Friday, 25 May 2012

Antibiotic Use Favours the Development of Resistance to an Antifungal

It has long been proposed that we should minimise the use of antibiotics for fear of promoting the growth of bacteria resistant to treatment with those antibiotics. This is not easy to achieve as some doctors feel heavily pressurised to prescribe antibiotics when they are not strictly needed e.g. when a patient clearly has a viral rather than bacterial infection.

Something similar is also being attempted for people who need treatment using antifungal medication as it is quite well understood that if someone has had treatment with an azole antifungal then they are more likely to have a Candida (yeast) infection that is resistant to Fluconazole should they be at risk in the near future (e.g. well-defined risk factors, include prolonged hospitalization, abdominal surgery, antibiotic treatment, neutropenia and central venous catheterization). If doctors know that a patient has been exposed to an azole in the recent past then they will often choose a different treatment for their Candida infection.

It now seems that doctors may have to also consider the recent use of antibiotics prior to the use of some antifungal drugs. A study on the fungus Candida  has shown that prior treatment of a patient using four different antibiotics increases their chance of having an infection by Candida that is resistant to Fluconazole. Doctors may now have to take this into consideration when they have patients at risk of Candida infection.

How could this happen? Antibiotics and antifungals are usually quite different and bacteria and fungi are very different organisms.
The author have 4 suggestions:

  1. by altering the resident gut flora, antibacterials may selectively impair colonization resistance in a way that favors gastrointestinal colonization with drug-resistant Candida species (1)
  2. many antibacterial agents have some degree of antifungal activity (2), which could explain selective pressure similar to that induced by azole exposure. 
  3. some antibacterials directly modulate azole resistance by inducing the expression of efflux pump-encoding genes (3). 
  4. the immunomodulatory effects of antibacterial drugs might predispose for certain fungal pathogens. For example, sulfonamides were shown to have both inhibitory and stimulatory effects on the host response against Candida spp. (45), whereas fluoroquinolones had no effect at therapeutic concentrations (6).

What does all this mean for Aspergillus?

Fluconazole is used against Aspergillosis under some circumstances but it is not the most commonly used antifungal for this infection. People taking antibiotics would probably take similar antibiotics to those used in the study too. Aspergillus is similar to yeast in some ways as both are fungi, but they are not similar in many ways too - some antifungals are more useful in yeast than they are in Aspergillus, so we cannot assume that Aspergillus antifungal resistance will increase after antibiotic treatment, Aspergillus does not tend to colonise the gut like Candida does.

This is an interesting precedent for antifungals that might apply to Aspergillus. Time and more experiments  will tell all.

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