increased – around the level to approx 10mg prednisolone – but without the pred side effects etc

    Ruby x

    • davidwaldock says :

      Yes, that also came up in our discussion, although for a slightly different reason.

      My immunoguy found one patient had very high ACE levels as well as renin, resulting in high blood pressure, so he’s now testing patients to see if they also have high ACE levels.

      Obviously, if you don’t need an ACE inhibitor, taking one can cause problems, specifically hypotension, so it’s not a combination prescribed unless clinically indicated. However, this would benefit heart disease precursors, such as atheroma.

      Thanks for your comment!

  2. Mike S says :

    I get the same effect from Timothy Taylor’s Landlord, David, but the formula is a trade secret in Yorkshire…i guess it’s some kind of genetical abnormality in the sheep there!

    • davidwaldock says :

      I think it’s worth making the point that slightly drunken dancing leading to unconsciousness is not technically the same effect as an anti-inflammatory, but is a Jolly Good Thing[tm] nonetheless.

      Nice to hear from you Mike 😉

  3. Gillie says :

    Thanks for helping me to understand just why I think such a lot of my dose of Azithromycin, David! My 6 weeks on this as a prophylactic is usually a span of time when I can actually plan ahead with some likelihood of the plans working!

  4. Carole says :

    Came to your blog via Bronchiectasis R Us. Thank you for the wonderfully clear article about Azithro. I have been taking Clarithromycin for about five years now and while I still have many exacerbations of pseudomonas in my lungs, I am sure it helps with the level of inflammation in my joints and muscles. Thanks again and I hope you are managing to stay well.

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