hospital-acquired invasive aspergillosis: how big is the problem? michael phillips, md nyu medical...
TRANSCRIPT
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Hospital-acquired Invasive Aspergillosis:
How Big is the Problem?
Michael Phillips, MD
NYU Medical Center
New York, NY
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Disclaimer & Disclosure
• The views expressed here are my own, and not necessarily those of NYU Medical Center
• Financial disclosures: none
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Objectives
• Review the epidemiology of invasive Aspergillosis (IA)
• Discuss the extent IA is a nosocomial infection
• Present a surveillance system for hospital-associated IA
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Aspergillus –
• 38 species cause disease• Common in the environment:
– Soil– Plants– Dust– Building materials– Food– Water
Image: Fungal Research Trust
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Is Aspergillus an Emerging Pathogen?
Images: Fungal Research Trust
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Prevalence of IA at Autopsy
Fungus
No. of Patients (%)
P1972-82(n=2956)
1983-87(n=2718)
1988-92(n=2450)
Candida 51 (1.7) 47 (1.7) 31 (1.3) 0.3
Aspergillus 11 (0.4) 32 (1.2) 76 (3.1) <0.001
Mucor 4 (0.1) -- 1 (<0.1) 0.1
Unclassified -- 2 (<0.1) 8 (0.3) 0.002
Groll AH, J of Infection 1996;33:23-32
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Prevalence of IA at Autopsy
Fungus
No. of Patients (%)
P1972-82(n=2956)
1983-87(n=2718)
1988-92(n=2450)
Candida 51 (1.7) 47 (1.7) 31 (1.3) 0.3
Aspergillus 11 (0.4) 32 (1.2) 76 (3.1) <0.001
Mucor 4 (0.1) -- 1 (<0.1) 0.1
Unclassified -- 2 (<0.1) 8 (0.3) 0.002
Groll AH, J of Infection 1996;33:23-32
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McNeil et al, Clin Infect Dis 2001;33:641
Changing Incidence of Invasive Fungal Disease in Patients without HIV
0.6
0.4
0.2
Ra
te p
er
100
,000
1981 1986 1991 1996
Year
Candida species
Aspergillus species
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Solid Organ Transplantation:United States, 1985 – 2005
Source: Organ Procurement and Transplantation Network
0
5,000
10,000
15,000
20,000
1985 1990 1995 2000 2005
kidney
liver
heart
lung
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Type% Incidence (mean, range) Risk Factor
Lung 8, 3–14Allograph rejection,
CMV infection
Heart 6, 0–11 No data
Liver 1.7, 1–8Allograph rejection, dialysis,
Kidney 0.7, 0–0.9Allograph rejection, augmented immunosuppression
Singh, JAC 2000;45:749-755
IA Incidence and Risk Factors in Solid Organ Transplant Recipients
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Type% Incidence (mean, range) Risk Factor
Lung 8, 3–14Allograph rejection,
CMV infection
Heart 6, 0–11 No data
Liver 1.7, 1–8Allograph rejection, dialysis,
Kidney 0.7, 0–0.9Allograph rejection, augmented immunosuppression
Singh, JAC 2000;45:749-755
IA Incidence and Risk Factors in Solid Organ Transplant Recipients
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Hematopoietic Stem Cell Transplantation: United States, 2000 – 2007
0
1,000
2,000
3,000
4,000
2000 2001 2002 2003 2004 2005 2006 2007
Source: US Department of Health and Human Services
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Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.
Marr, K. A. et al. Blood 2002;100:4358-4366
Incidence of IA: Allogeneic HSCT
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Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.
Marr, K. A. et al. Blood 2002;100:4358-4366
IA in Patients after HSCT
• 1682 patients after HSCT• Cases: 187• Controls: 1495
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IA in Patients with Hematologic Malignancies
Invasive AspergillosisControl(n=133) P
Proven(n=9)
Probable(n=3)
Possible(n=33)
Age
(mean years)46.8 50.3 45.3 44.9 0.65
Female
(%)33% 33% 54% 50% 0.86
Comorbidity score (mean) 0.22 0 0.24 0.25 0.74
Neutropenia (mean days) 18.7 37.6 19.6 9.9 <0.001
Mulemann K, et al, Leukemia 2005;19:545-550
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IA in Patients with Hematologic Malignancies
Invasive AspergillosisControl(n=133) P
Proven(n=9)
Probable(n=3)
Possible(n=33)
Age
(mean years)46.8 50.3 45.3 44.9 0.65
Female
(%)33% 33% 54% 50% 0.86
Comorbidity score (mean) 0.22 0 0.24 0.25 0.74
Neutropenia (mean days) 18.7 37.6 19.6 9.9 <0.001
Mulemann K, et al, Leukemia 2005;19:545-550
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Is IA a Nosocomial Infection?
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Difficult question!
Is IA a Nosocomial Infection?
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Difficult question!• Incubation period unknown
Is IA a Nosocomial Infection?
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Difficult question!• Incubation period unknown• Role of colonization
Is IA a Nosocomial Infection?
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Difficult question!• Incubation period unknown• Role of colonization• Community associated infections
Is IA a Nosocomial Infection?
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Is there a correlation between:environmental Aspergillus
concentrations and incidence of invasive Aspergillosis?
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Measurement of Environmental Fungal Contamination and IA in Hematology Patients
• Prospective study over a 4 years
• 3 units (BMT, 2 hematology wards)
Alberti C, et al J. Hospital Infection 2001,48:198-206
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Measurement of Environmental Fungal Contamination and IA in Hematology Patients
• Prospective study over a 4 years
• 3 units (BMT, 2 hematology wards)
• Inclusion: allogenic HSCT, acute leukemia
Alberti C, et al J. Hospital Infection 2001,48:198-206
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Measurement of Environmental Fungal Contamination and IA in Hematology Patients
• Prospective study over a 4 years
• 3 units (BMT, 2 hematology wards)
• Inclusion: allogenic HSCT, acute leukemia
• Probable and definite IA case definition
• Systematic air and surface sampling
Alberti C, et al J. Hospital Infection 2001,48:198-206
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Results
• 64 hospital-acquired IA cases identified
• No clusters or seasonal variation
Alberti C, et al J. Hospital Infection 2001,48:198-206
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Results
• 64 hospital-acquired IA cases identified
• No clusters or seasonal variation
• Incidence rate: 0 – 2.59 per 1000 pt-days
Alberti C, et al J. Hospital Infection 2001,48:198-206
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Results
• 64 hospital-acquired IA cases identified
• No clusters or seasonal variation
• Incidence rate: 0 – 2.59 per 1000 pt-days
• Increase in environmental fungal cultures
prior to hospital-acquired IA case
– Statistically significant in non-protected
areas
Alberti C, et al J. Hospital Infection 2001,48:198-206
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Efficacy of Protective Measures during Outbreaks
• 10 A. flavus infections in a hematology patients during 6 month period
Hahn TH, Inf Cont Hosp Epi 2002, 23;525
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Efficacy of Protective Measures during Outbreaks
• 10 A. flavus infections in a hematology patients during 6 month period
• Construction project
Hahn TH, Inf Cont Hosp Epi 2002, 23;525
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Efficacy of Protective Measures during Outbreaks
• 10 A. flavus infections in a hematology patients during 6 month period
• Construction project– 9 cases in 35 patients on unit without
HEPA filtration– 1 case in 20 patients on unit with HEPA
filtration
Hahn TH, Inf Cont Hosp Epi 2002, 23;525
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CDC Recommendations
• Enhanced protective measures HSCT recipients during construction– Specific steps at construction site to
reduce risk of exposure to dust– Consider HEPA air filtration for high risk
patients– Surveillance for IA
CDC, MMWR 2000,49(rr10);1-128
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Surveillance:
• Autopsy• Pathology specimens• Unit surveillance• Microbiology
– Culture results– Galactomannan EIA– Aspergillus PCR
• Radiology– Chest CT scan
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2002: International Consensus Statement• Standardized definition for invasive fungal
disease– Host factors– Clinical manifestations– Mycological evidence
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2002: International Consensus Statement• Standardized definition for invasive fungal
disease– Host factors– Clinical manifestations– Mycological evidence
• Proven, probable, possible categories
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2002: International Consensus Statement• Standardized definition for invasive fungal
disease– Host factors– Clinical manifestations– Mycological evidence
• Proven, probable, possible categories• Ascioglu S, Clin Inf Dis 2002;34,7
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2002: International Consensus Statement• Standardized definition for invasive fungal
disease– Host factors– Clinical manifestations– Mycological evidence
• Proven, probable, possible categories• Ascioglu S, Clin Inf Dis 2002;34,7
• Recent revision: DePauw B, Clin Inf Dis 2008;46,1813
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Microbiological Surveillance
0
1
2
3
4
5
6
7
Jan Mar May July Sept Nov Jan Mar
Month of culture
# of clinical cultures
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Methods
Surveillance criteria:• Inpatient 7 days with any of the following :
– Mycological evidence of Aspergillus sp.– CT scan (CT) report containing specific
key word(s)– Pathology reports consistent with invasive
fungal infection• Excluded: prior diagnosis of Aspergillosis
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Methods
Surveillance criteria:• Inpatient 7 days with any of the following :
– Mycological evidence of Aspergillus sp.– CT scan (CT) report containing specific
key word(s)– Pathology reports consistent with invasive
fungal infection• Excluded: prior diagnosis of Aspergillosis
Investigated using consensus case definition
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Results
• 45 patients met surveillance criteria
• 10 case-patients – 5 possible– 2 probable– 3 proven
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Epidemic curve
0
1
2
3
4
1st 2nd 3rd 4th 1st 2nd 3rd
Quarter
# meeting case definition
Proven
Probable
Possible
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Summary
• Incidence of IA is increasing
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Summary
• Incidence of IA is increasing
• IA is a healthcare-associated infection
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Summary
• Incidence of IA is increasing
• IA is a healthcare-associated infection
• Implementation of protective measures can
be successful
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Summary
• Incidence of IA is increasing
• IA is a healthcare-associated infection
• Implementation of protective measures can
be successful
• Systematic, ongoing surveillance for IA is
needed
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Thank you!
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Proven:Hyphae on histopathology or cytopathology from a specimen with evidence of tissue damage
orPositive culture from a normally sterile site with clinical or radiographic evidence of infection
Probable:Patient with specific host factors plus
Positive microbiology results and1 major or 2 minor clinical features
Possible:Patient with specific host factors and attending physician documentation that invasive Aspergillosis likely plus:
Positive microbiology results or1 major or 2 minor clinical features