Why Did the Chicken Cross the Road? To Get Antibiotics : A Review of Big Chicken

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One of the most pressing aspect of the antibiotic resistance crisis is the role of antibiotics in agriculture and the link with human infections. This is an aspect of the problem that has received mixed treatment in the past. It was clear that agricultural use of antibiotics was a problem but its impact on human infections was debated, not well known, and not conclusive though all doctors probably could recite the statistic that 80% of antibiotics sold in the US were for used in animals. Many people, myself included, focused heavily on the superbugs stalking our hospitals and ICU and thought almost exclusively about infection control and human antibiotic stewardship.

However, with the publication of Big Chicken: The Incredible Story of How Antibiotics Created Modern Agriculture and Changed the Way the World Eats, I suspect things will change. This book written by, in my opinion, the premier science journalist, Maryn McKenna, is something extraordinary. I read books in this genre continually and I can saw that McKenna’s ability to tell a compelling non-fiction story while weaving together history, politics, science, and medicine in a manner that teaches and leaves the reader completely captivated is unrivalled.

Big Chicken, which published in 2017, is much more than a book on unraveling antibiotic use in chickens, who are fed “routine doses of antibiotics on almost every day of their lives.” It is nothing short than a history of the chicken industry in the US — which breeds “for everything but flavor: for abundance, for consistency, for speed” — and it is only by understanding antibiotic use in that context that one can really grasp the issue. This is the book’s chief value.

The book teems with so much good information that it is impossible to capture in a short blog post. Some highlights include:

  • How antibiotics facilitated the transformation of grain into muscle making an “active backyard bird into a fast-growing, slow-moving, docile block of protein”. Slaughter weights of chickens have doubled in the past 70 years and can be achieved in half the time due largely to the use of growth promoting antibiotics, which allowed chickens to become more than just egg-layers to most farmers.

  • The story of the McNugget

  • The use of antibiotic-laced harpoons to shoot whales!

  • The questionable role of a Mississippi Democrat congressman

  • The change in culture that sparked companies like Chick-fil-A and Perdue to revaluate antibiotic use

The book also has great anecdotes of disease outbreak investigations — one featuring a young Mike Osterholm — and scientific studies that increasingly linked antibiotic use in animals to huma infections. The book also discusses how policy evolved with respect to this issue.

For anyone interested in a great story that traces the roots of a major scientific/medical problem, I highly recommend this book. For those who work in infectious disease, it is required reading (as are all of Maryn McKenna’s books).

Antibiotic Resistant Infections Kill More than Car Accidents: A Review of Superbugs

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I often say that the biggest infectious disease problem humans face is that of antimicrobial resistance. I am not alone in this assessment and today there are myriad books describing  this problem and its many facets. However, a recent book I read on this topic, Superbugs: An Arms Race Against Bacteria, provides a unique lens to view the problem: economics. Below I give a short overview of the prime value I took from this book.

Superbugs is a book that stems from a high level review of antimicrobial resistance commissioned by then UK prime minister David Cameron and is written, not by scientific subject matter experts, but by economists and policymakers (Jim O'Neill, William Hall, and Anthony McDonell).

I think it is not difficult for anyone to see that a drug-resistant infection will be, on average, more expensive to treat than a drug-sensitive one. This cost disparity exists for several reasons that include the expense of switching therapy to a an appropriate regimen, the expense of isolation of patients with drug resistant infections, and the increased severity of illness because time to appropriate antibiotic therapy is delayed. 

The book is divided into two parts that focus, respectively, on the problem and solutions to drug resistance. To me, the chief value of the book is the authors attempt to quantify the problem of antimicrobial resistance because as they note a whole different audience -- beyond the health one -- is more receptive to a quantitative analysis. Several of their estimates are worth noting.

  • 1.5 million people die of antimicrobial resistant infections annually (more than die i automobile accidents)
  • Total worldwide costs (direct and lost productivity) are approximately $864 billio

The book provides a comprehensive overview of the economic challenges inherent with antibiotics: namely, stewardship programs that diminish revenue from new antibiotics, low prices of antibiotics vs. other pharmaceuticals, and the ability to substitute antibiotics.

One of the most valuable portions of the book, to me, is their discussion of diagnostic tests. Much of inappropriate antibiotic prescribing is done for viral infections. It is thus obvious that by employing diagnostic tests to determine whether a patient's symptoms are caused by a virus or a bacteria and which virus it might be could curtail injudicious antibiotic prescribing (and provide valuable epidemiological information) however they are seldom employed despite their availability. Superbugs delves into the dilemma that has stifled the routine use of diagnostics for infectious disease contrasting it the use of advanced diagnostics tests that are standard of care for cancer. 

Chief amongst these obstacles, as they note and I have experienced first hand, is the hospital siloing of costs. Because a multiplex point-of-care molecular diagnostic test deployed during an office visit for bronchitis is more than the entire cost of the visit plus the inappropriate antibiotic prescription that will likely result, testing is foregone. But economics is not only about the seen, but also the unseen, and taking a wider perspective allows one to realize that the costs of antimicrobial resistance driven by the inappropriate prescribing outweighs the cost of running a diagnostic test. 

The book concludes with policy recommendations to solve what the authors believe to be a tractable problem that are informed by a thorough analysis of the problem that are familiar to those that follow this issue and include increasing awareness, increased R&D, and the inclusion of all relevant parties (including agriculture). 

I recommend Superbugs to those who would like an up-to-date holistic analysis of a pressing public-- and individual -- health threat. 

Don't Finish Your Antibiotics -- They Probably Weren't Necessary

It's a tale as old as time: when you're prescribed a course of antibiotics, finish it no matter if you feel better after a few doses. The implicit rationale behind that maxim was that if one is being prescribed antibiotics, it is because they have been accurately diagnosed with a bacterial infection in which antibiotic treatment will be helpful. 

Every antibiotic one takes has two aspects to its nature. Antibiotics, even narrow spectrum ones, impact not only the offending bacteria but also others who are bystanders. Those bystanders are reduced in population opening up space for more dangerous bacteria as well as putting pressure on bacterial populations to select for and evolve resistance (collateral selection). Broad spectrum antibiotics do this on a larger scale and that's why they should be used only when the clinical situation warrants it (i.e. wide uncertainty about the cause of a patient's symptoms). 

There is a risk benefit calculus that must occur with each dose of an antibiotic. Does the risk of antibiotic resistant bacteria developing and antibiotic side effects occurring outweigh the benefit of the antibiotic. Obviously, in a viral infection the risk strongly outweighs the benefit.

The other aspect of this issue is that often antibiotic courses, even when they are needed, are prescribed for arbitrary amounts of time. Courses of 7 days, 10 days, 14 days may have little to no rationale behind them. More and more studies are showing shorter course therapies are optimally effective and there has been a movement to shorten courses of antibiotics as much as possible. A new piece in the British Medical Journal is a tour de force  as is this excellent piece by Brad Spellberg. 

The point is that if an antibiotic is prescribed injudiciously -- as most are -- each unnecessary dose one takes is harmful. Also, each prolonged course of antibiotics that exceeds what is necessary confers unneeded risk. Of course, when a course is appropriately and rationally constructed to ameliorate the infection one should take the prescribed dose so as not to foster recrudescence of the infection with possibly resistant organisms (targeted selection).

Antibiotics are a precious resource that changed the face of medicine and improved human life immeasurably. The threat of antibiotic resistance is one of the most pressing problems medicine faces. Exploding arbitrary dogma to optimize antibiotic use will be essential.

Smog: What Lurks Within

The planet teems with bacteria in all niches imaginable, including the air we breath. Integrate this fact with the fact of the ubiquity of antibiotic resistant bacteria and it is not surprising that the air itself contains antibiotic resistant bacteria. A recent study, that the popular press has been reporting on, reveals that the smog (an amalgam of fog and particulate matter) of Beijing contains many antimicrobial resistance genes. 

Before anyone suits up in a gas mask before going outside (as if the air inside one's house is sterile), it is important to put the finding into context.

While the finding itself doesn't strike me as surprising, it does illustrate the magnitude and full scope of antibiotic resistance. I often emphasize that antibiotic resistance is a unrelenting process in nature that humans have exacerbated with injudicious use of antibiotics. Antibiotic resistance is how bacteria struggle and fight with other microbial species and everywhere you look resistance is present -- even in caves in which no human has set foot. It will always be present at some levels and that is why antibiotic stewardship that accounts for this fact and minimizes the acceleration of the process is crucial

What the implications are of this latest piece of research? I wonder if some of the community-acquired drug-resistant infections and colonization might be the result of acquisition from the air. This study noted the presence of antibiotic resistant genes -- not the presence of viable bacteria --- so follow up studies could attempt to cultivate antibiotic resistant bacteria from the air.

 

 

 

The Antibiotic Era: Required Reading

In the last few weeks antimicrobial resistance has been in the headlines with a frequency that has rarely been seen. The likely explanation is the unprecedented high level meeting convened by the United Nations that focused the world's attention on this public health crisis. To many, antimicrobial resistance seems to be a strictly modern problem with solutions only recently proffered. However, that is far from the truth and Harvard's Dr. Scott Podolsky's latest book The Antibiotic Era: Reform, Resistance, and the Pursuit of a Rational Therapeutics provides a comprehensive historical overview of a medical community grappling with a nascent technology that transformed medicine, the pharmaceutical industry, and the FDA.

This book, which should be required reading for anyone in the field, is the result of meticulous research that not only shows how antibiotics rippled through medicine but also how the entire medical subspecialty of infectious disease developed. The book is full of legendary figures in infectious disease such as Max Finland, Harry Dowling, Ed Kass and many others. 

One of the most valuable aspects of the book, to me, is that I know have a better understanding of how my field developed. I often wonder how physicians, who were once deluged with infections, lost their expertise and the need for a sub-specialty occurred. As Podolosky illustrates, in the post WWII era, civilization caused infectious diseases to recede in the US at the same time scores of new treatments (i.e. antibiotics) were coming to the market and experts who knew the (now rare) bug and the drugs used to treat them were valuable. This scenario culminated in the founding of the Infectious Diseases Society of America in 1963 and subspecialty certification in 1972. 

These early infectious disease physicians were on the vanguard in warning against antibiotic excess, the evolution of resistance, bacterial vs. viral diagnostic dilemmas, and the lure of shotgun empirical treatment approaches to cover all possibilities. Also detailed was the chasm between academic and community medicine ("town vs. gown", which still exists today) in which academic medical centers are ably equipped to use antibiotics judiciously but community hospitals are woefully behind. 

The book has many pearls of historical insight that are too numerous to list. A few of my favorite quotes I think will be sufficient to close with:

The “end” of antibiotics was envisioned almost from the beginning.

Patients are not born into this world with the view that antibiotics are required for common colds. It is learned from their friends who learned it from their doctors when they went, and so forth.