Thursday, October 16, 2014

Frontline - The Trouble with Antibiotics

On October 14, PBS Frontline aired the second installment in its series of antibiotic resistance called, “The Trouble with Antibiotics.”  Although I was asked to preview the story for this blog – I found myself without internet access to be able to watch the show because of storms in our area.  It took five days to reacquire access – hence my tardy blog on the subject. 

The show is a fascinating look at the debate on antibiotic use on farms in the US and antibiotic resistance in American patients.  There is also a follow-up on the NIH outbreak of KPC Klebsiella.  But I concentrated on the issue of antibiotic use on farms and the inability of the FDA to regulate this use. There were many talking heads on the show saying that the connection between the use of antibiotics in animals and the appearance of resistant infections have never been clearly linked and that even in the cases where the evidence is strong – the numbers of patients affected are very small.  Wow! To me, this issue was settled back in the 1980s.  Here are some pieces of evidence that I find persuasive.

1.     First there was a study by Wolfgang Witte and his co-workers in the old East Germany.  Wolfgang worked at the East German CDC where all resistant organisms – coming from farms animals and from human infections – were collected from the entire country.  There were some advantages to a strict communist government I guess. These investigators identified resistance to an antibiotic called nourseothricin used in animals as a growth promotant.  The antibiotic was not used in humans – so there would be no particular reason for humans to be colonized or infected with nourseothricin-resistant bacteria unless they had been exposed to resistance coming from farm animals. In their studies, the researchers showed that this gene was carried on a genetic element that also carried another gene causing resistance to trimethoprim – an antibiotic used to treat urinary tract and intestinal infections in humans.  They clearly showed the link between the bacteria isolated from animals on farms and from humans both genetically and epidemiologically.  This remains one of the strongest studies ever done in this regard.  It was not cited in the Frontline report – because it wasn’t a US study?
2.     To me, the avoparcin story and its connection to the rise and spread of VRE is also very persuasive.  Avoparcin is an antibiotic related to vancomycin.  Vancomycin-resistant enterococci were first detected in Europe – specifically in France – in the late 1980s.  They rapidly spread throughout Europe and the US.  In America, they are now responsible for 20,000 infections in US hospitals and 1300 deaths every year according to the CDC.  In order to become resistant to vancomycin, a key antibiotic for treating these infections, enterococci have to acquire the ability to make an entirely different kind of cell wall – requiring a number of new genes. These genes come on a genetic element that is easily transferred – but how did this element end up in enterococci? Its origin – believe it or not – seems to be in the bacteria that produce vancomycin-like antibiotics since they themselves have to be resistant to the antibiotic’s effects in order to survive.  Bacteria in the guts of animals were selected, apparently through use of avoparcin as a growth promotant, and were then spread to humans through food in Europe.  Again – to me – this has been clearly demonstrated.  Further, when avoparcin was removed from the market as a growth promotant in a number of European countries, human colonization with VRE declined substantially.
3.     Highly resistant strains of Salmonella (DT104) have clearly been shown to colonize animals, to contaminate meat during slaughter and subsequently to cause disease in humans.  This organism has been the origin of a number of large recalls of hamburger in the US over the last several decades.

The Frontline show clearly described the FDA's attempt to regulate antibiotic use in animals in the 1970s and their utter failure to persuade congress to go along.  Apparently, four decades later, the FDA is still feeling the effects of their interaction with congress.  As I noted previously, we do not have a congress right now that is capable of acting in any sort of positive way - they only act by inaction. 

In their exhaustive and excellent review on this topic, Marshall and Levy state that the gaps in data do not justify our failure to restrict antibiotic use in animals in the US in ways similar to regulations implemented by European authorities.  To my mind, once gain, Europe is leading the way!  This is amazing to me since Europe in many ways is so much more dysfunctional than the US - but there it is. 

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