I stared down at the tired, deteriorating woman sprawled across a bariatric bed before me. A breathing tube was in her throat while multiple catheters pierced her arms and neck, pouring powerful medications directly into her veins. Among several functions, these infusions would maintain her blood pressure high enough to keep her organs alive. This was my initial, visual impression of a patient I was responsible for during my first several months as a physician. Like the many providers who came before me, I sifted through her medical record in order to elucidate the primary cause of her suffering. Where did modern medicine fail her? After reading notes, scrolling through months of labs and speaking to several specialists I came to an unsettling conclusion: The antibiotics themselves were killing her.
The Centers for Disease Control and Prevention reported in 2013 that antibiotic resistant bacteria infect 2 million Americans annually, with 23,000 of these individuals dying. While these numbers are nowhere near as great as those affected by heart disease or cancer in the United States, they are large enough to warrant significant public health concern and action. Antibiotics are overused by physicians all the time and for a myriad of reasons not fully within their control.
In hospitals, over 50 percent of patients receive an antibiotic. Much of antibiotic administration scrutiny, however, is directed at overuse in an outpatient setting. Nearly 1/4 of patients diagnosed with an upper respiratory infection (URI) and 3/4 of patients diagnosed with bronchitis receive antibiotics in medical clinics despite the large majority of these infections being of viral etiology. Physicians typically feel pressured to prescribe antibiotics in these and other situations due to factors that range the gamut from economic incentive to increased pressure from patients themselves. With patient satisfaction becoming a component of physician reimbursement and the threat of lawsuits always on the table, physicians are more inclined to practice defensive medicine than ever.
In the clinical context of my patient, it is important to recognize that causes contributing to her decline were not only multifactorial but also that administration of antibiotics was a last resort. The first of her innumerable, major encounters with the health care system occurred several years ago when she received a hip replacement that subsequently became infected. She was advised at that time that she would need hip irrigation and as a last resort another hip replacement in order to clear the underlying disease. She stubbornly rejected all of these options. Faced with few alternatives, an infectious disease specialist placed her on oral antibiotic therapy for the next two years, successfully quelling but not eliminating the bacteria living inside of her. She eventually presented for the hospital stay during which I took care of her with a bacterial urinary tract infection that was pan-resistant to the majority of antibiotics we use in the hospital. The likely cause of this resistance was antibiotic overuse, requiring the initiation of several last-line antibiotics causing kidney failure, increased bleeding, and deteriorating liver function. The antibiotics we used to treat her were, in fact, killing her.
This case is not necessarily typical of all situations resulting from antibiotic overuse, but it speaks more broadly to the importance of our national conversation regarding the prescribing of antibiotics when alternative therapies exist. Azithromycin, for example, has been a popular and frequently prescribed therapy since the 1970s to treat patients with syphilis as an alternative to penicillin. While the 11 to 12 million annual cases of adult syphilis typically occur in developing countries, it has recently has resurged in developed countries (USA, China, Europe, etc.) and can be a major risk factor for contracting HIV. Recent studies are now showing that Syphilis is developing increased resistance in our communities, thus removing azithromycin from our shelf of treatment options. Practitioner prescribing of antibiotics such as “Z-Paks” (azithromycin) for URIs is just one of multiple practices that may be exacerbating this problem in our communities.
My incredibly sick patient also highlights the need for more robust antibiotic development so medical professionals aren’t resorting to toxic antimicrobial agents as last line therapies because no other safer, effective antibiotics exist. This last point is concerning because despite the current landscape of antibiotic resistance in the U.S. there is a dearth of new antibiotic development today.
Before a drug can safely be released onto the market, it must undergo years of expensive and resource-draining drug development prior to entering the four phases of drug testing. To put this into context, once a drug is invented and undergoes the hurdles of development through testing, only 60 percent of drugs entering phase 3 are typically approved to enter into the final phase. Financial and time barriers to developing antibiotics are enormous. It is generally more lucrative for pharmaceutical companies to invest in new medications with risks generally restricted to medication efficacy and eventual inter-pharmaceutical or generic drug competition. Resistance patterns therefore contribute to an additional risk of depreciation over time and is one factor driving many companies out of the antibiotic market — a trend that could have grave consequences for out communities within the next several decades.
Despite these concerns, all hope is not lost. There are a number of solutions and policy opportunities to address our antibiotic needs in the United States. Programs that attempt to limit the number of antibiotics prescribed, such as hospital antibiotic stewardship programs, have shown much initial promise. These programs are typically comprised of experienced pharmacists, physicians, and administrators aimed at assuring certain antibiotics are used only in the most appropriate circumstances. Studies have shown that reducing the use of high-risk antibiotics by 30 percent can lower serious diarrhea infections by over 25 percent.
Outside of hospital settings, the Choosing Wisely campaign is an example of a patient-based education initiative aimed at informing the public regarding evidence-based medical practice. This includes when medical intervention is or is not warranted. The initiative has published educational materials in a number of areas, including when antibiotics are necessary for treating pink eye, ear infections, sinus infections, and urinary tract infections and when they are not.
Furthermore, legislative efforts that address the many obstacles pharmaceutical companies encounter while developing drugs may also help in increasing our future antibiotic reservoir. In 2012, President Obama signed the GAIN (Generating Antibiotics Incentive Now) Act into law. This effectively extended the commercial life drugs considered “qualified infectious disease products” by 5 years prior to allowing generic competitors to come onto market. It also allows these drugs to receive fast track and priority review status within the FDA.
Likely as a result of this and other laws, as of September 2014 over 38 antibiotics were at some stage in the drug development pipeline. There are bills currently sitting in congressional committees that could allow for early approval of antifungal/antibacterial agents for combating serious, life threatening diseases. Regardless of whether or not this makes it out of committee and to the House floor, the fact that pieces of legislation like this are being presented and considered represent a promising future with hopeful progress in the antibiotic development market.
It was, unfortunately, too late for me to help my patient. As the duration of her required medical management remained unclear we were ultimately able to discharge her to a long-term care facility with a poor prognosis. It is frustrating and often sad to take care of patients such as this in the hospital. When I graduated medical school I took an oath to do no harm, but with tools and resources limited to what are available on the market there are infrequently options that can both quell pan-resistant bacteria yet avoid toxicity to other organ systems.
We can and should work to better educate our patients regarding the importance of antibiotic stewardship in our practices. It is also our duty as advocates of our patients push our legislators to incentivize innovation in the antibiotic development industry before new ones can’t come fast enough.
Michael Lubrano is a member, public health committee, resident and fellow section, American Medical Association.