Drugs in Development Might Help Fight Deadly Candida Auris

New antifungal agents that are being investigated for possible use against C. auris, such as Ibrexafungerp (Brexafemme), show promise—so far.

Infection preventionists (IPs) and other health care professionals know to be on the lookout for Candida auris, which has a mortality rate of anywhere from 30% to 60%. Adding to the problem: COVID-19 provides C. auris with cover. A study published in June 2020 in the Journal of Global Antimicrobial Resistance called C. auris a “lurking scourge.” Investigators warned the global medical community about the potential of C. auris as a confounding factor in COVID-19.

There may be some pharmaceutical help on the horizon. Jeffrey Rybak, PharmD, PhD, an instructor with the department of pharmaceutical sciences at St. Jude Children’s Research Hospital, has been conducting research on C auris in trying to identify novel targets for therapy, apply next-generation sequencing technologies, and develop molecular tools to advance the study of the fungus.

New antifungal agents such as Ibrexafungerp (Brexafemme) are being studied for C. auris treatmentRybak says these investigational agents show promise against the infection, but that they need undergo more clinical trials in order for researchers to better understand their full treatment utility.

Rybak also points out that isolates might become resistant while someone is on therapy. “Even while it might be susceptible upfront, after a week or two of therapy, we may find that the patient has an infection now caused by an isolate of the same Candida auris that has become resistant to the echinocandins and we are really left with nothing else.”

New pharmaceuticals against C. auris seem to be needed now more than ever. Earlier this year, two outbreaks of the deadliest form of C. auris occurred: 1 at a nursing home in Washington, DC, and the other at 2 hospitals in the Dallas area. This particular iteration of C. auris seems to be impervious to any antibiotic or antifungal thrown at it. During this outbreak, a cluster of 101 cases was detected in the Washington, DC, nursing home and a cluster of 22 cases was detected in 2 Dallas areas hospitals from January to April.

According to reports, some of these patients infected with C. auris did not show any clinical improvement after being treated with all 3 major classes of the antifungals. In fact, in 5 patients who were fully resistant to treatment, 3 of them died.

A study in the CDC’s Morbidity and Mortality Weekly Report (MMWR) said that “these two simultaneous, independent clusters of pan- or echinocandin-resistant C. auris cases in patients with overlapping inpatient health care exposures and without previous echinocandin use provide the first evidence suggesting that pan- or echinocandin-resistant C. auris strains might have been transmitted in U.S. health care settings. Surveillance, public health reporting, and infection control measures are critical to containing further spread. Clinicians should consider early antifungal susceptibility testing in patients with C. auris infection, especially in those with treatment failure.”

C. auris has been diagnosed in 40 countries since the first report about it in 2009, when clinicians found a single isolate from the discharge of the external ear canal of a 70-year-old inpatient at Tokyo Metropolitan Geriatric Hospital. By 2016, 13 cases had been identified in the United States, leading the Centers for Disease Control and Prevention (CDC) to issue interim recommendations, as well as a clinical alert, requesting laboratories to report cases and send samples to state and local health departments and the CDC.

As Infection Control Today® (ICT®) has reported, infection preventionists (IPs) and other health care professionals need to be on alert for C. auris, and need to move fast when it’s detected. That was the case at Scripps Memorial Hospital La Jolla in March 2020. A single case of C. auris prompted swift action by IPs, who—along with public health officials—implemented a robust infection prevention plan. That plan included isolation precautions, environmental cleaning, disinfection, and education of health care employees.

The patient was hospitalized for 47 days, and the county public health department recommended that the hospital conduct C. auris colonization screening for other patients to ensure that the infection hadn’t spread. It worked. No C. auris colonization and/or clinical isolates were identified at the hospital in the subsequent six months.

The CDC has outlined 3 main concerns about C. auris:

  • It is often multidrug-resistant;
  • It being a newer, emerging fungus, it can be challenging for labs to diagnose with standard laboratory methods, which can lead to misidentification and in turn lead to the incorrect treatment and management;
  • And lastly, it can quickly lead to outbreaks in health care facilities.

Although C auris fungal infection is still relatively rare, when it occurs in the health care setting, it can quickly take hold and become an outbreak if infection prevention measures are not taken.

Rybak notes that “the overwhelming majority of Candida auris clinical isolates are resistant to one of the 3 classes of antifungals that we have to treat invasive infections.”

ICT®’s sister publication Contagion® interviewed Rybak about the challenges of multidrug resistance with C auris, how diagnosing it is evolving, the merits of monotherapy over combination therapy, what to consider in seeing resolution of symptoms, and some of the big picture public health concerns associated with this infection.

Readers can see that interview here.