|By the Innovations Exchange Team, based on an interview with Edward J. Septimus, MD, FIDSA, FACP, FSHEA, Clinical Professor of Internal Medicine at Texas A&M Health Science Center|
The overuse and misuse of antimicrobial agents continues to accelerate the resistance of microorganisms to therapeutic drug treatment. Drug resistance develops when a microorganism mutates or acquires a resistant gene and often leads to prolonged illness and even death.
Innovations Exchange: What are common examples of drug-resistant infections?
Dr. Edward J. Septimus: Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are two drug-resistant infections that continue to be a threat. MRSA emerged in the 1990s due to antibiotic use and misuse in hospitals. Issues with continuing antibacterial stewardship, poor infection control, and the increasing severity of illness in hospitalized patients contributed to the sharp rise in the prevalence of MRSA in the 2000s.1 Since 2010, there has been a slight decrease in MRSA due to efforts to increase its awareness among medical professionals and improve adherence to infection prevention and control procedures.
When MRSA increased, physicians turned to vancomycin to treat MRSA infections. Its increased use contributed to the rise of VRE in the 1990s and 2000s. VRE accounted for almost 25% of enterococcus isolated in intensive care units (ICUs) in 1999,2 and 28.5% in 2003.3
A more recent public health challenge is bacteria that are resistant to multiple antibiotics, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Some public health experts also consider Clostridium difficile to be multidrug resistant due to its high-level resistance to a class of antibiotics called fluoroquinolones. There are no new drugs in the pipeline designed to treat these increasingly common infections.
Is this a global phenomenon?
Last year, the World Health Organization (WHO) identified antimicrobial resistance as the biggest global threat to public health. Approximately 440,000 new cases of multidrug-resistant tuberculosis (MDR-TB) occur annually, causing at least 150,000 deaths, according to the WHO. Extensively drug-resistant tuberculosis (XDR-TB) has been reported in 64 countries to date.4 The highest rates of resistance to antibiotics occur in developing countries in Latin America, Africa, and Southeast Asia where antibiotics are sold over the counter.5 In addition, travel facilitates the spread of drug-resistant organisms to other countries.
What health care settings are vulnerable to antimicrobial resistance?
Resistance to antibiotics occurs across the continuum of care from ambulatory to inpatient settings. Antibiotics are overused in outpatient offices to treat upper acute respiratory infections, which are mostly viral in nature. A recent study found a strong correlation between community use of antibiotics and resistance observed in the hospital, which indicates that restrictions on antibiotic use imposed at the hospital level are unlikely to be effective unless coordinated with campaigns to reduce unnecessary antibiotic use at the community level.6
In hospitals, patients are particularly vulnerable to infections when they have catheter lines inserted or surgery performed. Between 30 and 50 percent of all hospitalized patients receive an antibiotic, while up to 70 percent of patients in the ICU typically receive an antibiotic.7 Antibiotics are also prescribed for chronically ill people in long-term acute care facilities, skilled nursing homes, and rehabilitation facilities. When first-line antibiotics fail to work, patients often are admitted to hospitals for treatment, which increases the risk of exposing others to their infections.
What patterns are you seeing in antimicrobial resistance?
Most drug-resistant infections occur in hospitals and then spread to communities. But, we have begun to see patients being admitted to hospitals with multidrug-resistant infections that they acquired in community health care or long-term care settings. For example, a patient of mine—a young woman with poorly controlled type 2 diabetes—was admitted to the hospital for a kidney infection with a multidrug-resistant infection. She had a history of urinary tract infections and had developed resistance to most available antibiotics used to treat Escherichia coli.
What can hospitals do to respond to these trends?
Hospitals need to know local epidemiology and resistance patterns. Many hospital laboratories produce annual antibiograms for the entire hospital that document the most commonly occurring organisms, the effectiveness of antibiotics in treating them, and patients’ resistance levels. Some antibiograms summarize the results by specific wards or departments, which may reveal differences in susceptibility. This information helps clinicians make more informed decisions about prescribing antibiotics.
The information could be more useful, however, if it was more granular and available at the time that patients are seen. For example, if a patient in an ICU needs to be treated for pneumonia, a clinician would want to know the most common bacteria that caused pneumonia in the ICU and the susceptibility pattern during the last 6 months. The use of electronic health records by hospitals should facilitate real-time clinical decision support related to antibiotic prescribing.
Can you provide examples of the overuse or misuse of antibiotics that contributes to drug resistance?
Clinicians often prescribe antibiotics inappropriately for these conditions:
Upper respiratory infections that are viral in nature.
Asymptomatic bacteria in a patient’s bladder. There are two exceptions: pregnancy and invasive urological procedures in which bleeding is expected.
Fever that is not caused by an infection.
Contamination of blood cultures.
Colonization of bacteria in chronic wounds or due to long-term ventilator use.
Another contributing factor has been the duration of antimicrobial therapy. A decade ago, it was common practice to prescribe a 14-day course of antibiotics for various infections. Recent randomized controlled trials have shown that it can be just as effective to prescribe antibiotics for a 7-day course, which results in less selection of organisms for resistance and fewer side effects.8,9
Has overuse led to a lack of effective antibiotics, especially to treat multidrug-resistant infections?
Antibiotic overuse drives resistance up and increases the likelihood that clinicians will not be able to treat infections with newer, effective drugs. However, there are very few new antibiotic drugs in the pipeline because pharmaceutical companies lack the financial incentives to develop and market them. It takes $800 million to $1 billion to bring a new drug to market. The return on investment is low because antibiotics are taken for a short time, compared with years for drugs that treat chronic diseases.
Professional groups such as the Infectious Diseases Society of America are examining how to incentivize drug companies to invest in development of antimicrobial agents. The federal Generating Antibiotic Incentives Now (GAIN) Act encourages pharmaceutical research of antibiotic resistance by giving pharmaceutical companies that produce “qualified infectious disease products” an additional 5 years of market exclusively, with or without a patent.
What is the financial impact of antimicrobial resistance?
When patients don’t respond to first-line drugs, more expensive therapies are often required. Patients with resistant infections are sick longer and require longer hospitalizations, which increases health care costs. There are also societal costs after patients leave the hospital. People may be unable to work, resulting in lost productivity and wages.
What national efforts are underway to educate the public and physicians about the appropriate role of antibiotics?
The Centers for Disease Control and Prevention (CDC) has initiated a campaign, Get Smart: Know When Antibiotics Work, which is aimed at reducing the inappropriate use of antibiotics. The campaign provides resources for the public and for health care professionals in inpatient and outpatient settings. The CDC is also promoting the use of antimicrobial stewardship programs to ensure that “hospitalized patients receive the right antibiotic, at the right dose, at the right time, and for the right duration.”
How is the Infectious Diseases Society of America addressing antimicrobial resistance?
The professional society has launched a campaign to reduce the widespread use of antibiotics in animals, often for nontherapeutic reasons. The use of antibiotics in animals has been linked to antimicrobial resistance in humans. The society’s Antimicrobial Resistance Committee has been very active in addressing related translational research and new drug development. The organization also has raised legislators’ awareness of the issues surrounding antimicrobial resistance and successfully advocated for the GAIN Act, which became law in July of 2012. The professional society also continues to advocate for the Strategies to Address Antimicrobial Resistance Act, which, if enacted, would support the coordination of U.S. antimicrobial resistance efforts and elevate the overall Federal response.
This issue of the Innovations Exchange features two programs that address antimicrobial resistance. One is a Canadian family physician program that helped physicians use shared decisionmaking with patients regarding the appropriate use of antibiotics. What is the significance of this program?
Their intervention focused on helping clinicians understand the science behind antimicrobial resistance and explain to patients the pros and cons of prescribing antibiotics for viral respiratory infections. Patients often expect to receive a prescription, so it is critical to educate them about the risks of overusing antibiotics. The program significantly reduced the misuse of antibiotics for these viral infections. Patients as well as physicians indicated high satisfaction levels with the interventions.
Would this program work in family practices in the United States?
The shared decisionmaking program could work well in U.S. ambulatory settings. The challenge is getting doctors to commit to spending the time that’s required. It’s important to lay out the options objectively to patients and family members, and if there is no clear best practice, make the best decision possible based on their needs, costs, and side effects.
The second featured program, at Sonoma Valley Hospital in California, used telemedicine to monitor physicians’ prescribing habits, as part of an antimicrobial stewardship program. What is the significance of this program?
The use of telemedicine, which is unique in an antimicrobial stewardship program, enabled the hospital to support such a program despite not having an infectious disease specialist. The average community hospital in the United States lacks the resources to support a robust stewardship program or have a clinical pharmacist trained in infectious diseases. This program provides such resources in an innovative way. The critical ingredient is having a physician champion with good interpersonal skills to communicate effectively with executives and other stakeholders.
Do you think this program is transferable to other hospitals/ambulatory settings?
The use of telemedicine would work in inpatient and outpatient settings, although it may be more applicable to inpatient settings that have the resources to develop telemedicine programs.
What are the next steps for antimicrobial resistance efforts?
Some states have initiated or enacted legislation related to antimicrobial resistance. For example, California has a law that mandates hospitals to implement stewardship programs. The Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America are also interested in working with the Centers for Medicare and Medicaid Services to require antimicrobial stewardship programs to be a condition for hospital participation.
About Edward J. Septimus, MD, FIDSA, FACP, FSHEA
Dr. Septimus is a Clinical Professor of Internal Medicine at Texas A&M Health Science Center and an Affiliate Professor and Distinguished Senior Fellow in the School of Public Health at George Mason University. He is a Fellow of the Infectious Diseases Society of America (IDSA) and a member of IDSA’s Antimicrobial Resistance Committee. Dr. Septimus also serves on the Board of the International
Society for Antimicrobial Resistance and is the chair for the Institute for Healthcare Improvement’s Antibiotic Stewardship Project. He recently served as president of the Texas Infectious Disease Society.
Disclosure Statement: Dr. Septimus reported that he received payment from 3M for his service on an advisory committee and from Cubist for a lecture that was related to this article. His institution received CDC funds for his work on the IHI’s Antibiotic Stewardship Project.
Shorr A. Epidemiology of staphylococcal resistance. Clin Infect Dis. 2007;45(3):S171-6. [PubMed]
Fridkin SK, Edwards JR, Courval JM, et al. The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units. Ann Intern Med. 2001;135(3):175-83. [PubMed]
National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2003, issued August 2003. Am J Infect Control. 2003;31(8):481-498. [PubMed]
Morgan D, Okeke I, Laxminarayan R, et al. Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect Dis. 2011;11:692-701. [PubMed]
Sun L, Klein EY, Laxminarayan R. Seasonality and temporal correlation between community antibiotic use and resistance in the United States. Clin Infect Dis. 2012;55:687-94. [PubMed]
Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323-2329. [PubMed]
Pugh R, Grant C, Cooke RP, et al. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults (review). Cochrane Database Syst Rev. 2011;(10). [PubMed]
Avdic E, Cushinotto LA, Hughes A, et al. Impact of an antimicrobial stewardship intervention on shortening the duration of therapy for community-acquired pneumonia. Clin Infect Dis. 2012;54(11):1581-7. [PubMed]