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

2. Case report Male, 70 year-oldMale, 70 year-old Elective aortic valve replacementElective aortic valve replacement www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

3. Case report Male, 70 year-oldMale, 70 year-old Elective aortic valve replacementElective aortic valve replacement 4 months: fatigue and physical endurance4 months: fatigue and physical endurance www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

4. Case report Male, 70 year-oldMale, 70 year-old Elective aortic valve replacementElective aortic valve replacement 4 months: fatigue and physical endurance4 months: fatigue and physical endurance 7 months: profuse diarrhoea7 months: profuse diarrhoea www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

5. Case report Male, 70 year-oldMale, 70 year-old Elective aortic valve replacementElective aortic valve replacement 4 months: fatigue and physical endurance4 months: fatigue and physical endurance 7 months: profuse diarrhoea7 months: profuse diarrhoea One week later: chills + feverOne week later: chills + fever 19,000 x 10 6 leukocytes.19,000 x 10 6 leukocytes. www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

6. Case report TEE: large aortic vegetationTEE: large aortic vegetation www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

7. Case report TEE: large aortic vegetationTEE: large aortic vegetation Blood cultures: negativeBlood cultures: negative www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

8. Case report TEE: large aortic vegetationTEE: large aortic vegetation Blood cultures: negativeBlood cultures: negative Working diagnosis: viridans strep endocarditisWorking diagnosis: viridans strep endocarditis www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

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

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

11. Case 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 doxycycline were added.Vancomycin and doxycycline were added. www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

12. Case report After 2 days: hemiparesis and aphasiaAfter 2 days: hemiparesis and aphasia www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

13. Case report After 2 days: hemiparesis and aphasiaAfter 2 days: hemiparesis and aphasia He died three days laterHe died three days later www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

14. Case 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 haemorrhage –Embolus containing Aspergillus in the right middle cerebral artery www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

15. Case 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 haemorrhage –Embolus containing Aspergillus in the right middle cerebral artery –Endocarditis lesion: multiple hyphae www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

16. Case 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 haemorrhage –Embolus containing Aspergillus in the right middle cerebral artery –Endocarditis lesion: multiple hyphae –No other site of infection was found. www.aspergillus.man.ac.uk/secure/casehistories/case048.htm

17. Is that correct?

18. Would someone have suspected aspergillosis?

19. Aspergillosis Aspergillus are ubiquitousAspergillus are ubiquitous –Soil, water and decaying vegetation

20. Aspergillosis Aspergillus are ubiquitousAspergillus are ubiquitous –Soil, water and decaying vegetation Primarily acquired by inhalationPrimarily acquired by inhalation

21. Aspergillosis Aspergillus are ubiquitousAspergillus are ubiquitous –Soil, water and decaying vegetation Primarily acquired by inhalationPrimarily acquired by inhalation Nosocomial aspergillosis typically affects immunocompromised patients.Nosocomial aspergillosis typically affects immunocompromised patients.

22. That is not all the story …

23. The spectrum of aspergillosis Frequency of aspergillosis www.aspergillus.man.ac.uk

24. The spectrum of aspergillosis Immune system Frequency of aspergillosis www.aspergillus.man.ac.uk

25. The spectrum of aspergillosis Disfunction Frequency of aspergillosis Immune system www.aspergillus.man.ac.uk

26. The spectrum of aspergillosis Acute IA Frequency of aspergillosis Disfunction Immune system www.aspergillus.man.ac.uk

27. The spectrum of aspergillosis Acute IA Subacute IA Frequency of aspergillosis Disfunction Immune system www.aspergillus.man.ac.uk

28. The spectrum of aspergillosis Acute IA Subacute IA. Tracheobronchitis Fungus ball Chronic cavitary Chronic fibrosing Frequency of aspergillosis Disfunction Immune system Normal www.aspergillus.man.ac.uk

29. The spectrum of aspergillosis Acute IA Subacute IA ABPA Allergic sinusitis. Frequency of aspergillosis Disfunction Immune system NormalHyper immune Tracheobronchitis Fungus ball Chronic cavitary Chronic fibrosing www.aspergillus.man.ac.uk

30. What about postoperative aspergillosis?

31. Review of the world literature Medline, LILACS and EMBASEMedline, LILACS and EMBASE

32. References were reviewedReferences were reviewed Review of the world literature

33. Medline, LILACS and EMBASEMedline, LILACS and EMBASE References were reviewedReferences were reviewed Conference abstracts (www.aspergillus.man.ac.uk)Conference abstracts (www.aspergillus.man.ac.uk) Review of the world literature

34. Medline, LILACS and EMBASEMedline, LILACS and EMBASE References were reviewedReferences were reviewed Conference abstracts (www.aspergillus.man.ac.uk)Conference abstracts (www.aspergillus.man.ac.uk) Only cases of proven or probable aspergillosis were reviewed.Only cases of proven or probable aspergillosis were reviewed. Review of the world literature

35. Not included:Not included: –Primary cutaneous aspergillosis Review of the world literature

36. Not included:Not included: –Primary cutaneous aspergillosis Review of the world literature Neonate Andresen J, et al. Acta Paediatr 2005; 94: 761-2.

37. Not included:Not included: –Primary cutaneous aspergillosis Review of the world literature Neonate Diabetes mellitus

38. Not included:Not included: –Primary cutaneous aspergillosis Review of the world literature Neonate Diabetes mellitus Burn patient www.aspergillus.man.ac.uk

39. Not included:Not included: –Infections associated with intravascular devices Review of the world literature

40. Not included:Not included: –Infections associated with intravascular devices Review of the world literature Neutropenia

41. Not included:Not included: –Infections associated with intravascular devices Review of the world literature Neutropenia HIV

42. Literature review More than 500 cases were includedMore than 500 cases were included

43. Literature review –Heart surgery: 188 –Dental surgery: > 100 –Ophthalmologic surgery: > 90 –Wound infections: 22 –Neurosurgery: 25 –Vascular prosthetic surgery: 22 –Orthopaedic surgery: 42 –Bronchial infections: 30 –Abdominal surgery: 10 –Mediastinitis: 11 –Breast surgery: 5 –Pleural aspergillosis: 1 More than 500 cases were includedMore than 500 cases were included

44. Endocarditis and aortitis 124 cases124 cases

45. Endocarditis and aortitis 124 cases40 other cases124 cases40 other cases

46. Endocarditis and aortitis 124 cases124 cases Male gender: 69.9%Male gender: 69.9%

47. Endocarditis 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)

48. Endocarditis 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% –Mitral: 30.6%

49. Endocarditis 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% –Mitral: 30.6% Median 2.7 months after surgery ( 12).Median 2.7 months after surgery ( 12).

50. Key features Absence of immunosuppressionAbsence of immunosuppression

51. Key features Absence of immunosuppressionAbsence of immunosuppression No bronchopulmonary aspergillosisNo bronchopulmonary aspergillosis

52. Key features Absence of immunosuppressionAbsence of immunosuppression No bronchopulmonary aspergillosisNo bronchopulmonary aspergillosis Postoperative course consistent with culture-negative endocarditisPostoperative course consistent with culture-negative endocarditis

53. Key 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 late embolisation.Propensity to late embolisation.

54. Aspergillus species A. fumigatus: 58.7%A. fumigatus: 58.7%

55. Aspergillus species A. fumigatus: 58.7%A. fumigatus: 58.7% A. terreus: 12.5%A. terreus: 12.5%

56. Aspergillus species A. fumigatus: 58.7%A. fumigatus: 58.7% A. terreus: 12.5%A. terreus: 12.5% A. flavus: 11.2%A. flavus: 11.2% A. niger: 11.2%A. niger: 11.2% A. glaucus: 2.5%A. glaucus: 2.5% A. clavatus: 1.2%A. clavatus: 1.2% A. ustus: 1.2%A. ustus: 1.2% A. sydowi: 1.2%A. sydowi: 1.2% A. spp: 20.0%A. spp: 20.0%

57. Large destructive lesion on the mitral valve www.aspergillus.man.ac.uk

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

59. Diagnosis Antemortem diagnosis: 43.5%Antemortem diagnosis: 43.5%

60. Diagnosis –Vegetation, valve/graft examination: 23.4%

61. Diagnosis Antemortem diagnosis: 43.5%Antemortem diagnosis: 43.5% –Vegetation, valve/graft examination: 23.4% –Embolic material: 16.9%

62. Diagnosis Antemortem diagnosis: 43.5%Antemortem diagnosis: 43.5% –Vegetation, valve/graft examination: 23.4% –Embolic material: 16.9% –Positive blood culture: 6.4% (n=8)

63. Diagnosis Antemortem diagnosis: 43.5%Antemortem diagnosis: 43.5% –Vegetation, valve/graft examination: 23.4% –Embolic material: 16.9% –Positive blood culture: 6.4% (n=8) –Serology/precipitins: 2.4%.

64. Diagnosis Other diagnostic methods?Other diagnostic methods?

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

66. Diagnosis Other diagnostic methods?Other diagnostic methods? Negative galactomannan (ELISA) Pemán J, et al. 2 nd TIMM, Berlin 2005. P-048.

67. Mortality Overall mortality: 92.7%Overall mortality: 92.7%

68. Mortality Antemortem diagnosis: mortality 83.0%Antemortem diagnosis: mortality 83.0%(p<0.0001)

69. Mortality Overall mortality: 92.7%Overall mortality: 92.7% Antemortem diagnosis: mortality 83.0%Antemortem diagnosis: mortality 83.0%(p<0.0001) Surgical treatment: 80.9%.Surgical treatment: 80.9%.

70. Aortic graft infection

71. Aspergillus graft infection n=22n=22

72. Aspergillus graft infection n=22n=22 Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males

73. Aspergillus graft infection n=22n=22 Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males Median 8 months after surgeryMedian 8 months after surgery

74. Aspergillus graft infection n=22n=22 Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males Median 8 months after surgeryMedian 8 months after surgery –Candida graft infections: usually < 6 weeks

75. Aspergillus graft infection n=22n=22 Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males Median 8 months after surgeryMedian 8 months after surgery –Candida graft infections: usually < 6 weeks Similar to S. epidermidis infectionSimilar to S. epidermidis infection

76. Aspergillus graft infection n=22n=22 Almost all cases: immunocompetent malesAlmost all cases: immunocompetent males Median 8 months after surgeryMedian 8 months after surgery –Candida graft infections: usually < 6 weeks Similar to S. epidermidis infectionSimilar to S. epidermidis infection Suture line of a previous aortotomy.Suture line of a previous aortotomy.

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

79. Definitive diagnostic procedures Culture of the excised aortic graftCulture of the excised aortic graft

80. Culture of peripheral embolusCulture of peripheral embolus Definitive diagnostic procedures

81. 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 procedures

82. Treatment Effective treatment: removal of the graftEffective treatment: removal of the graft

83. Treatment Systemic antifungal therapySystemic antifungal therapy

84. Treatment Effective treatment: removal of the graftEffective treatment: removal of the graft Systemic antifungal therapySystemic antifungal therapy Extra-anatomic bypass through a clean field.Extra-anatomic bypass through a clean field.

85. Neurosurgical infection

86. Case report Female, 16 year-oldFemale, 16 year-old Elective neurosurgery for Chiari I malformationElective neurosurgery for Chiari I malformation www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

87. Case 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

88. Case 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 cefotaxime –Dexamethasone dose was increased. www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

89. Case report CSF culture (day 18): few colonies of A. fumigatus.CSF culture (day 18): few colonies of A. fumigatus. www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

90. Is that a contaminant?

91. Case report Symptoms persistedSymptoms persisted www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

92. Case report Symptoms persistedSymptoms persisted Wound exploration: sutures had dehiscedWound exploration: sutures had dehisced www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

93. Case report Symptoms persistedSymptoms persisted Wound exploration: sutures had dehiscedWound exploration: sutures had dehisced Cultures again revealed A. fumigatusCultures again revealed A. fumigatus Amphotericin B was started (day 28)Amphotericin B was started (day 28) www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

94. Case report Symptoms persistedSymptoms persisted Wound exploration: sutures had dehiscedWound exploration: sutures had dehisced Cultures again revealed A. fumigatusCultures again revealed A. 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

95. Case report A. fumigatus in the surgical specimensA. fumigatus in the surgical specimens www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

96. Case report A. fumigatus in the surgical specimensA. fumigatus in the surgical specimens She died 2 months after the 1 st surgeryShe died 2 months after the 1 st surgery www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

97. Case report A. fumigatus in the surgical specimensA. fumigatus in the surgical specimens She died 2 months after the 1 st surgeryShe died 2 months after the 1 st surgery Autopsy:Autopsy: –Abundant hyphae in the origin of the basilar artery and bilateral vertebral arteries –Multifocal transmural destruction of arterial walls www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

98. Case report A. fumigatus in the surgical specimensA. fumigatus in the surgical specimens She died 2 months after the 1 st surgeryShe died 2 months after the 1 st surgery Autopsy:Autopsy: –Abundant hyphae in the origin of the basilar artery and bilateral vertebral arteries –Multifocal transmural destruction of arterial walls –No other focus of aspergillosis was found. www.aspergillus.man.ac.uk/secure/casehistories/case050.htm

99. Aspergillosis after neurosurgery n=25n=25

100. Aspergillosis after neurosurgery n=25n=25 Male sex: 44.0%Male sex: 44.0%

101. n=25n=25 Male sex: 44.0%Male sex: 44.0% Steroids: 52.0%Steroids: 52.0% Aspergillosis after neurosurgery

102. n=25n=25 Male sex: 44.0%Male sex: 44.0% Steroids: 52.0%Steroids: 52.0% All proven cases: A. fumigatus.All proven cases: A. fumigatus. Aspergillosis after neurosurgery

103. Median 3 months after surgery ( 12)Median 3 months after surgery ( 12) Aspergillosis after neurosurgery

104. Median 3 months after surgery ( 12)Median 3 months after surgery ( 12) Different presentationsDifferent presentations –Meningitis –CNS abscess –Mycotic aneurisms –Infarction. Aspergillosis after neurosurgery

105. Antemortem diagnosis: 64.0%Antemortem diagnosis: 64.0% Aspergillosis after neurosurgery

106. Antemortem diagnosis: 64.0%Antemortem diagnosis: 64.0% –Abscess examination: 36.0% Aspergillosis after neurosurgery www.aspergillus.man.ac.uk/secure/image_library/invpulmonaryasp/cerebralaspkh.htm

107. Antemortem diagnosis: 64.0%Antemortem diagnosis: 64.0% –Abscess examination: 36.0% –Culture of CSF: 20.0% Aspergillosis after neurosurgery

108. Antemortem diagnosis: 64.0%Antemortem diagnosis: 64.0% –Abscess examination: 36.0% –Culture of CSF: 20.0% Mortality: 68.0%.Mortality: 68.0%. Aspergillosis after neurosurgery

109. Trans-sphenoidal surgery Endo T, et al. Surg Neurol 2001; 56: 195-200.

110. Wound infection

111. Definitions Skin or subcutaneous tissue of the incisionSkin or subcutaneous tissue of the incision

112. Definitions When both superficial and deep incision sites: classified as deep surgical site infectionWhen both superficial and deep incision sites: classified as deep surgical site infection

113. Definitions Skin or subcutaneous tissue of the incisionSkin or subcutaneous tissue of the incision When both superficial and deep incision sites: classified as deep surgical site infectionWhen both superficial and deep incision sites: classified as deep surgical site infection Similar to CDCs criteria for SSI.Similar to CDCs criteria for SSI.

114. Definitions The wound itself had to be non-healing with standard antibiotics, and other pathogens were absent or minimally presentedThe wound itself had to be non-healing with standard antibiotics, and other pathogens were absent or minimally presented

115. Definitions Topographic relation between the surgery and the infectionTopographic relation between the surgery and the infection

116. Definitions The wound itself had to be non-healing with standard antibiotics, and other pathogens were absent or minimally presentedThe wound itself had to be non-healing with standard antibiotics, and 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.

117. The first case reported 19331933 Frank L, Alton OM. JAMA 1933; 100: 2007-8.

118. The 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.

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

120. The 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. niger grew in the surgical dressings covered with a dark powder.A. niger grew in the surgical dressings covered with a dark powder. Frank L, Alton OM. JAMA 1933; 100: 2007-8.

121. Particularities Median 17 days after surgery (<7 to 180)Median 17 days after surgery (<7 to 180)

122. Particularities Many patients were immunosuppressedMany patients were immunosuppressed

123. Particularities Median 17 days after surgery (<7 to 180)Median 17 days after surgery (<7 to 180) Many patients were immunosuppressedMany patients were immunosuppressed Aspergillus species:Aspergillus species: –A. fumigatus: 42.1% –A. flavus: 36.8% –A. niger: 10.5% –A. spp: 10.5%

124. Risk of dissemination Aggressive combined medical therapy and debridement is required for all patients.Aggressive combined medical therapy and debridement is required for all patients.

125. Outbreaks Outbreak of wound aspergillosisOutbreak of wound aspergillosis –Contamination during hospital construction of the outside packages of dressing supplies Bryce EA, et al. Infect Control Hosp Epidemiol 1996; 17: 170-2.

126. Outbreaks Outbreak of wound aspergillosisOutbreak of wound aspergillosis –Contamination during hospital construction of the outside packages of dressing supplies Outbreaks of cutaneous aspergillosisOutbreaks of cutaneous aspergillosis –Wound dressing and tape should be cultured Bryce EA, et al. Infect Control Hosp Epidemiol 1996; 17: 170-2.

127. Outbreaks Outbreak of wound aspergillosisOutbreak of wound aspergillosis –Contamination during hospital construction of the outside packages of dressing supplies Outbreaks of cutaneous aspergillosisOutbreaks of cutaneous aspergillosis –Wound dressing and tape should be cultured A. flavus sternal wound infection coinciding with hospital renovation activities.A. flavus sternal wound infection coinciding with hospital renovation activities. Bryce EA, et al. Infect Control Hosp Epidemiol 1996; 17: 170-2.

128. Risk factors Chronic lung diseaseChronic lung disease –Independent risk factor for A. fumigatus sternal wound infection after open-heart surgery Richet HM, et al. Am J Epidemiol 1992; 135: 48-58.

129. Risk factors Chronic lung diseaseChronic lung disease –Independent risk factor for A. fumigatus sternal wound infection after open-heart surgery –A. fumigatus grew at the same time from the bronchial washing of one patient Richet HM, et al. Am J Epidemiol 1992; 135: 48-58.

130. Risk factors Chronic lung diseaseChronic lung disease –Independent risk factor for A. fumigatus sternal wound infection after open-heart surgery –A. fumigatus grew at the same time from the bronchial washing of one patient –Colonised patients may be at increased risk. Richet HM, et al. Am J Epidemiol 1992; 135: 48-58.

131. Ophthalmological surgery

132. Usually keratitis; rarely endophthalmitisUsually keratitis; rarely endophthalmitis Tabbara KF, et al. Ophthalmology 1998; 105: 522-6.Sridhar MS, et al. Am J Ophthalmol 2000; 129: 802-4.

133. Ophthalmological surgery Usually keratitis; rarely endophthalmitisUsually keratitis; rarely endophthalmitis Many different proceduresMany different procedures –Penetrating keratoplasty –Radial keratotomy –Excimer laser photorefractive keratectomy –Laser-assisted in situ keratomileusis –Pterygium excision –Cataract surgery –Scleral buckling procedures –Hydroxyapatite orbital implant surgery –Sutureless surgery –Trabeculectomy

134. Ophthalmological 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

135. Ophthalmological 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 construction

136. Ophthalmological 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 construction –Contaminated irrigating fluids used during surgery

137. Ophthalmological 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 construction –Contaminated irrigating fluids used during surgery –Many occurred after non-surgical corneal trauma.

138. Surgical dental procedure

139. Connection between endodontic treatment and non-invasive sinus aspergillosisConnection between endodontic treatment and non-invasive sinus aspergillosis

140. Surgical 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

141. Surgical 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 material –Promote aeration –Antifungals only if invasion.

142. Treatment

143. Treatment Optimal therapy: not specifically studiedOptimal therapy: not specifically studied

144. Treatment Excision of the infected tissueExcision of the infected tissue

145. Treatment 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

146. Treatment 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

147. Treatment 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

148. Treatment 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: unknown.Duration: unknown.

149. Prevention

150. Main sources of infection Contaminated graftsContaminated grafts

151. Main sources of infection Contaminated graftsContaminated grafts Contaminated suturesContaminated sutures

152. Main sources of infection Contaminated graftsContaminated grafts Contaminated suturesContaminated sutures Intra-operative dispersion of spores.Intra-operative dispersion of spores.

153. Linking the infection with the surgical room Pigeon excreta in the immediate vicinity of the ventilator intake port were found to harbour large numbers of Aspergillus sporesPigeon excreta in the immediate vicinity of the ventilator intake port were found to harbour large numbers of Aspergillus spores Gage AA, et al. Arch Surg 1970; 101: 384-87.

154. Linking the infection with the surgical room Air conditioner cooling coils and pigeon droppings on the ledges outside the suite were found to harbour Aspergillus spores in large amounts.Air conditioner cooling coils and pigeon droppings on the ledges outside the suite were found to harbour Aspergillus spores in large amounts. Mehta G. J Hosp Infect 1990; 15: 245-53.

156. Infection acquired in the ICU Carlson GL, et al. J Infect 1996; 33: 119-21 Carlson GL, et al. J Infect 1996; 33: 119-21. Multiple abdominal visceral infection by A. fumigatus occurred after laparostomyMultiple abdominal visceral infection by A. fumigatus occurred after laparostomy

157. Infection acquired in the ICU Carlson GL, et al. J Infect 1996; 33: 119-21 Carlson GL, et al. J Infect 1996; 33: 119-21. Dark patches on the liver invading liver capsule Multiple abdominal visceral infection by A. fumigatus occurred after laparostomyMultiple abdominal visceral infection by A. fumigatus occurred after laparostomy

158. Infection acquired in the ICU Multiple abdominal visceral infection by A. fumigatus occurred after laparostomyMultiple abdominal visceral infection by A. fumigatus occurred after laparostomy Sampling of air from the ICU yielded one isolate that matched the patient's isolates.Sampling of air from the ICU yielded one isolate that matched the patient's isolates. Carlson GL, et al. J Infect 1996; 33: 119-21.

159. Grilles of heat exchanger used to maintain extracorporeal blood at the proper temperature.Grilles of heat exchanger used to maintain extracorporeal blood at the proper temperature. Diaz-Guerra TM, et al. J Clin Microbiol 2000; 38: 2419-22. Fomites as a reservoir

160. Diaz-Guerra TM, et al. J Clin Microbiol 2000; 38: 2419-22. RAPD patterns Three primersThree primers (A, B, C) 1, 2:1, 2: –Environmental 3:3: –Aortic prosthesis

161. Prevention Tap water: not on surgical woundsTap water: not on surgical wounds

162. Prevention Conventional ventilation and filters only remove airborne particles 5 mConventional ventilation and filters only remove airborne particles 5 m

163. Prevention Tap water: not on surgical woundsTap water: not on surgical wounds Conventional ventilation and filters only remove airborne particles 5 mConventional ventilation and filters only remove airborne particles 5 m Laminar airflow systems and HEPA filtrationLaminar airflow systems and HEPA filtration

164. Prevention Tap water: not on surgical woundsTap water: not on surgical wounds Conventional ventilation and filters only remove airborne particles 5 mConventional ventilation and filters only remove airborne particles 5 m Laminar airflow systems and HEPA filtrationLaminar airflow systems and HEPA filtration –Lack of data revealing survival benefit –Costs

165. Prevention Tap water: not on surgical woundsTap water: not on surgical wounds Conventional ventilation and filters only remove airborne particles 5 mConventional ventilation and filters only remove airborne particles 5 m Laminar airflow systems and HEPA filtrationLaminar airflow systems and HEPA filtration –Lack of data revealing survival benefit –Costs –Lack of consensus about the level of airborne conidia at which the risk can be numerically defined.

166. Heinemann S, et al. J Hosp Infect 2004; 57: 149-55. HEPAfiltration Offices, meeting rooms, lounges, utilities, storage rooms HEPA filtration is important but maybe not enough HEPAfiltration

167. Heinemann S, et al. J Hosp Infect 2004; 57: 149-55. Outbreak of A. flavus wound infection Heavily contaminated areas

168. Heinemann S, et al. J Hosp Infect 2004; 57: 149-55. Outbreak of A. flavus wound infection Water leakage

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

170. Investigating Aspergillus infections Fox BC. Am J Infect Control 1990; 18: 300-6. Penicillium in the OR

171. 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. Penicillium in the OR

172. Fox BC. Am J Infect Control 1990; 18: 300-6. Terminal units lined with fibreglass served as a substrate for fungal growth. Penicillium in the OR

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

174. Conclusion

175. Conclusion Underappreciated problemUnderappreciated problem

176. Conclusion Mortality: high in non-cutaneous infectionsMortality: high in non-cutaneous infections

177. Conclusion Underappreciated problemUnderappreciated problem Mortality: high in non-cutaneous infectionsMortality: high in non-cutaneous infections Different organs and surgical proceduresDifferent organs and surgical procedures

178. Conclusion 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

179. Conclusion 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 medical and surgical therapy.Combined aggressive medical and surgical therapy.

180. Conclusion Prevention:Prevention: –Special care with the ventilation system in the surgical room

181. Conclusion Prevention:Prevention: –Special care with the ventilation system in the surgical room –Proper storage and disinfection of surgical material.

182. Acknowledgments David W. DenningDavid W. Denning

183. Acknowledgments Fungal Research TrustFungal Research Trust

184. Acknowledgments David W. DenningDavid W. Denning Fungal Research TrustFungal Research Trust CAPESCAPESalessandro.pasqualotto@manchester.ac.uk