Antibiotic-resistant bacteria: A pandemic in the making

Issue: April 2015

ByJason Newland, MD

Alexander Fleming stated in The New York Times in 1945:

“The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out which can be passed to other individuals and from them to others until they reach someone who gets a septicaemia or pneumonia which penicillin cannot save.”

Today we don’t discuss bacteria developing resistance to penicillin because that has already happened. Instead, we worry about the resistance to drugs that are commonly used (eg, cefdinir, vancomycin) or last-line antibiotics to treat resistant bacterial infections such as carbapenems (eg, meropenem).

Recently, President Barack Obama recognized the importance of antibiotic resistance by signing an executive order and developing a national strategy to combat the problem. Furthermore, the President’s Council of Advisors on Science and Technology published a report addressing the issue of antibiotic resistance.

Jason Newland

The impact of antibiotic resistance is not trivial. The CDC published a threat report in 2013 demonstrating that approximately 2 million Americans contract an antibiotic-resistant infection annually, 23,000 of whom die as a direct result of these infections. An additional 250,000 Americans become infected with Clostridium difficile each year, due in part to the emergence of new strains resistant to vancomycin, fidaxomicin and metronidazole. The financial impact of antibiotic resistance on the U.S. health care system has been estimated to be as high as $35 billion annually.

Antibiotic use drives antibiotic resistance. In hospitalized children, up to 60% will receive an antibiotic during their admission; additionally, 49 million antibiotic prescriptions are provided annually for children in the ambulatory setting. These numbers would not necessarily present a problem if not for the fact that up to 50% of our hospital use is inappropriate and 11 million unnecessary prescriptions are provided to children in ambulatory pediatric clinics. Inappropriate use puts undue pressure on bacteria, further increasing the rate of bacterial resistance.

A significant amount of inappropriate antibiotic use also occurs in the agriculture industry. Since the 1940s, antibiotics have been utilized for growth promotion and infection prevention for food-producing animals. An FDA report from 2009 said that 29 million pounds of antibiotics were used in the agriculture industry in 1 year, representing more than 80% of the total antibiotics used in the U.S. Importantly, a link does exist between this excess antibiotic use in agriculture and resistant human infections. For example, an animal-derived strain of MRSA has been observed in human MRSA infections. Fluoroquinolone- and cephalosporin-resistant Salmonella infections and fluoroquinolone-resistant Campylobacter infections in humans also have been increasingly observed.

Antibiotic resistance will always be a challenge. A study from Bhullar and colleagues published in PLoS One demonstrated that caves previously untouched by humans featured bacteria resistant even to new antibiotics such as daptomycin. Microorganisms have been fighting with one another to survive long before humans were present on Earth and are known to be capable of adapting quickly to develop resistance. Nobel laureate Joshua Lederberg, PhD, probably stated it best: “The future of humanity and microbes will likely evolve as … episodes of our wits versus their genes.”

In order to stay ahead of bacterial resistance, we will need a unified approach that includes everyone.

First, clinicians must treat only bacterial infections. Mechanisms such as antimicrobial stewardship programs should be embraced in hospitals, and additional stewardship interventions are needed to support and improve antibiotic use in the ambulatory clinics;
Second, families and patients must accept that antibiotics are not necessary for illnesses that their clinician believes are not bacterial in origin;
Third, researchers and funding agencies must dedicate time and financial resources to conduct clinical trials to establish the shortest duration of therapies for common infections and develop rapid diagnostic tools to support appropriate antibiotic use;
Fourth, industry must dedicate more time to research and development of new antibiotics, and the regulatory agencies must provide pathways that allow for the approval of antibiotics that are only needed for the most resistant infections. The large clinical trials that currently are required are not feasible or practical to allow for the approval of these much-needed therapeutic agents; and
Finally, the agriculture industry also must use antibiotics more appropriately. While they have started to remove the use of antibiotics for growth promotion, additional measures are needed to identify areas where excess prophylactic use is likely unnecessary.

A couple of years ago my daughter suffered from orbital cellulitis. She had surgery and was treated with antibiotics. She did well. What would have happened if this occurred 100 years ago? Without an improvement in our overall antibiotic use (human and animal) and antibiotic development, we will no longer be guaranteed the continued good outcomes for common, life-threatening bacterial infections and possibly could be practicing medicine like they did before antibiotics were available.

Incidence rates of C. difficile infection and illness are increasing in children, and although guidelines for diagnosis and treatment in children and adults are available, more data specific to infants and children are needed. A new pharmacotherapeutic agent, fidaxomicin, has recently been labeled for use in treating C. difficile, although only in the adult population.

One of the most promising treatment strategies for C. difficile infection is quickly evolving, fecal transplantation, although many unknowns still exist. As prevention may be one of the best strategies overall, an argument for the judicious use of antibiotics for all infants and children becomes even more persuasive.

References:

Bhullar K, et al. PLoS One. 2012;doi:10.1371/journal.pone.0034953.
Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;doi:10.1086/651706.
Gerber JS, et al. Pediatrics. 2010;doi:10.1542/Peds.2010-1275.
IDSA Statement on Antibiotic Resistance: Promoting Judicious Use of Medically Important Antibiotics in Animal Agriculture. Accessed Jan.19, 2015 at: www.idsociety.org/uploadedFiles/IDSA/Policy_and_Advocacy/Current_Topics_and_Issues/Advancing_Product_Research_and_Development/Vaccines/Statements/Testimony%20on%20Judicious%20Use%20of%20Antibiotics%20in%20Animals%20House%20EC%20Subcommittee%20on%20Health%20071410.pdf.
Kronman MP, et al. Pediatrics. 2014;doi:10.1452/Peds.2014-0605.

For more information:

Jason Newland, MD, is medical director of patient safety and systems reliability at Children’s Mercy Hospital in Kansas City, Mo.

Disclosure: Newland reports financial ties with Pfizer and Cubist.