CANDIDA AURIS: DETECTION, PREVENTION
AND MANAGEMENT
Dr. Siddhartha Chakraborty
DrNB PDT (CCM)
AMRI, Dhakuria
Background
• Candida auris has emerged as serious threat to health care
system over last decade causing serious invasive fungal
infection and nosocomial outbreaks.
• Due rapid and easy transmission, environmental
contamination with resilience to heat and disinfection-
develop antifungal resistance and high mortality (23-72%).
• 2nd rank among the critical pathogens in WHO fungal
pathogen priority list (FPPL)
• The contemporary challenges specially in India:
1. Recently C.auris emerged as 1st rank among fungal blood isolates
in some indian ICUs
2. Rate of C.auris candidemia increased during COVID 19 pandemic
due to compromise of infection control practice (ICP)
3. Unmet need for rapid and accurate test for detection of C.auris
in routine laboratory
4. Emerging echinocandin resistance
Resistance Mechanism
Detection of Candida Auris
• Challenges:
1. Easily grows in routine culture but difficult to identify
2. Biochemical function of C.auris which form the basis of
identication by commercial systems, are nondistinct and overlap
with other closely related specieces
3. C.auris has 4 distinct clades along with possible 5th one in Iran
4. C.auris was not incorporated in any of the database of
commercial identification sytem
5. Many commercial system (API, Microscan, BD Pheonix and Vitek
2 YST) gives erroneous results.
Upgraded Vitek 2 YST version 8 can identify clade IV but not I and III
Detection of Candida Auris
1. Commercial Identification
systems
2. Chromogenic agar
3. MALDI TOF MS (Matrix-
associated laser desorption
ionization time – of – flight
mass spectrometry)
4. Molecular tests
Chromogenic Agar
• CHROMagar Candida plus (France) and HiCrome C.auris MDR
selective agar (India): can reliably detect C.auris with few false
positive reactions by Candida pseudohaemulonii and Candida
vulturna.
• Modification of CHROMagar:
1. Incorporation of Pal’s medium- differentiate between Candida
pseudohaemulonii and Candida auris
2. Yeast extract peptone dextrose (YPD) with 12.5 % salt, ferrous
sulphate
3. Enrichment broth with 10% salt, crystal violet and mannitol
MALDI TOF MS
• One of the most efficient techniques: shortest turn around
time (<1 hr from culture) in comparison to conventional and
molecular test
• Expensive
• MC type: Biotyper and Vitek MS
Molecular tests
• Most accurate: sequencing of internal transcribed spacer (ITS)
region or D1-D2 subunit of 28S- expensive and time consuming
• Type:
1. PCR- simpliest
2. RT PCR- highly sensitive and specific, more expensive than PCR
3. LAMP (Loop mediated isothermal amplification)
4. Commercial molecular kit (AurisID Real time, Fungiplex Real
Time etc)
Detection of colonization
• High risk patients: critically ill, prolong hospital stay, contacts
with known case
• Swab from nares, axilla, groin: inoculation onto Sabouraud’s
broth
• Auris ID (olm Diagnostic) real time PCR detect C.auris
colonization within 1.5hrs
Detection of antifungal resistance
• Fluconazole resistance: Clade I – 97%, Clade II- 11 to 14%,
CladeIII- 60-80%, Clade IV- 11%
• Clade I- 49% isolates MDR to fluconazole, voriconazole and/or
Amphotericin B
• Major challenge : lack of break point
• CDC provided a tentative breakpoint based on MIC, animal study,
molecular characterization of resistance conferring gene- but not
endorsed by Clinical and Laboratory Standard Institute (CLSI)
PREVENTION
Prevention of Candida Auris
A] Preventing C. auris from entering the ICU
a) Proactive screening
b) Augmentation of Infection control practice (ICP)
B] To get rid of already existing C. auris in ICU
a) Isolates
b) Clean the environment
c) Decolonization
d) Educate and re-educate
Preventing C. auris from entering the ICU
a) Proactive screening:
• All candida isolated from sterile or nonsterile site should be
identified upto species level (if clinically indicated)
• Close health care contacts of C.auris patients and new patients
referred from facility reporting C.auris should be subjected to
screening by surveillance swab
b) Augmentation of ICP:
• Contact precautions, transmission based precautions, cleaning of
medical equipment in between patients, personal protective
precautions and hand hygiene.
• Care bundle for blood and urinary catheter
To get rid of already existing C. auris in ICU
a)Isolation and notification of all C.auris case
b) Clean the environment
• Using 1000 ppm sodium hypochlorite
• Environmental sampling for isolation C.auris
• C.auris patients should be last in queue for imaging/surgery,
followed by terminal cleaning
c) Decolonization
• No valid protocol
• Try Chlorhexidine body wash, oral wash and gurgle
d) Educate and re-educate
All health stuff
MANAGEMENT
Management of C.auris Infection
A] Management of invasive disease
B] Management of C.auris UTI
C] Management of colonization
D] Newer therapy
Management of invasive disease
• Issues:
1. Predisposition toward critically ill patients
2. High anti fungal resistance
3. Absence of clinical breakpoint for MIC
4. No randomized controlled studies on efficacy of antifungal
agents
5. Prone to therapeutic failure and high mortality
• Current Drug of choice: Echinocandins
1. Caspofungin:
• Adults: 70mg IV loading  50mg IV OD
• Paed (>2 months): 70mg/m2 IV loading  50mg/m2 IV OD
• Infants (<2months): 25mg/m2/day IV
2. Micafungin:
• Adults: 100mg/day IV
• Paed (>2 months): 2-4 mg/kg/day IV
• Infants (<2months): 10mg/kg/day IV
3. Anidulafungin:
• Adults: 200mg IV loading  100mg/day
4. Liposomal Amphotericin B: If no clinical response/ persistent
candidemia for > 5days  5mg/kg/day IV
5. Azoles: Posaconazole and Isavuconazole (If susceptibility
confirmed by testing only)
Management of C.auris UTI
• Echinocandin monotherapy: insufficient  relapse and
resistance
• Caspofungin and Anidulafungin may not achieve sufficient
urinary concentration
• Combination therapy:
1. Micafungin plus Amphotericin B
2. Triazole and Micafungin
3. Amphotericin and Flucytosine
• Bladder irrigation with Amphotericin B for resistant infection
Management Of Colonization
• CDC does not recommend treating C.auris colonization
(Isolation from nonsterile sites in absence of invasive disease)
• Strict ICP to be maintained to prevent invasive disease
(catheter bandle, ventilator care bundle, periodic monitoring,
meticulous skin preparation for surgery and antifungal
stewardship)
Newer Therapy
• Role of combination therapy in case of CNS infection
o Micafungin with voriconazole
o 5- flucytosine with voriconazole/amphotericine B
o Sulfamethoxazole with voriconazole/itraconazole
o Alternative agents including antimicrobial peptides,nanoparticles,
natural compounds of quotum sensing, plant products etc
• Newer Antifungal:
1. Ibrexafungerp (Glucan synthase inhibitor)- FDA approved for
vulvovaginal candidiasis
2. Rezafungin – lower MIC against C. auris
3. PC945- topical agent, potent than Posaconazole and
Voriconazole in vitro
THANK YOU

Candida Auris Detection, Prevention and Management.pdf

  • 1.
    CANDIDA AURIS: DETECTION,PREVENTION AND MANAGEMENT Dr. Siddhartha Chakraborty DrNB PDT (CCM) AMRI, Dhakuria
  • 2.
    Background • Candida aurishas emerged as serious threat to health care system over last decade causing serious invasive fungal infection and nosocomial outbreaks. • Due rapid and easy transmission, environmental contamination with resilience to heat and disinfection- develop antifungal resistance and high mortality (23-72%). • 2nd rank among the critical pathogens in WHO fungal pathogen priority list (FPPL)
  • 7.
    • The contemporarychallenges specially in India: 1. Recently C.auris emerged as 1st rank among fungal blood isolates in some indian ICUs 2. Rate of C.auris candidemia increased during COVID 19 pandemic due to compromise of infection control practice (ICP) 3. Unmet need for rapid and accurate test for detection of C.auris in routine laboratory 4. Emerging echinocandin resistance
  • 8.
  • 9.
    Detection of CandidaAuris • Challenges: 1. Easily grows in routine culture but difficult to identify 2. Biochemical function of C.auris which form the basis of identication by commercial systems, are nondistinct and overlap with other closely related specieces 3. C.auris has 4 distinct clades along with possible 5th one in Iran 4. C.auris was not incorporated in any of the database of commercial identification sytem 5. Many commercial system (API, Microscan, BD Pheonix and Vitek 2 YST) gives erroneous results. Upgraded Vitek 2 YST version 8 can identify clade IV but not I and III
  • 12.
    Detection of CandidaAuris 1. Commercial Identification systems 2. Chromogenic agar 3. MALDI TOF MS (Matrix- associated laser desorption ionization time – of – flight mass spectrometry) 4. Molecular tests
  • 13.
    Chromogenic Agar • CHROMagarCandida plus (France) and HiCrome C.auris MDR selective agar (India): can reliably detect C.auris with few false positive reactions by Candida pseudohaemulonii and Candida vulturna. • Modification of CHROMagar: 1. Incorporation of Pal’s medium- differentiate between Candida pseudohaemulonii and Candida auris 2. Yeast extract peptone dextrose (YPD) with 12.5 % salt, ferrous sulphate 3. Enrichment broth with 10% salt, crystal violet and mannitol
  • 15.
    MALDI TOF MS •One of the most efficient techniques: shortest turn around time (<1 hr from culture) in comparison to conventional and molecular test • Expensive • MC type: Biotyper and Vitek MS
  • 16.
    Molecular tests • Mostaccurate: sequencing of internal transcribed spacer (ITS) region or D1-D2 subunit of 28S- expensive and time consuming • Type: 1. PCR- simpliest 2. RT PCR- highly sensitive and specific, more expensive than PCR 3. LAMP (Loop mediated isothermal amplification) 4. Commercial molecular kit (AurisID Real time, Fungiplex Real Time etc)
  • 18.
    Detection of colonization •High risk patients: critically ill, prolong hospital stay, contacts with known case • Swab from nares, axilla, groin: inoculation onto Sabouraud’s broth • Auris ID (olm Diagnostic) real time PCR detect C.auris colonization within 1.5hrs
  • 20.
    Detection of antifungalresistance • Fluconazole resistance: Clade I – 97%, Clade II- 11 to 14%, CladeIII- 60-80%, Clade IV- 11% • Clade I- 49% isolates MDR to fluconazole, voriconazole and/or Amphotericin B • Major challenge : lack of break point • CDC provided a tentative breakpoint based on MIC, animal study, molecular characterization of resistance conferring gene- but not endorsed by Clinical and Laboratory Standard Institute (CLSI)
  • 22.
  • 23.
    Prevention of CandidaAuris A] Preventing C. auris from entering the ICU a) Proactive screening b) Augmentation of Infection control practice (ICP) B] To get rid of already existing C. auris in ICU a) Isolates b) Clean the environment c) Decolonization d) Educate and re-educate
  • 24.
    Preventing C. aurisfrom entering the ICU a) Proactive screening: • All candida isolated from sterile or nonsterile site should be identified upto species level (if clinically indicated) • Close health care contacts of C.auris patients and new patients referred from facility reporting C.auris should be subjected to screening by surveillance swab b) Augmentation of ICP: • Contact precautions, transmission based precautions, cleaning of medical equipment in between patients, personal protective precautions and hand hygiene. • Care bundle for blood and urinary catheter
  • 25.
    To get ridof already existing C. auris in ICU a)Isolation and notification of all C.auris case b) Clean the environment • Using 1000 ppm sodium hypochlorite • Environmental sampling for isolation C.auris • C.auris patients should be last in queue for imaging/surgery, followed by terminal cleaning c) Decolonization • No valid protocol • Try Chlorhexidine body wash, oral wash and gurgle d) Educate and re-educate All health stuff
  • 27.
  • 28.
    Management of C.aurisInfection A] Management of invasive disease B] Management of C.auris UTI C] Management of colonization D] Newer therapy
  • 29.
    Management of invasivedisease • Issues: 1. Predisposition toward critically ill patients 2. High anti fungal resistance 3. Absence of clinical breakpoint for MIC 4. No randomized controlled studies on efficacy of antifungal agents 5. Prone to therapeutic failure and high mortality • Current Drug of choice: Echinocandins
  • 31.
    1. Caspofungin: • Adults:70mg IV loading  50mg IV OD • Paed (>2 months): 70mg/m2 IV loading  50mg/m2 IV OD • Infants (<2months): 25mg/m2/day IV 2. Micafungin: • Adults: 100mg/day IV • Paed (>2 months): 2-4 mg/kg/day IV • Infants (<2months): 10mg/kg/day IV 3. Anidulafungin: • Adults: 200mg IV loading  100mg/day 4. Liposomal Amphotericin B: If no clinical response/ persistent candidemia for > 5days  5mg/kg/day IV 5. Azoles: Posaconazole and Isavuconazole (If susceptibility confirmed by testing only)
  • 32.
    Management of C.aurisUTI • Echinocandin monotherapy: insufficient  relapse and resistance • Caspofungin and Anidulafungin may not achieve sufficient urinary concentration • Combination therapy: 1. Micafungin plus Amphotericin B 2. Triazole and Micafungin 3. Amphotericin and Flucytosine • Bladder irrigation with Amphotericin B for resistant infection
  • 33.
    Management Of Colonization •CDC does not recommend treating C.auris colonization (Isolation from nonsterile sites in absence of invasive disease) • Strict ICP to be maintained to prevent invasive disease (catheter bandle, ventilator care bundle, periodic monitoring, meticulous skin preparation for surgery and antifungal stewardship)
  • 34.
    Newer Therapy • Roleof combination therapy in case of CNS infection o Micafungin with voriconazole o 5- flucytosine with voriconazole/amphotericine B o Sulfamethoxazole with voriconazole/itraconazole o Alternative agents including antimicrobial peptides,nanoparticles, natural compounds of quotum sensing, plant products etc
  • 35.
    • Newer Antifungal: 1.Ibrexafungerp (Glucan synthase inhibitor)- FDA approved for vulvovaginal candidiasis 2. Rezafungin – lower MIC against C. auris 3. PC945- topical agent, potent than Posaconazole and Voriconazole in vitro
  • 41.