postoperative aspergillosis alessandro c. pasqualotto school of medicine, the university of...

184
Postoperative Postoperative aspergillosis aspergillosis Alessandro C. Pasqualotto Alessandro C. Pasqualotto School of Medicine, The University of Manchester School of Medicine, The University of Manchester Wythenshawe Hospital, UK Wythenshawe Hospital, UK

Upload: xavier-bolton

Post on 28-Mar-2015

222 views

Category:

Documents


6 download

TRANSCRIPT

Page 1: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Postoperative Postoperative aspergillosisaspergillosis

Alessandro C. PasqualottoAlessandro C. Pasqualotto

School of Medicine, The University of ManchesterSchool of Medicine, The University of ManchesterWythenshawe Hospital, UKWythenshawe Hospital, UK

Page 2: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Male, 70 year-oldMale, 70 year-old

• Elective aortic valve replacementElective aortic valve replacement

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 3: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Male, 70 year-oldMale, 70 year-old

• Elective aortic valve replacementElective aortic valve replacement

• 4 months:4 months: fatigue and fatigue and physical endurance physical endurance

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 4: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Male, 70 year-oldMale, 70 year-old

• Elective aortic valve replacementElective aortic valve replacement

• 4 months: fatigue and 4 months: fatigue and physical endurance physical endurance

• 7 months:7 months: profuse diarrhoea profuse diarrhoea

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 5: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• Male, 70 year-oldMale, 70 year-old

• Elective aortic valve replacementElective aortic valve replacement

• 4 months: fatigue and 4 months: fatigue and physical endurance physical endurance

• 7 months: profuse diarrhoea7 months: profuse diarrhoea

• One week later:One week later: chills + fever chills + fever

• 19,000 x 1019,000 x 1066 leukocytes. leukocytes.

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 6: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• TEE:TEE: large aortic vegetation large aortic vegetation

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 7: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• TEE: large aortic vegetationTEE: large aortic vegetation

• Blood cultures:Blood cultures: negative negative

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 8: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• TEE: large aortic vegetationTEE: large aortic vegetation

• Blood cultures: negativeBlood cultures: negative

• Working diagnosis:Working diagnosis: viridans strep endocarditis viridans strep endocarditis

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 9: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• TEE: large aortic vegetationTEE: large aortic vegetation

• Blood cultures: negativeBlood cultures: negative

• Working diagnosis: viridans strep endocarditisWorking diagnosis: viridans strep endocarditis

• DischargedDischarged on ceftriaxone and metronidazole on ceftriaxone and metronidazole

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 10: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• TEE: large aortic vegetationTEE: large aortic vegetation

• Blood cultures: negativeBlood cultures: negative

• Working diagnosis: viridans strep endocarditisWorking diagnosis: viridans strep endocarditis

• Discharged on ceftriaxone and metronidazoleDischarged on ceftriaxone and metronidazole

• ReadmittedReadmitted for fever and CHF for fever and CHF

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 11: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• TEE: large aortic vegetationTEE: large aortic vegetation

• Blood cultures: negativeBlood cultures: negative

• Working diagnosis: viridans strep endocarditisWorking diagnosis: viridans strep endocarditis

• Discharged on ceftriaxone and metronidazoleDischarged on ceftriaxone and metronidazole

• Readmitted for fever and CHFReadmitted for fever and CHF

• Vancomycin and doxycyclineVancomycin and doxycycline were added. were added.

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 12: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• After 2 days:After 2 days: hemiparesis and aphasia hemiparesis and aphasia

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 13: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• After 2 days: hemiparesis and aphasiaAfter 2 days: hemiparesis and aphasia

• He He dieddied three days later three days later

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 14: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• After 2 days: hemiparesis and aphasiaAfter 2 days: hemiparesis and aphasia

• He died three days laterHe died three days later

• Autopsy:Autopsy:

– Massive cerebral haemorrhageMassive cerebral haemorrhage

– Embolus containing Embolus containing AspergillusAspergillus in the right middle cerebral arteryin the right middle cerebral artery

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 15: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• After 2 days: hemiparesis and aphasiaAfter 2 days: hemiparesis and aphasia

• He died three days laterHe died three days later

• Autopsy:Autopsy:

– Massive cerebral haemorrhageMassive cerebral haemorrhage

– Embolus containing Embolus containing Aspergillus Aspergillus in the right middle cerebral arteryin the right middle cerebral artery

– Endocarditis lesion:Endocarditis lesion: multiple hyphae multiple hyphae

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 16: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• After 2 days: hemiparesis and aphasiaAfter 2 days: hemiparesis and aphasia

• He died three days laterHe died three days later

• Autopsy:Autopsy:

– Massive cerebral haemorrhageMassive cerebral haemorrhage

– Embolus containing Embolus containing Aspergillus Aspergillus in the right middle cerebral arteryin the right middle cerebral artery

– Endocarditis lesion: multiple hyphaeEndocarditis lesion: multiple hyphae

– No other site of infection was found.No other site of infection was found.

www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

Page 17: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Is that correct?Is that correct?

Page 18: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Would someone have Would someone have suspected aspergillosis?suspected aspergillosis?

Page 19: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillosisAspergillosis

• Aspergillus Aspergillus are are ubiquitousubiquitous

– Soil, water and decaying vegetationSoil, water and decaying vegetation

Page 20: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillosisAspergillosis

• Aspergillus Aspergillus are ubiquitous are ubiquitous

– Soil, water and decaying vegetationSoil, water and decaying vegetation

• Primarily acquired by Primarily acquired by inhalationinhalation

Page 21: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillosisAspergillosis

• Aspergillus Aspergillus are ubiquitous are ubiquitous

– Soil, water and decaying vegetationSoil, water and decaying vegetation

• Primarily acquired by inhalationPrimarily acquired by inhalation• Nosocomial aspergillosis typically affects Nosocomial aspergillosis typically affects

immunocompromised patients.immunocompromised patients.

Page 22: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

That is not all the story …That is not all the story …

Page 23: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The spectrum of aspergillosisThe spectrum of aspergillosisF

req

uen

cy o

f as

per

gil

losi

s

www.aspergillus.man.ac.uk

Page 24: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The spectrum of aspergillosisThe spectrum of aspergillosis

Immune system

Fre

qu

ency

of

asp

erg

illo

sis

www.aspergillus.man.ac.uk

Page 25: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The spectrum of aspergillosisThe spectrum of aspergillosis

Disfunction

Fre

qu

ency

of

asp

erg

illo

sis

Immune system www.aspergillus.man.ac.uk

Page 26: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The spectrum of aspergillosisThe spectrum of aspergillosis

Acute IA

Fre

qu

ency

of

asp

erg

illo

sis

Disfunction

Immune system www.aspergillus.man.ac.uk

Page 27: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The spectrum of aspergillosisThe spectrum of aspergillosis

Acute IA

Subacute IA

Fre

qu

ency

of

asp

erg

illo

sis

Disfunction

Immune system www.aspergillus.man.ac.uk

Page 28: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The spectrum of aspergillosisThe spectrum of aspergillosis

Acute IA

Subacute IA

.

TracheobronchitisTracheobronchitisFungus ballFungus ballChronic cavitaryChronic cavitaryChronic fibrosingChronic fibrosing

Fre

qu

ency

of

asp

erg

illo

sis

Disfunction

Immune system

Normal

www.aspergillus.man.ac.uk

Page 29: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The spectrum of aspergillosisThe spectrum of aspergillosis

Acute IA

Subacute IA

ABPAAllergic sinusitis

.

Fre

qu

ency

of

asp

erg

illo

sis

Disfunction

Immune system

Normal Hyper immune

TracheobronchitisTracheobronchitisFungus ballFungus ballChronic cavitaryChronic cavitaryChronic fibrosingChronic fibrosing

www.aspergillus.man.ac.uk

Page 30: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

What about postoperative What about postoperative aspergillosis?aspergillosis?

Page 31: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Review of the world literatureReview of the world literature

• Medline, LILACS and EMBASEMedline, LILACS and EMBASE

Page 32: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Medline, LILACS and EMBASEMedline, LILACS and EMBASE

• References References were reviewedwere reviewed

Review of the world literatureReview of the world literature

Page 33: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Medline, LILACS and EMBASEMedline, LILACS and EMBASE

• References were reviewedReferences were reviewed

• Conference abstracts Conference abstracts (www.aspergillus.man.ac.uk)(www.aspergillus.man.ac.uk)

Review of the world literatureReview of the world literature

Page 34: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Medline, LILACS and EMBASEMedline, LILACS and EMBASE

• References were reviewedReferences were reviewed

• Conference abstracts Conference abstracts (www.aspergillus.man.ac.uk)(www.aspergillus.man.ac.uk)

• Only cases of Only cases of proven or probableproven or probable aspergillosis were reviewed. aspergillosis were reviewed.

Review of the world literatureReview of the world literature

Page 35: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Not included:Not included:

– Primary cutaneous aspergillosis

Review of the world literatureReview of the world literature

Page 36: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Not included:Not included:

– Primary cutaneous aspergillosis

Review of the world literatureReview of the world literature

Neonate

Andresen J, et al. Acta Paediatr 2005; 94: 761-2.

Page 37: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Not included:Not included:

– Primary cutaneous aspergillosis

Review of the world literatureReview of the world literature

Neonate

Diabetes mellitus

Page 38: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Not included:Not included:

– Primary cutaneous aspergillosis

Review of the world literatureReview of the world literature

Neonate

Diabetes mellitus Burn patient

www.aspergillus.man.ac.uk

Page 39: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Not included:Not included:

– Infections associated with intravascular devices

Review of the world literatureReview of the world literature

Page 40: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Not included:Not included:

– Infections associated with intravascular devices

Review of the world literatureReview of the world literature

Neutropenia

Page 41: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Not included:Not included:

– Infections associated with intravascular devices

Review of the world literatureReview of the world literature

Neutropenia HIV

Page 42: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Literature reviewLiterature review

• More than More than 500 cases500 cases were included were included

Page 43: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Literature reviewLiterature review

– Heart surgery: 188Heart surgery: 188

– Dental surgery: > 100Dental surgery: > 100

– Ophthalmologic Ophthalmologic

surgery: > 90surgery: > 90

– Wound infections: 22Wound infections: 22

– Neurosurgery: 25Neurosurgery: 25

– Vascular prosthetic Vascular prosthetic

surgery: 22surgery: 22

– Orthopaedic surgery: 42Orthopaedic surgery: 42

– Bronchial infections: 30Bronchial infections: 30

– Abdominal surgery: 10Abdominal surgery: 10

– Mediastinitis: 11Mediastinitis: 11

– Breast surgery: 5Breast surgery: 5

– Pleural aspergillosis: 1Pleural aspergillosis: 1

• More than More than 500 cases500 cases were included were included

Page 44: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Endocarditis and aortitisEndocarditis and aortitis

• 124 cases124 cases

Page 45: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Endocarditis and aortitisEndocarditis and aortitis

• 124 cases124 cases 40 other cases40 other cases

Page 46: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Endocarditis and aortitisEndocarditis and aortitis

• 124 cases124 cases

• Male gender:Male gender: 69.9% 69.9%

Page 47: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Endocarditis and aortitisEndocarditis and aortitis

• 124 cases124 cases

• Male gender: 69.9%Male gender: 69.9%

• Median age:Median age: 43.5 years-old (0.8 to 71) 43.5 years-old (0.8 to 71)

Page 48: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Endocarditis and aortitisEndocarditis and aortitis

• 124 cases124 cases

• Male gender: 69.9%Male gender: 69.9%

• Median age: 43.5 years-old (0.8 to 71)Median age: 43.5 years-old (0.8 to 71)

• Main valves:Main valves:

– Aortic: involved in 60.5%Aortic: involved in 60.5%

– Mitral: 30.6%Mitral: 30.6%

Page 49: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Endocarditis and aortitisEndocarditis and aortitis

• 124 cases124 cases

• Male gender: 69.9%Male gender: 69.9%

• Median age: 43.5 years-old (0.8 to 71)Median age: 43.5 years-old (0.8 to 71)

• Main valves:Main valves:

– Aortic: involved in 60.5%Aortic: involved in 60.5%

– Mitral: 30.6%Mitral: 30.6%

• Median Median 2.7 months after surgery2.7 months after surgery (<1 to > 12). (<1 to > 12).

Page 50: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Key featuresKey features

• Absence of immunosuppressionAbsence of immunosuppression

Page 51: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Key featuresKey features

• Absence of immunosuppressionAbsence of immunosuppression

• No bronchopulmonary aspergillosisNo bronchopulmonary aspergillosis

Page 52: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Key featuresKey features

• Absence of immunosuppressionAbsence of immunosuppression

• No bronchopulmonary aspergillosisNo bronchopulmonary aspergillosis

• Postoperative course consistent with Postoperative course consistent with culture-negative endocarditisculture-negative endocarditis

Page 53: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Key featuresKey features

• Absence of immunosuppressionAbsence of immunosuppression

• No bronchopulmonary aspergillosisNo bronchopulmonary aspergillosis

• Postoperative course consistent with culture-negative endocarditisPostoperative course consistent with culture-negative endocarditis

• Propensity to Propensity to late embolisation.late embolisation.

Page 54: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus species species

• A. fumigatusA. fumigatus: : 58.7%58.7%

Page 55: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus species species

• A. fumigatusA. fumigatus: 58.7%: 58.7%

• A. terreusA. terreus:: 12.5% 12.5%

Page 56: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus species species• A. fumigatusA. fumigatus: 58.7%: 58.7%

• A. terreusA. terreus: 12.5%: 12.5%

• A. flavusA. flavus:: 11.2% 11.2%

• A. nigerA. niger:: 11.2% 11.2%

• A. glaucusA. glaucus: 2.5%: 2.5%

• A. clavatusA. clavatus: 1.2%: 1.2%

• A. ustusA. ustus: 1.2%: 1.2%

• A. sydowiA. sydowi: 1.2%: 1.2%

• AA. spp:. spp: 20.0% 20.0%

Page 57: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Large destructive lesion on Large destructive lesion on the mitral valve the mitral valve

www.aspergillus.man.ac.uk

Page 58: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Hosking MC, et al. Ann Thorac Surg 1995; 59: 1015-7.

Large vegetationsLarge vegetations

Page 59: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Antemortem diagnosis:Antemortem diagnosis: 43.5% 43.5%

Page 60: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Antemortem diagnosis:Antemortem diagnosis: 43.5% 43.5%

– Vegetation, valve/graft examination:Vegetation, valve/graft examination: 23.4% 23.4%

Page 61: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Antemortem diagnosis:Antemortem diagnosis: 43.5% 43.5%

– Vegetation, valve/graft examination: 23.4%Vegetation, valve/graft examination: 23.4%

– Embolic material:Embolic material: 16.9% 16.9%

Page 62: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Antemortem diagnosis:Antemortem diagnosis: 43.5%43.5%

– Vegetation, valve/graft examination: 23.4%Vegetation, valve/graft examination: 23.4%

– Embolic material: 16.9%Embolic material: 16.9%

– Positive blood culture:Positive blood culture: 6.4% (n=8) 6.4% (n=8)

Page 63: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Antemortem diagnosis:Antemortem diagnosis: 43.5%43.5%

– Vegetation, valve/graft examination: 23.4%Vegetation, valve/graft examination: 23.4%

– Embolic material: 16.9%Embolic material: 16.9%

– Positive blood culture: 6.4% (n=8)Positive blood culture: 6.4% (n=8)

– Serology/precipitins:Serology/precipitins: 2.4%. 2.4%.

Page 64: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Other diagnostic methods?Other diagnostic methods?

Page 65: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Other diagnostic methods?Other diagnostic methods?

Pemán J, et al. 2nd TIMM, Berlin 2005. P-048.

Page 66: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DiagnosisDiagnosis

• Other diagnostic methods?Other diagnostic methods?

Negative galactomannan

(ELISA)

Pemán J, et al. 2nd TIMM, Berlin 2005. P-048.

Page 67: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

MortalityMortality

• Overall mortality:Overall mortality: 92.7%92.7%

Page 68: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

MortalityMortality

• Overall mortality: 92.7%Overall mortality: 92.7%

• Antemortem diagnosis:Antemortem diagnosis: mortality 83.0%mortality 83.0%

(p<0.0001)(p<0.0001)

Page 69: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

MortalityMortality

• Overall mortality: 92.7%Overall mortality: 92.7%

• Antemortem diagnosis: mortality 83.0%Antemortem diagnosis: mortality 83.0%

(p<0.0001)(p<0.0001)

• Surgical treatment:Surgical treatment: 80.9%. 80.9%.

Page 70: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Aortic graft infectionAortic graft infection

Page 71: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus graft infection graft infection

• n=22n=22

Page 72: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus graft infection graft infection

• n=22n=22

• Almost all cases: Almost all cases: immunocompetent malesimmunocompetent males

Page 73: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus graft infection graft infection

• n=22n=22

• Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males

• Median Median 8 months 8 months after surgeryafter surgery

Page 74: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus graft infection graft infection

• n=22 n=22

• Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males

• Median Median 8 months 8 months after surgeryafter surgery

– Candida Candida graft infections: usually < 6 weeksgraft infections: usually < 6 weeks

Page 75: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus graft infection graft infection

• n=22 n=22

• Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males

• Median 8 months after surgeryMedian 8 months after surgery

– Candida Candida graft infections: usually < 6 weeksgraft infections: usually < 6 weeks

• Similar to Similar to S. epidermidisS. epidermidis infectioninfection

Page 76: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AspergillusAspergillus graft infection graft infection

• n=22 n=22

• Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males

• Median 8 months after surgeryMedian 8 months after surgery

– Candida Candida graft infections: usually < 6 weeksgraft infections: usually < 6 weeks

• Similar to Similar to S. epidermidis S. epidermidis infectioninfection

• Suture lineSuture line of a previous aortotomy. of a previous aortotomy.

Page 77: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Brandt SJ, et al. Am J Med 1985; 79: 259-62.

Page 78: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Brandt SJ, et al. Am J Med 1985; 79: 259-62.

Page 79: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Definitive diagnostic proceduresDefinitive diagnostic procedures

• Culture of the excised aortic graftCulture of the excised aortic graft

Page 80: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Culture of the excised aortic graftCulture of the excised aortic graft

• Culture of peripheral embolusCulture of peripheral embolus

Definitive diagnostic proceduresDefinitive diagnostic procedures

Page 81: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Culture of the excised aortic graftCulture of the excised aortic graft

• Culture of peripheral embolusCulture of peripheral embolus

• Biopsy of the contiguously affected vertebral disk.Biopsy of the contiguously affected vertebral disk.

Definitive diagnostic proceduresDefinitive diagnostic procedures

Page 82: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Effective treatment:Effective treatment: removal of the graft removal of the graft

Page 83: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Effective treatment: removal of the graftEffective treatment: removal of the graft

• Systemic Systemic antifungal therapyantifungal therapy

Page 84: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Effective treatment: removal of the graftEffective treatment: removal of the graft

• Systemic antifungal therapySystemic antifungal therapy

• Extra-anatomic bypassExtra-anatomic bypass through a clean field. through a clean field.

Page 85: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Neurosurgical infectionNeurosurgical infection

Page 86: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Female, Female, 16 year-old16 year-old

• Elective Elective neurosurgeryneurosurgery for Chiari I malformation for Chiari I malformation

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 87: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Female, 16 year-oldFemale, 16 year-old

• Elective neurosurgery for Chiari I malformationElective neurosurgery for Chiari I malformation

• Long course of dexamethasoneLong course of dexamethasone

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 88: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• Female, 16 year-oldFemale, 16 year-old

• Elective neurosurgery for Chiari I malformationElective neurosurgery for Chiari I malformation

• Long course of dexamethasoneLong course of dexamethasone

• Clinical deteriorationClinical deterioration

– Vancomycin and cefotaximeVancomycin and cefotaxime

– Dexamethasone dose was increased.Dexamethasone dose was increased.

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 89: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• CSF culture (day 18):CSF culture (day 18): few colonies of few colonies of

A. fumigatus.A. fumigatus.

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 90: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Is that a contaminant?Is that a contaminant?

Page 91: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Symptoms persistedSymptoms persisted

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 92: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Symptoms persistedSymptoms persisted

• Wound exploration:Wound exploration: sutures had dehisced sutures had dehisced

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 93: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• Symptoms persistedSymptoms persisted

• Wound exploration: sutures had dehiscedWound exploration: sutures had dehisced

• CulturesCultures again revealed again revealed A. fumigatusA. fumigatus

• Amphotericin BAmphotericin B was started (day 28) was started (day 28)

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 94: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• Symptoms persistedSymptoms persisted

• Wound exploration: sutures had dehiscedWound exploration: sutures had dehisced

• Cultures again revealed Cultures again revealed A. fumigatusA. fumigatus

• Amphotericin B was started (day 28)Amphotericin B was started (day 28)

• Symptoms did not improveSymptoms did not improve

• Dural graft was removed.Dural graft was removed.

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 95: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• A. fumigatus A. fumigatus in the surgical specimensin the surgical specimens

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 96: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report

• A. fumigatus A. fumigatus in the surgical specimens in the surgical specimens

• She She dieddied 2 months after the 1 2 months after the 1stst surgery surgery

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 97: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• A. fumigatus A. fumigatus in the surgical specimens in the surgical specimens

• She died 2 months after the 1She died 2 months after the 1stst surgery surgery

• Autopsy:Autopsy:

– Abundant hyphae in the origin of the basilar artery and bilateral vertebral arteriesAbundant hyphae in the origin of the basilar artery and bilateral vertebral arteries

– Multifocal transmural destruction of arterial wallsMultifocal transmural destruction of arterial walls

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 98: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Case reportCase report• A. fumigatus A. fumigatus in the surgical specimens in the surgical specimens

• She died 2 months after the 1She died 2 months after the 1stst surgery surgery

• Autopsy:Autopsy:

– Abundant hyphae in the origin of the basilar artery and bilateral vertebral arteriesAbundant hyphae in the origin of the basilar artery and bilateral vertebral arteries

– Multifocal transmural destruction of arterial wallsMultifocal transmural destruction of arterial walls

– No other focus of aspergillosis was found.No other focus of aspergillosis was found.

www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

Page 99: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

• n=25n=25

Page 100: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

• n=25n=25

• Male sex:Male sex: 44.0% 44.0%

Page 101: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• n=25 n=25

• Male sex: 44.0%Male sex: 44.0%

• Steroids:Steroids: 52.0%52.0%

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

Page 102: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• n=25 n=25

• Male sex: 44.0%Male sex: 44.0%

• Steroids: 52.0%Steroids: 52.0%

• All proven cases: All proven cases: A. fumigatus.A. fumigatus.

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

Page 103: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Median Median 3 months after surgery3 months after surgery (<1 to > 12) (<1 to > 12)

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

Page 104: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Median 3 months after surgery (<1 to > 12) Median 3 months after surgery (<1 to > 12)

• Different presentationsDifferent presentations

– MeningitisMeningitis

– CNS abscessCNS abscess

– Mycotic aneurismsMycotic aneurisms

– Infarction.Infarction.

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

Page 105: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Antemortem diagnosis:Antemortem diagnosis: 64.0%64.0%

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

Page 106: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Antemortem diagnosis:Antemortem diagnosis: 64.0%64.0%

– Abscess examination:Abscess examination: 36.0% 36.0%

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

www.aspergillus.man.ac.uk/secure/image_library/invpulmonaryasp/cerebralaspkh.htm

Page 107: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Antemortem diagnosis:Antemortem diagnosis: 64.0%64.0%

– Abscess examination: 36.0%Abscess examination: 36.0%

– Culture of CSF:Culture of CSF: 20.0%20.0%

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

Page 108: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Antemortem diagnosis: 64.0%Antemortem diagnosis: 64.0%

– Abscess examination: 36.0%Abscess examination: 36.0%

– Culture of CSF: 20.0%Culture of CSF: 20.0%

• Mortality:Mortality: 68.0%. 68.0%.

Aspergillosis after neurosurgeryAspergillosis after neurosurgery

Page 109: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Trans-sphenoidal surgeryTrans-sphenoidal surgery

Endo T, et al. Surg Neurol 2001; 56: 195-200.

Page 110: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Wound infectionWound infection

Page 111: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DefinitionsDefinitions

• Skin or subcutaneous tissueSkin or subcutaneous tissue of the incision of the incision

Page 112: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DefinitionsDefinitions

• Skin or subcutaneous tissue of the incisionSkin or subcutaneous tissue of the incision

• When both superficial and deep When both superficial and deep incision sites: incision sites:

classified as deep surgical site infectionclassified as deep surgical site infection

Page 113: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DefinitionsDefinitions

• Skin or subcutaneous tissue of the incisionSkin or subcutaneous tissue of the incision

• When both superficial and deep incision sites: When both superficial and deep incision sites:

classified as deep surgical site infectionclassified as deep surgical site infection

• Similar to CDC’s criteria for SSI.Similar to CDC’s criteria for SSI.

Page 114: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DefinitionsDefinitions

• The wound itself had to be The wound itself had to be non-healing with non-healing with

standard antibioticsstandard antibiotics, and other pathogens , and other pathogens

were absent or minimally presentedwere absent or minimally presented

Page 115: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DefinitionsDefinitions

• The wound itself had to be non-healing with standard The wound itself had to be non-healing with standard

antibiotics, and other pathogens were absent or minimally antibiotics, and other pathogens were absent or minimally

presentedpresented

• Topographic relation Topographic relation between the surgery and the infectionbetween the surgery and the infection

Page 116: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

DefinitionsDefinitions• The wound itself had to be non-healing with standard antibiotics, The wound itself had to be non-healing with standard antibiotics,

and other pathogens were absent or minimally presentedand other pathogens were absent or minimally presented

• Topographic relation between the surgery and the infectionTopographic relation between the surgery and the infection

• n=22.n=22.

Page 117: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The first case reportedThe first case reported

• 19331933

Frank L, Alton OM. JAMA 1933; 100: 2007-8.

Page 118: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The first case reportedThe first case reported

• 19331933

• Female, 40 year-oldFemale, 40 year-old

• Operated on for an abdominal tumourOperated on for an abdominal tumour

Frank L, Alton OM. JAMA 1933; 100: 2007-8.

Page 119: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The first case reportedThe first case reported• 19331933

• Female, 40 year-oldFemale, 40 year-old

• Operated on for an abdominal tumourOperated on for an abdominal tumour

• After 16 days:After 16 days: ulcer under the dressing ulcer under the dressing

• No systemic manifestationsNo systemic manifestations

Frank L, Alton OM. JAMA 1933; 100: 2007-8.

Page 120: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

The first case reportedThe first case reported• 19331933

• Female, 40 year-oldFemale, 40 year-old

• Operated on for an abdominal tumourOperated on for an abdominal tumour

• After 16 days: ulcer under the dressingAfter 16 days: ulcer under the dressing

• No systemic manifestationsNo systemic manifestations

• A. nigerA. niger grew in the surgical dressings covered with a dark powder. grew in the surgical dressings covered with a dark powder.

Frank L, Alton OM. JAMA 1933; 100: 2007-8.

Page 121: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ParticularitiesParticularities

• Median Median 17 days after surgery 17 days after surgery (<7 to 180)(<7 to 180)

Page 122: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ParticularitiesParticularities

• Median 17 days after surgery (<7 to 180)Median 17 days after surgery (<7 to 180)

• Many patients were Many patients were immunosuppressedimmunosuppressed

Page 123: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ParticularitiesParticularities

• Median 17 days after surgery (<7 to 180)Median 17 days after surgery (<7 to 180)

• Many patients were immunosuppressedMany patients were immunosuppressed

• Aspergillus Aspergillus species:species:

– A. fumigatusA. fumigatus: 42.1%: 42.1%

– A. flavusA. flavus: 36.8%: 36.8%

– A. nigerA. niger: 10.5%: 10.5%

– A.A. spp: 10.5% spp: 10.5%

Page 124: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Risk of disseminationRisk of dissemination

• Aggressive combined medical therapy and debridement is Aggressive combined medical therapy and debridement is

required for all patients.required for all patients.

Page 125: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

OutbreaksOutbreaks

• Outbreak of wound aspergillosisOutbreak of wound aspergillosis

– Contamination during hospital construction of the outside packages of dressing suppliesContamination during hospital construction of the outside packages of dressing supplies

Bryce EA, et al. Infect Control Hosp Epidemiol 1996; 17: 170-2.

Page 126: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

OutbreaksOutbreaks

• Outbreak of wound aspergillosisOutbreak of wound aspergillosis

– Contamination during hospital construction of the outside packages of dressing suppliesContamination during hospital construction of the outside packages of dressing supplies

• Outbreaks of cutaneous aspergillosisOutbreaks of cutaneous aspergillosis

– Wound dressing and tape should be culturedWound dressing and tape should be cultured

Bryce EA, et al. Infect Control Hosp Epidemiol 1996; 17: 170-2.

Page 127: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

OutbreaksOutbreaks

• Outbreak of wound aspergillosisOutbreak of wound aspergillosis

– Contamination during hospital construction of the outside packages of dressing suppliesContamination during hospital construction of the outside packages of dressing supplies

• Outbreaks of cutaneous aspergillosisOutbreaks of cutaneous aspergillosis

– Wound dressing and tape should be culturedWound dressing and tape should be cultured

• A. flavus A. flavus sternal wound infection coinciding with sternal wound infection coinciding with hospital renovation activities.hospital renovation activities.

Bryce EA, et al. Infect Control Hosp Epidemiol 1996; 17: 170-2.

Page 128: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Risk factorsRisk factors

• Chronic lung diseaseChronic lung disease

– Independent risk factorIndependent risk factor for for A. fumigatus A. fumigatus sternal wound infection after open-heart surgerysternal wound infection after open-heart surgery

Richet HM, et al. Am J Epidemiol 1992; 135: 48-58.

Page 129: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Risk factorsRisk factors

• Chronic lung diseaseChronic lung disease

– Independent risk factor for Independent risk factor for A. fumigatus A. fumigatus sternal wound infection after open-heart surgerysternal wound infection after open-heart surgery

– A. fumigatusA. fumigatus grew at the same time from the grew at the same time from the bronchial washingbronchial washing of one patient of one patient

Richet HM, et al. Am J Epidemiol 1992; 135: 48-58.

Page 130: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Risk factorsRisk factors

• Chronic lung diseaseChronic lung disease

– Independent risk factor for Independent risk factor for A. fumigatus A. fumigatus sternal wound infection after open-heart surgerysternal wound infection after open-heart surgery

– A. fumigatusA. fumigatus grew at the same time from the bronchial washing of one patient grew at the same time from the bronchial washing of one patient

– Colonised patients may be at increased risk.Colonised patients may be at increased risk.

Richet HM, et al. Am J Epidemiol 1992; 135: 48-58.

Page 131: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Ophthalmological Ophthalmological surgerysurgery

Page 132: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Ophthalmological surgeryOphthalmological surgery

• Usually keratitisUsually keratitis; rarely endophthalmitis; rarely endophthalmitis

Tabbara KF, et al. Ophthalmology 1998; 105: 522-6. Sridhar MS, et al. Am J Ophthalmol 2000; 129: 802-4.

Page 133: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Ophthalmological surgeryOphthalmological surgery

• Usually keratitis; rarely endophthalmitisUsually keratitis; rarely endophthalmitis

• Many different proceduresMany different procedures

– PPenetrating keratoplastyenetrating keratoplasty

– Radial keratotomyRadial keratotomy

– Excimer laser photorefractive Excimer laser photorefractive

keratectomykeratectomy

– Laser-assisted in situ Laser-assisted in situ

keratomileusiskeratomileusis

– Pterygium excisionPterygium excision

– Cataract surgeryCataract surgery

– Scleral buckling proceduresScleral buckling procedures

– Hydroxyapatite orbital Hydroxyapatite orbital

implant surgeryimplant surgery

– Sutureless surgerySutureless surgery

– TrabeculectomyTrabeculectomy

Page 134: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Ophthalmological surgeryOphthalmological surgery

• Sampling at the site of infection:Sampling at the site of infection: best chance for best chance for

obtaining a positive cultureobtaining a positive culture

Page 135: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Ophthalmological surgeryOphthalmological surgery

• Sampling at the site of infection: best chance for obtaining a positive cultureSampling at the site of infection: best chance for obtaining a positive culture

• Source of infection:Source of infection:

– Hospital constructionHospital construction

Page 136: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Ophthalmological surgeryOphthalmological surgery

• Sampling at the site of infection: best chance for obtaining a positive cultureSampling at the site of infection: best chance for obtaining a positive culture

• Source of infection:Source of infection:

– Hospital constructionHospital construction

– Contaminated irrigating fluids used during surgeryContaminated irrigating fluids used during surgery

Page 137: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Ophthalmological surgeryOphthalmological surgery

• Sampling at the site of infection: best chance for obtaining a positive cultureSampling at the site of infection: best chance for obtaining a positive culture

• Source of infection:Source of infection:

– Hospital constructionHospital construction

– Contaminated irrigating fluids used during surgeryContaminated irrigating fluids used during surgery

– Many occurred after Many occurred after non-surgical corneal trauma.non-surgical corneal trauma.

Page 138: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Surgical dental Surgical dental procedureprocedure

Page 139: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Surgical dental procedureSurgical dental procedure

• Connection between Connection between endodontic treatmentendodontic treatment and non- and non-

invasive sinus aspergillosisinvasive sinus aspergillosis

Page 140: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Surgical dental procedureSurgical dental procedure

• Connection between endodontic treatment and non-invasive sinus aspergillosisConnection between endodontic treatment and non-invasive sinus aspergillosis

• Obturating pastes containing Obturating pastes containing zinc oxidzinc oxid within the maxillary antrum within the maxillary antrum

Page 141: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Surgical dental procedureSurgical dental procedure

• Connection between endodontic treatment and non-invasive sinus aspergillosisConnection between endodontic treatment and non-invasive sinus aspergillosis

• Obturating pastes containing zinc oxid within the maxillary antrumObturating pastes containing zinc oxid within the maxillary antrum

• Surgical treatmentSurgical treatment

– Removal of all materialRemoval of all material

– Promote aerationPromote aeration

– Antifungals only if invasion.Antifungals only if invasion.

Page 142: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

Page 143: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Optimal therapy:Optimal therapy: not specifically studied not specifically studied

Page 144: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Optimal therapy: not specifically studiedOptimal therapy: not specifically studied

• Excision of the infected tissueExcision of the infected tissue

Page 145: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Optimal therapy: not specifically studiedOptimal therapy: not specifically studied

• Excision of the infected tissueExcision of the infected tissue

• Placement of a Placement of a new prosthesisnew prosthesis in a non-infected field in a non-infected field

Page 146: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Optimal therapy: not specifically studiedOptimal therapy: not specifically studied

• Excision of the infected tissueExcision of the infected tissue

• Placement of a new prosthesis in a non-infected fieldPlacement of a new prosthesis in a non-infected field

• Systemic antifungal agentsSystemic antifungal agents

Page 147: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Optimal therapy: not specifically studiedOptimal therapy: not specifically studied

• Excision of the infected tissueExcision of the infected tissue

• Placement of a new prosthesis in a non-infected fieldPlacement of a new prosthesis in a non-infected field

• Systemic antifungal agentsSystemic antifungal agents

• Longer term Longer term oral therapyoral therapy

Page 148: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

TreatmentTreatment

• Optimal therapy: not specifically studiedOptimal therapy: not specifically studied

• Excision of the infected tissueExcision of the infected tissue

• Placement of a new prosthesis in a non-infected fieldPlacement of a new prosthesis in a non-infected field

• Systemic antifungal agentsSystemic antifungal agents

• Longer term oral therapyLonger term oral therapy

• Duration:Duration: unknown. unknown.

Page 149: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

PreventionPrevention

Page 150: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Main sources of infectionMain sources of infection

• Contaminated graftsContaminated grafts

Page 151: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Main sources of infectionMain sources of infection

• Contaminated graftsContaminated grafts

• Contaminated suturesContaminated sutures

Page 152: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Main sources of infectionMain sources of infection

• Contaminated graftsContaminated grafts

• Contaminated suturesContaminated sutures

• Intra-operative dispersion of spores.Intra-operative dispersion of spores.

Page 153: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Linking the infection with Linking the infection with the surgical room the surgical room

• ““Pigeon excretaPigeon excreta in the immediate vicinity of the ventilator intake in the immediate vicinity of the ventilator intake

port were found to harbour large numbers of port were found to harbour large numbers of Aspergillus sporesAspergillus spores””

Gage AA, et al. Arch Surg 1970; 101: 384-87.Gage AA, et al. Arch Surg 1970; 101: 384-87.

Page 154: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Linking the infection with Linking the infection with the surgical room the surgical room

• ““Air conditioner cooling coils and pigeon droppings on the ledges outside Air conditioner cooling coils and pigeon droppings on the ledges outside

the suite were found to harbour Aspergillus spores in large amounts”.the suite were found to harbour Aspergillus spores in large amounts”.

Mehta G. J Hosp Infect 1990; 15: 245-53.Mehta G. J Hosp Infect 1990; 15: 245-53.

Page 155: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK
Page 156: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Infection acquired in the ICUInfection acquired in the ICU

Carlson GL, et al. J Infect 1996; 33: 119-21Carlson GL, et al. J Infect 1996; 33: 119-21.

• Multiple abdominal visceral infectionMultiple abdominal visceral infection by by A. A.

fumigatusfumigatus occurred occurred afterafter laparostomylaparostomy

Page 157: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Infection acquired in the ICUInfection acquired in the ICU

Carlson GL, et al. J Infect 1996; 33: 119-21Carlson GL, et al. J Infect 1996; 33: 119-21.

Dark patches on the liver invading liver capsule

• Multiple abdominal visceral infectionMultiple abdominal visceral infection by by A. A.

fumigatusfumigatus occurred occurred afterafter laparostomylaparostomy

Page 158: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Infection acquired in the ICUInfection acquired in the ICU

• Multiple abdominal visceral infection by Multiple abdominal visceral infection by A. fumigatusA. fumigatus occurred after laparostomy occurred after laparostomy

• Sampling of air from the ICU yielded one isolate that Sampling of air from the ICU yielded one isolate that matched matched the patient's isolates.the patient's isolates.

Carlson GL, et al. J Infect 1996; 33: 119-21.Carlson GL, et al. J Infect 1996; 33: 119-21.

Page 159: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Grilles of heat exchanger Grilles of heat exchanger used to maintain used to maintain

extracorporeal blood at the proper extracorporeal blood at the proper

temperature.temperature.

Diaz-Guerra TM, et al. J Clin Microbiol 2000; 38: 2419-22.Diaz-Guerra TM, et al. J Clin Microbiol 2000; 38: 2419-22.

Fomites as a reservoirFomites as a reservoir

Page 160: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Diaz-Guerra TM, et al. J Clin Microbiol 2000; 38: 2419-22.Diaz-Guerra TM, et al. J Clin Microbiol 2000; 38: 2419-22.

RAPD patternsRAPD patterns• Three primers Three primers

(A, B, C)(A, B, C)

• 1, 2:1, 2:

– EnvironmentalEnvironmental

• 3: 3:

– Aortic prosthesisAortic prosthesis

Page 161: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

PreventionPrevention

• Tap water:Tap water: not on surgical wounds not on surgical wounds

Page 162: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

PreventionPrevention

• Tap water: not on surgical woundsTap water: not on surgical wounds

• Conventional ventilation and filters Conventional ventilation and filters onlyonly remove airborne particles remove airborne particles 5 5 mm

Page 163: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

PreventionPrevention

• Tap water: not on surgical woundsTap water: not on surgical wounds

• Conventional ventilation and filters only remove airborne particles Conventional ventilation and filters only remove airborne particles 5 5 mm

• Laminar airflow systems and HEPA filtrationLaminar airflow systems and HEPA filtration

Page 164: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

PreventionPrevention

• Tap water: not on surgical woundsTap water: not on surgical wounds

• Conventional ventilation and filters only remove airborne particles Conventional ventilation and filters only remove airborne particles 5 5 mm

• Laminar airflow systems and HEPA filtrationLaminar airflow systems and HEPA filtration

– Lack of dataLack of data revealing survival benefit revealing survival benefit

– CostsCosts

Page 165: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

PreventionPrevention

• Tap water: not on surgical woundsTap water: not on surgical wounds

• Conventional ventilation and filters only remove airborne particles Conventional ventilation and filters only remove airborne particles 5 5 mm

• Laminar airflow systems and HEPA filtrationLaminar airflow systems and HEPA filtration

– Lack of data revealing survival benefitLack of data revealing survival benefit

– CostsCosts

– Lack of consensusLack of consensus about the level of airborne conidia at which the risk can be numerically defined. about the level of airborne conidia at which the risk can be numerically defined.

Page 166: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Heinemann S, et al. J Hosp Infect 2004; 57: 149-55.

HEPAHEPA

filtrationfiltration

Offices, meeting rooms, Offices, meeting rooms, lounges, utilities, lounges, utilities,

storage roomsstorage rooms

HEPA filtration is importantHEPA filtration is importantbut maybe not enoughbut maybe not enough

HEPAHEPA

filtrationfiltration

Page 167: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Heinemann S, et al. J Hosp Infect 2004; 57: 149-55.

Outbreak of Outbreak of A. flavusA. flavus wound infectionwound infection

Heavily Heavily contaminated areascontaminated areas

Page 168: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Heinemann S, et al. J Hosp Infect 2004; 57: 149-55.

Outbreak of Outbreak of A. flavusA. flavus wound infectionwound infection

Water leakageWater leakage

Page 169: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Heinemann S, et al. J Hosp Infect 2004; 57: 149-55.

RAPD resultsRAPD results

Page 170: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Investigating Aspergillus infections

Fox BC. Am J Infect Control 1990; 18: 300-6.Fox BC. Am J Infect Control 1990; 18: 300-6.

PenicilliumPenicillium in the OR in the OR

Page 171: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

• Investigating Aspergillus infections

• Heavy contamination by Penicillium in the heating, ventilation, and air conditioning (HVAC) system

of the OR.

Fox BC. Am J Infect Control 1990; 18: 300-6.Fox BC. Am J Infect Control 1990; 18: 300-6.

PenicilliumPenicillium in the OR in the OR

Page 172: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Fox BC. Am J Infect Control 1990; 18: 300-6.Fox BC. Am J Infect Control 1990; 18: 300-6.

Terminal units lined Terminal units lined with fibreglass with fibreglass served as a served as a substrate for substrate for fungal growth.fungal growth.

PenicilliumPenicillium in the OR in the OR

Page 173: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

Lutz G, et al. Clin Infect Dis 2003; 37: 786-93.Lutz G, et al. Clin Infect Dis 2003; 37: 786-93.

Deteriorated ventilation systemsDeteriorated ventilation systems

Page 174: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

Page 175: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

• Underappreciated problemUnderappreciated problem

Page 176: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

• Underappreciated problemUnderappreciated problem

• Mortality:Mortality: high in non-cutaneous infections high in non-cutaneous infections

Page 177: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

• Underappreciated problemUnderappreciated problem

• Mortality: high in non-cutaneous infectionsMortality: high in non-cutaneous infections

• Different organs and surgical proceduresDifferent organs and surgical procedures

Page 178: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

• Underappreciated problemUnderappreciated problem

• Mortality: high in non-cutaneous infectionsMortality: high in non-cutaneous infections

• Different organs and surgical proceduresDifferent organs and surgical procedures

• Usually Usually indolentindolent

Page 179: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

• Underappreciated problemUnderappreciated problem

• Mortality: high in non-cutaneous infectionsMortality: high in non-cutaneous infections

• Different organs and surgical proceduresDifferent organs and surgical procedures

• Usually indolentUsually indolent

• Combined aggressive Combined aggressive medical and surgical therapy.medical and surgical therapy.

Page 180: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

• Prevention:Prevention:

– Special care with the ventilation system in the surgical roomSpecial care with the ventilation system in the surgical room

Page 181: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

ConclusionConclusion

• Prevention:Prevention:

– Special care with the ventilation system in the surgical roomSpecial care with the ventilation system in the surgical room

– Proper storage and disinfection of surgical material.Proper storage and disinfection of surgical material.

Page 182: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AcknowledgmentsAcknowledgments

• David W. DenningDavid W. Denning

Page 183: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AcknowledgmentsAcknowledgments• David W. DenningDavid W. Denning

• Fungal Research TrustFungal Research Trust

Page 184: Postoperative aspergillosis Alessandro C. Pasqualotto School of Medicine, The University of Manchester Wythenshawe Hospital, UK

AcknowledgmentsAcknowledgments• David W. DenningDavid W. Denning

• Fungal Research TrustFungal Research Trust

• CAPESCAPES

[email protected]@manchester.ac.uk