Infections...
Is a New World Coming?

Recently, we've been hearing quite a bit in the news about infectious diseases, with Ebola being in the forefront. I also recently heard a story on the radio about carbapenem-resistant enterobacteriaciae (CRE) infections in Georgia. According to the Centers for Disease Control and Prevention, CRE infections may contribute to up to 50% of deaths in patients who become infected.¹ Apparently, these bacteria produce a Klebsiella pneumoniae carbapenemase (KPC) enzyme responsible for the increased resistance of this group of gram negative organisms.² Luckily for most of society, these infections so far have been isolated to immunocompromised, very sick patients in hospitals. Of course, that's how VRE and MRSA also started.

Considering the rapidly increasing rate of multidrug resistant infections, it makes one wonder how much longer our current stock of antimicrobials are going to last and be effective. Will we see a time in the near future where we live in a post-antibiotic world? Some infectious disease experts have been warning of this possibility. In April of 2014, the World Health Organization released a report that the "post-antibiotic era" is near.³

I can only imagine what it must have been like practicing medicine in the years before Alexander Fleming discovered penicillin in 1928 (with mass production in 1944). Picture this: you live in a world in which antibiotics don't yet exist (or they no longer work, in our case). Your postoperative patient returns to the office four days after an elective bunionectomy with new onset mild redness, edema, pain, and drainage from the incision site, but with no constitutional symptoms. In the past, this was a relatively small issue, for which you might prescribe oral antibiotics. But in the post-antibiotic era, you have no effective method of treatment outside of incision and drainage, and supportive treatment like hydration, nutrition, etc. Just imagine, for a moment, how you as the doctor and your patient will feel in this situation. Without antibiotics, your patient quickly becomes worse, eventually risking septis and death. This could lead to a world without elective surgery. Pretty sobering.

In my non-expert opinion (on this matter), we as a medical society around the world, have made two primary mistakes that are not impossible to rectify. The first is the non-judicious overprescribing of antimicrobials. One common example from the general medical community is the prescription of antibiotics for otitis media in otherwise healthy children, which is commonly viral in origin.⁴

Another one common to us in the podiatric community is the unnecessary prescribing of antibiotics for onychocryptosis and paronychia. I often see patients prescribed antibiotics by their primary care physicians for this problem that is, in reality, a foreign body reaction that simply requires removal of the offending nail. In fact, Reyzelman and colleagues found antibiotics to be unnecessary in a prospective study of 54 otherwise healthy adults.⁵ It, of course, goes without saying that we have been completely irresponsible in our use of antibiotics in livestock animals. That simply needs to stop, along with different methods to process cattle.

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The second mistake is the significant diminution of new antimicrobial drug research and production. Previously, many years had gone by before new antimicrobials hit the market. The explanation for this is obvious: money. If research into new antimicrobials is not profitable for the drug companies, then it simply will not happen. Consider this quote from a World Health Organization bulletin explaining some of the reasons for our shortage of antibiotics:⁶

"Another reason is commercial. Antibiotics, in particular, have a poor return on investment because they are taken for a short period of time and cure their target disease. In contrast, drugs that treat chronic illness, such as high blood pressure, are taken daily for the rest of a patient's life. "Companies have figured out that they make a lot more money selling the latter drugs than they do selling antibiotics," Spellberg says, highlighting the lack of incentive for companies to develop antibiotics."

What To Do Now?

Is it too late? Are we actually at the cusp of a "post-antibiotic era?" Should we give up and call it a day? Obviously the answer is no. There is actually a lot that can be done on multiple levels to improve the situation. Here are a few ideas:

1. Create incentives for drug companies to investigate and produce new antimicrobials. Perhaps federal and state tax incentives in exchange for demonstrated actual new medications will provide some motivation.
2. Medical societies should provide better guidelines for physicians regarding antibiotic prescribing practices. Solid societal backing can help physicians with those patients that may be medicolegal risks. For example, many physicians will prescribe antibiotics for pediatric otitis media, even if unnecessary, due to litigation concerns if a child ends up deaf after a bacterial infection. Solid, well-researched guidelines can help physicians provide appropriate care, while providing medicolegal evidence and protection.
3. Increase federal funding for research investigating infectious disease topics such as new drugs and mechanisms of resistance.
4. Stop giving antibiotics to livestock. This is a common practice, due to the large numbers of animals penned together in places such as feedlots where disease runs riot and animals are smaller than desired.
5. "Crop rotation" methods of antibiotic availability – Infectious disease societies should consider researching this. Darwinian evolution demonstrates that if we pull a certain antibiotic from use for a certain time period, currently active bacteria will eventually lose their resistance factors, and the previously ineffective antibiotics will become useable again.

Despite the looming potential for disaster, we're not out of options. An organized, community approach to this problem will prevent the ugly future scenario I pointed out earlier. Or we can let it go and do nothing. Whether we enter a new world without useable antibiotics or a continued world with the ability to fight infection, is up to us.

Best wishes,

Jarrod Shapiro, DPM
PRESENT Practice Perfect Editor
[email protected]

References:

1. Carbapenem-resistant Enterobacteriaciae in Healthcare Settings. Centers for Disease Control and Prevention. https://www.cdc.gov/hai/organisms/cre/ Last accessed August 22, 2014.
2. Guidance for Control of Carbapenem-resistant Enterobacteriaciae: 2012 CRE Toolkit, Centers for Disease Control and Prevention.
3. Antibiotic Resistance: Global Report on Surveillance. World Health Organization. 2014.
4. Klein J, et al. Acute otitis media in children: Epidemiology, microbiology, clinical manifestations, and complications. UpToDate. Topic 6021, version 16.0. Last accessed August 21, 2014.
5. Reyzelman A, et al. Archives of Family Medicine, Sept-Oct 2000;9:930-932.
6. Race against time to develop new antibiotics. World Health Organization Bulletin, 2011;89:88-89. https://www.who.int/bulletin/volumes/89/2/11-030211/en/ Last accessed August 21, 2014.

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