postoperative aspergillosis alessandro c. pasqualotto school of medicine, the university of...
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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
Case reportCase report
• Male, 70 year-oldMale, 70 year-old
• Elective aortic valve replacementElective aortic valve replacement
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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
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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
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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.
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Case reportCase report
• TEE:TEE: large aortic vegetation large aortic vegetation
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Case reportCase report
• TEE: large aortic vegetationTEE: large aortic vegetation
• Blood cultures:Blood cultures: negative negative
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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
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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
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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
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.
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Case reportCase report
• After 2 days:After 2 days: hemiparesis and aphasia hemiparesis and aphasia
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Case reportCase report
• After 2 days: hemiparesis and aphasiaAfter 2 days: hemiparesis and aphasia
• He He dieddied three days later three days later
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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
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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
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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.
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Is that correct?Is that correct?
Would someone have Would someone have suspected aspergillosis?suspected aspergillosis?
AspergillosisAspergillosis
• Aspergillus Aspergillus are are ubiquitousubiquitous
– Soil, water and decaying vegetationSoil, water and decaying vegetation
AspergillosisAspergillosis
• Aspergillus Aspergillus are ubiquitous are ubiquitous
– Soil, water and decaying vegetationSoil, water and decaying vegetation
• Primarily acquired by Primarily acquired by inhalationinhalation
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.
That is not all the story …That is not all the story …
The spectrum of aspergillosisThe spectrum of aspergillosisF
req
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www.aspergillus.man.ac.uk
The spectrum of aspergillosisThe spectrum of aspergillosis
Immune system
Fre
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www.aspergillus.man.ac.uk
The spectrum of aspergillosisThe spectrum of aspergillosis
Disfunction
Fre
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Immune system www.aspergillus.man.ac.uk
The spectrum of aspergillosisThe spectrum of aspergillosis
Acute IA
Fre
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of
asp
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sis
Disfunction
Immune system www.aspergillus.man.ac.uk
The spectrum of aspergillosisThe spectrum of aspergillosis
Acute IA
Subacute IA
Fre
qu
ency
of
asp
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Disfunction
Immune system www.aspergillus.man.ac.uk
The spectrum of aspergillosisThe spectrum of aspergillosis
Acute IA
Subacute IA
.
TracheobronchitisTracheobronchitisFungus ballFungus ballChronic cavitaryChronic cavitaryChronic fibrosingChronic fibrosing
Fre
qu
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of
asp
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Disfunction
Immune system
Normal
www.aspergillus.man.ac.uk
The spectrum of aspergillosisThe spectrum of aspergillosis
Acute IA
Subacute IA
ABPAAllergic sinusitis
.
Fre
qu
ency
of
asp
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illo
sis
Disfunction
Immune system
Normal Hyper immune
TracheobronchitisTracheobronchitisFungus ballFungus ballChronic cavitaryChronic cavitaryChronic fibrosingChronic fibrosing
www.aspergillus.man.ac.uk
What about postoperative What about postoperative aspergillosis?aspergillosis?
Review of the world literatureReview of the world literature
• Medline, LILACS and EMBASEMedline, LILACS and EMBASE
• Medline, LILACS and EMBASEMedline, LILACS and EMBASE
• References References were reviewedwere reviewed
Review of the world literatureReview of the world literature
• 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
• 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
• Not included:Not included:
– Primary cutaneous aspergillosis
Review of the world literatureReview of the world literature
• 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.
• Not included:Not included:
– Primary cutaneous aspergillosis
Review of the world literatureReview of the world literature
Neonate
Diabetes mellitus
• 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
• Not included:Not included:
– Infections associated with intravascular devices
Review of the world literatureReview of the world literature
• Not included:Not included:
– Infections associated with intravascular devices
Review of the world literatureReview of the world literature
Neutropenia
• Not included:Not included:
– Infections associated with intravascular devices
Review of the world literatureReview of the world literature
Neutropenia HIV
Literature reviewLiterature review
• More than More than 500 cases500 cases were included were included
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
Endocarditis and aortitisEndocarditis and aortitis
• 124 cases124 cases
Endocarditis and aortitisEndocarditis and aortitis
• 124 cases124 cases 40 other cases40 other cases
Endocarditis and aortitisEndocarditis and aortitis
• 124 cases124 cases
• Male gender:Male gender: 69.9% 69.9%
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)
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%
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).
Key featuresKey features
• Absence of immunosuppressionAbsence of immunosuppression
Key featuresKey features
• Absence of immunosuppressionAbsence of immunosuppression
• No bronchopulmonary aspergillosisNo bronchopulmonary aspergillosis
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
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.
AspergillusAspergillus species species
• A. fumigatusA. fumigatus: : 58.7%58.7%
AspergillusAspergillus species species
• A. fumigatusA. fumigatus: 58.7%: 58.7%
• A. terreusA. terreus:: 12.5% 12.5%
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%
Large destructive lesion on Large destructive lesion on the mitral valve the mitral valve
www.aspergillus.man.ac.uk
Hosking MC, et al. Ann Thorac Surg 1995; 59: 1015-7.
Large vegetationsLarge vegetations
DiagnosisDiagnosis
• Antemortem diagnosis:Antemortem diagnosis: 43.5% 43.5%
DiagnosisDiagnosis
• Antemortem diagnosis:Antemortem diagnosis: 43.5% 43.5%
– Vegetation, valve/graft examination:Vegetation, valve/graft examination: 23.4% 23.4%
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%
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)
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%.
DiagnosisDiagnosis
• Other diagnostic methods?Other diagnostic methods?
DiagnosisDiagnosis
• Other diagnostic methods?Other diagnostic methods?
Pemán J, et al. 2nd TIMM, Berlin 2005. P-048.
DiagnosisDiagnosis
• Other diagnostic methods?Other diagnostic methods?
Negative galactomannan
(ELISA)
Pemán J, et al. 2nd TIMM, Berlin 2005. P-048.
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)
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%.
Aortic graft infectionAortic graft infection
AspergillusAspergillus graft infection graft infection
• n=22n=22
• Almost all cases: Almost all cases: immunocompetent malesimmunocompetent males
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
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
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
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.
Brandt SJ, et al. Am J Med 1985; 79: 259-62.
Brandt SJ, et al. Am J Med 1985; 79: 259-62.
Definitive diagnostic proceduresDefinitive diagnostic procedures
• Culture of the excised aortic graftCulture of the excised aortic graft
• Culture of the excised aortic graftCulture of the excised aortic graft
• Culture of peripheral embolusCulture of peripheral embolus
Definitive diagnostic proceduresDefinitive diagnostic procedures
• 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
TreatmentTreatment
• Effective treatment:Effective treatment: removal of the graft removal of the graft
TreatmentTreatment
• Effective treatment: removal of the graftEffective treatment: removal of the graft
• Systemic Systemic antifungal therapyantifungal therapy
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.
Neurosurgical infectionNeurosurgical infection
Case reportCase report
• Female, Female, 16 year-old16 year-old
• Elective Elective neurosurgeryneurosurgery for Chiari I malformation for Chiari I malformation
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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
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.
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Case reportCase report
• CSF culture (day 18):CSF culture (day 18): few colonies of few colonies of
A. fumigatus.A. fumigatus.
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Is that a contaminant?Is that a contaminant?
Case reportCase report
• Symptoms persistedSymptoms persisted
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Case reportCase report
• Symptoms persistedSymptoms persisted
• Wound exploration:Wound exploration: sutures had dehisced sutures had dehisced
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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)
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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.
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Case reportCase report
• A. fumigatus A. fumigatus in the surgical specimensin the surgical specimens
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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
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
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.
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Aspergillosis after neurosurgeryAspergillosis after neurosurgery
• n=25n=25
Aspergillosis after neurosurgeryAspergillosis after neurosurgery
• n=25n=25
• Male sex:Male sex: 44.0% 44.0%
• n=25 n=25
• Male sex: 44.0%Male sex: 44.0%
• Steroids:Steroids: 52.0%52.0%
Aspergillosis after neurosurgeryAspergillosis after neurosurgery
• 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
• Median Median 3 months after surgery3 months after surgery (<1 to > 12) (<1 to > 12)
Aspergillosis after neurosurgeryAspergillosis after neurosurgery
• 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
• Antemortem diagnosis:Antemortem diagnosis: 64.0%64.0%
Aspergillosis after neurosurgeryAspergillosis after neurosurgery
• 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
• 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
• 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
Trans-sphenoidal surgeryTrans-sphenoidal surgery
Endo T, et al. Surg Neurol 2001; 56: 195-200.
Wound infectionWound infection
DefinitionsDefinitions
• Skin or subcutaneous tissueSkin or subcutaneous tissue of the incision of the incision
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
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.
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
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
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.
The first case reportedThe first case reported
• 19331933
Frank L, Alton OM. JAMA 1933; 100: 2007-8.
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.
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.
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.
ParticularitiesParticularities
• Median Median 17 days after surgery 17 days after surgery (<7 to 180)(<7 to 180)
ParticularitiesParticularities
• Median 17 days after surgery (<7 to 180)Median 17 days after surgery (<7 to 180)
• Many patients were Many patients were immunosuppressedimmunosuppressed
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%
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.
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.
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.
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.
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.
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.
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.
Ophthalmological Ophthalmological surgerysurgery
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.
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
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
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
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
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.
Surgical dental Surgical dental procedureprocedure
Surgical dental procedureSurgical dental procedure
• Connection between Connection between endodontic treatmentendodontic treatment and non- and non-
invasive sinus aspergillosisinvasive sinus aspergillosis
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
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.
TreatmentTreatment
TreatmentTreatment
• Optimal therapy:Optimal therapy: not specifically studied not specifically studied
TreatmentTreatment
• Optimal therapy: not specifically studiedOptimal therapy: not specifically studied
• Excision of the infected tissueExcision of the infected tissue
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
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
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
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.
PreventionPrevention
Main sources of infectionMain sources of infection
• Contaminated graftsContaminated grafts
Main sources of infectionMain sources of infection
• Contaminated graftsContaminated grafts
• Contaminated suturesContaminated sutures
Main sources of infectionMain sources of infection
• Contaminated graftsContaminated grafts
• Contaminated suturesContaminated sutures
• Intra-operative dispersion of spores.Intra-operative dispersion of spores.
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.
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.
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
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
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.
• 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
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
PreventionPrevention
• Tap water:Tap water: not on surgical wounds not on surgical wounds
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
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
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
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.
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
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
Heinemann S, et al. J Hosp Infect 2004; 57: 149-55.
Outbreak of Outbreak of A. flavusA. flavus wound infectionwound infection
Water leakageWater leakage
Heinemann S, et al. J Hosp Infect 2004; 57: 149-55.
RAPD resultsRAPD results
• 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
• 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
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
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
ConclusionConclusion
ConclusionConclusion
• Underappreciated problemUnderappreciated problem
ConclusionConclusion
• Underappreciated problemUnderappreciated problem
• Mortality:Mortality: high in non-cutaneous infections high in non-cutaneous infections
ConclusionConclusion
• Underappreciated problemUnderappreciated problem
• Mortality: high in non-cutaneous infectionsMortality: high in non-cutaneous infections
• Different organs and surgical proceduresDifferent organs and surgical procedures
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
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.
ConclusionConclusion
• Prevention:Prevention:
– Special care with the ventilation system in the surgical roomSpecial care with the ventilation system in the surgical room
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.
AcknowledgmentsAcknowledgments
• David W. DenningDavid W. Denning
AcknowledgmentsAcknowledgments• David W. DenningDavid W. Denning
• Fungal Research TrustFungal Research Trust
AcknowledgmentsAcknowledgments• David W. DenningDavid W. Denning
• Fungal Research TrustFungal Research Trust
• CAPESCAPES
[email protected]@manchester.ac.uk