ѻý

The Next Pandemic Is Already Here

<ѻý class="mpt-content-deck">— Tools for stopping it are readily available, if only we agree to use them
MedpageToday
An illustration of a pill capsule surrounded by bacteria

The casualties of a global pandemic are now vivid to everyone, and many wished we could have acted earlier to stem the death toll. But another pandemic has already started. It's not one that rips through countries in months. It's a to kill 10 million people a year by 2050. Even so, it has received little attention.

We're talking about the global pandemic of antimicrobial resistance -- a pandemic increasingly claiming the lives of patients on our hospital floors. Unlike pandemics caused by novel viruses, this one can be addressed through our prescribing routines and the purchasing decisions and food choices made on a societal level.

The antimicrobial resistance crisis stems from the simple fact that new antibiotic development cannot keep pace with the rate of bacterial resistance.

image

Because of a smaller market size and profit incentive for pharma companies to develop new antibiotics compared to lifestyle medications and other therapies with broader indications, the number of new antibiotics that the FDA approved annually has slowed to a trickle. Over the same time, the rate of bacterial mutation is growing exponentially. It used to take 21 years on average for bacteria to become resistant when antibiotics were first used. Now it takes just 1 year on average for bacteria to develop drug resistance. Today, the CDC lists of antibiotic-resistant bacteria and classifies five as urgent threats to human health.

image

Among the most concerning mutating bacteria are carbapenem-resistant Enterobacteriaceae (CRE), carbapenem being a "drug of last resort." CREs already pose a major concern for patients and healthcare professionals, infections in hospitalized patients and killing 1,100 every year in the U.S. The CDC estimated mortality infection to be as high as 40%-50%. Antibiotic-resistant bacteria found in the healthcare setting, including CRE and methicillin-resistant Staphylococcus aureus, represented over 85% of the antibiotic-resistant deaths in the CDC analysis. Yet this early stage pandemic has received almost no media attention.

This pandemic has already started. . Increasingly, we as surgeons will remove an organ simply because there is no other way to manage the infection. In the case of Clostridioides difficile (C. diff) colitis, an emergency colectomy is performed when patients don't respond to antibiotics or fecal bacteriotherapy. CDC data show in half a million patients each year, and at least 29,000 had fatal outcomes within one month of initial diagnosis; 15,000 of those deaths were directly attributable to the pathogen. Again, this pandemic has received almost no media attention. Today, of patients with severe C. diff colitis and sepsis will require emergency surgery, and the mortality of patients who undergo the surgery remains high.

Prophetically, Alexander Fleming, the discoverer of penicillin, warned of antimicrobial resistance from the overuse of antibiotics in his 1945 . His discovery was an accident, but his warning was deliberate.

image
Alexander Fleming, the discoverer of penicillin

Overuse of antibiotics is the primary driver of antibiotic resistance today. According to the CDC, in 2018 an astonishing seven antibiotic for every 10 Americans. One-third were deemed unnecessary, and were for viral illnesses that do not respond to antibiotics including sinus infections, ear infections, viral sore throats, and the common cold. Clinicians writing these prescriptions frequently argue that the antibiotic can help if the infection includes a small bacterial component or creates opportunity for bacterial infection.

In medical school, it's amazing how much time is spent on memorizing and regurgitating information, only to forget it days later, as a method for getting familiar with a new medical vocabulary. In all that time spent on rote memorization, a reflex is created, pairing bacteria with antibiotics. But in that education, what is lost is the appropriateness of treatment. We should be teaching not just what antibiotic to use, but when to use it. We need to emphasize thresholds for treating patients and how to stand firm when patients are begging for antibiotics that are clearly not indicated.

Nowhere has the overuse of antibiotics been more apparent than in the treatment of the COVID-19 virus. In a recent in the Journal of Clinical and Infectious Diseases of 18 studies, of 2,010 patients hospitalized with COVID-19, a stunning 72% of them received an antibiotic, even though only 8% had a bacterial co-infection. (Azithromycin was commonly given early in the pandemic because some questionable evidence suggested it had an antiviral effect.)

Data actually suggest that antimicrobial resistance might be during the COVID-19 pandemic. As global health efforts focus on the growing viral pandemic, antibiotic resistance eradication efforts have been neglected.

The adoption of mitigation strategies to prevent the spread of COVID-19 suggest that we can take action now to battle antibiotic resistance. In addition, current infection control measures may also be beneficial to reducing the risk of spread and incidence of antibiotic-resistant infection.

The comparison table below, adapted from a , exhibits the differences in urgency and action for both pandemics.

image

a. From the

b. Estimate based on (Solomon et al.), U.S. data for COVID cases, and U.S. share of global population 2.8 million annually and 4.31% of the global population

c. Estimate based on same sources

Medications clinicians prescribe, however, are not the only source of our antibiotic resistance crisis. In the U.S., 70%-80% of all antibiotics are , where crowded conditions facilitate mutations. Once the animals develop drug resistance to the bacteria, it can spread to the environment and to our food, eventually transferring to people who eat that food.

Beyond land-based livestock, antibiotics are rampant in salmon farms, which is especially concerning, considering that eaten in the U.S. comes from farms. In response to a growing resistance threat in the food industry, fast food chains such as Chipotle and Panera have championed antibiotic-free animal products. Many fast-food chains, in fact, have shown progress in reducing antibiotic use in chickens, though beef practices have yet to catch up. The public interest group PIRG has to compare antibiotic practice patterns of popular fast-food chains which can help guide consumers away from antibiotic-using establishments.

image

Growing public demand can move markets towards better health and address the next antimicrobial resistance pandemic.

Despite the U.S. government's comprehensive action plan for combating antibiotic resistance, efforts to carry it out have been inconsistent. In 2017, the FDA banned the use of antibiotics to promote growth in livestock. That same year, the U.S. proposed major budget cuts to agencies that fund research for new antimicrobials and work to curtail the global spread of multidrug-resistant pathogens; these agencies include the CDC through its Antibiotic Resistance Solution Initiative, the National Institute of Allergy and Infectious Diseases, and the U.S. Agency for International Development. The U.S. Department of Agriculture also removed federal oversight of meat inspection at pork processing plants, effectively eliminating up to 40% of the inspection staff at plants.

Clinicians -- doctors, nurses, physician assistants, and others -- play a critical role in preventing antimicrobial resistance and improving the appropriateness of antibiotic use both in the clinical setting, and in the food industry. Explaining the situation to patients, or hospital food service administrators, can ultimately move food markets by creating increased demand for antibiotic-free products. In the same way that clinicals tackled smoking with a concerted educational effort, clinicians can be leaders in explaining the health, social, and economic benefits of conscious consumption of responsibly sourced animal products.

In summary, here are some actionable stands that we can all take to combat this pandemic in our everyday clinical routines:

  • about the importance of buying antibiotic-free foods
  • Discuss with them the potential direct harms such as allergic reactions -- as many as one in five antibiotics come with side effects
  • to use antibiotic-free foods only to help fight the antimicrobial resistance pandemic
  • When prescribing, remember that antibiotics are not always appropriate, such as for viral infections, open wounds, and minor improving infections
  • Encourage fellow clinicians to adopt safe antibiotic practices in hospitals and clinics
  • When prescribing, make sure to use the right dose, duration, and coverage of the antibiotic
  • Promote hand hygiene to prevent transmission of resistant bacteria. Remember that alcohol-based gels do not kill spores like C. diff
  • Promote antibiotic stewardship programs in your clinical setting. Find

To learn more about this topic, see Makary's TED talk on antimicrobial resistance .

Marty Makary MD, MPH, is editor-in-chief of ѻý as well as professor of surgery and health policy at the Johns Hopkins University School of Medicine and author of . is a medical student at Weill Cornell Medicine and researcher at the Johns Hopkins University School of Medicine. is a research fellow at Johns Hopkins Medicine. , is director of clinical research at Johns Hopkins Medicine.