Klebsiella and wbc – David Dorward, NIAID, PHIL
Brace yourselves. The scary antibiotic resistance gene, mcr-1, has been found in the U.S. for the first time, in a 49-year-old Pennsylvania woman with symptoms of a urinary tract infection.
This gene was first discovered in China last winter, then in the Netherlands and more recently in two Canadian patients. The affected bacteria were found in animals, meat samples, and isolates from patients—including bloodstream. The gene confers resistance to colistin, a last-ditch antibiotic rarely used because it is so toxic. The gene has now spread to multiple countries.
It’s no great surprise the gene has reached the U.S. Travelers readily acquire another superbug called ESBL. This is a major reason I suggested delaying or moving the Rio Olympics—the adjacent bay’s water is teeming with raw sewage and resistant bacteria including CRE, which causes the infections we now have to treat with colistin.
Disturbingly, the mcr-1 gene was also found in a pig’s intestine.
Why is this important?
As I explained in an earlier post, “The mcr-1 gene transfers resistance to E. coli, Klebsiella, Pseudomonas—common bacteria—by plasmids, small bits of DNA that can be transferred to different types of bacteria. Previously, colistin resistance was transferred on chromosomes, and therefore affected only those bacteria and their descendants. Plasmid-borne resistance genes are more likely to be rapidly spread widely, and can spread between species of bacteria.” Dr. Lance Price, director of the Antibiotic Resistance Action Center at George Washington University describes the novel IncF plasmid as being “promiscuous” and explains “that the gene jumping around from plasmid to plasmid increases the likelihood that it will find its way into CRE,” making it the nightmare bacteria resistant to all antibiotics.
National Action Plan for Combating Antibiotic Resistant Bacteria
Last year, President Obama released a new plan, based on recommendations from co-chairs Department of Defense (DoD), Department of Agriculture (USDA) and Department of Health and Human Services (HHS).
As part of that program, active surveillance for resistant organisms began in a more organized fashion, via Multidrug-resistant Organism Repository and Surveillance Network (MRSN). Isolates of ESBL bacteria from military facilities are sent to Walter Reed Army Institute of Research (WRAIR) for further testing—and within three weeks of the program’s start, this first colistin resistant bacteria was discovered. The isolate contained 15 different antibiotic-resistance genes on two plasmids. “This strain of E. coli was sensitive pretty much to only one class of drugs, the carbapenems, so one step away from pan-resistance. There have been reports in the literature recently of mcr-1 strains with genes that encode enzymes that inactivate carbapenems, and these are particularly grim,” observed Dr. Gerry Wright of McMaster University.
Similarly, the USDA has beefed up their screening through the National Antimicrobial Resistance Monitoring System (NARMS), finding the resistant isolate from a pig. The colistin-resistant E. coli was also resistant to other antibiotics including ampicillin, streptomycin, sulfisoxazole, and tetracycline. The isolates from the patient and pig were different.
Without such a concerted effort at surveillance, short-staffed hospital, private, and public health laboratories would likely have missed the growing resistance.
Several things struck me as curious in the initial reports. For one, the case report specifies that the woman had not traveled outside the country in the preceding five months. Why five months? Had she at six or seven? Where had she been previously? Had other family members traveled or been stationed abroad? I was unable to reach the authors for comment or clarification.
The Health and Human Services post says part of their plan is to “identify close contacts, including household and healthcare contacts, of the Pennsylvania patient to determine whether any of them may have been at risk.”
That’s nice, but then what are they going to do? If a patient with such a multi-resistant organism is identified during hospitalization, then the patient is likely to be placed on “contact” isolation, with staff and visitors using barrier precautions of gown and gloves. There are no specific precautions taken when a patient goes home, and many nursing homes don’t isolate patients as carefully. So pretty much, the cat’s out of the bag.
Colistin is not used in agriculture in the US, though it is commonly used overseas. How did the pig acquire the superbug? We know that the China’s Shuanghui International group bought Smithfield ham in 2013, but they are not returning processed pork to the U.S. Tilapia is imported from China, and some of it has been contaminated by manure from animals likely exposed to antibiotics. Is there some other international exchange of select animals not widely publicized?
A further wrinkle is the recent finding from Chinese researchers “that mcr-1–producing E. coli can colonize companion animals and be transferred between companion animals and humans.”
What do we do now?
Antibiotics are widely overprescribed to people, with a recent study suggesting that one third of prescriptions are needless. But human use pales in comparison to that of agribusiness.
Perhaps we could start by listening to Congresswoman Louise M. Slaughter, who is also a microbiologist. She has advocated for years for a bill that would save eight critical classes of antibiotics from being routinely fed to healthy animals as growth promoters. This restriction of antibiotics needs to be done globally, not just in the U.S.
Just as I criticized Congress last week for their shortsighted delay in funding Zika preparedness forcing President Obama to take funding from Ebola, and for decimating public health funding, some lay the blame for antibiotic resistance on policymakers at many levels, both here and overseas.
As Dr. Price concluded, “This is yet another clear case where the misuse of antibiotics in livestock production has come back to haunt us. If our policymakers were waiting for the brink of disaster to wake up and do something about antibiotic resistance, they don’t need to wait any longer.”
For more medical/pharma news and perspective, follow me on Twitter @drjudystone or here at Forbes