Focus on Drug-Resistant Organisms
By Allen Lefkovitz
At the heart of antibiotic stewardship is the prevention of infections caused by drug-resistant organisms (DRO). DRO develop when infectious organisms adapt to defeat antimicrobial agents (e.g., antibiotics, antifungals) designed to combat them, making the antimicrobial agent less effective or ineffective. While use of antibiotics in food production, use of metals in agriculture (e.g., copper as a fungicide), increased world travel, inadequate sanitation, and variations in access to quality healthcare increase the development of DRO, the overuse and misuse of antibiotics is considered the most significant driving force. The Infectious Diseases Society of America (IDSA) has called antimicrobial resistance “one of the greatest threats to human health worldwide”. The “Core Elements of Antibiotic Stewardship for Nursing Homes” by the Centers for Disease Control and Prevention (CDC) begins by stating, “Improving the use of antibiotics in healthcare to protect patients and reduce the threat of antibiotic resistance is a national priority.” Organizations,including IDSA and CDC, continue to warn that DRO “seriously threaten” our ongoing ability to provide both life-changing surgeries (e.g., joint replacement, organ transplant) and effective treatment of common infections, especially in vulnerable, high-risk individuals (e.g., infants, older adults, those with cancer). DRO are associated with increased utilization of healthcare resources, increased lengths of stay, use of more toxic antimicrobials (e.g., colistin), and increased mortality.
In November 2019, CDC released a report entitled Antibiotic Resistance Threats in the United States, 2019 (available for free at: ), which classifies 18 DRO as “Urgent”, “Serious”, or “Concerning”. A CDC-funded study published in April 2020 estimated that over 620,000 hospital infections each year were caused by six of the identified 18 DRO. A summary of these six DRO is in Table 1.
The 2019 CDC report estimates that annually DRO cause more than 2.8 million infections and 35,000 deaths. To help raise awareness, CDC also maintains an “Antibiotic Resistance & Patient Safety Portal” (available at: https://arpsp.cdc.gov/), which includes additional state and national data on many of these DRO as well as some emerging DRO (e.g., daptomycin-resistant Enterococcus faecalis, fluoroquinolone-resistant Pseudomonas aeruginosa). Although stewardship efforts have begun to show success in the decreasing
prevalence of some DRO infections, CDC has observed that DRO infections are increasingly originating within the community, which includes long-term care facilities (LTCF), instead of in hospitals (83% vs. 17%).
Since at least 2006, CDC has recognized LTCF as “reservoirs and vehicles” for both colonization and infection with DRO that “can cause serious disease and mortality”. Nearly 16,000 residents of skilled nursing facilities have an infection caused by a DRO in any given week according to minimum data set (MDS) 3.0 data. However, full awareness of DRO infections may be lacking as demonstrated by a 2019 study involving 21 southern California LTCF in which 65% to 80% of residents tested positive for a DRO, but only 18% to 49% of those residents had documentation that they were infected with a DRO.
Other important strategies may include:
- frequent educational efforts to remind all caregivers about both infection prevention and control best practices, as well as criteria for the appropriate use of antibiotics
- avoiding unnecessary or prolonged use of catheters and other invasive medical devices
- providing prescribers with local antibiotic resistance patterns
- implementing formulary restrictions on broad spectrum antibiotics
To help expedite their potential approval, the US Food and Drug Administration (FDA) has assisted in the fight against DRO by giving “priority review” to new antibacterial and antifungal agents. Although significant concerns remain about the development “pipeline” of new antimicrobials, since June 2017, eight new antibiotics that target various DRO have been approved (see Table 2). While empiric use of these agents may be considered before culture and sensitivity results return, to help avoid emergence of drug resistance to these newer agents, the FDA-approved labeling urges that these newer antibiotics only be used to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.