Antifungal Susceptibility of Respiratory Aspergillus Isolates from - - PowerPoint PPT Presentation

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Antifungal Susceptibility of Respiratory Aspergillus Isolates from - - PowerPoint PPT Presentation

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1 Antifungal Susceptibility of Respiratory Aspergillus 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

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Antifungal Susceptibility of Respiratory Aspergillus 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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Invasive Aspergillosis

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Aspergillus Resistance – Current Knowledge

  • A. fumigatus is the most prevalent species (~70%)
  • A. flavus, A. niger, A. terreus are increasing
  • Antifungal resistance in Aspergillus is ‘rare’
  • No published Canadian surveillance studies
  • ID and susceptibility testing is not standard practice
  • ECOFF (ECVs) values available for common species

– Based on MIC, identify isolates that are less likely to be clinically susceptible to treatment with a specific antimicrobial agent due to acquired resistance mechanisms

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Aspergillus Resistance – Current Knowledge

  • Azole R in A. fumigatus is increasing, particularly in

Europe and Asia; estimated at 3-6% globally

– Correlates to the intensity of fungicide use in agriculture

  • de novo selection of azole resistance on therapy is

increasingly being reported in A. fumigatus, A. flavus, and A. terreus

  • Intrinsic azole R in A. calidoustus, A. lentulus, and A.

pseudofisheri

  • Reduced activity of AmB against A. flavus and A. terreus
  • Echinocandins and MEC challenge in vitro detection of R
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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

  • Respiratory Aspergillus surveillance

– Characterize the species and MIC distribution of Aspergillus spp. – 2012 to 2013 – Central test site, University of Alberta Hospital, Edmonton

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Methods – CANWARD 2012 to 2016

  • Participating sites:

– Tertiary care medical centres from 8 provinces – 13 clinical laboratories

  • Isolate collection and inclusion:

– Aspergillus isolated from clinical specimens; respiratory – Patients attending hospital clinics, emergency rooms, medical/surgical wards, and intensive care units

  • Antifungal susceptibility testing:

– CLSI M38, Broth microdilution guidelines

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  • Dr. D. Roscoe – Vancouver Hospital, Vancouver
  • Dr. J. Fuller – University of Alberta Hospital, Edmonton
  • Dr. J. Blondeau – Royal University Hospital, Saskatoon
  • Dr. D.J. Hoban, Dr. G.G. Zhanel – Health Sciences Centre, Winnipeg
  • 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. R. Pelletier – CHU de Québec, l'Hôtel-Dieu, Quebec City
  • 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

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Temporal Distribution of the Most Common Aspergillus Species Isolated

% Annual Total 10 20 30 40 50 60 70 80 2012 (n=563) 2013 (n=692)

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Geographic Distribution of Surveillance Isolates

% Annual Total 5 10 15 20 25 30 35 40 45 50 NB/NS QC ON MB/SK AB/BC 2012 (n=563) 2013 (n=692)

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Distribution of Aspergillus Species Based on Patient Location

% Annual Total 10 20 30 40 50 60 70 2012 (n=563) 2013 (n=692)

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Agent Year No. Tested Mode MIC90 Geom Mean ECV % Non- wildtype (#) VORI 2013 480 0.5 0.5 0.479 <1 1 (5) 2012 418 0.5 1 0.486 <1 0.7 (3) POSA 2013 480 0.06 0.125 0.076 <0.5 2012 418 0.12 0.25 0.198 <0.5 ITRA 2013 480 0.5 0.5 0.369 <1 2012 418 0.5 0.5 0.432 <1

Azole MIC Distribution Against A. fumigatus

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Voriconazole MIC Distribution Against A. fumigatus

50 100 150 200 250 300 350 400 0.06 0.125 0.25 0.5 1 2 4 8 16 2013 2012 MIC (mg/L)

  • No. Isolates

ECOFF: <1 mg/L

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Echinocandin MIC Distribution Against A. fumigatus

Agent Year No. Tested Mode MIC90 Geom Mean ECV % Non- wildtype (#) CASP 2013 480 0.12 0.25 0.135 <0.5 2012 418 0.25 0.5 0.215 <0.5 0.7 (3) MICA 2013 480 0.007 0.015 0.008

  • 2012

418 0.007 0.015 0.008

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Caspofungin MIC Distribution Against A. fumigatus

MIC (mg/L)

  • No. Isolates

ECOFF: <0.5 mg/L 50 100 150 200 250 300 350 400 450 0.007 0.015 0.03 0.06 0.125 0.25 0.5 1 2013 2012

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Caspofungin and Micafungin MIC Distribution Against A. fumigatus

MIC (mg/L)

  • No. Isolates

50 100 150 200 250 300 350 400 450 0.007 0.015 0.03 0.06 0.125 0.25 0.5 1 CASP 2013 CASP 2012 MICA 2013 MICA 2012

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Agent Year No. Tested Mode MIC90 Geom Mean ECV % Non- wildtype (#) VORI 2013 74 1 2 0.614 <2 4.1 (3) 2012 55 0.5 1 0.619 <2 POSA 2013 74 0.12 0.5 0.177 <0.5 4.1 (3) 2012 55 0.25 0.5 0.212 <0.5 1.8 (1) ITRA 2013 74 0.5 1 0.769 <2 6.8 (5) 2012 55 1 2 0.617 <2 1.7 (1)

Azole MIC Distribution Against A. niger

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Echinocandin MIC Distribution Against A. niger

Agent Year No. Tested Mode MIC90 Geom Mean ECV % Non- wildtype (#) CASP 2013 74 0.12 0.12 0.119 <0.25 2012 55 0.12 0.25 0.117 <0.25 1.7 (1) MICA 2013 74 0.007 0.007 0.007

  • 2012

55 0.007 0.007 0.007

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Agent Year No. Tested Mode MIC90 Geom Mean ECV % Non- wildtype (#) VORI 2013 61 1 2 1.050 <2 4.9 (3) 2012 43 1 2 1.033 <2 4.7 (2) POSA 2013 61 0.25 1 0.173 <1 2012 43 0.25 0.5 0.178 <1 ITRA 2013 61 0.5 1 0.368 <1 2012 43 0.5 1 0.436 <1

Azole MIC Distribution Against A. flavus

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Echinocandin MIC Distribution Against A. flavus

Agent Year No. Tested Mode MIC90 Geom Mean ECV % Non- wildtype (#) CASP 2013 61 0.12 0.25 0.129 <0.25 4.9 (3) 2012 43 0.12 0.25 0.174 <0.25 6.7 (3) MICA 2013 61 0.007 0.03 0.010

  • 2012

43 0.007 0.03 0.008

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Amphotericin B MIC Distribution Against

  • A. fumigatus

ECOFF: <2 mg/L MIC (mg/L)

  • No. Isolates

50 100 150 200 250 300 0.06 0.125 0.25 0.5 1 2

  • A. fumigatus
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21 5 10 15 20 25 30 35 40 45 0.03 0.06 0.125 0.25 0.5 1 2 4 8

  • A. niger
  • A. flavus
  • A. terreus

Amphotericin B MIC Distribution Against Uncommon Aspergillus Species

ECOFF: <2 mg/L for A. niger, A. flavus; <4 mg/L A. terreus MIC (mg/L)

  • No. Isolates
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  • A. calidoustus
  • Intrinsically resistant to azoles
  • ~50% resistant to caspofungin
  • Possible emergence linked to azole prophylaxis and lung

transplant patients CANWARD

  • 2013 - 12 isolates from 5 laboratory sites

– Azole MICs >16 mg/L – Caspofungin MECs >4 mg/L for 5 isolates

  • 2012 – 4 isolates submitted

Egli, Fuller, et al. 2012. Transplant. 2012; 94(4):403.

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CANWARD - Aspergillus Resistance Rates

2013 Overall Resistance (%) Species VORI POSA ITRA CASPO MICA AMB

  • A. fumigatus

1 (0)

  • A. flavus

4.9 4.9 (0)

  • A. niger

4.1 4.1 6.8 (0)

  • Antifungal activities of azoles and echinocandins are high against

the most common species of Aspergillus in Canada

  • Overall azole resistance (all isolates) was 4.5%
  • A. flavus (and A. calidoustus) azole resistance will be important for

continued surveillance

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Summary

  • Species prevalence indicates that the epidemiology has

not significantly changed

  • MIC results confirm that activity of available antifungals

remains excellent

  • ECOFFs discriminate non-wildtype isolates against

azoles, amphotericin B, and caspofungin

  • Reference method and ECOFFs provide tool for

surveillance and detection of emergent acquired resistance

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CANWARD Aspergillus is supported, in part, by grant support from Astellas and Pfizer