Stewardship / Resistance Scan for Mar 06, 2018

MCR-1, CPE in Portugal
New CARB-X funding

Klebsiella with MCR-1, carbapenemase genes found in Portuguese patients

Researchers in Portugal have identified 16 patients from a previously unnoticed hospital outbreak with carbapenemase-producing and MCR-1-producing Klebsiella pneumoniae, according to a case report yesterday in Emerging Infectious Diseases.

Using rectal swabs specimens from more than 5,000 patients admitted to Centro Hospitalar do Porto from October 2015 through July 2017, the researchers identified 359 carpenemase-producing Enterobacteriaceae (CPE) isolates from 283 patients. They then screened the isolates for other resistance genes, including MCR-1, which confers resistance to the last-resort antibiotic colistin.

Overall, the researchers found 26 carbapenemase-producing and MCR-1 producing K pneumoniae isolates from samples collected from 16 patients; 17 isolates were colonizers (found in the patients' gastrointestinal tract) and 7 were from other parts of the body (3 in urine, 2 in blood, and 2 in other biologic fluids). The patients were 50-87 years of age, and their clinical history included prolonged hospitalization, complicated conditions, surgical intervention, and previous antibiotic use, but none had used colistin or traveled abroad before MCR-1 detection. Five patients developed infections.

In addition to colistin, the K pneumoniae isolates were resistant to third- and fourth-generation cephalosporins (100%), nalidixic acid (100%), ciprofloxacin (96%), tigecycline (96%), tetracycline (92%), tobramycin (88%), gentamicin (88%), fosfomycin (83%), trimethoprim/sulfamethoxazole (79%), and chloramphenicol (67%). All but one of the isolates belonged to K pneumoniae sequence type (ST) 45. In all of the isolates, the MCR-1 gene was located on an IncX4-type plasmid, which has been circulating among humans, pigs, and poultry in many different countries.

"High rates of CPE and colistin use together with an ongoing community-based dissemination of mcr forebodes of future similar events," the authors write. "Our data stresses the need for a concerted action involving different professionals and healthcare institutions to monitor and contain the spread of mcr across human and veterinary niches, the food chain, and the environment."
Mar 5 Emerg Infect Dis dispatch


CARB-X announces funding for new antibiotic and diagnostic tests

CARB-X, a public-private collaboration that supports companies in early-stage discovery and development of antibiotics, diagnostics, and novel antibacterial treatments, has announced funding for two more partners.

Yesterday CARB-X announced an initial award of up to $2.5 million to MicuRx Pharmaceuticals to support early development of its polymixin antibiotic MRX-8 to treat the most serious multidrug-resistant infections. Polymixin antibiotics, which include colistin and polymixin B, are a last-resort drug for treatment of multidrug-resistant infections, but are associated with high incidence of kidney toxicity. Preclinical data for MRX-8 has shown high efficacy with reduced nephrotoxicity when compared with current polymixins, according to a CARB-X press release.

Today, CARB-X announced an initial award of up to $1.1 million to T2 Biosystems to support the development of new tests that would enable doctors to quickly diagnose and treat life-threatening, drug-resistant bacterial infections in whole blood. The tests, which use the company's T2 Magnetic Resonance technology, aim to identify 20 infectious bacterial species, including carbapenem-resistant Enterobacteriaceae and methicillin-resistant Staphylococcus aureus, and resistance genes directly from whole blood. The current method of diagnosing invasive bacterial infections using blood cultures can take several days.

"The ability to rapidly diagnose and treat drug-resistant bacteria will save lives by enabling doctors to treat patients more quickly and effectively than is possible with today's diagnostic tools," Kevin Outterson, JD, executive director of CARB-X, said in a press release.

Both projects will receive additional CARB-X funding based on achievement of certain project milestones. Since it was established in 2016, CARB-X has awarded more than $68 million to accelerate the development of antibiotics and other products.
Mar 5 CARB-X press release
Mar 5 CARB-X press release

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