Candida auris. An emerging pathogen of concern. Dr Chong Wei Ong. 22 Nov 2017

Transcription

1 Candida auris An emerging pathogen of concern Dr Chong Wei Ong Clinical Microbiologist, ACT Pathology / Canberra Hospital and Health Services Infectious Diseases Physician, Canberra Hospital and Health Services Infectious Diseases Physician, Calvary Public Hospital Bruce, Bruce 22 Nov 2017

2 DISCLOSURE I have no conflicts of interest to declare.

3 1 July 2016 Daily Mail Australia. Accessed 5 Mar 2017.

4 Candida auris Emergence 2009, Japan novel organism isolated; ear canal 70F inpatient in , S. Korea isolated from 15 patients; chronic otitis media from , S. Korea 3 cases of nosocomial candidemia (2 deaths); from By 2016, India, Pakistan, Kuwait, S. Africa, Venezuela, Israel, Kenya, UK, USA, Brazil, Spain, Germany, Norway all reporting cases 2016 CDC, ECDC and PHE alerts issued By 2017, Colombia, Israel, Oman, Panama, Canada also reporting cases Satoh K et al. Microbiol Immunol 2009;53(1):41 4. Kim et al. Clin Infect Dis 2009;48(6):e Lee WG et al. J Clin Microbiol Sep;49(9): ECDC. Candida auris in healthcare settings Europe. 19 Dec Sears D et al. Int J Infect Dis Oct;63: Schwartz IS et al. Can Commun Dis Rep. 2017;43 (7/8):150-3.

5 Emergence of multidrugresistant clinical Candida auris strains in 5 continents? Chowdhary A et al. PLoS Pathog May 18;13(5):e

6 Amplified Fragment Length Polymorphism Schelenz S et al Oct 19;5:35.

7 Whole-Genome Sequencing India / Pakistan South Africa Japan Venezuel a Lockhart SR et al. Clin Infect Dis Jan 15;64(2):

8 Candida auris cases - USA Aug 2016 May 2017 Sep 2017 Screening cases Clinical Cases Vallabhaneni S et al. MMWR Morb Mortal Wkly Rep Nov 11;65(44): Tsay S et al. MMWR Morb Mortal Wkly Rep May 19;66(19): CDC. Tracking Candida auris. Accessed 15 Nov 2017.

9 Candida auris United Kingdom July 2017 : detections in 20 separate NHS Trusts and independent hospitals involved 3 hospitals large nosocomial outbreaks - all over by Aug 2017 over 35 other hospitals with cases over 200 patients colonised or infected About 75% = colonised patients (enhanced surveillance) About 25% = clinical infections, including 27 blood stream infections There has been no attributable mortality to C. auris within the UK Public Health England Health Protection Report 11(18): news (11 August). Accessed 15 Nov 2017.

10 Clinical syndromes Otitis media Fungaemia Meningitis Osteomyelitis Peritonitis Pericarditis Wound infections Intravascular catheter infections Urinary catheter infections Urine?colonization vs infection Sputum?colonization vs infection ECDC. Candida auris in healthcare settings Europe. 19 Dec Khillan V et al. JMM Case Reports Sep 1;1(3): doi: /jmmcr.0.T00018 Schelenz S et al. Antimicrob Resist Infect Control Oct 19;5:35. Morales-López SE et al. Emerg Infect Dis Jan;23(1):

11 Potential associations / risk factors ICU / NICU admission Prematurity Surgery (especially abdominal) Intra-abdominal infection Central venous line Urinary Catheter Immunosuppression Diabetes mellitus Prior/current use of antifungals Prior/current use of broad spectrum antibiotics Prolonged hospital stay Schelenz S et al. Antimicrob Resist Infect Control Oct 19;5:35. Calvo B et al. J Infect Oct;73(4): Chowdhary A et al. J Hosp Infect Nov;94(3): Chowdhary A et al. Emerg Infect Dis Oct;19(10):

12 Potential associations / risk factors ICU / NICU admission Prematurity Surgery (especially abdominal) Immunosuppression Diabetes mellitus Prior/current use of antifungals Intra-abdominal infection Prior/current use of broad Central venous line spectrum antibiotics Urinary Catheter Prolonged hospital stay Prior hospitalization in other countries with known C. auris transmission (India, Pakistan, South Africa, and Venezuela) CDC. Candida auris Clinical Update - September Accessed 20 Nov Schelenz S et al. Antimicrob Resist Infect Control Oct 19;5:35. Calvo B et al. J Infect Oct;73(4): Chowdhary A et al. J Hosp Infect Nov;94(3): Chowdhary A et al. Emerg Infect Dis Oct;19(10):

13 A serious infection Series Region Cases Deaths Mortality Lockhart et al. India, Pakistan, Venezuela, South Africa % Vallabhaneni et al. USA % Chowdhary et al. India % Morales-López et al. Colombia % Calvo et al. Venezuela % Araúz et al. Panama 9 2 at 30 d [7] 22% at 30d [78%] Most cases in above series were fungaemia Overall mortality reported rather than attributable Lockhart SR et al. Clin Infect Dis Jan 15;64(2): Vallabhaneni S et al. MMWR Morb Mortal Wkly Rep Nov 11;65(44): Chowdhary A et al. Emerg Infect Dis Oct;19(10): Morales-López SE et al. Emerg Infect Dis Jan;23(1): Calvo B et al. J Infect Oct;73(4): Araúz AB et al. Mycoses Sep 25. doi: /myc [Epub ahead of print]

14 Candida auris features of concern multidrug-resistant difficult to identify with standard laboratory methods outbreaks in healthcare settings CDC, USA. Accessed 4 Mar 2017.

15 Drug resistance Drugs available for systemic treatment azoles (fluconazole, itraconazole, isavuconazole, posaconazole, and voriconazole) polyenes (conventional amphotericin B and its lipid formulations) echinocandins (anidulafungin, caspofungin, and micafungin pyrimidine analogue (flucytosine) No standard definition for MDR and XDR Candida spp. multidrug-resistant (MDR) = nonsusceptible to 1 agent in 2 drug classes extensively drug-resistant (XDR) = non-susceptible to 1 agent in 3 drug classes Arendrup MC et al. J Infect Dis Aug 15;216(suppl_3):S445-S451.

16 Drug resistance 54 isolates tested (Pakistan, India, South Africa, and Venezuela) 93% fluconazole resistant 54% voriconazole resistant 35% amphotericin B resistant 7% echinocandin resistant 6% flucytosine resistant 22 (41%) isolates were resistant to 2 classes of antifungals [ multi-drug resistant ] 2 (4%) isolates were resistant to fluconazole, voriconazole, echinocandins, and amphotericin Lockhart SR et al. Clin Infect Dis Jan 15;64(2): Clancy CJ et al. Clin Infect Dis Jan 15;64(2): CDC, USA. Accessed 6 Nov Public Health England Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris. London.

17 Drug resistance 54 isolates tested (several countries) 93% fluconazole resistant 54% voriconazole resistant 35% amphotericin B resistant 7% echinocandin resistant 6% flucytosine resistant CDC USA data 90% fluconazole resistant 30% amphotericin B resistant 5% echinocandin resistant 22 (41%) isolates were resistant to 2 classes of antifungals [ multi-drug resistant ] 2 (4%) isolates were resistant to fluconazole, voriconazole, echinocandins, and amphotericin Lockhart SR et al. Clin Infect Dis Jan 15;64(2): Clancy CJ et al. Clin Infect Dis Jan 15;64(2): CDC, USA. Accessed 6 Nov Public Health England Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris. London.

18 Antifungal treatment Optimal therapy unknown Empirical treatment : echinocandin at usual doses Drug Adult dosing Pediatric dosing [age 2 months] Anidulafungin loading dose 200 mg IV, then 100 mg IV daily not approved for use in children Caspofungin loading dose 70 mg IV, then 50 mg IV daily loading dose 70mg/m 2 /day IV, then 50mg/m 2 /day IV Micafungin 100 mg IV daily 2mg/kg/day IV; 4mg/kg/day IV in children over 40 kg Note: echinocandin resistance has emerged on serial isolates from a single patient after exposure to the drug Consider switching to or adding liposomal amphotericin B (5 mg/kg daily) if not clinically responding or has fungaemia for >5 days UK : nystatin and terbinafine active in vitro CDC, USA. Accessed 9 Nov Tsay S et a. Clin Infect Dis Aug 17. doi: /cid/cix744. [Epub ahead of print] Public Health England Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris (version 2). London.

19 Laboratory misidentification Isolate Species tested API 20C AUX BD Phoenix Vitek-2 MicroScan 1 C. auris R. glutinis C. catenulata C. haemulonii C. famata 2 C. auris R. glutinis C. haemulonii C. haemulonii C. famata 3 C. auris R. glutinis C. haemulonii C. haemulonii C. famata 4 C. auris R. glutinis C. haemulonii C. haemulonii C. lusitaniae 5 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii 6 C. auris R. glutinis C. haemulonii C. haemulonii C. famata 7 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii 8 C. auris R. glutinis C. haemulonii C. haemulonii C. parapsilosis 9 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii 10 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii Labs should use EITHER : matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) OR DNA sequencing of ITS region or D1-D2 region of the 28s rdna Mizusawa M et al. J Clin Microbiol Feb;55(2): CDC, USA. Accessed 20 Nov 2017.

20 Laboratory misidentification Isolate Species tested API 20C AUX BD Phoenix Vitek-2 MicroScan 1 C. auris R. glutinis C. catenulata C. haemulonii C. famata 2 C. auris R. glutinis C. haemulonii C. haemulonii C. famata 3 C. auris R. glutinis C. haemulonii C. haemulonii C. famata 4 C. auris R. glutinis C. haemulonii C. haemulonii C. lusitaniae 5 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii 6 C. auris R. glutinis C. haemulonii C. haemulonii C. famata 7 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii 8 C. auris R. glutinis C. haemulonii C. haemulonii C. parapsilosis 9 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii 10 C. auris R. glutinis C. haemulonii C. haemulonii C. guilliermondii Labs should use EITHER : matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) OR DNA sequencing of ITS region or D1-D2 region of the 28s rdna In-house multiplex realtime PCR method and melting-curve analysis recently published Mizusawa M et al. J Clin Microbiol Feb;55(2): CDC, USA. Accessed 20 Nov Kordalewska M et al. J Clin Microbiol Aug;55(8):

21 MALDI-TOF MS identification 102 clinical isolates from India previously identified as Candida haemulonii or Candida famata by Vitek 2 underwent ITS sequencing 90 isolates identified as C. auris 12 isolates identified as C. haemulonii (n = 6), C. haemulonii var. vulnera (n = 1), and C. duobushaemulonii (n= 5) ethanol-formic acid extraction procedure per manufacturer 100% identified as C. auris by MALDI Biotyper OC version 3.1 (Bruker Daltonics, Bremen, Germany) Score 1 st attempt = C. auris 2 nd attempt = C. auris Other species correct identity >2 77 (86%) (100%) >1.7 but <2 13 (14%) n/a n/a Kathuria S et al. J Clin Microbiol Jun; 53(6):

22 Laboratory suspicion of Candida auris [updated] if species level identity cannot be determined (significant isolates) Identification Method Vitek 2 YST API 20C BD Phoenix yeast identification system Microscan Organism C. auris can be misidentified as Candida haemulonii Candida duobushaemulonii Rhodotorula glutinis (characteristic red color not present) Candida sake Candida haemulonii Candida catenulate Candida famata Candida guilliermondii * Candida lusitaniae * Candida parapsilosis * CDC, USA. Accessed 6 Nov 2017.

23 Outbreaks in Healthcare settings Venezuela, India, S Korea, UK, US, Spain, Colombia, Israel, Oman UK outbreak : Royal Brompton Hospital first in Europe; n=50 Period : Apr 2015 Jul 2016 [ongoing] ICU / Cardiothoracic Unit (ICU Closure) 44 % (n = 22/50) of patients with possible or proven infection 18 % (n = 9/50) of patients with Candidemia contamination of the floor, trollies, radiators, windowsills, equipment monitors and key pads, and also one air sample cleaning / disinfection - sodium hypochlorite products and hydrogen peroxide vapour 3 month gap then recurrence Schelenz S et al Oct 19;5:35.

24 Transmission Direct contact with case Contact with contaminated environment Schelenz S et al Oct 19;5:35.

25 Environmental persistence C. auris suspended in Artificial Test Soil inoculated on plastic healthcare surface then dried; 25 C; 55 to 57% relative humidity Method to determine viability Culture Esterase activity Duration 14 days 28 days Compared to C. parapsilosis [known nosocomial infections] Shorter duration for culture Higher esterase activity Hospital study : C. auris persisted on dry linen and mattresses for up to seven days Welsh RM et al. J Clin Microbiol Oct;55(10): Biswal M et al. J Hosp Infect Sep 19. pii: S (17) doi: /j.jhin [Epub ahead of print]

26 Infection Control Recommendations, CDC (USA) Inpatient settings (acute care hospitals, long-term acute care hospitals, and nursing homes) Dialysis clinics and infusion centers Outpatient settings (e.g., primary care office, wound clinic, etc.) Home healthcare settings Home and family members Website : [Accessed 20 Nov 2017]

27 Infection Control Recommendations, PHE (UK) Candida auris: laboratory investigation, management and infection prevention and control Candida auris: infection control in community care settings Website: [Accessed 20 Nov 2017]

28 Management Single room & contact precautions for carriage or infection Contact tracing / outbreak investigation Surveillance / screening swabs (axilla, groin, other sites) Decolonization??? Environmental cleaning / decontamination Cohorting staff a single case in a healthcare facility should prompt an aggressive response and investigation Antifungal Stewardship Review of historical microbiology records Enhanced laboratory surveillance If > 1 case : environmental or healthcare worker sampling Outbreak : Point-prevalence surveys [Public Health Notification] Tsay S et al. Clin Infect Dis Aug 17. doi: /cid/cix744. [Epub ahead of print] CDC, USA. Accessed 4 Mar ECDC. Candida auris in healthcare settings Europe. 19 Dec Public Health England Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris. London.

29 Duration of Infection Control Precautions For as long as the person is colonized with C. auris Periodic reassessments for colonization (e.g., every 3 months) in positive patients Test swabs of the axilla and groin PLUS any previous culture-positive sites (e.g., urine and sputum) Patient should not be on antifungals active against C. auris within past one week Patient should not have had topical antiseptic (e.g., chlorhexidine) within past 48 hours If patient is negative, obtain at least one more negative assessment result 1 week later before discontinuing C. auris specific-infection control precautions CDC. Recommendations for Infection Control for Candida auris. Accessed 3 Nov 2017.

30 Duration of Infection Control Precautions For as long as the person is colonized with C. auris Periodic reassessments for colonization (e.g., every 3 months) in positive patients Test swabs of the axilla and groin PLUS any previous culture-positive sites (e.g., urine and sputum) Patient should not be on antifungals active against C. auris within past one week Patient should not have had topical antiseptic (e.g., chlorhexidine) within past 48 hours PHE If guidelines patient is : negative, There is currently obtain no at least evidence one to more support negative the de-isolation assessment of patients result found 1 week to be later colonised before infected discontinuing with C. C. auris auris as the specific-infection length of carriage is unknown. control precautions Public Health England Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris (ver 2). London. CDC. Recommendations for Infection Control for Candida auris. Accessed 3 Nov 2017.

31 Effectiveness of disinfectants Active Components Contact time (min) log 10 CFU reduction Sodium hypochlorite 0.65% 1 6 Sodium hypochlorite 0.39% 1 6 Sodium hypochlorite 0.825% when diluted 1 6 Peracetic acid 1200 parts per million, hydrogen peroxide <1%, acetic acid 3 5 to 6 Hydrogen peroxide 1.4% 1 6 Hydrogen peroxide 0.5% 10 5 to 6 Acetic acid >5% (ph 2.0) 3 4 to 5 Ethyl alcohol 29.4% to 3 Alkyl dimethyl benzyl ammonium chlorides 10 1 to 2 Didecyl dimethyl ammonium chloride, n-alkyl dimethyl benzyl ammonium chloride 10 1 Adapted from : Cadnum JL et al. Infect Control Hosp Epidemiol Oct;38(10):

32 In vitro efficacy of disinfectants / antiseptics Note : 4% chlorhexidine gluconate (i.e. the antimicrobial hand and body wash) diluted 1:1 failed to eliminate 4 C. auris and the C. albicans ATCC strains Moore G et al. J Hosp Infect Sep 1. pii: S (17) doi: /j.jhin [Epub ahead of print]

33 CDC recommendations environmental disinfection Thorough daily and terminal cleaning of patient s room and any mobile/shared equipment used Cleaning and disinfection of areas outside of their rooms where they receive care (e.g., radiology, physical therapy) Environmental Protection Agency registered hospitalgrade disinfectant effective against Clostridium difficile spores Quaternary ammonia compounds not sufficiently effective against C. auris After terminal cleaning with sodium hypochlorite based products, room sampling did not yield C. auris growth Tsay S et al. Clin Infect Dis Aug 17. doi: /cid/cix744. [Epub ahead of print] CDC, USA. Accessed 20 Nov 2017.

34 CDC recommendations environmental disinfection PHE guidelines : hypochlorite at 1000 ppm of available chlorine Thorough daily and terminal cleaning of patient s room and any mobile/shared equipment used Cleaning and disinfection of areas outside of their rooms where they receive care (e.g., radiology, physical therapy) Environmental Protection Agency registered hospitalgrade disinfectant effective against Clostridium difficile spores Public Health England Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris (ver 2). London. Quaternary ammonia compounds not sufficiently effective against C. auris After terminal cleaning with sodium hypochlorite based products, room sampling did not yield C. auris growth Tsay S et al. Clin Infect Dis Aug 17. doi: /cid/cix744. [Epub ahead of print] CDC, USA. Accessed 20 Nov 2017.

35 CDC recommendations hand hygiene alcohol-based hand rub or soap and water Tsay S et al. Clin Infect Dis Aug 17. doi: /cid/cix744. [Epub ahead of print]

36 CDC recommendations hand hygiene alcohol-based hand rub or soap and water PHE guidelines : soap and water followed by alcohol hand rub on dry hands Public Health England Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris (ver 2). London. Tsay S et al. Clin Infect Dis Aug 17. doi: /cid/cix744. [Epub ahead of print]

37 Unanswered questions Where did C. auris come from and why is it emerging now? What should salvage treatment consist of in cases where the organism is resistant to the 3 main classes of antifungals? How can C. auris colonization be rapidly detected? How long can a person remain colonized with C. auris? What methods are effective for reducing the burden of C. auris colonization? What are risk factors for infection in a patient colonized with C. auris? How effective are the recommended infection control strategies at containing C. auris? What is the prevalence of C. auris in the community and does transmission occur there? How rapidly and under what circumstances does C. auris become resistant to antifungal drugs? Tsay S et al. Clin Infect Dis Aug 17. doi: /cid/cix744. [Epub ahead of print]

38 Candida auris Summary Newly emerging multidrug-resistant pathogen High mortality Misidentified by conventional laboratory tests Healthcare-associated outbreaks, unlike C. albicans and other species Skin colonization and environmental persistence Prevention and containment - same interventions as for other multi-resistant organisms Treatment options limited Guidelines from overseas work in progress!

39 Thank you