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

▶
antifungal susceptibility of aspergillus isolates from
SMART_READER_LITE
LIVE PREVIEW

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

Feb 17, 2024 602 likes •871 views

1 Antifungal Susceptibility of Aspergillus Isolates from the Respiratory Tract of Patients in Canadian Hospitals: Results of the CANWARD 2016 Study. J. FULLER 1,3 , A. BULL 2 , S. SHOKOPLES 2 , T.C. DINGLE 2,3 , H. ADAM 4,5 , M. BAXTER 4 , D. J.

slide-1
SLIDE 1

1

Antifungal Susceptibility of Aspergillus Isolates from the Respiratory Tract of Patients in Canadian Hospitals: Results of the CANWARD 2016 Study.

  • J. FULLER1,3, A. BULL2, S. SHOKOPLES2, T.C. DINGLE2,3, H. ADAM4,5,
  • M. BAXTER4, D. J. HOBAN4,5 and G. G. ZHANEL4

1 Pathology and Laboratory Medicine, Western University, London, ON; 2 Provincial Laboratory,

Alberta Health Services, Edmonton, AB; 3 Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB; 4 Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB; 5 Diagnostic Services of Manitoba, Winnipeg, MB.

slide-2
SLIDE 2

2

COI Disclosures

Research Grants

  • Astellas
  • Merck
  • Pfizer

2

slide-3
SLIDE 3

3

Aspergillus Disease in Canada

  • 2nd most common cause of invasive fungal infection

– Predominantly invasive pulmonary disease – Estimated 1.6 cases of IA per 100,000 population – 5 to 13% incidence in HSCT and haematological malignancy patients and 25% attributable mortality

  • Non-invasive pulmonary aspergillosis

– 381.8 cases per 100,000 population

  • A. fumigatus >>> A. flavus / A. niger

Dufresne et al. EJCMID.2017;36:987-992. Haider. AMMI-CACMID 2015. Haider, et al. CJIDMM. 2014;25(1):17-23.

slide-4
SLIDE 4

4

Aspergillus Antifungal Susceptibility Testing

  • Species ID and susceptibility testing is not routine

– Recent improvements in MS-ID technology and CLSI standards have reduced challenges for clinical laboratories

  • Epidemiological cutoff values (ECV) available for

common species (microbiological breakpoints)

– CLSI M59 2nd edition, M61 1st edition – Distinguish wild-type MICs from abnormally elevated MICs, indicative of acquired resistance – ECVs have no correlation to clinical response to therapy but, in the absence of clinical breakpoints, are critical for antifungal resistance surveillance

slide-5
SLIDE 5

5

Aspergillus Epidemiology and Resistance

  • Increasing reports of azole resistance in A. fumigatus

– 3 to 30% in Europe, Asia, and Middle East – Environmental association (intensity of agricultural fungicide use) – Not associated with prolonged therapeutic exposure to azoles

  • Increases in azole resistant A. flavus and A. terreus
  • Intrinsic azole resistance in A. calidoustus, A. lentulus,

and A. pseudofisheri

  • Standardized surveillance needs driven by limited

understanding of resistance implications and treatment

  • ptions

Resendiz Sharpe et al. Med Mycol. 2018;56:S83-S92 Hagiwara et al. Front Micro. 2016;7:

slide-6
SLIDE 6

6

CANWARD

  • A national population-based surveillance study of pathogens and

antimicrobial susceptibility in hospitals across Canada

– Coordinated out of Health Sciences Centre, University of Manitoba

  • Aspergillus surveillance

– Characterize species and MIC distribution of Aspergillus spp. from respiratory specimens – Determine the rate of azole resistance

  • Participating sites:

– 15 clinical laboratories at tertiary care hospitals from 8 provinces – Isolates collected from patients admitted to hospital clinics, emergency rooms, medical/surgical wards, and intensive care units – Coordinated out of University of Alberta, Edmonton

slide-7
SLIDE 7

7

CANWARD Participating Investigators

  • D. Roscoe – Vancouver Hospital, Vancouver
  • J. Fuller – University of Alberta Hospital, Edmonton
  • J. Blondeau – Royal University Hospital, Saskatoon
  • D. Hoban, G. Zhanel – Health Sciences Centre,

Winnipeg

  • M. John – London Health Sciences Centre, London
  • S. Poutanen – University Health Network / Mount

Sinai Hospital, Toronto

  • L. Matukas – St. Michael’s Hospital, Toronto
  • R. Davidson – Queen Elizabeth II HSC, Halifax
  • M. Laverdière – Hôpital Maisonneuve-Rosemont,

Montreal

  • R. Pelletier – CHU de Québec, l'Hôtel-Dieu, Quebec
  • M. Goyette – CHRTR Pavillon Ste. Marie, Trois-

Rivières

  • M. Bergevin - Hôpital de la Cité-de-la-Santé, Laval
  • C. Ellis, Moncton Hospital, Moncton
  • B. Toye – Children’s Hospital of Eastern Ontario,

Ottawa

  • D. Roscoe – Vancouver Hospital, Vancouver
  • J. Fuller – University of Alberta Hospital, Edmonton
  • J. Blondeau – Royal University Hospital, Saskatoon
  • D. Hoban, G. Zhanel – Health Sciences Centre,

Winnipeg

  • M. John – London Health Sciences Centre, London
  • S. Poutanen – University Health Network / Mount

Sinai Hospital, Toronto

  • L. Matukas – St. Michael’s Hospital, Toronto
  • R. Davidson – Queen Elizabeth II HSC, Halifax
  • M. Laverdière – Hôpital Maisonneuve-Rosemont,

Montreal

  • R. Pelletier – CHU de Québec, l'Hôtel-Dieu, Quebec
  • M. Goyette – CHRTR Pavillon Ste. Marie, Trois-

Rivières

  • M. Bergevin - Hôpital de la Cité-de-la-Santé, Laval
  • C. Ellis, Moncton Hospital, Moncton
  • B. Toye – Children’s Hospital of Eastern Ontario,

Ottawa

slide-8
SLIDE 8

8

2016 Patient Demographics

8

Patient Characteristics

  • No. (%)

Mean age 55.1 <18 years 35 (7.7) 18 – 65 years 231 (51.0) >65 years 187 (41.3) Female 217 (47.9) Male 236 (52.1)

  • 453 respiratory tract isolates of Aspergillus spp.
slide-9
SLIDE 9

9

Distribution of Aspergillus Species Isolated from Respiratory Specimens

% Annual Total 10 20 30 40 50 60 70 80

2012 (n=563) 2013 (n=692) 2014 (n=822) 2015 (n=757) 2016 (n=453)

slide-10
SLIDE 10

10 % Annual Total

Distribution of Aspergillus Species Based on Patient Location in Healthcare Setting

10 20 30 40 50 60 70 Clinic Medicine ICU Surgical Emergency

2012 (n=563) 2013 (n=692) 2014 (n=809) 2015 (n=757) 2016 (n=453)

slide-11
SLIDE 11

11

Respiratory Specimen Distribution

Year Location

  • No. Isolates

% Sputum % BAL or BW % ETT 2012-15 Clinic 1594 62 30 5 Medicine 681 47 45 4 ICU 236 23 50 22 Surgical 76 38 41 13

11

Year Location

  • No. Isolates

% Sputum % BAL or BW % ETT 2016 Clinic 227 54 30 9 Medicine 163 64 32 3 ICU 25 28 48 24 Surgical 19 37 63

slide-12
SLIDE 12

12 % Isolate Total

Itraconazole MIC Distribution Against A. fumigatus

10 20 30 40 50 60 70 80 0.06 0.12 0.25 0.5 1 2 4 8 >=16 2016 (n=352) 2012‐15 (n=1984)

MIC >4 mg/L infers cyp51A mutation

MIC (mg/L)

2012-16 (n=5) ECV

slide-13
SLIDE 13

13 % Isolate Total

Voriconazole MIC Distribution Against A. fumigatus

10 20 30 40 50 60 70 0.06 0.12 0.25 0.5 1 2 4 8 >=16 2016 (n=352) 2012‐15 (n=1984) MIC (mg/L)

ECV

slide-14
SLIDE 14

14 % Isolate Total

Posaconazole MIC Distribution Against A. fumigatus

5 10 15 20 25 30 35 40 45 0.015 0.03 0.06 0.12 0.25 0.5 1 2 2016 (n=352) 2012‐15 (n=1984) MIC (mg/L)

slide-15
SLIDE 15

15

Azole Resistance in A. fumigatus; 2012-16

  • 5 isolates of 2336 with ITRA MIC >4 mg/L
  • Independent of year and participating centre
  • Patient locations include 2 Clinic, 2 Medicine, and 1 ICU
  • 3 of 5 had Voriconazole MICs > 1mg/L (ECV)
  • cyp51A sequence mutations TBD
slide-16
SLIDE 16

16

Caspofungin MIC Distribution Against A. fumigatus

Year No. Tested Mode MIC90 ECV % Non- wildtype (#) 2016 355 0.125 0.25 <0.5

200 400 600 800 1,000 1,200 1,400 0.015 0.03 0.06 0.12 0.25 0.5 1 2 MIC (mg/L)

2012-15 (n=1984)

  • No. Isolates
slide-17
SLIDE 17

17

AmB MIC Distribution Against A. fumigatus

Year No. Tested Mode MIC90 ECV % Non- wildtype (#) 2016 355 0.5 0.5 <2

100 200 300 400 500 600 700 800 900 1,000 0.06 0.12 0.25 0.5 1 2 MIC (mg/L)

2012-15 (n=1984)

  • No. Isolates
slide-18
SLIDE 18

18 20 40 60 80 100 0.12 0.25 0.5 1 2 4 >16

Agent Year No. Tested Mode MIC90 ECV % Non- wildtype (#) ITRA 2016 44 1 16 <4 29.5 (13) VORI 2016 44 1 4 <2 11.4 (5) POSA 2016 44 0.12 0.5 <2

Azole MIC Distribution Against A. section Nigri

MIC (mg/L)

Itraconazole 2012-15 (n=228)

  • No. Isolates
slide-19
SLIDE 19

19

20 40 60 80 0.03 0.06 0.12 0.25 0.5 1 Agent Year No. Tested Mode MIC90 ECV % Non- wildtype (#) ITRA 2016 28 0.5 0.5 <1 VORI 2016 28 1 2 <2 POSA 2016 28 0.12 0.5 <0.5

Azole MIC Distribution Against A. flavus

MIC (mg/L)

Itraconazole 2012-15 (n=191)

  • No. Isolates
slide-20
SLIDE 20

20

Caspofungin MIC Distributions

Agent Year No. Tested Mode MIC90 ECV % Non- wildtype (#)

  • A. Section Nigri

2016 46 0.12 0.12 <0.25 2012-15 228 0.12 0.12 <0.25

  • A. flavus

2016 28 0.12 0.25 <0.5 2012-15 191 0.12 0.25 <0.5

slide-21
SLIDE 21

21

Isolates with Itraconazole MIC>16 mg/L (2012-16)

21

5 10 15 20 25 30

  • No. Isolates
slide-22
SLIDE 22

22

  • A. calidoustus
  • Aspergillus section Usti
  • Intrinsically resistant to azoles
  • ~50% resistant to caspofungin
  • Possible emergence linked to azole prophylaxis and lung transplant

patients

  • CANWARD 2012-16

– 31 isolates collected – 7th most common overall (4.1% of non-A. fumigatus) – 22 from bronchial specimens – 18 from clinic patients and 7 from medicine patients

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

slide-23
SLIDE 23

23

  • A. tubingensis
  • Aspergillus section Nigri

– Includes A. nigri sensu stricto

  • Variable resistance to azoles has been reported
  • Caspofungin MIC90 = 0.12 mg/L
  • Bronchial colonization, invasive aspergillosis, otomycosis

– MALDI and sequence ID efforts are rewriting our understanding of this species and human disease

  • CANWARD 2012-16

– Itraconazole resistant species are sequence-confirmed – 25 isolates collected – 10% of A. section Nigri isolates and 3.4% of non-A. fumigatus species – 14 from bronchoscopy specimens – 17 from clinic patients and 5 from medicine patients

Gautier, et al. Med Mycol. 2016; 54:459.

slide-24
SLIDE 24

24

CANWARD - Aspergillus 2016

  • 453 Aspergillus isolates from respiratory specimens
  • A. fumigatus, A. section Nigri, A. flavus, A. terreus, and A. calidoustus

represented 78.4%, 10.2%, 6.4%, 2.2%, and 1.1% of the population

  • A. fumigatus isolates were recovered primarily from

– Sputa (60.0%) and bronchoscopy (31%) specimens – Clinic outpatients (47.0%) and inpatients admitted to Medicine (38.5%) and Critical care (5.6%) services

  • A. fumigatus exhibited WT MIC values against the azoles, CASP and AmB

– 1 isolate exhibited azole resistance with an ITRA MIC >16 mg/L

  • 13 presumptive A. tubingensis were detected with ITRA MICs >16 mg/L
  • Five A. calidoustus isolates exhibited azole resistance (ITRA >4 mg/L)

24

slide-25
SLIDE 25

25

CANWARD – Aspergillus Resistance in Respiratory Specimens

2012-16 % Resistance (no.) Species (n) ITRA CASP AMB

  • A. fumigatus (2339)

0.2 (5) 0.1 (3)

  • A. Section Nigri (274)

9.2 (25) 0.4 (1)

  • A. flavus (221)

0.5 (1)

  • A. calidoustus (31)

93.6 (29)

  • Azole resistance in A. fumigatus is extremely rare in Canadian patients
  • Significant azole resistance in A. section Nigri (ie. A. tubingensis)
  • MS-ID for moulds is not common; conventional ID = A. niger
  • In total, 78 (2.5%) isolates resistant to azoles (ITRA >16 mg/L)