Antifungal Susceptibility of Invasive Candida Isolates from Canadian - - PowerPoint PPT Presentation

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Antifungal Susceptibility of Invasive Candida Isolates from Canadian - - PowerPoint PPT Presentation

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1 Antifungal Susceptibility of Invasive Candida Isolates from Canadian Hospitals: Results of the CANWARD 2013 Study J. FULLER 1 , S. SHOKOPLES 1 , L. TURNBULL 1 , R. RENNIE 1 , H. ADAM 2,3 , M. BAXTER 2 , D. J. HOBAN 2,3 and G. G. ZHANEL 2 1

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Antifungal Susceptibility of Invasive Candida Isolates from Canadian Hospitals: Results of the CANWARD 2013 Study

  • J. FULLER1, S. SHOKOPLES1, L. TURNBULL1, R. RENNIE1, H. ADAM2,3,
  • M. BAXTER2, D. J. HOBAN2,3 and G. G. ZHANEL2

1 Provincial Laboratory, Alberta Health Services, University of Alberta,

Edmonton, AB; 2 Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB; 3 Diagnostic Services of Manitoba, Winnipeg, MB

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Candidemia

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Canadian Surveillance of Candidemia

  • Several published Canadian surveillance studies

– 2006 is the most recent study period reported – Most are single-centre, retrospective

  • Species distribution comparable to other studies and

unchanging

– C. albicans > C. glabrata > C. parapsilosis

  • Activitiy of antifungal agents in vitro were excellent

– No significant resistance issues identified with azoles and AmB – Echinocandins experience was limited (new class)

Claude-Labbe. CJIDMM 2009; St-Germain CJIDMM 2008;

  • Laupland. CID 2005; Karlowsky DMID 1997.
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CANWARD

  • A national population-based surveillance study of

pathogens and antimicrobial susceptibility in medical centres across Canada

– Coordinated out of HSC, University of Manitoba

  • Invasive Candida surveillance

– Characterize the species and MIC distribution of Candida spp. causing candidemia – 2007, 2010 – 2011 to 2013 – Central test site, University of Alberta Hospital, Edmonton

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Methods – CANWARD 2011 to 2015

  • Participating sites:

– Tertiary care medical centres from 8 provinces – 12 clinical laboratories

  • Isolate collection and inclusion:

– Candida isolated from automated blood cultures – Patients attending hospital clinics, emergency rooms, medical/surgical wards, and intensive care units

  • Antifungal susceptibility testing:

– CLSI M27-S4, Broth microdilution guidelines

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  • Dr. D. Roscoe – Vancouver Hospital, Vancouver
  • Dr. R. Rennie/J. Fuller – University of Alberta Hospital, Edmonton
  • Dr. J. Blondeau – Royal University Hospital, Saskatoon
  • Drs. D.J. Hoban/G.G. Zhanel – Health Sciences Centre, Winnipeg
  • Dr. M. John– London Health Sciences Centre, London
  • Dr. S. Poutanen – University Health Network / Mount Sinai Hospital, Toronto
  • Dr. L. Matukas – St. Michael’s Hospital, Toronto
  • Dr. F. Chan – Children’s Hospital of Eastern Ontario, Ottawa
  • Dr. M. Desjardins – The Ottawa Hospital, Ottawa
  • Dr. M. Laverdière – Hôpital Maisonneuve-Rosemont, Montreal
  • Dr. M. Goyette – CHRTR Pavillon Ste. Marie, Trois-Rivières
  • Dr. M. Kuhn – South East Regional Health Authority, Moncton
  • Dr. R. Davidson – Queen Elizabeth II HSC, Halifax

CANWARD Participating Investigators / Centres

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Temporal Distribution of the Most Common Candida Species Causing Candidemia

10 20 30 40 50 60 70 2011 (n=238) 2012 (n=290) 2013 (n=355) % Annual Total

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Geographic Distribution of Surveillance Isolates

5 10 15 20 25 30 35 40 NB/NS QC ON MB/SK AB/BC 2011 (n=238) 2012 (n=290) 2013 (n=355) % Annual Total

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Distribution of Candida Species Causing Candidemia Based on Patient Location

5 10 15 20 25 30 35 40 45 50 ICU Medicine Surgical Emergency Clinic 2011 (n=238) 2012 (n=290) 2013 (n=355) % Annual Total

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Rank Distribution of the Most Common Species by Ward per Year

0% 20% 40% 60% 80% 100%

2011 2012 2013

ICU

0% 20% 40% 60% 80% 100%

2011 2012 2013

Medicine

0% 20% 40% 60% 80% 100% 2011 2012 2013

Surgery

Other

  • C. dubliniensis
  • C. tropicalis
  • C. parapsilosis
  • C. glabrata
  • C. albicans
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Species

Agent

Year No. Tested Mode MIC90 Geom Mean CBP % Non- susceptible (#)

  • C. albicans

MICA 2011 145 0.015 0.015 0.015 <0.25 2012 159 0.007 0.007 0.007 <0.25 0.63 (1) 2013 181 0.007 0.007 0.008 <0.25 CASP 2011 145 0.015 0.06 0.021 <0.25 1.38 (2) 2012 159 0.03 0.125 0.038 <0.25 2013 181 0.007 0.125 0.03 <0.25 0.55 (1)

  • C. albicans MIC Distribution Summary
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Echinocandin MIC Distribution Against C. albicans

Year Agent Number of Isolates at MIC (no. tested)

0.007 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32

2011 MICA 144 1 (145) CASP 112 13 9 8 1 2 2012 MICA 152 5 1 1 (159) CASP 19 32 40 29 28 11 2013 MICA 163 13 4 1 (181) CASP 51 28 26 34 31 10 1

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Species

Agent

Year No. Tested Mode MIC90 Geom Mean CBP % Non- susceptible (#)

  • C. glabrata

MICA 2011 39 0.015 0.015 0.016 <0.06 2.56 (1) 2012 49 0.007 0.015 0.010 <0.06 2013 74 0.007 0.015 0.011 <0.06 6.76 (5) CASP 2011 39 0.25 0.5 0.166 <0.12 2012 49 0.25 0.5 0.261 <0.12 2013 74 0.25 0.5 0.254 <0.12

  • C. glabrata MIC Distribution Summary
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Echinocandin MIC Distribution Against C. glabrata

Year Agent Number of Isolates at MIC (no. tested)

0.007 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32

2011 MICA 37 1 1 (39) CASP 2 2 1 12 17 4 1 2012 MICA 38 8 3 (49) CASP 1 1 2 1 29 14 1 2013 MICA 55 12 2 2 2 1 (74) CASP 1 1 1 12 42 12 4 1

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Interlaboratory Variability of Caspofungin MICs for Candida Species

  • Unacceptably high interlaboratory variation in caspofungin

MIC values for Candida species increasingly being reported

– Modal MIC values differ by up to 5 doubling dilutions – Effect most severe with C. glabrata

  • Source of variation has yet to be identified

– Limited number of laboratories contributing to MIC data pool used for CBP analysis likely prevented earlier discovery

  • Evidence sufficient to allow micafungin as surrogate

marker to predict susceptibility

Pfaller et al. JCM. 2014;52:108-114. Espinel-Ingroff et al. AAC. 2013;57:5836-5842.

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Species

Agent

Year No. Tested Mode MIC90 Geom Mean CBP % Non- susceptible (#)

  • C. albicans

FLUC 2011 145 0.125 0.25 0.149 <2 1.38 (2) 2012 159 0.125 0.25 0.175 <2 1.26 (2) 2013 181 0.125 0.25 0.147 <2 VORI 2011 145 0.015 0.015 0.018 <0.12 1.38 (2) 2012 159 0.015 0.015 0.016 <0.12 0.63 (1) 2013 181 0.015 0.015 0.016 <0.12

  • C. albicans MIC Distribution Summary
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Azole MIC Distribution Against C. albicans

Year Agent Number of Isolates at MIC (no. tested)

0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 >64

2011 FLUC 15 109 12 3 1 3 2 (145) VORI 138 4 1 2 2012 FLUC 5 86 63 3 1 1 (159) VORI 153 3 2 1 2013 FLUC 17 110 49 4 1 (181) VORI 170 9 2

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Species

Agent

Year No. Tested Mode MIC90 Geom Mean CBP (ECV) % Non- susceptible (#)

  • C. glabrata

FLUC 2011 39 4 4 1.79 <32 2012 49 2 8 2.65 <32 2013 74 2 4 2.78 <32 4.05 (3) VORI 2011 39 0.06 0.25 0.079 (<0.5) 2.56 (1) 2012 49 0.125 0.25 0.125 (<0.5) 2.04 (1) 2013 74 0.06 0.25 0.100 (<0.5) 8.11 (6)

  • C. glabrata MIC Distribution Summary
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Azole MIC Distribution Against C. glabrata

Year Agent Number of Isolates at MIC (no. tested)

0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64

2011 FLUC 1 4 4 2 10 15 1 2 (39) VORI 4 6 12 10 3 3 1 2012 FLUC 1 2 4 18 18 5 1 (49) VORI 1 3 12 19 12 1 1 2013 FLUC 2 2 5 8 24 20 3 2 5 3 (74) VORI 5 9 26 18 5 5 3 3

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20 50 100 150 200 250 0.03 0.06 0.125 0.25 0.5 1 2 4

  • C. albicans
  • C. glabrata

Amphotericin B MIC Distribution Against

  • C. albicans and C. glabrata

ECOFF <2 mg/L Ca, n=485; Cg, n= 162

MIC (mg/L)

  • No. isolates
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21 10 20 30 40 50 60 0.007 0.015 0.03 0.06 0.125 0.25 0.5 1 2 4 CASP MICA

Echinocandin MIC Distribution Against

  • C. parapsilosis

n=104 isolates

MIC (mg/L)

  • No. isolates
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Azole MIC Distribution Against C. parapsilosis

n=104 isolates

MIC (mg/L)

  • No. isolates

10 20 30 40 50 60 70 80 90 0.015 0.03 0.06 0.125 0.25 0.5 1 2 4 FLUC VORI 2 1

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Less Common Candida Species

  • C. tropicalis, C. dubliniensis, C. krusei, C. lusitaniae

identified in surveillance (<5% prevalence each)

  • Numbers are too small to identify trends or changes
  • Fully susceptible or within the wild-type population
  • It remains important to follow these less common

species

– Selection pressures of antifungal practices may promote species expansion

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CANWARD - Total Candida Resistance

2011-13 Overall Resistance (%) Species Fluconazole Voriconazole Micafungin Ampho B

  • C. albicans

0.83 0.62 0.20

  • C. glabrata

1.85 (4.94) 3.70

  • C. parapsilosis

1.92 0.96

  • Antifungal activities of azoles and echinocandins are high against

the most common causes of candidemia in Canada

  • C. glabrata and resistance will be important for continued

surveillance

  • MIC distributions are normal with unchanging mode and geometric

mean values (wild-type population)

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Summary

  • CANWARD 3-year surveillance has collected ~900

Candida isolates bloodstream infections

  • Species prevalence indicates that the epidemiology has

not significantly changed

  • MIC results confirm that activity of available antifungals

remains excellent

  • Azole and echinocandin resistance in C. glabrata

warrants continued surveillance

  • CBP revisions have improved the quality of antifungal

susceptibility testing, detection of resistance, and clinical relevance of laboratory results for the treating physician

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CANWARD Candidemia is supported, in part, by grant support from Astellas