Stewardship / Resistance Scan for May 11, 2017

Potential Candida auris drug
Prehistoric enterococci
Non-susceptible pneumococcus

Novel antifungal drug shows early promise against Candida auris

A novel antifungal drug has shown in vitro activity against the emerging fungal pathogen Candida auris, researchers report in Antimicrobial Agents and Chemotherapy.

In lab experiments, investigators from the Mycotic Diseases Branch of the Centers for Disease Control and Prevention (CDC) and biotechnology company SCYNEXIS evaluated the in vitro susceptibility of SCY-078, a triterpine glucan synthase inhibitor that has shown activity against other Candida species, against a collection of 100 isolates of C auris. The collection of isolates came from all over the world, represented the four known clades of C auris, and included isolates known to have elevated minimum inhibitory concentrations against echinocandins—a class of glucan synthase inhibitors used to treat Candida and other fungal infections.

The investigators report that SCY-078 showed potent activity against all the clades of C auris, with little variation in activity, and also retained its activity against the isolates that were resistant to echinocandins.

C auris was originally discovered in 2009 in Japan and since then has emerged as a global health threat due to its growing resistance to all three major classes of antifungals used in Candida infections. The CDC estimates the mortality from drug-resistant yeast, which can cause bloodstream, wound, and ear infections, at approximately 60%. More than 60 C auris cases have been reported in the United States.

"These initial results are extremely encouraging and highlight the potential of SCY-078 to address this growing public health crisis," David Angulo, MD, study co-author and chief medical officer at SCYNEXIS, said in a company press release. "We look forward to continuing to accelerate the development of this promising therapy."
May 8 Antimicrob Agents Chemother abstract
May 11 SCYNEXIS press release


Researchers uncover prehistoric origins of enterococci

A study today in the journal Cell suggests that enterococci, the bacterial organisms that live in the human and animal gut and have become a significant source of drug-resistant hospital infections, emerged more than 400 million years ago, and that their exposure to environmental stresses enabled them to build up defenses against antibiotics.

In the study, researchers from Harvard Medical School, Massachusetts Eye and Ear, and the Broad Institute selected 24 enterococcal species representing all major phylogenetic branches and sequenced their genomes in an attempt to understand how these organisms adapted to the modern hospital environment. Then, using molecular clock estimation, along with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, they were able to determine that these organisms emerged around 425 million years ago, right around the same time as land animals. And as new species of animals emerged, so did new species of enterococci.

As animals crawled onto land, they carried enterococci with them in their intestines, and when the microbes were excreted, they were exposed to cycles of isolation, starvation, and desiccation until they re-entered the food chain. Over millions of years of exposure to these environmental stresses, the researchers argue, enterococci developed hardened cell walls and acquired genes that made them resistant to drying out—the same traits that today make them resistant to many antibiotics and hospital disinfectants.

As a result, the authors of the study write, "The emergence of enterococci as leading hospital pathogens appears to have been foreordained by events of at least 425 million years ago."

The authors say discovering that the environment in which microbes live leads to new properties could enable scientists to predict how microbes will adapt to the products intended to control their spread, and inform efforts to develop new solutions to drug resistance.
May 11 Cell abstract
May 11 Massachusetts Eye and Ear Infirmary news release


CDC notes rise of pneumococcal strain not susceptible to penicillin

Experts from the US Centers for Disease Control and Prevention yesterday noted the concerning recent rise of a pneumococcal serotype not susceptible to penicillin that they say should be considered for inclusion in any vaccine that would replace the current 13-strain pneumococcal conjugate vaccine (PCV13).

Writing in Emerging Infectious Diseases, the investigators detailed their analysis of 199 nonvaccine serotype 35B pneumococcal strains isolated from patients in 2015 and 2016. The incidence of this strain increased from 1.2 to 1.3 cases per million population in 1998 and 1999 to 2.1 to 3.7 cases per million in the post–pneumococcal 7-valent conjugate vaccine (PCV7) years (2001-2009). It then jumped again post-PCV13, to 3.3 to 4.8 cases per million. PCV13 was introduced in 2010.

In addition, "penicillin-nonsusceptible" strains of 35B increased in the post-PCV7 years and increased even more post-PCV13. This shift was propelled primarily by a 35B lineage called ST558. This 35B/ST558 strain then combined genes with a serotype 9V/ST156 strain in 2015 and 2016, spawning new 35B/ST156 progeny in at least six states.

The authors conclude, "Spread of 35B/ST156 is of concern in view of past global predominance of pathogenic ST156 vaccine serotype strains. Protection against serotype 35B should be considered in next-generation pneumococcal vaccines."
May 10 Emerg Infect Dis report

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