A Medical-Skeptical Classic

The medical literature slowly becomes outdated. As a result there are not that many ‘classics’ in the field, since their content becomes less relevant. The medical aphorism is that 10 years after graduation from medical school, half of everything you learned will no longer be valid. The problem for medical students is trying to figure out which half of their curriculum is not worth learning.

Old studies become increasingly irrelevant as diagnosis and treatment changes over time under the relentless pressure of medicine. I once came across the best of Osler, with his descriptions of typhoid fever and pneumococcal pneumonia. The essays were far more literary in style than today’s journal articles, describing the presentation of these diseases in Dickens-like detail, but of little practical help given the advances in treatment and the understanding of the microbiology of diseases.

Technology also expands and limits what papers are available. If there is not an electronic form of an article, it might as well not exist. Many classic articles are not yet available in digital form, and the article in question for this post I had to get as a scanned version of the original paper, rather than a pdf. As a result of time and lack of electronic access, much of the older medical literature is not easily accessible, and journal publishers are not particularly interested in the free dissemination of information. Which is a shame. There is the occasional older reference that is as applicable today as when it was published.

There was never, to the best of my recollection, a time when I was not a skeptic. But there was a time when I had neither the time nor the knowledge to be able to think skeptically about medicine. The torrent of information that needs to be assimilated in medical school, residency and the first part of a fellowship makes reflection about that information almost impossible.

I do remember an article that was a turning point in my thinking about thinking about the practice of medicine. It was from 1989, the last year of my Fellowship, and was published in the American Journal of Medicine, entitled “Observations on spiraling empiricism: its causes, allure, and perils, with particular reference to antibiotic therapy” by Kim and Gallis (hence forth called OOSE, pronounced “ooze”, I suppose).

If you can scrounge up a copy, by all means do so, as it is a classic. It is a collection of logical fallacies and critical thinking as applied to infectious diseases. It was the first time I read an article that discussed how to think about thinking in medicine. I had no idea that there were logical fallacies. Most of what passed for critical thinking in my training concerned understanding the statistics, materials, and methods of studies. Important, but limited.

OOSE starts with a description of the discovery of antibiotics and the amazement of physicians that for the first time diseases that were often fatal were now curable. It must have been an amazing time for physicians when infections that routinely killed were suddenly vanquished. I have witnessed a similar revolution with the advent of HAART, where AIDS has gone from a nine-month life expectancy to a chronic disease with perhaps a normal life expectancy. At my hospital is Dr. Charles Grossman, now in his 90’s and still attending conferences. His long and productive medical career started at Boston Hospital where, as an intern, he was involved in giving the first dose of IV penicillin to a lady who was dying of a streptococcal infection, who survived another 50 years.2

Antibiotics have been developed to kill increasingly resistant and virulent bacteria, and until recently we have managed to keep one step ahead of the organisms. Unfortunately, the ability to become resistant is outstripping out ability to develop new agents and we are slowly, and inexorably, losing the battle, sliding in to the post antibiotic era.

Part of the evolution of resistance occurs from the inappropriate use antibiotics, which can often be due to uncertainly of the diagnosis. But inappropriate antibiotic use can also due to faulty thinking.

As the authors of OOSE note, “The imprecision of clinical practice establishes context, the litigious nature of our society unnerves; the absence of toxicity permits; and the sum of these encourages the incontinent, extemporaneous use of these antimicrobial agent.”

Incontinent use of antibiotics leads to increasing bacterial resistance, and the use of antibiotics when they have not been needed has accelerated the evolution of pathogens, occasionally to the point where there are infections I cannot cure and bacteria that I cannot kill.

The term spiraling empiricism describes the inappropriate treatment, or the unjustifiable escalation of treatment, of suspected but undocumented infectious diseases. Empiricism and empirical therapy, defined as the carefully considered, presumptive treatment of disease prior to the establishment of a diagnosis, often are necessary in the proper practice of medicine. On the other hand, ill-considered or inappropriate use of antibiotics, incurring unnecessary risk and expense, should be indicted and condemned. The difficulty lies in distinguishing reasonable or appropriate from unreasonable or inappropriate therapy.

As a teaching physician in a teaching hospital, I notice that sometimes it is the FUD, Fear Uncertainty and Doubt, combined with faulty thinking that sometimes leads to the inappropriate use of antibiotics.

OOSE provide a conceptual framework for approaching diseases and potential therapy (see table below). Observation, prophylaxis, empirical therapy, therapeutic trial, and specific therapy. Of these the first and the last are, sadly, the least used. For interns and resident, the motto is ‘Don’t just stand there, do something’, and with the pressures to shorten a hospital stay as much as possible, simply watching the patient is a luxury few can afford. As an experienced physician, I feel much more comfortable with the motto, ‘Don’t just do something, stand there’, or as the paper calls it “masterly inactivity.” As my wife can attest, I am the master of doing nothing.

Specific therapy in infectious diseases is not as common as I would like given the vagaries of growing the infecting organisms and the degree to which one wants to maximize diagnostic certainty. I could probably get the etiology of every pneumonia admitted to the hospital with an open lung biopsy, but it would hardly be worth the resultant morbidity and mortality.

Most of the time the patient is ill enough to be admitted to the hospital and, after appropriate studies and cultures are done, empiric therapy is started. That is often not an unreasonable course of action. These days you have to be ill to get admitted and it is the rare patient who comes into the hospital who can wait for cultures to be positive before beginning antibiotics. I cannot emphasize enough how ill patients are when they are admitted to the hospital, and how unclear the proper diagnosis can be at the beginning of a hospitalization. After a day or two all the diagnostic information has returned and, with the 20:20 vision of hindsight, the correct diagnosis may become clear and as a result the proper course of therapy is clarified.

Since cultures are often negative, the empiric course of therapy may morph into a therapeutic trial.

After setting the therapeutic framework in place, OOSE proceeds, with case reports, to describe fallacies in antibiotic therapy that lead to the wrong therapeutic interventions. There is, in medicine, a long tradition of using cases as illustrative of problems, but not as anecdotal evidence for the proof of a hypothesis. We all remember concepts when they are applied to specific patients and specific cases.

Their Fallacies in Antibiotic Therapy are

  • Broader is better.
  • Failure to respond is failure to cover.
  • When in doubt, change or add another.
  • Sickness requires immediate treatment.
  • Response implies diagnosis.
  • Bigger disease, bigger drugs.
  • Bigger disease, newer drugs.
  • Antibiotics are non-toxic.

I will add my own.

  • Once started, an antibiotic cannot be stopped.
  • Once a class of antibiotic is started, you need to stay in class.
  • Gotta double cover (i.e. give two antibiotics) a particular organism.
  • The primary reason a particular antibiotic is given is “I like it.”

I will not repeat the OOSE case studies as examples to support the fallacies, but instead will make comments and substitute my own examples. These fallacies are used a minority of the time, but it is not common to explicitly discuss the ways in which medical reasoning can go wrong in the context of faulty thinking. These fallacies are not unique to infectious diseases, and I am sure a neurologist or oncologic surgeon could generate a similar list in their own specialty. I doubt, however, that the same could be said of a chiropractor, naturopath, or homeopath. Perhaps one will prove me wrong in the comments, but logical fallacies are the sine qua non of alternative medicine. They are parallels and subsets of the standard logical fallacies beloved by skeptics everywhere. They are examples of the endless number of ways we can all think inaccurately.

Broader is better

Broad spectrum means an antibiotic that covers every conceivable pathogen. For most infections, the potential causes are often few in number, based on the history and potential exposures. You will always be surprised by the unexpected positive culture and any therapy will have gaps.

Residents do not want to be accused of not covering some particular organism if it turns out that one of the patients with an odd organism growing in their blood. So they give antibiotics that kill everything, adding expense and driving resistance without necessarily improving care.

Failure to respond is failure to cover

Few infections get better immediately, and some will be symptomatic for days. Staphylococcal endocarditis will have fever for up to 2 weeks, and often the reason a patient does not respond is not because they are on the wrong or inadequate antibiotic but it is either the natural history of the disease under treatment or, more often, there is a need to drain some pus. The old aphorisms “Nothing heals like cold steel” and “A chance to cut is a chance to cure,” remain as true today as they did in the pre antibiotic area. One of my colleagues does an impression of me when I am 85 and demented in a nursing home, banging my hand on the table, shouting over and over “drain the pus.”

Adding antibiotics may add only cost, potential toxicity and accelerated resistance.

When in doubt, change or add another antibiotic

Medicine is filled with uncertainty, and often it is the case that if an infection is thought of, it is treated, no matter how unlikely it is that it may be causing the disease. I have a fantasy where oncology is practiced like infectious disease. “It might be lymphoma, so let’s start with CHOP, but we don’t want to miss adenocarcinoma, so let’s add bleomycin, and in case it’s breast cancer we need to include tamoxifen and it could be prostate so let’s add…etc , etc.”

When in doubt, increase your diagnostic certainty.

Sickness requires immediate treatment

Sometimes it does, sometimes it doesn’t. It depends on the patient and how clinically stable they are. All too often, people receive therapy for diseases that do not need antibiotics or the antibiotics are given before a firm diagnosis is made. This is driven, in part, by CMS core measurements. Community-acquired pneumonia guidelines mandated that antibiotics be given within 4 hours of the presentation to the ER, if not the hospital gets a demerit. The result? Perhaps one in five patients who get treatment for pneumonia did not turn out to have pneumonia and would have benefited from watching and waiting.3 No good deed ever goes unpunished.

Healthcare providers appear to be particularly hesitant to not treat a fever with antibiotics. I like to say, antibiotics are not antipyretics, if you want to treat a fever, give Tylenol.

Response implies diagnosis

This is the most difficult fallacy for people to abandon. Patient has a fever, no diagnosis is evident, but the fever went away at some point after the institution of antibiotics.

Most fevers go away. Many diseases that are not infectious will have a fever. This is the medical equivalent of the skeptical motto ‘association is not causation’. The worst cognitive error physicians and patients make is the assumption that in the absence of a good diagnosis, the improvement when a therapy is given is due to the therapy. Rigorously and consciously avoiding this error is key to being a good healthcare provider.

Bigger disease, bigger drugs

MRSA is a current bane of infectious diseases. It is a bug that I cannot always kill with the current antibiotics, and the three or four antibiotics to which the organism is susceptible are all equally bad. So, when there is a severe MRSA pneumonia, the urge is to add rifampin, even though the data to support its use is problematic at best. But if one drug is good, are not two better? Perhaps. Sometimes combining antibiotics may be antagonistic and decrease the efficacy of therapy.

Bigger disease, newer drugs

Of course newer is better. New and improved. It is as American as Procter and Gamble. Not necessarily. For MRSA, there are no better drugs than nafcillin or cefazolin, and the newer agents are less efficacious in head-to-head trials. However, newer drugs are heavily advertised and detailed, <sarcasm> not that any physician would ever be swayed by advertisements instead of data </sarcasm>.

Antibiotics are non-toxic

All drugs have side effects, some common, some rare. Certainly antibiotics are less toxic than chemotherapy agents, but they do have the potential to cause significant harm. We all have our irrational beliefs. Here is mine (besides believing in critical thinking): The chance of an adverse reaction is inversely related to the need for the antibiotic. So if the patient has little need for the antibiotic, then the chance of an adverse effect is almost 100%. I know that it is not true, but some days the universe sure seems to conspire to function as if it were.

Some antibiotics are a big gun, are strong, or powerful

There are few things in medicine with 100% sensitivity and specificity. However, if your healthcare provider uses the adjectives “big gun”, “strong”, or “powerful” in reference to an antibiotic, they are either 1) talking out their backside or 2) ignorant about antibiotic use. 100% sensitive and specific.

If I had neurosyphilis, and there are those who suspect I do, the ‘strong’ or ‘powerful’ ciprofloxicin would do nothing to treat my infection, but ancient, weak old penicillin remains the treatment of choice. What you want to give are appropriate antibiotics: something that will reliably kill the organisms in whatever space is infected. These adjectives are advertising ploys used on fool gullible rubes, er, I mean healthcare providers, to think they are doing what is best for their patient. They provide a false security that you are giving the patient the best therapy.

Once started, an antibiotic cannot be stopped

People have trouble stopping an antibiotic, even when the cultures come back suggesting a particular therapy is not needed. A patient comes in septic and antibiotics are begun. Even when it turns out that the blood grows a penicillin-sensitive S. pneumoniae, the multiple initial empiric antibiotics may be continued. One of my colleagues only half-jokingly says the reason she consults me is to have me stop the antibiotics. When there is reasonable data to suggest that shorter courses of antibiotics are no better than longer, the endless allure of 10, the number of fingers, or 14, twice two weeks, is often the default duration of therapy. I once saw a patient who had been on IV vancomycin for 6 months for osteomyelitis of the foot; the provider just couldn’t bring themselves to stop the therapy.

Once a class of antibiotic is started, you need to stay in class

If a patient is admitted with an infection and started on an intravenous quinolone and grows something than can be treated with a less expensive, narrower spectrum agent like amoxicillin, at discharge the patient is likely to go home on expensive oral quinolone. They responded to a class of antibiotics, and so it needs to be continued, even if the cultures say otherwise. Magical thinking, as best I can tell, and one that I occasionally participate in.

Gotta double cover (i.e. give two antibiotics) a particular organism

There is a persistent myth that some infections, like Pseudomonas, always require two antibiotics. That is true occasionally, but for most cases a single antibacterial is no worse than two, and the more antibiotics you give the more you increase the toxicity and the faster you drive antibiotic resistance.

The primary reason a particular antibiotic is given is that “I like it”

I like to say that the three most dangerous words in medicine, especially when it comes to therapeutic interventions, are “In my experience.” In my experience you can’t trust anyone who uses that phrase. Remembering hits and forgetting misses drives antibiotic use more than I would like to admit. Infectious disease docs are sometimes the opposite. We put too much emphasis on the antibiotics that have failed us in the past. It is one extreme or the other.

Patient is admitted with a complicated infection and started on X. Why X? I ask. It worked for me in the past is the reply. What are you trying to kill? I might then ask. Often, they say the boogie man of the ICU, “Pseudomonas”. What, I will continue, is the chance drug X will be effective against Pseudomonas? They don’t know. So why again are you using X? It is what we do. They have used it successfully in the past, so it should work again.


Fortunately, most drugs work most of the time in most patients, but that rule is slowly being lost as the organisms become increasingly-resistant to our current armamentarium of antibiotics and there are few, if any, replacements in the pipeline. At my institution there is 2% resistance for Pseudomonas to ceftazadime and 4% to pipercillin/tazobactam. We get a few cases a year at best of a bloodstream infection and sepsis from Pseudomonas. Most physicians are not going to see enough infections by a given organism to get a sense of what does and does not work. It is why you cannot trust your experience.

I have not yet read the book “How Doctors Think” although being in a teaching hospital I try, however poorly, to demonstrate how I think about thinking about infections. I often give the residents on service a copy of the article on which this post is based. Once, when I was ranting about this at a conference, one of the attendees said I was an arrogant subspecialty who didn’t understand the pressures faced by general internists.

I don’t know. Perhaps they are right. But often getting the right diagnosis and therapy is less about what you know and more about being rigorous about understanding how you know. Only when you are conscious of your ability to think poorly, can you compensate. In the era of Google, any knowledge gap is a search away, but you have to be aware of the knowledge gap first.

To finish quoting this under-read and under-appreciated article:

…fashion and marketing forces, not science, shape clinical practice. Within an intensive care unit, gravity of illness amplifies the effects of delay and presses for preemptive, urgent empiricism, but the selection and manipulation of therapy can sometimes be justly criticized. The intensive care unit mentality, which treats all illness as life-threatening, favors therapy over careful consideration of diagnostic maneuvers…The potential for, and tendency toward, spiraling (as opposed to appropriate) empiricism appears disturbingly pervasive – reinforced by fashion, compensation, and litigation.

True, but driven more by the urge to help people get better and the fear of doing harm by missing an infection. OOSE does overstate the problem, but such is the nature of polemics.

Osler’s comment that the ‘practice of medicine is an art, based on science’ underscores the dichotomy and the dilemma, of medical science. Empiric therapy at its best is set between the Scylla of unnecessary delay and the Charybdis of therapeutic voyeurism. Knowledge of the science of medicine and the natural history of disease should temper and compliment the art.

This article was one of the few epiphanies in my medical career. I re-read it several times a year and consciously endeavor to keep its concepts in the front of my thought processes. It stays fresh with each reading, because my capacity to think badly is limitless and only by constantly reminding myself of that fact can I hope not to stray into illogic.

Part of applying the art of medicine is to recognize the fallacies of medical thinking and to question your decisions and interventions in the light of understanding yourself and how you think.

The bumper sticker “Don’t believe everything you think” should be a motto for all health care providers.


  1. Kim JH, Gallis HA. (1989). “Observations on spiraling empiricism: its causes, allure, and perils, with particular reference to antibiotic therapy.” Am J Med, 87(2):201-6. PMID: 2667357
  2. Grossman CM. (2008). “The first use of penicillin in the United States.” Ann Intern Med, 149(2):135-6. PMID: 18626052
  3. Wachter RM, Flanders SA, Fee C, Pronovost PJ. (2008). “Public Reporting of Antibiotic Timing in Patients with Pneumonia: Lessons from a Flawed Performance Measure.” Ann Intern Med, 149:29-32. PMID: 18591635

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