Just how super is the latest superbug? The good news is that the infected U.S. patient has recovered. The bad news: mcr-1, the resistance gene identified in this strain of E. coli, has brought us another frightening step closer to a “post-antibiotic” era.
In recent years, antimicrobial resistance among Gram-negative bacteria (E. coli, Klebsiella, Pseudomonas, Acinetobacter, Salmonella, and others) has been a growing public health concern. Most of the increase in resistance has been the result of mobile genetic elements that can easily transfer resistance from one bacterium to another, allowing bacteria to “catch” antibiotic resistance from one another.
To make matters worse, resistance enzymes are often packaged together. One genetic “cassette” can carry multiple resistance determinants, thereby spreading resistance to more than one class of antibiotics at the same time.
Early on, we relied on the carbapenem class of antibiotics to treat infections caused by multidrug-resistant (MDR) organisms such as the “ESBLs” (extended-spectrum beta-lactamase-producing organisms). But carbapenemase-producing organisms soon developed, and resistance to carbapenems spread quickly.
In 2009, the emergence of a “super” kind of carbapenem resistance gene, ndm-1 (New Delhi metallo-beta-lactamase) was found to be highly resistant to many antibiotic classes, including:
- the carbapenems and other beta-lactams (penicillin derivatives and cephalosporins)
- the fluoroquinolones (ciprofloxacin, levofloxacin, et al)
- the aminoglycosides (gentamicin, amikacin, et al).
These antibiotic classes include the main drugs used to treat Gram-negative infections.
Et tu, colistin? As ndm-producing bacteria quickly spread around the globe, colistin became the new antibiotic of last resort. This is why last month’s E. coli infection in Pennsylvania created headlines: the organism carried the mcr-1 gene that encodes resistance to the antibiotic colistin, setting the stage for the rapid rise of pan-resistant organisms.
Beth Bell, MD, MPH, director of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, describes pan-resistance as a puzzle. Different pieces—different genetic elements, encoded for resistance to various classes of antibiotics—are required in order for the puzzle of pan-resistance to be completed.
The identification of mcr-1 in this case (as well as in a pig intestine sample, discovered in screening unrelated to the clinical case) means that the last piece of the pan-resistance puzzle for Gram-negative organisms is now in place in the U.S.
Fortunately, this patient’s infection was not pan-resistant. The strain of E. coli causing this urinary tract infection was susceptible to carbapenems. The entire palette of resistance genes had not come together in this patient’s strain of E. coli.
The U.S. is not the only country to identify mcr-1 in a human or animal; the gene was first identified late last year in China, where colistin is used in pig and poultry farming, and since then has been found in Europe, Canada, Algeria, Japan, and southeast Asia. Air travel, migration, medical tourism, plus halfhearted infection control practices, ensure that organisms incorporating mcr-1 will continue to spread.
As always, frontline staff need to scrupulously clean their hands and attend to the details of contact isolation precautions. Facility administrators, in turn, need to make the ready availability of PPE, alcohol hand sanitizer, soap and paper towels a higher priority—every bit as necessary as keeping drugs, sutures, and IV tubing in stock.
Also essential to countering the pan-resistance threat are realistic numbers of nursing, microbiology, infection prevention, and housekeeping staff, along with the education and support necessary to keep these departments functioning at high levels.
Antibiotic stewardship programs. With no new antibiotics in the drug industry pipeline or likely to emerge soon, antibiotic stewardship programs are the key to our pushback against these organisms. In the January issue of Clinical Infectious Disease, Olans and colleagues remind us that nurses have an important, rarely recognized role in antibiotic stewardship that includes the following responsibilities:
- Prompt isolation of patients when transmissible infection or colonization is suspected
- “Medication allergy reconciliation” that investigates patients’ reports of “allergies” in order to differentiate adverse reactions from true allergies (to avoid ruling out the future use of the most appropriate antibiotics)
- Appropriately timed and collected specimens for culture, without awaiting a physician/NP order
- Careful documentation of patient progress to assist in antibiotic deescalation where possible
- Owning as routine nursing functions the “bundle” measures that can prevent CLABSI, CAUTI, and other infections
- Teaching patients about appropriate antibiotic use
If only Marty McFly could take us back to the future. A glimpse of a world without antibiotics might spur a more determined approach to antibiotic stewardship today.