Candida auris: Emerging, Frequently Resistant, and Often Deadly

May 17, 2017

Question

Given frequent multidrug resistance, what drug therapy is appropriate for treating Candida auris?

Response from Adrienne M. Rouiller, PharmD
Pharmacy Resident, Albany Medical Center, Albany, New York

Candida auris is a yeast that was first described in Japan in 2009 and has since emerged as a pathogen in several countries, including the United States.[1]C auris can cause serious bloodstream infections, may spread between patients, and can survive for months on common hospital room surfaces.[2] Up to 60% of patients infected with C auris have died.[1,3] This high mortality rate is most likely attributable to a combination of factors, including the severity of illness in these patients, the difficulty of timely identification of C auris, and the subsequently delayed initiation of effective therapy.[1,3,4]C auris has relatively weak expression of known virulence factors compared with Candida albicans,but attributable mortality may be due to its intrinsic multidrug resistance.[1,5]

In June 2016, the Centers for Disease Control and Prevention (CDC) issued a clinical alert requesting that US healthcare facilities report all cases of C auris to the organization as well as to their local and state health departments.[6] As of April 13, 2017, some 70 cases of C auris were reported in the United States, with the bulk of cases reported in New York.[7]

The most common site of C auris isolation is the blood, but the yeast also has been found in the urine, respiratory tract, and other sites. Patients infected with C auris are commonly critically ill. Many have had central venous catheters, urinary catheters, or surgery within 90 days of infection. The median time to diagnosis of C auris is 19 days after admission.While the mortality rate of C auris is approximately 60%, it rises to almost 70% for patients with bloodstream infections.[1]

C auris Resistance and Implications for Therapy

Susceptibility testing performed on 54 isolates of C auris from Pakistan, India, South Africa, and Venezuela found that 50 (93%) were resistant to fluconazole, 29 (54%) were resistant to voriconazole, 19 (35%) were resistant to amphotericin B, 4 (7%) were resistant to echinocandins, and 3 (6%) were resistant to flucytosine.[1] In addition, about 40% of the C auris isolates evaluated to date were resistant to at least two classes of antifungals among fluconazole, voriconazole, amphotericin B, and the echinocandins.[1]

While Candida minimum inhibitory concentration (MIC) breakpoints are not defined for isavuconazole, itraconazole, or posaconazole, susceptibility trends can be identified. Isavuconazole appears to be the most active azole in susceptibility testing performed in a small study of 16 C auris isolates from Germany, Japan, India, and South Korea. Posaconazole and itraconazole were less active, while fluconazole demonstrated the lowest rate in the azole class against C auris.[5]

The first seven cases of C auris identified in the United States found that five were resistant to fluconazole, one of which was also resistant to amphotericin B and another to echinocandins. None of these isolates were resistant to all three classes of antifungals.[2]

Fluconazole is typically the first agent used when Candida albicans is isolated; however, when the Candida species is unknown or when a patient is critically ill or presenting with a bloodstream infection, echinocandins are more commonly used as first-line agents.Due to the high resistance of C auris to fluconazole and with frequent concurrent resistance to amphotericin B, the agents of choice for C auris infection in the United States are the echinocandins.[3] Unfortunately, resistance of C auris to the echinocandins has also occurred, making susceptibility testing imperative to guide treatment.[1]

Empiric treatment of C auris is recommended by the CDC as follows[9]:

If a patient is clinically unresponsive to treatment with an appropriately dosed echinocandin and/or has persistent fungemia for more than 5 days, treatment with liposomal amphotericin B 3-5 mg/kg IV daily should be considered if susceptibility testing results have not returned. Isavuconazonium also would be an appropriate treatment option, based on favorable susceptibility trends.[5,8] While dosing is not defined for C auris, the treatment doses for invasive aspergillosis or mucormycosis can be used, which would include a loading dose ofisavuconazonium 372 mg orally or intravenously every 8 hours for six doses, followed by 372 mg orally or intravenously daily.[10] Treatment should be tailored on the basis of susceptibility data; however, most strains of C auris isolated in the United States have been susceptible to echinocandins. The CDC is recommending that all isolates of C auris be tested for susceptibility.[9]

The recommended minimum duration of treatment for candidiasis is 2 weeks after documented clearance of C auris from the blood, as long as symptoms have resolved. Keep in mind, however, that this guidance is not based on any experience with C auris. The treatment duration may be longer depending on the infection site, such as is the case with endocarditis.[11]

Hospital Preparations

Institutions should check with their laboratory for the methods and limitations for identification of yeasts.

It is thought that antifungal selection pressure may play a role in the development of C auris, due to the observation that patients have been receiving antifungal treatment while C auris was isolated.[1] Antibiotic stewardship can be used to monitor the appropriate use of antifungal prophylaxis and broad-spectrum antibiotics to minimize the risk factors for infection with C auris and other invasive fungal infections.

C auris may be nosocomial in origin due to the fact that the median onset of infection is 19 days after admission and that isolates analyzed from certain hospitals have been found to be nearly identical.[1] It is also concerning that three patients in the United States were found to be colonized with C auris 1-3 months after initial detection. Along with this, C auris has been isolated from multiple surfaces in the hospital rooms of a patient who was infected with C auris 3 months prior.[2] It is therefore recommended that standard contact precautions be used for patients with C auris infection or colonization, including placement in single rooms.[9] Patient isolation and proper cleaning of hospital rooms of patients infected or colonized with C auris, including terminal decontamination at times, will be important in the control of the nosocomial spread of this fungus.

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