In my last post I discussed prebiotics and probiotics. Now it’s on to antibiotics. At first glance it may seem odd that I am skeptical about a class of drugs that has saved countless lives, but it’s their effectiveness going forward and widespread misuse that concerns me. Unfortunately, when it comes to antibiotics these concerns are inextricably linked. In their 2012 annual report, the World Economic Forum did not name war, climate change, or the possibility of the global economic collapse as the biggest threat to human health, citing instead the growing problem of antibiotic-resistant bacteria. The hubris of past physicians, like Nobel laureate Macfarlane Burnet, who declared in 1962 that antibiotics had led to “the virtual elimination of the infectious diseases as a significant factor in social life” seems almost laughable today. Just a few decades later, we now have multi-drug resistant strains of TB, malaria, staph, gonorrhea, and enterococcus to name just a few.

It wasn’t always this way. From Dr. Paul Ehrlich’s first “magic bullet” to treat syphilis in 1908 to the discovery of sulfonamides in 1936 and penicillin 7 years later, it seemed that man’s ingenuity was winning the war. For instance, the development of antibiotics lowered the absolute mortality of community-acquired pneumonia by 25%, endocarditis (an infection of the heart valves) by 75%, and meningitis by 60%. In the pre-antibiotic era, the mortality for even simple skin infections like cellulitis was greater than that associated with heart attack today. But bacteria preceded us and they will outlive us still. The simple truth is that the more antibiotics we use today, the less effective they will be tomorrow. And boy, do we use a lot of antibiotics. Each year more than 6 million pounds of antibiotics are prescribed to patients in the US alone, with another 26 million pounds fed to our livestock. That’s a mountain of antibiotics. And there are consequences.

 

 

So what is an antibiotic anyway? Literally meaning “against life,” antibiotics are compounds that kill or prevent the replication of bacteria. It’s important to note here that antibiotics are only effective in treating bacterial infections; they have no benefit against viral infections. What’s the difference? Whereas bacteria are living unicellular organisms equipped with a cell wall surrounding a cytoplasm rich in DNA, ribosomes, and storage granules, viruses are little more than a protein coat encasing a bit of genetic material. Technically, viruses aren’t even alive as they are incapable of self-replication, instead high-jacking the DNA and RNA machinery of the cells they invade to make copies of themselves. They are roughly 100 times smaller than bacteria and much simpler in structure, factors that make it harder to kill them with drugs. Diseases ranging from the common cold to AIDS are caused by viruses, and the very best way to prevent them is through vaccination. Examples of viral infections prevented through vaccination include: rotavirus (previously the most common cause of pediatric diarrhea), mumps, measles, rubella, influenza, polio, chicken pox, small pox, rabies, genital warts (HPV), and hepatitis A and B. Pretty impressive list, huh?

Then there are the bacterial infections, the ones we can—theoretically, at least—defend ourselves against by taking antibiotics when infected. But even better are vaccinations that can prevent some bacterial infections like tetanus, diphtheria, and whooping cough from occurring altogether. Examples of bacterial infections not prevented by vaccination include strep throat, MRSA (methicillin resistant staph aureus), dysentery, and gonorrhea. Almost all cases of sepsis—defined as a whole body inflammatory response to infection—are bacterial in origin. It may come as a surprise to learn that, despite our many antibiotics, sepsis remains the leading killer of hospitalized patients in the US. We still have a long way to go.

 

 

Antibiotic resistance is inevitable. Bacteria replicate quickly and often, conferring them an advantage over time against the drugs used to kill them. We will never conquer the problem of resistance; it’s in the DNA. But we can slow it down. According to the CDC, Americans receive nearly 900 antibiotic prescriptions per 1,000 people annually. This number places us in the middle of antibiotic use compared to other developed nations. The problem is far greater in China where most patients in rural areas are treated by non-physicians. In a recent chart review of Chinese clinics, antibiotics were inappropriately prescribed to 78% of patients with colds and 93% of patients with coughs (bronchitis). In more than half of cases, two or more broad spectrum antibiotics were prescribed. In the US we do better, but not by much. Here, it is estimated that nearly half of all antibiotic prescriptions are issued for viral infections of the upper respiratory tract. When antibiotics are prescribed for viruses the patient receives no benefit but all the potential harm. Furthermore, the certain and inevitable outcome of such misuse is the more rapid development of antibiotic-resistant strains of bacteria.

Let’s take a look at 3 illnesses for which antibiotics are commonly prescribed: 1) colds and coughs, 2) sore throats, 3) ear infections. All winter long, I am confronted with patients suffering from head and chest colds requesting antibiotics. Many mistakenly believe that if the mucus is green then it means that a bacterial infection is present, when in reality this is just a sign of a well-functioning immune system. The color of the mucus has to do with the duration of symptoms, not the source of them. There remains a good bit of misunderstanding. In a survey of Brits nearly two-thirds believed that antibiotics work to treat colds and coughs, and nearly half believed that antibiotics can kill viruses. Neither is true. On the flip side, 20% were unaware that antibiotics do kill bacteria. There is no reason to think that Americans are better educated, which is why doctors’ offices, urgent care centers, and ERs continue to be flooded with patients during the winter months. Recall from an earlier post that antibiotics are ineffective for routine coughs (bronchitis), and that the CDC recommends against their use irrespective of the cough’s duration.

 

 

We don’t do much better for sore throats. In adults, only about 10% of sore throats are due to strep and yet 60% of the time antibiotics are prescribed. Even in children, where strep is far more common, the number receiving antibiotics is much higher than the actual number harboring the bacteria.

What about ear infections which, in this country, are almost always treated with antibiotics? If ear pain accompanies a cold caused by a virus, then you can be pretty certain that the infection behind the eardrum is viral as well. Here, antibiotics only cause harm; there is no benefit from their use. The number of ear infections needed to be treated for one person to benefit is generally recognized at 15, meaning that 14 of 15 patients treated receive no benefit from the drug either because the infection is viral or because the body’s own defenses would have rapidly cleared the infection anyway. Interestingly, a Cochrane Collaborative review of antibiotic treatment versus no treatment for ear infections in children found no difference in ear pain at 3 to 7 days, no difference in complications like ruptured eardrums, no difference in recurrence rates, and no difference in hearing loss at 4 weeks in those who underwent audiometric testing. In fact, antibiotics didn’t seem to help kids at all. Meanwhile, the number of children experiencing harm from antibiotics approaches 20%, mostly from side effects like diarrhea, nausea, and vomiting. Most allergic reactions are mild and consist only of rash and itching although serious anaphylactic reactions do sometimes occur resulting in death. The data suggests that for most infections antibiotics are not needed (e.g. they shorten the duration of strep throat symptoms by about a day, don’t work at all for coughs and colds, and have dubious benefit for ear infections). Since doctors know this (or should), then why are so many antibiotics still being prescribed to so many people?

Studies examining whether patient satisfaction is improved when antibiotics are prescribed have yielded mixed results, but those of us in practice have all encountered patients who really want a prescription. Of patients with colds who see a doctor and don’t receive one, roughly 1 in 7 will return to the same or a different physician for treatment of ongoing symptoms. What’s clear is that if the second visit results in an antibiotic prescription, patients are very unhappy with the first doctor (even when it’s usually the second doctor who is acting inappropriately). Patients who perceive that their doctor withheld a drug capable of curing them rapidly turn elsewhere. So while physicians want to do the right thing, they also want a full docket of patients. Their livelihoods depend upon it.

 

 

It’s not surprising that most physicians look for a reason to prescribe antibiotics rather than a reason to withhold them. And here is where it becomes ethically sticky, because while it’s often not in the best interest of the patient to receive antibiotics, it’s almost always in the best interest of the physician to prescribe them. In the vast majority of cases, it’s simply not possible to know with certainty that the patient sitting in front of you is sick with a viral rather than a bacterial infection. And woe to the doctor failing to prescribe antibiotics to a patient who returns 2 days later with sepsis. This is a sure way to garner censure and a trip to peer review. Errors of omission are deemed more egregious than errors of commission, and it’s far easier to defend why an unnecessary antibiotic was prescribed than why a necessary one wasn’t.

With regard to side effects, the fact is that the majority of patients don’t experience them and those that do generally hold their physician blameless, recognizing that some side effects are inevitable. Here again, the balance tips toward over-prescribing.

Science, however, has a funny way of not caring about the wants and needs of patients. And the science behind antibiotic resistance assures us that we cannot keep feeding tons of antibiotics to our livestock and taking them ourselves for every cough, cold, sore throat, and ear infection without facing the consequence of multi-drug resistant bacteria. It’s already happening. So we need to be better stewards. The low hanging fruit has been plucked, and it has become increasingly difficult to find new avenues of attack. In fact, there hasn’t been a new class of antibiotic to treat Gram negative bacterial infections in more than 45 years. Between 1983 to 2002 the FDA’s approval of new antibiotics dropped by more than half. This is one of the few places where it’s hard to blame the pharmaceutical industry. The hurdles for drug approval are high, the costs enormous, and the return on investment low. Drug companies overwhelmingly seek to treat diseases that yield a lifetime of profit, which is why so little R&D money is spent on new antibiotics taken for 7 to 10 days and so much is spent on the big four that require a lifetime of treatment (hypertension, high cholesterol, depression, and diabetes). An analysis by the London School of Economics estimated that the net value to develop a new IV antibiotic stands at minus $50 million. Not a lot of incentive there.

Scandinavian countries use about half the antibiotics we do here in the States and yet their children aren’t hearing impaired from untreated ear infections, their heart valves aren’t eroded from untreated strep, and their ICUs aren’t filled with ventilator patients from untreated coughs and colds. In fact, these countries spend less per capita, take fewer antibiotics, and provide universal healthcare with better overall health outcomes than we do. Spending less while living longer? How is this possible? I believe the main reason has to do with cultural expectations. Here in the States, we expect a pill for every ill. Direct to consumer advertising by pharmaceutical companies is largely responsible for this crazy notion. Besides New Zealand, the US is the only other country that allows it. Drug ads aren’t designed to inform or educate; they’re designed to sell product. Our culture has trouble accepting even minor illnesses without a pixie dust cure. Instead, seek to find your inner Viking while viewing coughs and colds as “pump-priming” events for your immune system. That way, when a serious infection comes along, you’ll be ready to fight it. The body works beautifully if you don’t mess with it too much. Finally, try eating less meat as most antibiotics in this country are administered to livestock in the attempt to keep them fat and infection-free. Send a message that you don’t want folks messing too much with your food either. You’ll undoubtedly be healthier and live longer. Last question: Do I practice what I preach? Sure, I haven’t taken an antibiotic in more than 20 years (although I still enjoy a good burger now and then).

 

References:

• Anthony Fauci and David Morens, “The Perpetual Challenge of Infectious Diseases,” NEJM 2012; 366 (5): 454-61.
• Carl Nathan and Otto Cars, “Antibiotic Resistance—Problems, Progress, and Prospects,” NEJM 2014; 371 (19): 1761-63.
• Wang et al., “Use and Prescription of Antibiotics in Primary Health Care Settings in China,” JAMA Internal Med 2014; 174 (12): 1914-20.
• Brad Spellberg, “The Future of Antibiotics,” Critical Care 2014; 18: 228.
• Dimitri Christakis et al., “Association Between Parental Satisfaction and Antibiotic Prescription for Children with Cough and Cold Symptoms,” Ped Infect Dis Journal 2005; 24 (9): 774-77.
• P. Venekamp et al., “Antibiotics for Acute Otitis Media in Children (Review),” The Cochrane Collaborative; John Wiley & Sons Ltd., 2015.
• Cliodna McNulty et al., “The Public’s Attitudes to and Compliance with Antibiotics,” J of Antimicrob Chemo 2007; 60 (Suppl i): i63-i68.
• The McDonnell Norms Group, “Antibiotic Overuse: The Influence of Social Norms,” J Am Coll of Surgeons 2008; 207 (2): 265-75.
• “Antibiotic Resistance Threats in the United States, 2013,” U.S Dept. of Health and Human Services, Centers for Disease Control and Prevention, http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.