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Resistance to Antibiotics

Fifty percent of the time when physicians use antibiotics, it is either unnecessary or it is inappropriate. The biggest implication is that it tends to indicate lack of familiarity with the fact that when we use antibiotics, they are different than a lot of the other drugs that we use antibiotic resistance, resistance to antibiotics. Antibiotics affect the bacterial milieu of the entire environment and that is a fact that you always have to keep in your mind when you are using antibiotics and treating a 

We tend to use antibiotics inappropriately for prophylaxis and that's true whether you are in medicine or whether you are in surgery. If you are in medicine, we tend to try to prevent infections and we usually just select for resistant infections. In the surgical setting, although surgical prophylaxis is important, what the surgeons tend to do is continue the prophylactic antibiotics for too long of a period. There is still significant impact on detailing and what we are seeing more and more in younger physicians is what two researchers at Duke, Kim and Gallis, have called spiraling empiricism. Spiraling empiricism just refers to the fact that it has gotten much easier to prescribe an antibiotic than it is to do a careful diagnostic evaluation and figure out what's going on in the patient that you are

For instance, the approach that we used to take was careful observation while doing appropriate diagnostic tests and then choosing antibiotic therapy, either giving it as a therapeutic trial or specific therapy. What we are seeing more and more of today is that people are using antibiotics more and more for prophylaxis, or empirically without having a diagnosis and what we are

Now, the way physicians use antibiotics is unfortunately based a lot of fallacies that people hold about antibiotics. What I call this is lies your parents told you about antibiotics. What I'm going to do now is run through a series of cases that illustrate ways

The first fallacy, or the first lie, is that antibiotics are cheap and easy. Well, they certainly are easy; it is very easy to write a prescription. However, they aren't cheap. Antibiotics are the second most commonly used class of drugs in the United States. Any guesses as to one and three? H2 blockers and proton pump inhibitors are #4. The whole class of narcotics, nonsteroidal anti-inflammatory drugs and anxiolytics are classified as neurologic agents and they are #1. All of the cardiovascular agents are

There are other newer mechanisms that I don't have on there that are starting to become elucidated. For instance, certain organisms now are actually producing efflux pumps, so that when an antibiotic does gain access to a bacteria, they spit it out. So there are a lot of new mechanisms that are actually coming into being. This is just a slide that shows where the various antibiotics act. Regardless of where the antibiotics act, whether it is at the cell wall, the DNA level, like the quinolones, the RNA level, like tetracycline and aminoglycosides, or in folate metabolism, like co-trimoxazole or Bactrim, there can be mutations at every step and you can have resistance emerging at any step of the activity.

How do you acquire or transmit resistance? There are a lot of different mechanisms. The bacteria can have a spontaneous mutation of a chromosomal gene, for instance, a porin molecule or penicillin-binding protein, and then in the presence of an antibiotic that mutant organism will be selected. Additionally, organisms contain resistance genes on their chromosomes that are induced by the presence of antibiotics. The expression of these resistance genes is induced by the presence of antibiotics and

If you take a look at the organisms that are now resistant to antibiotics, it is quite staggering. When I first trained, we used to use penicillin to treat gonorrhea and we certainly can't do that nowadays. We used to use ampicillin or amoxicillin to treat haemophilus and now pretty much across the board about thirty-five percent of H. flu are beta lactamase producing and you really can't use those compounds. We are seeing a big problem with resistance in all of the agents of infectious diarrhea, be it Salmonella, Shigella or Campylobacter. We are still having significant problems with methicillin-resistant Staph. aureus and in larger tertiary care centers the coagulase negative Staph., or Staph. epi., also tends to be multidrug resistant. I mentioned the big 

This is an older slide from the CDC that showed the increasing incidence of MERSA infections in the United States, and I'll tell you that between 1992 and 2006, these curves have continued to go up along the same slope. The main reason I show it is to point out that this problem is a problem regardless of what size hospital you're practicing in, whether it is a large hospital, an intermediate-size hospital or a smaller hospital. This again is an older slide from the CDC looking at the incidence of VRE. This slide ends in 1994, where the incidence is somewhere between twelve and thirteen percent in the intensive care unit setting. I'll tell you that in 2006, this incidence has risen to thirty-five percent in the data from the CDC. We have seen a marked increase in these numbers.

Taking a look at this a little closer, we are seeing a problem with enzymes called extended spectrum beta lactamases. These extended spectrum beta lactamases are enzymes that were initially encoded on the chromosomes of Enterobacter species, then transmitted to a plasmid via transposon and we now find them in E. coli and Klebsiella. So what we are starting to see are urinary tract infections that you can only treat with imipenem, because organisms that contain this enzyme are only susceptible to imipenem and amikacin. Similarly, Acinetobacter balmani is an organism that pops up in the intensive care units frequently only