Superbugs: The Rise of Antibiotic Resistance
The Problem of Antibiotic Resistance
Bacteria that are resistant to multiple antibiotics, aka “Superbugs”, infect 22 million people annually; 23,000 die. These superbugs have been agents of nosocomial infections and outbreaks in some of the nation’s most prestigious hospitals. Surgical patients, patients undergoing chemotherapy, renal dialysis, and organ transplants, and those with autoimmune disorders are at high risk for this type of infection. Without a concerted effort by healthcare professionals, patients and their families, and the pharmaceutical industry, the problem will rapidly escalate.
Why is this happening?
Antibiotics, those wonder drugs of years past, have been misused and overused leading to bacteria with the ability to withstand the strongest medications doctors have to throw at them.
- When a patient does not complete a course of antibiotics, those bacteria remaining are less sensitive to that agent. They pass on this resistance through plasmids (loops of DNA) creating a larger pool of resistant bacteria.
- When a physician routinely prescribes antibiotics for viral infections, either in the hope of staving off a secondary bacterial infection or to placate a patient, another opportunity is created for resistant bacteria to survive while killing off both the pathogenic bacteria still sensitive to the antibiotic and normal gut flora as well. This sets the stage for an overgrowth of opportunistic bacteria plus delivering resistance to any remaining pathogens.
- When antibiotics are fed to domestic animals in the food supply, the same scenario is set up as that mentioned above. This includes providing antibiotics to chickens that lay eggs or are slaughtered for market, beef cattle providing milk and meat, and pigs.
- A resistant bacterium can pass genetic material containing the ability for resistance to species other than its own.
Exacerbating the problem is the lack of new antibiotics in development. Pharmaceutical companies obtain much less revenue from antibiotic sales than from other types of drugs and so have little motivation to expend research and development dollars in this space.
Bringing a new antibiotic to market can easily cost up to $1 billion for something that can only be used for short periods of time and to which bacteria will eventually become resistant. Pfizer was making great progress in the area but was forced to drop its antibiotic development team and close a cutting edge pharmaceutical development facility in Groton, CT in 2011 due to high costs and Pfizer’s responsibility to shareholders.
The Path of Resistance
Which Bacteria Are Threats?
In a 2013 report the Center for Disease Control in the United States provided a listing by threat level of the most virulent, multiply-resistant bacteria. In a page taken from Homeland Security, the CDC has designated categories for these so-called superbugs based on the severity of infection and the chances for an uncontrollable outbreak.
- Carbapenem Resistant Enterobacteriaceae (CRE)*: Enterobacteriaceae are gram-negative rods that appear as gray colonies on blood agar. While many members are part of normal gut flora this group includes Salmonella spp., Shigella spp., Klebsiella spp., and E. coli. E. coli is the bacterium found in several recent cases of mass food poisoning. Carbepenem resistant Klebsiella pneumoniae (KPC) is the subject of an extensive Wired Magazine article in which an outbreak at the National Institutes of Health was, for the first time, digitally tracked by a bioinformatics specialist while in progress. Carbapenem is considered the “big gun” of antibiotics; resistance to it is extremely problematic for infection control.
- Neisseria gonorrhoeae: N. gonorrhoeae is a gram negative diplococcus that requires chocolate agar to grow. Well known as a sexually transmitted disease, gonorrhea is easily spread and can cause severe damage to the reproductive organs. As the second most reportable bacterial infection, gonorrhea is becoming a greater public health issue due to its increasing resistance to antibiotics.
- Clostridium difficile: C. difficile is a barbell shaped gram positive rod that best grows anaerobically on blood agar. C. diff is both an antibiotic resistant pathogen and an opportunistic bacterium that rapidly overgrows the intestine when the normal gut flora has been killed off. Infection causes life-threatening diarrhea. Hospitalized patients are especially at risk but those taking acid-suppressing drugs are also susceptible.
*CRE is responsible for the largest U.S. outbreak of antibiotic resistant infection reported in January 2014. Advocate Lutheran General Hospital in Chicago reported 44 cases in a single event. Previously the largest number of infections in an outbreak was 12 in Denver, CO in 2012.
The CDC lists a dozen micro-organisms in this category. All are resistant to one or more antibiotics such as vancomycin or methicillin. Included in this list is Fluconazole-resistant Candida spp., yeast that is both resistant to the primary treatment agent and is an opportunistic micro-organism that becomes problematic due to overgrowth.
Urinary tract, surgical site, and bloodstream infection, pneumonia
Methicillin-resistant Staphylococcus aureus (MRSA)
Skin, wound, and bloodstream infection, pneumonia
Even more worrisome is the inclusion of tuberculosis on this list. Tuberculosis (caused by Mycobacterium tuberculosis), lethal in 50% of active cases, has always been difficult to treat. Drug resistance has caused this disease to become nearly impossible to conquer.
The CDC also calls out Salmonella serotype Typhi, the agent of typhoid fever.
The CDC has a short list of bacteria that are becoming threats due to the spread of antibiotic resistance. The list will likely grow shortly.
- Vancomycin resistant Staph aureus (VRSA): usually also resistant to methicillin (see above).
- Erythromycin resistant Group A Streptococcus: includes Streptococcal necrotizing fasciitis and strep throat.
- Clindamycin resistant Group B Streptococcus (aka GBS): found in bloodstream and skin infections, pneumonia, and meningitis. This is bacteria most threatening to the infant during childbirth if it is present in the birth canal. It is also resistant to erythromycin and azithromycin and its resistance to vancomycin is growing.
Fighting the Good Fight
What Can Be Done?
Preventive measures work best. From thorough hand-washing to vaccinations most people can avoid infection in the first place. Enforcing proper hand-washing techniques as part of standard and contact precautions for health care workers is another method that yields exceptional results. Efforts are also being made to educate health care workers and their patients about antibiotic stewardship. The hope is to decrease or eliminate inappropriate antibiotic prescriptions, including dosages and durations.
Faster diagnosis and earlier infection pattern recognition are both areas of accelerating effort. PCR, a rapid method of identifying bacteria, is becoming common in larger hospital laboratories. There is no systematic international surveillance of this problem. Tracking resistance patterns in the U.S. is carried out by several organizations; the CDC is attempting to more closely integrate reports from multiple sites.
Finally, the pipeline for new antibiotics must be ramped up. From 1983 through 1987 sixteen systematic antibiotics were approved by the FDA. In the period from 2008 to 2011 the FDA approved only two. Since antibiotic resistance is a result of evolution, new antibiotics will always be needed. The CDC is trying to find a way to motivate major drug and device companies to bring more drugs to market and to design faster, more accurate tests for early detection.
- “Superbugs” infect 22 million people annually; 23,000 die.
- Antibiotics have been misused and overused leading to bacteria with the ability to withstand the strongest medications.
- The CDC has designated categories for these so-called superbugs based on the severity of infection and the chances for an uncontrollable outbreak.
- Preventive measures work best.
Antibiotic resistance has been growing since the 1940s. It has now reached epidemic proportions. The CDC is leading the way with a four pronged approach that includes preventive enforcement, better detection and tracking, and new drug development. However, the healthcare establishment, the public, and industry must band together to bring the problem under control. While the federal government is trying to address the issue it is unlikely to provide any relief in the short term.