As health officials in New Jersey, Illinois and New York State scramble to contain the spread of a highly infectious and deadly fungus, microbiologists at Beth Israel Deaconess Medical Center (BIDMC) have shown that a combination of anti-fungal and anti-bacterial medications may be an effective weapon against the recently discovered multidrug resistant, Candida auris (C. auris).
BIDMC’s Thea Brennan-Krohn, MD, presented the findings Friday, June 21, 2019, at ASM Microbe 2019, the annual meeting of the American Society for Microbiology.
“Few treatment options are available for patients infected with Candida auris, which causes invasive, life-threatening infections, usually in patients who are already critically ill or have compromised immune systems,” said Brennan-Krohn, MD, a post-doctoral research fellow in the lab of James E. Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC.
“It has an alarming propensity to spread from patient to patient and survive on surfaces in rooms, resulting in hospital outbreaks.”
First discovered in Japan in 2009, C. auris has been detected in patients in more than 20 countries and, as of April 2019, has sickened 643 Americans in 11 U.S. states, according to the U.S. Centers for Disease Control and Prevention (CDC).
At present, most cases of C. auris are resistant to at least one antifungal drug, with about a third impervious to two or more.
In order to identify new treatment approaches for C. auris, Brennan-Krohn and colleagues used a modified inkjet printer – a method pioneered for rapid and uniform antimicrobial screening in the Kirby lab – to test three antifungal drugs, one from each of the main classes of antifungals, combined with two antibacterial antibiotics, which by themselves have no activity against fungal infections.
Using the inkjet technology to dispense uniform samples of C. auris into each of the 96 wells in a standard lab testing plate, Brennan-Krohn tested 10 combinations against 10 strains of C. auris, a painstaking process that would have taken at least 50 hours if done by hand.
It took less than two hours in total using the inkjet dispenser for Brennan-Krohn to find three novel combinations of antifungal and antibacterial drugs that demonstrated activity against this insidious new pathogen.
Using a different method known as a time-kill test, Brennan-Krohn showed that two of the antibacterial-antifungal treatments not only prevented C. auris from growing but also succeeded in killing some of the strains tested.
While the drugs have not yet been tested in combination in humans infected with C. auris, all of the drugs Brennan-Krohn evaluated – the antifungals amphotericin and caspofungin and the antibacterials minocycline and rifampin – are FDA-approved antibiotics, currently in use patients with a variety of infections.
If the drugs’ combined power to inhibit or kill C. auris that they demonstrated in the lab is confirmed in studies in humans, it could mean physicians caring for patients with C. auris infections already have access to effective treatment options.
Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections, is associated with high mortality, and can spread in healthcare settings.
This yeast was first described in 2009 and has since been reported in over 20 countries on five continents. C. auris poses a global health threat for several reasons:
- Multidrug resistance is common, and a few isolates are resistant to all three of the main classes of antifungal drugs, severely limiting treatment options.1
- C. auris is commonly misidentified in clinical laboratories. Unless laboratories are aware of possible misidentification and have the ability to perform further evaluation, cases of C. auris could go undetected.
- C. auris can be transmitted between patients in healthcare settings and cause healthcare-associated outbreaks. C. auris can colonize patients, especially on the skin, perhaps indefinitely, and persist for weeks in the healthcare environment. The lack of decolonization methods and suboptimal efficacy of some commonly used hospital environmental disinfectants compounds the challenge of controlling its spread.
The genus Candida comprises an array of phenotypically similar yet genetically highly divergent yeasts. C. auris differs markedly from common pathogenic Candidaspecies like Candida albicans and Candida glabrata.
In healthcare settings, C. aurisbehaves more like transmissible bacterial multidrug-resistant organisms (MDROs), such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriacea (CRE), than other Candida species.
Unlike other Candidainfections, which are generally thought to result from autoinfection from host flora, C. auris can be transmitted between patients.
Unlike for most other Candida species, for which transmission-based precautions are generally not required, C. aurisrequires implementation of specific infection control measures, much like those used for control of MRSA and CRE.
With its multidrug resistance, transmissibility, and severe outcomes, C. auris has all the makings of a “superbug.” Control of C. auris requires better understanding of the organism itself, vigilance and accurate identification, appropriate treatment and infection control measures, and a coordinated public health response.
We review the emergence of C. auris, examining the global advent, biology, challenges of identification, multidrug resistance, clinical manifestations, treatment, risk factors for infection, transmission, and control of C. auris
Since its description in 2009, C. auris has been reported from 23 countries spanning five continents (Table 1, Fig. 1). Because clinical laboratories often do not identify Candida isolates to the species level, and because C. auris is misidentified by commonly available laboratory methods, C. auris may be present in other countries, but has not been detected or has not yet been reported.Figure 1.
Countries from which Candida auris cases have been reported, as of March 31, 2018.‡ *Single cases of C. auris have been reported from Austria, Belgium, Kuwait, Malaysia, Norway, and the United Arab Emirates. †Multiple cases of C. auris have been reported from Canada, Colombia, France, Germany, India, Israel, Japan, Kenya, Oman, Pakistan, Panama, South Africa, South Korea, Spain, the United Kingdom, the United States, and Venezuela; in some of these countries, extensive transmission of C. auris has been documented in more than one hospital. ‡Other countries not highlighted on this map may also have undetected or unreported C. auris cases.
Countries where Candida auris cases have been reported, as of March 2018.*
|Country||Year of first report||Year of earliest isolate reported||Single case or multiple cases reported|
|South Korea5||2011||1996||Multiple cases|
|South Africa9||2014||2012||Multiple cases|
|United Kingdom39||2016||2013||Multiple cases|
|United States20,91||2016||2013||Multiple cases|
|United Arab Emirates92||2018||2017||Single case|
NR, Not reported.
*References are the earliest publication for each data point. When a country has reported multiple cases by having more than one single case report, the first two single case reports are cited.
†Iguchi S, Mizushima R, Kamata K, et al. Candida auris detection from clinical isolates in Japan. 91st Annual Meeting of Japanese Society for Bacteriology, Fukuoka, Japan, March 27–29, 2018, P-011.
‡Okinda N, Kagotho E, Castanheira M et al. Candidemia at a referral hospital in sub-Saharan Africa: emergence of Candida auris as a major pathogen. European Conference on Clinical Microbiology and Infectious Diseases, Barcelona, May 10–13, 2014, P0065.
§Farooqi JQ, Soomro A, Sajjad S et al. Outbreak of Candida auris in a tertiary care hospital in Karachi, Pakistan. International Meeting on Emerging Diseases and Surveillance, Vienna, Austria, November 4–7, 2016, 03.004.
||GenBank accession no. MG736297
Outbreaks of C. auris infections have been reported in healthcare facilities in Colombia,a India,8,11 Pakistan, Panama,12 Spain,b the United Kingdom,13 the United States,14 and Venezuela.15 One European outbreak involved 382 cases.16
Several recent reports about C. auris describe not just a few sporadic cases or distinct outbreaks, but rather that C. auris has become a common cause of Candida infection. In South Africa, C. auris is now a leading cause of candidemia, having caused hundreds of confirmed cases.17
In India, a study of 27 intensive care units across the country found 5.7% of candidemia cases from April 2011 to September 2012 were due to C. auris.18
According to a report from Kenya, 38% of candidemia cases during 2010 to 2013 at one hospital were caused by C. auris. These changes represent a remarkable shift in species distribution, considering that C. auris had rarely been detected before 2009 anywhere in the world.
In the United States, over 250 C. auris cases have been identified through specimens collected during routine clinical care as of February 2018.19
The earliest known case in the United States was from 2013 in a patient who was transferred for care to the United States from a hospital in the United Arab Emirates.20
All other reported US cases occurred after mid-2015. Cases have been identified in 10 states but have been primarily concentrated in New Jersey and the New York metropolitan area.19 In New York and New Jersey, most patients have received care at interconnected healthcare facilities in concentrated geographic areas.14
Epidemiologic links between cases have also been found in Illinois, where one healthcare facility was associated with at least three cases.14
Provided by Beth Israel Deaconess Medical Center