Antibiotics are strange little molecules. In low-to-medium concentrations they are used by bacteria to protect their territory and (possibly) to signal to neighbouring bacteria. At higher concentrations they can be used to kill the bacteria that injure us, but at concentrations too high they can also cause serious damage to our own internal bacteria and our own bodies, or in some cases even provide a helping hand for bacteria infections. The difference between that ‘high’ and ‘too high’ can be fairly small, and often overlaps.
Azithromycin is a widely-used antibiotic that interferes with the protein synthesis machinery of bacteria. As well as helping against bacterial infections, it also has little-understood anti-inflamatory properties. It’s used against a whole range of bacterial diseases, and can be used in long-term chronic lung diseases such as cystic fibrosis to help with the inflammation and prevent the development of bacterial infections.
A recent paper in the Journal of Clinical Investigation (ref 1 below) finds that although azithromycin is useful in reducing the inflammatory symptoms in cystic fibrosis sufferers, it wasn’t so much of a help against the bacteria. Long-term high doses of azithromycin are often associated with increased infection by nontuberculous mycobacteria – a group of bacteria that are very similar to tuberculosis, without actually being tuberculosis.
The reason suggested for this is that at high concentrations (the concentrations usually used for cystic fibrosis treatment) azithromycin can block autophagy, which is the process used by white blood cells to eat up invading bacteria. By measuring the concentrations of a protein associated with autophagy (LC3-II) it was found that the antibiotic does not prevent the autophagosome from forming (i.e the bacteria still get internalised) but prevented acidification. The bacteria were getting into the white blood cells, but not getting destroyed. This is particularly relevant in the case of tuberculosis, because living unharmed within white-blood cells is how these bacteria work anyway. The antibiotic just helps them with that.
It’s an area that definitely needs more study, but it does bring up an important point about antibiotics. In the case of the azithromycin it seems that reducing the amount of autophagy in white blood cells (which probably helps to prevent inflammatory effects) makes infection a lot easier for certain types of bacteria. This is particularly relevant in a hospital as many of the nontuberculous mycobacteria are highly drug resistant. Either modifications to the dosage are needed, or it may be more efficient to use alternative anti-inflammatory drugs, particularly in those patients whose immune system may already be compromised by other diseases.
Ref 1 = Renna M, Schaffner C, Brown K, Shang S, Tamayo MH, Hegyi K, Grimsey NJ, Cusens D, Coulter S, Cooper J, Bowden AR, Newton SM, Kampmann B, Helm J, Jones A, Haworth CS, Basaraba RJ, Degroote MA, Ordway DJ, Rubinsztein DC, & Floto RA (2011). Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection. The Journal of clinical investigation PMID: 21804191
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