Monday, December 20, 2010

Beating resistance? Yes it can be done!

Dr. Steven J. Projan is the Senior Vice President of Research and Development and Innovative Medicines Head of Infectious Diseases and Vaccines at MedImmune.

The question posed is: In an ideal world, what would be your approach to accelerating drug development and strengthening antibiotic stewardship? First and foremost we need to do a better job of encouraging basic research in microbiology because it is from a profound understanding of the underlying biology that all drug discovery comes. The good news is that funding in this area has improved (although given the recent political events this may be a transitory phenomenon) and technology marches on allowing new insights on the microbial ecology of the human being. And when those novel discoveries are made we need a far more sophisticated approach to both drug development and regulatory processes such as basing decisions on “Real World Evidence” rather than the artificiality of Phase III clinical trials. But in terms of stewardship it is becoming increasingly clear that the best way to deal with infections due to resistant bacteria is to prevent them in the first place. As such an increased emphasis on prophylaxis is the best approach from a public health point of view. The success of the pneumococcal conjugate vaccine in reducing the use of antibiotics has been well documented; however another important way to curtail the use of antibacterial drugs is to prevent viral respiratory infections, especially lower respiratory infections (it should be noted that 1/3rd to 2/3rd of the mortality in H1N1 influenza patients was due to secondary bacterial pneumonias and other respiratory viruses such RSV or human rhinovirus type C are likely to play role here as well). Therefore vaccines and immunoprophylactics for both viral and bacterial infections should play an increasing role in both public health practices and industrial research. To further focus our industrial efforts (and stimulate additional research) I support the Infectious Disease Society of America’s call for longer periods of market exclusivity for novel infectious disease products.


  1. One problem with the antibiotic industry is that it is overun with biologists who find new and better ways to study the problem and incidence of resistance, but doesn't answer the problem. We need new drugs, we have known for some time it is a problem.

    I would encourage the NSF and the NIH to increase the funding to the chemical sciences at all the levels, so that the next generations of scientists able to emerge and generate the next waves of compounds happens.

    Look at the graduate schools. There are 10 to 1 biology grad students to chemistry, and logically 10 to 1 in industry.

    This imbalance is the core problem in developing newer agents.

    Too many biologists and not enough chemists!

  2. The information that sewer plants are major generators of resistant organisms has been around for at least four decades. Statistics show that about 60% of the generated sewage sludge in this nation goes on US farms.

    Our research here in Santa Barbara has been mainly with recycled (reclaimed) water. As good sources of drinkable water dry up or are contaminated, there is a large push to substitute reclaimed water. This makes good sense only if that water is safe---which we and others are showing it is not.

    Reclaimed water is a major source of dispersed antibiotic resistance. It becomes critical when this water is used to irrigate crops that are consumed raw. Peer-reviewed papers document that reclaimed water carries pathogens that are not detected by the simple standard tests and also contains pharmaceuticals and contaminants of emerging concern. These pollutants can be and are taken into the edible portions of these crops along with antibiotic resistant microbes. Thus no amount of washing at the kitchen sink has effect.

    We have tested this water from two separate sewer plants in the vicinity of Santa Barbara. If we use the state-approved multi-tube MPN test and test the water where the industry typically tests (at the point of release into the delivery pipes), we typically get non-detect. But if we go to the end of the pipe at the point of use (POU) we often find bacterial counts that wildly exceed the allowed counts. In some cases, our results at the ends of the pipe are so high they are off the charts. This is water being used, at least in Santa Barbara, for crops consumed raw from community gardens.

    If we test the reclaimed water at these same points, i.e., point of release to the delivery pipes and again at the end of the pipe, i.e., POU, using SensiDisc diffusion on Muller Hinton, we are finding multi-drug resistant organisms. In some cases these organisms are resistant to 11 of the 12 challenge antibiotics in our Kirby Bauer. This is going out the pipes and sprinklers, becoming aerosolized and drifting into adjoining homes. It certainly is available to those playing on lawns irrigated with this water such as the school playing fields and golf courses.

    Then, in many sewer plants, there is the use of UV. Meckes noted that in cases, the bacteria that were resistant and coming out of sewer plants saw enhanced resistance when exposed to UV. Additionally, Amy Pruden (personal communication) notes that the DNA from UV-killed bacteria is not altered. Thus, there is no assurance that non-pathogens will not pick up this genetic information, thence becoming resistant and pathogenic.
    It is critical to understand that there are sources of released antibiotic resistant microbes that the regulators are well aware of but essentially refuse to effectively deal with. Until there is enough political pressure applied to this subject, it will remain an undisclosed source to confound the treatment of resistant infections and at the same time see our diminishing tools yet faster depleted.

    Dr Edo McGowan