Hospital-acquired Invasive Aspergillosis: How Big is the Problem? Michael Phillips, MD NYU Medical Center New York, NY

Disclaimer & Disclosure The views expressed here are my own, and not necessarily those of NYU Medical Center Financial disclosures: none

Objectives Review the epidemiology of invasive Aspergillosis (IA) Discuss the extent IA is a nosocomial infection Present a surveillance system for hospital-associated IA

Image: Fungal Research Trust Aspergillus – 38 species cause disease Common in the environment: Soil Plants Dust Building materials Food Water Over 200 species worldwide Spore forming head of Asp. Fumigatus Inhale 100-200 spores daily Image: Fungal Research Trust

Is Aspergillus an Emerging Pathogen? Images: Fungal Research Trust Aspergillus flavus on left Aspergillus fumigatus on right Both: malt extract agar Images: Fungal Research Trust

Prevalence of IA at Autopsy Fungus No. of Patients (%) P 1972-82 (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

Prevalence of IA at Autopsy Fungus No. of Patients (%) P 1972-82 (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

Changing Incidence of Invasive Fungal Disease in Patients without HIV 0.6 0.4 0.2 Rate per 100,000 1981 1986 1991 1996 Year Candida species Aspergillus species McNeil et al, Clin Infect Dis 2001;33:641

Solid Organ Transplantation: United States, 1985 – 2005 Source: Organ Procurement and Transplantation Network

IA Incidence and Risk Factors in Solid Organ Transplant Recipients Type % Incidence (mean, range) Risk Factor Lung 8, 3–14 Allograph rejection, CMV infection Heart 6, 0–11 No data Liver 1.7, 1–8 Allograph rejection, dialysis, Kidney 0.7, 0–0.9 Allograph rejection, augmented immunosuppression Singh, JAC 2000;45:749-755

IA Incidence and Risk Factors in Solid Organ Transplant Recipients Type % Incidence (mean, range) Risk Factor Lung 8, 3–14 Allograph rejection, CMV infection Heart 6, 0–11 No data Liver 1.7, 1–8 Allograph rejection, dialysis, Kidney 0.7, 0–0.9 Allograph rejection, augmented immunosuppression Singh, JAC 2000;45:749-755

Hematopoietic Stem Cell Transplantation: United States, 2000 – 2007 Source: US Department of Health and Human Services

Incidence of IA: Allogeneic HSCT Figure 1. One-year cumulative incidence of proven or probable IA among allogeneic graft recipients through the 1990s. Data for years 1990 through 1992 were abstracted from a previously published study.2 Diagnoses established after second transplantation, relapsed malignancy, or death are not included. MR = HLA matched related MM = mismatched; UR = unrelated Marr, K. A. et al. Blood 2002;100:4358-4366 Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.

IA in Patients after HSCT Cases: 187 Controls: 1495 Marr, K. A. et al. Blood 2002;100:4358-4366 Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.

IA in Patients with Hematologic Malignancies Invasive Aspergillosis Control (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% 54% 50% 0.86 Comorbidity score (mean) 0.22 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

IA in Patients with Hematologic Malignancies Invasive Aspergillosis Control (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% 54% 50% 0.86 Comorbidity score (mean) 0.22 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

Is IA a Nosocomial Infection?

Is IA a Nosocomial Infection? Difficult question!

Is IA a Nosocomial Infection? Difficult question! Incubation period unknown

Is IA a Nosocomial Infection? Difficult question! Incubation period unknown Role of colonization

Is IA a Nosocomial Infection? Difficult question! Incubation period unknown Role of colonization Community associated infections

Is there a correlation between: environmental Aspergillus concentrations and incidence of invasive Aspergillosis?

Alberti C, et al J. Hospital Infection 2001,48:198-206 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

Alberti C, et al J. Hospital Infection 2001,48:198-206 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

Alberti C, et al J. Hospital Infection 2001,48:198-206 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

Alberti C, et al J. Hospital Infection 2001,48:198-206 Results 64 hospital-acquired IA cases identified No clusters or seasonal variation Alberti C, et al J. Hospital Infection 2001,48:198-206

Alberti C, et al J. Hospital Infection 2001,48:198-206 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

Alberti C, et al J. Hospital Infection 2001,48:198-206 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

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

Efficacy of Protective Measures during Outbreaks 10 A. flavus infections in a hematology patients during 6 month period Construction project Comment on air sampling results (HEPA filtered unit: <4 CFU/m3, nonHEPA unit: >100 CFU/m3) Hahn TH, Inf Cont Hosp Epi 2002, 23;525

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 Comment on air sampling results (HEPA filtered unit: <4 CFU/m3, nonHEPA unit: >100 CFU/m3) Hahn TH, Inf Cont Hosp Epi 2002, 23;525

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

Surveillance: Autopsy Pathology specimens Unit surveillance Microbiology Culture results Galactomannan EIA Aspergillus PCR Radiology Chest CT scan

2002: International Consensus Statement Standardized definition for invasive fungal disease Host factors Clinical manifestations Mycological evidence

2002: International Consensus Statement Standardized definition for invasive fungal disease Host factors Clinical manifestations Mycological evidence Proven, probable, possible categories

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

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

Microbiological Surveillance

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

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

Results 45 patients met surveillance criteria 10 case-patients 5 possible 2 probable 3 proven Test type Test results meeting surveillance criteria (%) Test results in HIA case-patients possible probable1 proven all Microbiology 20 (36) 2 4 Pathology 4 (7) 1 Chest CT 31 (56) 5 6 Total 55 (100) 3 11 Test type Test results meeting surveillance criteria (%) Test results in HIA case-patients possible probable1 proven all Microbiology 20 (36) 2 4 Pathology 4 (7) 1 Chest CT 31 (56) 5 6 Total 55 (100) 3 11

Epidemic curve 2006 2007 Education and work site practices to minimize construction dust enhanced 2006 2007

Summary Incidence of IA is increasing

Summary Incidence of IA is increasing IA is a healthcare-associated infection 44

Summary Incidence of IA is increasing IA is a healthcare-associated infection Implementation of protective measures can be successful 45

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 46

Thank you!

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Patient with specific host factors plus Positive microbiology results Proven: Hyphae on histopathology or cytopathology from a specimen with evidence of tissue damage or Positive culture from a normally sterile site with clinical or radiographic evidence of infection Probable: Patient with specific host factors plus Positive microbiology results and 1 major or 2 minor clinical features Possible: Patient with specific host factors and attending physician documentation that invasive Aspergillosis likely plus: 49