Feb 13, 2016

News About Superbugs Resistant To All Antibiotics Worsens

Judy Stone, Contributor

While I was engrossed in the excitement of emerging and newly discovered infections, I hardly noticed that there’s more bad news in the fight against superbugs. There have been two notable recent announcements.
New information from Europe this week is disappointing, but not all that surprising. As the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC) report, resistance to ciprofloxacin, a commonly used antibiotic for food poisoning, is growing, paralleling use in poultry production.
The new report illustrates how closely animal and human health are intertwined. Resistance was particularly high for Campylobacter, the most commonly reported cause of foodborne illness in the European Union. Cipro resistance in Campylobacter reached 69.8% in broiler chickens, and 60% of isolates from people. Cipro resistance reached 69.8% in broiler chickens, and 60% in Campylobacter isolates from people.
Similarly, Salmonella isolates showed resistance to multiple antibiotics in 26% of human isolates and 25-30% of poultry samples.

There were huge differences in antibiotic resistance across countries, with German samples showing 69% resistance vs. only 15% in Denmark. Why the difference? It’s likely related to the quinolone antibiotic used being made by Bayer, a German company, and probably being used more extensively. “Antibiotic stewardship is not implemented equally across member states,” explained Lance Price, PhD, founder of the Antibiotic Resistance Action Center at George Washington University. He then shared the fascinating history of the FDA’s 5 year battle with Bayer over the agency’s attempt to ban agricultural use of Baytril, an antibiotic very similar to the ciprofloxacin antibiotic too commonly used in people (and also made by Bayer). In the U.S., in comparison, Campylobacter’s resistance to Cipro is now down to 11%; it is only 2% in Australia. Dr. Price stressed the lessons of these country wide difference is also that “Stewardship doesn’t just stop with banning growth promotion; stewardship also involves stopping unnecessary therapeutic use.
This antibiotic resistance is not just of academic interest. As Vytenis Andriukaitis, EU Commissioner for Health and Food Safety noted, “Every year in the EU, infections caused by antimicrobial resistance lead to about 25,000 deaths – but the threat is not confined to Europe.
While this European report of 2014 data showed no cross resistance to the carbapenem class of antibiotics, another new report from China just showed this worrisome problem of cross-resistance has been confirmed. (Carbapenems are a class of broad-spectrum beta-lactam antibiotics related to cephalosporins. Carbapenem-¬resistant Enterobacteriaceae (CRE) are a group of Gram negative bacteria that have acquired resistance to carbapenems, and which cause use of colistin, an antibiotic of last resort, due to its serious side effects).
As a quick recap from my explanation here⁠, last fall Yi-Yun Liu’s team discovered the mcr-1 gene. This gene conveys resistance to colistin, a toxic antibiotic. Then Frank Aarestrup’s team, from the Danish National Food Institute, found the mcr-1 gene in the blood of a patient and in 5 poultry samples that originated in Germany. The patient was believed to have become infected by eating contaminated meat. The genes found in the poultry were identical to those from the Danish patient and from China. As I explained why this is scary, “The mcr-1 gene transfers resistance to E. coli, Klebsiella, and 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.”
Recently, Hong Du and colleagues⁠ reported that the mcr-1 gene is now established in a strain of CRE carrying the NDM-5 (type of carbapenem resistance) plasmid. This produced a highly drug resistant strain, where now even colistin and the new β-lactam– β-lactamase inhibitor, ceftazidime–avibactam, are ineffective.
At the same time, Yao et. al., also reported in The Lancet Infectious Disease an E coli strain, THSJ02, “from a chicken wing sample purchased at a large supermarket in Guangzhou in July, 2014, was resistant to all antimicrobial drugs tested except doxycycline and tigecycline.” The authors expressed surprise at finding the coexistence of the mcr-1 (colistin) and carbapenem resistance genes, given that carbapenems and fosfomycin (a different antibiotic) are not approved for agricultural use in China. They explain the added significance of their findings of these multiple resistance genes coexisting, and concern that these resistance plasmids might transfer the resistance to other bacteria in peoples’ gastrointestinal tract. While this superbug has not yet been found in the U.S., Dr. Price shared this concern, suggesting that we need to have active surveillance in people’s stool samples.
In the meantime, now that the nasty mcr-1 colistin resistance gene also has carbapenem resistance, making it resistant to virtually all antibiotics, the only thing we can do to staunch the rapid emergence of almost untreatable superbugs is to work harder on education, antibiotic stewardship and limiting the use of antibiotics—especially colistin now—as growth promoters in agriculture. The only moderately good news about “last ditch” antibiotic resistance comes from Maryn McKenna, who reported last week that China and Europe are looking at implementing colistin restrictions for agricultural use.
While Zika and the new Lyme bacteria are scary, these antibiotic-resistant bacteria will have a far wider global impact. Zika and Lyme will cause illness and possibly birth defects, but these newly combined colistin and carbapenem resistant bacteria will cause thousands of otherwise needless deaths.