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Open Forum Infectious Diseases

BRIEF REPORT

no known epidemiological links to other cases or healthcare


The Emergence and Persistence of
contact outside his immediate community. The main underly­
Candida auris in Western New York ing factor appeared to be excess antibiotic exposure.
With No Epidemiologic Links: A
Failure of Stewardship? METHODS

Patrick McGann,1 Francois Lebreton,1 Abhimanyu Aggarwal,2 Jason Stam,1 In January 2022, C auris was isolated from a urine culture in a
Rosslyn Maybank,1 Matthew Ficinski,2 Melissa Bronstein,3 Jason W. Bennett,1 68-year-old male on the 51st day of hospitalization at a commu­
and Emil Lesho3
nity hospital in Western New York. In the 6 months before ad­
1
Multidrug-Resistant Organism Repository and Surveillance Network (MRSN), Walter Reed
Army Institute of Research, Silver Spring, Maryland, USA, 2Infectious Diseases Department,
mission, he had no healthcare contact or travel outside his

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Rochester Regional Health, Rochester, New York, USA, and 3Quality and Safety Department, immediate community in central Genesee County. Before and
Rochester Regional Health, Rochester, New York, USA
during hospitalization he had no identified exposures to other
Reports of Candida auris infection in patients without patients or family members known to be colonized or infected
epidemiologic links to prior outbreaks are scarce. We with C auris. He had no history of (or current malignancy) organ
describe the genomic epidemiology of such a case in Western transplantation, hemodialysis, decubitus ulcers, feeding tubes, or
New York. Before emergence, the patient received >60 days nursing home stays. He was active and in fair health with a his­
of excess antibiotics. Candida auris was recovered on near- tory of mild vascular dementia. Two days before admission, he
patient surfaces after enhanced terminal cleanings. was diagnosed with community-acquired pneumonia and pre­
Keywords. antibiotic stewardship; Candida auris; scribed azithromycin. Upon admission for progressive dyspnea,
outbreak; Western New York. he tested positive for severe acute respiratory syndrome corona­
virus 2 and received 6 mg of dexamethasone daily for 10 days
Candida auris is a fungal pathogen classified as an urgent public and remdesivir 200 mg once followed by 100 mg daily for 5
threat due to its association with increased mortality, potential days. A chest radiograph showed left lobar consolidation and
for developing pan-drug resistance, and its ability to become the patient received empiric ceftriaxone and azithromycin. He
entrenched in the hospital environment [1–3]. In fact, a recent received no other immunosuppressive therapies. Over the next
study revealed that surfaces near patients with C auris frequent­ week, as a result of worsening respiratory status, he received non­
ly become recontaminated within hours of cleaning [4]. The bi­ invasive positive pressure ventilation, followed by 8 days of en­
ology and environmental reservoirs of C auris remain poorly dotracheal intubation before he was successfully extubated. He
understood [5]. However, past infections have predominantly had a peripherally inserted central line in his arm and indwelling
occurred in patients with cancer, feeding tubes, breakdowns urinary catheter. Both devices were in place for 35 days, 23 of
in environmental cleaning and infection control processes, or which occurred before the isolation of the C auris. He also had
with epidemiologic links to other cases [6–8]. intermittent fevers, for which he received 73 days of antimicro­
In the United States, the first incidence of C auris has been bial therapy including micafungin, piperacillin-tazobactam, cefe­
traced to New York [9], but subsequent reports and surveil­ pime meropenem, and vancomycin (Table 1). However, the
lance in this region have mainly focused on larger outbreaks microbiologic work-up remained negative, including urine,
in New York City [3, 6–8]. Reports from rural communities blood, bronchoalveolar lavage, Legionella antigen and cultures,
in Western New York and incident cases without links to other and fungal and mycobacterial stains and cultures. Serum procal­
C auris cases are scarce [10]. We describe an emergence of C citonin levels also remained within normal limits. On the 22nd
auris in a patient hospitalized at a small community hospital and 24th day of hospitalization, Candida albicans was isolated
in Genesee County, New York. Unlike the facility >50 miles from respiratory cultures. On the 51st day of hospitalization,
away and described in the 2017 report [10], this patient had blood, sputum, and urine cultures were obtained in response
to an episode of fever and hypotension. Due to his altered mental
Received 26 November 2022; editorial decision 01 March 2023; accepted 03 March 2023;
status, he was unable to report any urinary symptoms. The urine
published online 6 March 2023 culture grew azole-resistant C auris identified by mass spectro­
Correspondence: Emil Lesho, DO, FACP, FIDSA, FSHEA, 1425 Portland Avenue, Rochester,
scopy (VITEK MS; Biomérieux, St. Louis, MO) [10] (Table 1).
New York 14621 (carolinelesho@yahoo.com); Melissa Bronstein, RN, 1425 Portland Avenue,
Rochester, New York 14621 (melissa.bronstein@rochesterregional.org). Identity and susceptibility of the isolate were confirmed accord­
Open Forum Infectious Diseases® ing to Clinical and Laboratory Standards Institute reference
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.
This work is written by (a) US Government employee(s) and is in the public domain in the US.
methodology M27-A4 by the laboratory of New York State
https://doi.org/10.1093/ofid/ofad123 Department of Health, Albany, New York, using MALDI-TOF

BRIEF REPORT • OFID • 1


Table 1. Antibiotic Susceptibilities and Surface Contamination Results

Total DOT Before Isolation Minimum Inhibitory/Concentration No. Surfaces PCR Positive Culture Positive
Drug of C. auris (mcg/mL) Interpretation Location Tested n (%) n (%)

AZM 3 … … After Terminal Cleaning


FEP 7 … … ICU 9 6 (66) 0
MEM 16 … … Ward 8 6 (75) 2 (25)
MFG 15 … … … After Directly Observed Recleaning
TZP 8 … … ICU 9 0 0
VAN 17 … … Ward 8 0 0
Total 73 … … … … … …
FLC … >256 R … … …
VRC … 1 U … … …
ICT … 0.06 U … … … …
ISA … 0.25 U … … … …

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CAS … 0.06 S … … … …
MFG … 0.12 S … … … …
AFG … 2 S … … … …
AMB … 0.06 S … … … …
Abbreviations: AFG, anidulafungin; AMB, amphotericin B; AZM, aztreonam; CAS, caspofungin; DOT, days of therapy; FEP, cefepime; FLC, fluconazole; ICT, itraconazole; ICU, intensive care
unit; ISA, isavuconazole; MEM, meropenem; MFG, micafungin; PCR, polymerase chain reaction; R, resistant; S, susceptible; TZP, piperacillin tazobactam; U, uninterpretable; VAN,
vancomycin; VRC, voriconazole.

Figure 1. Core genome phylogeny and pairwise single-nucleotide polymorphism (SNP) distance matrix. (A) Core genome phylogeny for 5 Candida auris isolates from a
hospital network in Western New York and 2 reference isolates from India. Phylogenetic tree was built using the GTR-GAMMA model in RAxML v8.2.11 and a core genome
alignment from panseq (fragmentation size of 500 base pairs to find sequences with ≥95% identity in ≥95% of the isolates). Genomes of reference strains CA-VPCI (GenBank
accession number PRJEB9463) and CA-6684 (GenBank accession number PRJNA267757) were obtained from public databases, and newly generated genomes were depos­
ited under GenBank accession PRJNA903931. The carriage of a K143R substitution in ERG11 is indicated (closed circle). (B) Pairwise SNP distance matrix (obtained from
whole-genome SNP analysis using snippy and snp-dist) for 5 highly genetically related isolates from Western New York.

MS (Bruker, Bremen, Germany) and custom TREK frozen broth auris results during the previous 12 months. During admission,
microdilution panels (Thermo Fisher Scientific, Marietta, OH) the patient occupied 4 different rooms in the intensive care unit
and by Etest as recommended by the manufacturer (AB (55 days), followed by 12 days on the medical surgical ward
Biodisk; bioMérieux, Solna, Sweden) [8, 11]. No further C auris (Supplementary Figure 1). The index patient’s roommate was
was isolated from this patient. relocated and the room was closed to further patients. After dis­
charge, the room was terminally cleaned with hydrogen perox­
Outbreak Response ide and peracetic acid (Oxicide), then treated with ultraviolet-C
This isolate (MRSN101498) was forwarded to the light. It remained closed until results of environmental cultures,
Multidrug-Resistant Organism Repository and Surveillance taken as previously described [8, 10], were available. All 4 pa­
Network (MRSN), where it underwent whole-genome se­ tients who had either spent more than 24 hours in the same
quencing on a Miseq benchtop sequencer, as previously de­ room with the index patient or in immediately adjacent rooms
scribed [10]. Laboratory records were queried for other C were placed on enhanced contact precautions and underwent

2 • OFID • BRIEF REPORT


surveillance culturing of nares, axilla, and groin. Their rooms available at GenBank for Bioproject, PRJNA903931; https://
and equipment were terminally cleaned in the same manner. www.ncbi.nlm.nih.gov/bioproject/PRJNA903931.)
All staff and trainees who had contact with the patient were in­
terviewed. None were found to have possible links to other C DISCUSSION
auris cases. Department of Health representatives examined
the patient’s home and interrogated the patient’s family and This report is noteworthy for several reasons. First, unlike prior
ruled those out as potential sources of infection. Two infectious reports, there were no exposures or epidemiologic links to
disease physicians separately reviewed the patient’s medical re­ known cases. Second, reports from rural community hospitals
cord to determine appropriateness of antibiotic usage. Excess are uncommon and may represent surveillance “blind spots”.
or inappropriate antibiotic days were determined by the total Third, it highlights important knowledge gaps pertaining to
days of antibiotic received before the emergence of C auris unrecognized reservoirs of C auris [5]. Despite these genomic
and not supported by culture or other microbiologic data, mi­ results, the potential reservoir(s) of MRSN101498 in Western
nus 3 days allowed for empiric treatment for each unexplained New York remain unclear. Both hospitals had previously im­
plemented sporicidal (not quaternary ammonium) disinfec­

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fever or fever not attributed to coronavirus disease 2019.
tants for environmental cleaning as part of Clostridioides
difficile reduction measures, because quaternary ammonium
RESULTS is known to be less effective against C difficile and C auris
Candida auris had not been isolated at the facility in the past [2]. However, nucleic acid and cultivable C auris were recov­
year. All exposed patient samples were negative for C auris. ered from near-patient surfaces in rooms that housed the index
Environmental cultures from nearby rooms and surfaces after repeated terminal cleanings. It was not until terminal
were negative. However, as in the report by Sansom et al [4] cleaning was performed under direct observation by infection
in the rooms that the index patient occupied, up to 75% preventionists (IPs) that no cultivable C auris and C auris nu­
of surfaces tested after terminal cleaning had detectable cleic acid was detected. All terminal cleaning protocols were the
nucleic acid, and 25% had cultivable C auris (Table 1 and same, and all included ultraviolet irradiation and sporicidal
Supplementary Figures 2 and 3). Both physician reviewers in­ cleaning agent as described earlier. The only difference during
dependently concluded that the patient received at least 60 ex­ the cleanings after which no C auris was recovered was the di­
cess or inappropriate days of broad-spectrum antibiotics rect observation by the IP that occurred during those cleaning
including 15 days of micafungin, before the appearance of C process. Unlike previous outbreaks in New York, there were no
auris (Table 1). infection control lapses or use of quaternary ammonium for
A comparison of the MRSN101498 genome sequence with disinfection [2, 6, 12]. Furthermore, the patient had no epide­
known reference strains obtained from National Center for miologic links to the Rochester facility involved in the 2017
Biotechnology Information (NCBI) revealed that MRSN101498 outbreak, nor did any of the staff.
was most closely genetically related to the 2013 Indian CA-6684
strain, differing by 209 variable sites across the 11 753 726 base CONCLUSIONS
pair core genome alignment (Figure 1). It is notable that the This case underscores the potential role antibiotic exposure
MRSN101498 carried the K143R mutation in ERG11 that has may play in the emergence of C auris and the challenges it poses
been linked to increased triazole resistance in C albicans. This mu­ to cleaning and disinfection. We propose that detailed antibiot­
tation is absent in the closely related CA-6684 but found in the ic exposure and cleaning regimens be included in future out­
more distantly related Indian 2105 VPCI reference strain break reports of drug-resistant pathogens.
(Figure 1). Furthermore, whole-genome single-nucleotide poly­
morphism (SNP) analysis revealed that MRSN101498 was also Supplementary Data
highly genetically related to 4 previous isolates involved in an out­ Supplementary materials are available at Open Forum Infectious Diseases
break in March 2017 from a hospital 47 miles to the northeast in online. Consisting of data provided by the authors to benefit the reader, the
Rochester, New York, differing by just 39–43 SNPs across the en­ posted materials are not copyedited and are the sole responsibility of the
authors, so questions or comments should be addressed to the correspond­
tire 12.4 Mb genome (Figure 1). This amount of genetic differenc­ ing author.
es, accumulated over 5 years, is in agreement with the estimated
evolution rate of C auris (5.75 mutations per genome per year) Acknowledgments
[2] and suggests all 5 isolates from Western New York shared a Author contributions. PM, MB, and EL contributed to conception and
recent common ancestor. In addition, similar to the most recent design; MB, MF, and AA contributed to data collection; FL, JS, RM, and
JWB contributed to data analysis; all authors contributed to manuscript
MRSN101498 isolate, the 4 earlier outbreak isolates from
preparation and revision.
Rochester, New York carried an identical SNP causing the Potential conflicts of interest. All authors: No reported conflicts of
K143R substitution in the ERG11 gene. (Genomic data are interest.

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