Miracle drugs in need of a miracle

David N. Gilbert, M.D.
Infectious disease consultant
Providence Portland Medical Center

Oct. 16, 2013

A recent report by the Centers for Disease Control and Prevention details the increasing threat of antibiotic resistance, which has been declared a crisis by the world’s largest health organizations.

In recent years, a confluence of events has given this crisis greater urgency in the United States. Development of antibiotics has stalled, despite the fact that drug-resistant bacteria kill at least 2 million Americans a year. Widespread abuse has led to the United States consuming 46 percent of the world’s antibiotic market. And despite infection-prevention efforts, patients entering a U.S. hospital are 40 times more likely to acquire methicillin-resistant Staphylococcus aureus, or MRSA, than hospital patients in the Netherlands.

We may be able to ward off a catastrophic threat with multipronged approach we’ll call an “antibiotic salvage bundle”:

Get more data. The European Union has been gathering detailed information on antibiotic use and resistance for 15 years. As a result, it has been able to profile overuse by geography and develop targeted interventions. For example, in Greece, which uses the most antibiotics of all the union’s 26 countries, more than half of the Staphylococci are resistant to methicillin-type drugs. The result is the need to overuse the less effective antibiotic, vancomycin. In contrast, the Netherlands has the lowest use of antibiotics, and reports a resistance rate of only 1.6 percent. The United States has no comparable surveillance methods.

Focus on the farm. Eighty percent of antibiotics sold in the United States are used to promote growth and prevent infection in livestock. Resistant bacteria and resistance genes can be traced from the farm, to the meat sold in grocery stores, to blood cultures in patients. Denmark stopped using antibiotics for growth many years ago with no apparent economic or animal health consequences.

Be better antibiotic stewards:

  • Several studies have shown that testing for procalcitonin levels, which reflect bacterial replication, can guide decisions on when to use or stop using antibiotics.
  • Short courses of antibiotics are often therapeutically equivalent to longer, “standard” durations.
  • Switching to oral medication for appropriate antibiotics such as linezolid, metronidazole, fluoroquinolones and some cephalosporins, can speed discharge and reduce risks associated with IV lines.
  • Redundancy contributes to antibiotic abuse. One report found that 23 percent of Veterans Affairs patients were given metronidazole on top of another anaerobic drug.

Educate patients. Patients often expect a prescription to treat their viral respiratory tract infection, but the literature has found that the “three-day script” is the only method with documented success in preventing abuse while still comforting patients. This means telling the patient with sinusitis that he probably has a viral infection that’s likely to get better in three days.

Physicians need a greater presence online to counter common misconceptions that now have a global platform. Consider this ill-informed tweet, which was shared with 850,375 followers: “Finally over my cold. Thank God for Z-Pak.”

Develop rapid diagnostic tests. Molecular methods are coming fast. We now have polymerase chain reaction for detecting MRSA, vancomycin-resistant enterococci, Neisseria gonorrhoeae, Chlamydia trachomatis, group B strep, tuberculosis and many others.

Tests are coming soon that will detect nearly all bacteria and other pathogens, allowing for an etiologic diagnosis within one or two hours of the sampling. Interpretation will be tricky, however, since many specimens will need quantitation and there will be a predictable need for substantial stewardship.

Develop new drugs. Years ago, pharmaceutical companies produced new products based on the continuum of resistance. Companies no longer can break even by producing low-cost drugs for short-term use, which is why the last new antibiotic class for gram-negative bacteria – trimethoprim – was developed four decades ago.

Creative economic models are needed, such as the public-private partnership between the Bill & Melinda Gates Foundation, Janssen Therapeutics and the TB Alliance. Together, they have produced the first new U.S. Food and Drug Administration-approved drug for tuberculosis, bedaquiline, in 40 years.

Focus on prevention. Health reform expects us to save lives while saving money – values that aren’t mutually exclusive. In Michigan, 103 ICUs adopted a common-sense, step-by-step protocol to prevent central-line infections. The impressive results led the study authors to conclude that “If every hospital did this it would save 27,000 lives and $1.8 billion every year.”

This article is adapted from “Seven Ways to Preserve the Miracle of Antibiotics,” by Dr. Gilbert and co-authors John G. Bartlett, M.D., Johns Hopkins University School of Medicine, and Brad Spelling, M.D., Liu Vaccine Center, Torrance, Calif.: Clin Infecti Dis. 2013; 56(10):1445-50. The authors published a separate article on antibiotic resistance in the January 2013 New England Journal of Medicine.