Importation, Mitigation, and Genomic Epidemiology of Candida auris at a Large Teaching Hospital

2017 ◽  
Vol 39 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Emil P. Lesho ◽  
Melissa Z. Bronstein ◽  
Patrick McGann ◽  
Jason Stam ◽  
Yoon Kwak ◽  
...  
Keyword(s):  
New York ◽  
Teaching Hospital ◽  
Index Case ◽  
Index Patient ◽  
Multidrug Resistant ◽  
Multidisciplinary Teams ◽  
Nucleotide Polymorphisms ◽  
Case Patient ◽  
Candida Auris ◽  
Genomic Epidemiology

OBJECTIVECandida auris (CA) is an emerging multidrug-resistant pathogen associated with increased mortality. The environment may play a role, but transmission dynamics remain poorly understood. We sought to limit environmental and patient CA contamination following a sustained unsuspected exposure.DESIGNQuasi-experimental observation.SETTINGA 528-bed teaching hospital.PATIENTSThe index case patient and 17 collocated ward mates.INTERVENTIONImmediately after confirmation of CA in the bloodstream and urine of a patient admitted 6 days previously, active surveillance, enhanced transmission-based precautions, environmental cleaning with peracetic acid-hydrogen peroxide and ultraviolet light, and patient relocation were undertaken. Pre-existing agreements and foundational relationships among internal multidisciplinary teams and external partners were leveraged to bolster detection and mitigation efforts and to provide genomic epidemiology.RESULTSCandida auris was isolated from 3 of 132 surface samples on days 8, 9, and 15 of ward occupancy, and from no patient samples (0 of 48). Environmental and patient isolates were genetically identical (4–8 single-nucleotide polymorphisms [SNPs]) and most closely related to the 2013 India CA-6684 strain (~200 SNPs), supporting the epidemiological hypothesis that the source of environmental contamination was the index case patient, who probably acquired the South Asian strain from another New York hospital. All isolates contained a mutation associated with azole resistance (K163R) found in the India 2105 VPCI strain but not in CA-6684. The index patient remained colonized until death. No surfaces were CA-positive 1 month later.CONCLUSIONCompared to previous descriptions, CA dissemination was minimal. Immediate access to rapid CA diagnostics facilitates early containment strategies and outbreak investigations.Infect Control Hosp Epidemiol 2018;39:53–57

scholarly journals Genomic Epidemiology of Candida auris in Qatar Reveals Hospital Transmission Dynamics and a South Asian Origin

2021 ◽  
Vol 7 (3) ◽  
pp. 240
Author(s):  
Husam Salah ◽  
Sathyavathi Sundararaju ◽  
Lamya Dalil ◽  
Sarah Salameh ◽  
Walid Al-Wali ◽  
...  
Keyword(s):  
South Asian ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Nucleotide Polymorphisms ◽  
Resistance Mutations ◽  
Candida Auris ◽  
Single Nucleotide ◽  
Genomic Epidemiology ◽  
East Region ◽  
Middle East Region

Candida auris is an emerging, multidrug-resistant fungal pathogen that has become a public health threat with an increasing incidence of infections worldwide. Candida auris spreads easily among patients within and between hospitals. Infections and outbreaks caused by C. auris have been reported in the Middle East region including Oman, Kuwait, Saudi Arabia, and Qatar; however, the origin of these isolates is largely unknown. Pathogen whole genome sequencing (WGS) was used to determine the epidemiology and drug resistance mutations of C. auris in Qatar. Forty-four samples isolated from patients in three hospitals and the hospital environment were sequenced by Illumina NextSeq. Core genome single nucleotide polymorphisms (SNPs) revealed that all isolates belonged to the South Asian lineage with genetic heterogeneity that suggests previous acquisition from foreign healthcare. The genetic variability among the outbreak isolates in the two hospitals (A and B) was low. Four environmental isolates clustered with the related clinical isolates, and epidemiologically linked isolates clustered together, suggesting that the ongoing transmission of C. auris could be linked to infected/colonized patients and the hospital environment. Prominent mutations Y132F and K143R in ERG11 linked to increased fluconazole resistance were detected.

scholarly journals 1579. Multidrug-Resistant Candida auris Isolates From New York Hospitals and Healthcare Facilities Are Susceptible to Antifungal Combinations

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S576-S577
Author(s):  
Brittany O’Brien ◽  
Sudha Chaturvedi ◽  
Vishnu Chaturvedi
Keyword(s):  
New York ◽  
Diagnostic System ◽  
Multidrug Resistant ◽  
Drug Combinations ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Candida Auris ◽  
Current Case ◽  
Healthcare Facilities ◽  
Broth Microdilution Method

Abstract Background Candida auris outbreak continues unabated in New York with the current case counts exceeding 300 patients. We used a modification of standard CLSI broth microdilution method (BMD) if two-drug combinations are efficacious against C. auris isolates with high-resistance to fluconazole (FZ, MIC50 >256 mg/L), and variable resistance to other broad-spectrum antifungal drugs. Methods BMD plates were custom-designed and quality controlled by TREK Diagnostic System. The combination tests of 15 drug-resistant C. auris involved microtiter wells with the initial 144 two-drug combinations and their two-fold dilutions (1/2–1/32) to get 864 two-drug combinations finally. We utilized MIC100 endpoints for the drug combination readings as reported earlier for the intra- and inter-laboratory agreements obtained against Candida species and Aspergillus fumigatus (Antimicrob Agents Chemother. 2015. 59:1759–1766). We also tested minimum fungicidal concentrations (MFC). Results We tested all possible 864 two-drug antifungal combinations for nine antifungal drugs in use to yield 12,960 MIC100 readings, and MFC readings for 15 C. auris isolates. Flucytosine (FLC) at 2.0 mg/L potentiated most successful combinations with other drugs. Micafungin (MFG), Anidulafungin (AFG), Caspofungin (CAS) at individual concentrations of 0.25 mg/L combined well with FLC (2.0 mg/L) to yield MIC100 for 14, 13, and 12 of 15 C. auris isolates tested, respectively. MFG/FLC combination was also fungicidal for 4 of 15 isolates. AMB / FLC (0.25/1.0 mg/L) yielded MIC100 for 13 isolates and MFC for three test isolates. Posaconazole (POS), and Isavuconazole (ISA) and Voriconazole (VRC) also combined well with FLC (0.25/2.0 mg/L) to yield MIC100 for 12, 13, and 13 isolates, respectively. POS/FLC combination was fungicidal for three isolates. Conclusion We identified seven two drug-combinations of antifungals efficacious against drug-resistant C. auris strains. The modified BMD combination susceptibility testing could be used by the clinical laboratories to assist providers with the selection of optimal treatment for C. auris candidemia. Disclosures All authors: No reported disclosures.

scholarly journals 2267. Epidemiology of Candida auris Candidemia in a Teaching Hospital in North of Oman: One-Year Survival

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S776-S776
Author(s):  
Arash Eatemadi ◽  
Aiman Al Wahibi ◽  
Hilal Al shibli ◽  
Ali Al reesi
Keyword(s):  
Public Health ◽  
Teaching Hospital ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Fungal Treatment ◽  
Candida Auris ◽  
Coagulase Negative Staphylococci ◽  
Central Public Health ◽  
Antibiotic Susceptibility Test ◽  
Recent Emergence

Abstract Background Recent emergence of Candida auris as a multidrug resistant fungal pathogen, is a serious concerns for public health. However, there is a paucity of reported cases from Oman. Literature search resulted in finding only 7 cases from Oman, reporting C. auris infections in the articles first published in 2017. However, the rate of isolatin is increasing. Methods In this study, we included the results of all positive blood cultures of C. auris in Suhar teaching hospital from May 2018 (date of first detection) till end of April 2019. Further confirmation of the species was performed by MALDI-TOF and antibiotic susceptibility test (AST) by Vitek 2 in central public health laboratory (CPHL) of Oman. Results We detected 13 patients (9 females, 4 males). The mean age was 58.61% years (28–76 years). All candidemic patients had serious underlying conditions, including prolonged hospital stay or extensive and prolonged antimicrobial exposure or medical comorbidities (8 of 13). The time from hospital admission to onset of C. auris candidemia was 8–49 days, with a median of approximately 27 days. The most common isolated co- pathogen from blood culture was K. pneumonia (without regard to Coagulase-negative staphylococci). As average, every patient received 4.8 kind of different antibiotics in mean 88 doses before candidemia developed and piperacillin–tazobactam was the most common used antibiotics. AST was done just for 5 patients and revealed high-level resistance to fluconazole and Amphotricin B while, Echinocandins (anidulafungin, caspofungin) were fully sensitive and voricunazole had intermediate sensitivity. Mean duration of anti-fungal treatment was 12.5 days (5 – 26 days). 8 patients treated by Echinocandins (4/8 died), 4 by Fluconazole (3/4 died) and one without treatment discharged. 30-day all-cause mortality was 61.5%. Conclusion In Oman, C. auris has been reported from many hospitals. Resistance to several antifungal agents and persistence in the hospital environment make this organism a potential menace for the treating physician and the infection control personnel. In our hospital, every candidemic patient should be treated with Echinocandins and assumed to be resistant to Fluconazole until proven otherwise according to results of AST. Disclosures All authors: No reported disclosures.

scholarly journals In Vitro Evaluation of Antifungal Drug Combinations against Multidrug-Resistant Candida auris Isolates from New York Outbreak

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Brittany O’Brien ◽  
Sudha Chaturvedi ◽  
Vishnu Chaturvedi
Keyword(s):  
New York ◽  
Drug Combination ◽  
Multidrug Resistant ◽  
Drug Combinations ◽  
Health Care Facilities ◽  
Antifungal Drugs ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Content Type

ABSTRACT Since 2016, New York hospitals and health care facilities have faced an unprecedented outbreak of the pathogenic yeast Candida auris. We tested over 1,000 C. auris isolates from affected facilities and found high resistance to fluconazole (MIC > 256 mg/liter) and variable resistance to other antifungal drugs. Therefore, we tested if two-drug combinations are effective in vitro against multidrug-resistant C. auris. Broth microdilution antifungal combination plates were custom manufactured by TREK Diagnostic System. We used 100% inhibition endpoints for the drug combination as reported earlier for the intra- and interlaboratory agreements against Candida species. The results were derived from 12,960 readings, for 15 C. auris isolates tested against 864 two-drug antifungal combinations for nine antifungal drugs. Flucytosine (5FC) at 1.0 mg/liter potentiated the most combinations. For nine C. auris isolates resistant to amphotericin B (AMB; MIC ≥ 2.0 mg/liter), AMB-5FC (0.25/1.0 mg/liter) yielded 100% inhibition. Six C. auris isolates resistant to three echinocandins (anidulafungin [AFG], MIC ≥ 4.0 mg/liter; caspofungin [CAS], MIC ≥ 2.0 mg/liter; and micafungin [MFG], MIC ≥ 4.0 mg/liter) were 100% inhibited by AFG-5FC and CAS-5FC (0.0078/1 mg/liter) and MFG-5FC (0.12/1 mg/liter). None of the combinations were effective for C. auris 18-1 and 18-13 (fluconazole [FLC] > 256 mg/liter, 5FC > 32 mg/liter) except MFG-5FC (0.1/0.06 mg/liter). Thirteen isolates with a high voriconazole (VRC) MIC (>2 mg/liter) were 100% inhibited by the VRC-5FC (0.015/1 mg/liter). The simplified two-drug combination susceptibility test format would permit laboratories to provide clinicians and public health experts with additional data to manage multidrug-resistant C. auris.

scholarly journals In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
YanChun Zhu ◽  
Shannon Kilburn ◽  
Mili Kapoor ◽  
Sudha Chaturvedi ◽  
Karen Joy Shaw ◽  
...  
Keyword(s):  
New York ◽  
Fungal Infections ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Wild Type ◽  
Candida Auris ◽  
Content Type

ABSTRACT An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are panresistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug fosmanogepix is currently in phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New York C. auris isolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50 and MIC90, 0.03 mg/liter; range, 0.004 to 0.06 mg/liter). The local epidemiological cutoff value (ECV) for MGX indicated all C. auris isolates were within the population of wild-type (WT) strains; 0.06 mg/liter defines the upper limit of wild type (UL-WT). MGX was 8- to 32-fold more active than the echinocandins, 16- to 64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators’ MIC50, MIC90, or geometric mean (GM) values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris panresistant isolates was 0.008 to 0.015 mg/liter, and the median and mode MIC values were 0.015 mg/liter, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates.

scholarly journals Genomic Characterization of Salmonella typhimurium DT104 Strains Associated with Cattle and Beef Products

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 529
Author(s):  
Craig T. Parker ◽  
Steven Huynh ◽  
Aaron Alexander ◽  
Andrew S. Oliver ◽  
Kerry K. Cooper
Keyword(s):  
Phage Type ◽  
Ground Beef ◽  
Multidrug Resistant ◽  
Snp Analysis ◽  
Nucleotide Polymorphisms ◽  
Deletion Event ◽  
Genomic Epidemiology ◽  
Serovar Typhimurium ◽  
Beef Products ◽  
Utilization Pathway

Salmonella enterica subsp. enterica serovar Typhimurium DT104, a multidrug-resistant phage type, has emerged globally as a major cause of foodborne outbreaks particularly associated with contaminated beef products. In this study, we sequenced three S. Typhimurium DT104 strains associated with a 2009 outbreak caused by ground beef, including the outbreak source strain and two clinical strains. The goal of the study was to gain a stronger understanding of the genomics and genomic epidemiology of highly clonal S. typhimurium DT104 strains associated with bovine sources. Our study found no single nucleotide polymorphisms (SNPs) between the ground beef source strain and the clinical isolates from the 2009 outbreak. SNP analysis including twelve other S. typhimurium strains from bovine and clinical sources, including both DT104 and non-DT104, determined DT104 strains averaged 55.0 SNPs between strains compared to 474.5 SNPs among non-DT104 strains. Phylogenetic analysis separated the DT104 strains from the non-DT104 strains, but strains did not cluster together based on source of isolation even within the DT104 phage type. Pangenome analysis of the strains confirmed previous studies showing that DT104 strains are missing the genes for the allantoin utilization pathway, but this study confirmed that the genes were part of a deletion event and not substituted or disrupted by the insertion of another genomic element. Additionally, cgMLST analysis revealed that DT104 strains with cattle as the source of isolation were quite diverse as a group and did not cluster together, even among strains from the same country. Expansion of the analysis to 775 S. typhimurium ST19 strains associated with cattle from North America revealed diversity between strains, not limited to just among DT104 strains, which suggests that the cattle environment is favorable for a diverse group of S. typhimurium strains and not just DT104 strains.

scholarly journals 1275. Evaluation of in vitro activity of manogepix against multidrug-resistant and pan-resistant Candida auris from the New York Outbreak

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S654-S654
Author(s):  
Yan Chun Zhu ◽  
Shannon N Kilburn ◽  
Mili Kapoor ◽  
Sudha Chaturvedi ◽  
Karen J Shaw ◽  
...  
Keyword(s):  
New York ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Candida Auris ◽  
Microsoft Excel ◽  
York Metropolitan Area ◽  
Clinical Surveillance

Abstract Background An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. NY C. auris isolates demonstrate resistance to fluconazole and variable resistance to other antifungals. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug, fosmanogepix, is in clinical development for the treatment of invasive fungal infections. Methods We evaluated the susceptibility of 200 NY C. auris isolates (2017-2020) to MGX and 10 comparators. Testing was performed using TREK frozen broth microdilution panels for FLC, VRC, ITC, ISA, POS, AFG, CAS, and MFG. MGX MICs were evaluated (CLSI M27-A3 guidelines) using a 50% reduction in fungal growth endpoint at 24 h. MICs were determined by ETEST® at 24 h for AMB and FLC. We defined pan-resistant C. auris as isolates with in vitro resistance to two or more azoles, all echinocandins, and AMB. The epidemiological cutoff values (ECVs, ECOFFs) for MGX were estimated using the Microsoft Excel spreadsheet calculator ECOFFinder. Results MGX demonstrated lower MICs than comparators (MIC50 and MIC90 0.03 mg/L; range 0.004-0.06 mg/L). MGX was 8-32-fold more active that the echinocandins, 16-64-fold more active than the azoles, and 64-fold more active than AMB. No differences were found in the MGX or comparators’ MIC50, MIC90, or GEOMEAN values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris pan-resistant isolates was 0.008-0.015 mg/L, and the median and mode MIC values were 0.015 mg/L, demonstrating that MGX retains activity against these isolates. The MGX epidemiological cutoff value (ECV, 99% cutoff) was 0.06 mg/L. Conclusion MGX MICs were low against C. auris isolates including those with variable patterns of resistance to AMB, azoles, and echinocandins. In addition, MGX retained potent activity against six pan-resistant isolates. These data support the continued clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates. Disclosures Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Vishnu Chaturvedi, PhD, Amplyx (Grant/Research Support)

Multidrug-Resistant Candida auris Concern Stems From New York Cases

JAMA ◽  
2020 ◽  
Vol 323 (8) ◽  
pp. 702
Author(s):  
Bridget M. Kuehn
Keyword(s):  
New York ◽  
Multidrug Resistant ◽  
Candida Auris

scholarly journals Evaluation of in vitro activity of manogepix against multidrug-resistant and pan-resistant Candida auris from the New York Outbreak

2020 ◽  
Author(s):  
YanChun Zhu ◽  
Shannon Kilburn ◽  
Mili Kapoor ◽  
Sudha Chaturvedi ◽  
Karen Joy Shaw ◽  
...  
Keyword(s):  
New York ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Candida Auris ◽  
York Metropolitan Area ◽  
Clinical Surveillance ◽  
Laboratory Surveillance

ABSTRACTAn ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are pan-resistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug, fosmanogepix, is currently in Phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New York C. auris isolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50 and MIC90 0.03 mg/L; range 0.004-0.06 mg/L). The MGX epidemiological cutoff value (ECV, 99% cutoff) for the tested C. auris isolates was 0.06 mg/L. MGX was 8-32-fold more active than the echinocandins, 16-64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators’ MIC50, MIC90, or GEOMEAN values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris pan-resistant isolates was 0.008-0.015 mg/L, and the median and mode MIC values were 0.015 mg/L, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates.

scholarly journals Mitigating Candida auris at a Busy Community Hospital: A Quasi-Experimental Near Real-Time Approach

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S72-S72
Author(s):  
Emil Lesho ◽  
Melissa Bronstein ◽  
Jodi McNamara ◽  
Megan Callahan ◽  
Yoon Kwak ◽  
...  
Keyword(s):  
Public Health ◽  
New York ◽  
Uv Light ◽  
Multidrug Resistant ◽  
Community Hospitals ◽  
Candida Auris ◽  
Local Public Health ◽  
Before And After ◽  
Quasi Experimental ◽  
Hygiene Compliance

Abstract Background Candida auris, an emerging multidrug-resistant pathogen associated with increased mortality, can disseminate on hospital surfaces and resist disinfection. Transmission dynamics remain poorly understood at community hospitals. Immediately following identification of a C. auris infection in an unsuspected patient admitted to a semi-private room 6 days previously, we sought to limit and determine the extent of C. auris contamination at Rochester General (RG), a 528-bed hospital in New York, using available resources. Methods The index and roommate were placed on enhanced contact precautions and moved to private rooms. Their former room was terminally cleaned with peracetic acid/hydrogen peroxide (PAHP) and UV light. Ten high-touch environmental surfaces in the new rooms of the index and roommate, the nursing stations, and throughout the ward were sampled immediately before and after, and between daily cleaning. The nares, axillae, and groin of the index, the roommate, and all concurrent ward patients were also sampled. All patients on the involved ward were sequentially moved from their initial rooms into vacated rooms that were terminally cleaned with PAHP and UV light. Prior to the index event, RG laboratory began sending all possible C. auris isolates to the state public health laboratory for confirmation, and using PAHP for all cleaning. RG also leverages preexisting agreements with other referral laboratories to support outbreak investigations. Hand-hygiene compliance averaged 80–90% on the ward. Hospital leaders, laboratory, nursing, environmental services, and local public health personnel regularly participate in infection prevention efforts. Results C. auris was isolated from 3 of 132 surface samples on the eighth, nineth, and 15th day of ward occupancy, and 0 of 48 patient samples from 18 co-located patients. The index remained colonized until death on hospital Day 21. No surfaces were C. auris-positive 1 month later. Conclusion Compared with prior reports, dissemination at RG was limited. This, the first such quantitative assessment, illustrates how community hospitals can enhance surveillance and patient safety when formal agreements, vigilance, and multi-disciplinary and interagency teamwork exist before outbreaks occur. Disclosures All authors: No reported disclosures.

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