Hospital-acquired Invasive Aspergillosis: How Big is the Problem? Michael Phillips, MD NYU Medical...

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

Aspergillus –

• 38 species cause disease• Common in the environment:

– Soil– Plants– Dust– Building materials– Food– Water

Image: Fungal Research Trust

Is Aspergillus an Emerging Pathogen?

Images: Fungal Research Trust

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

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

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

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

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

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

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

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

Is IA a Nosocomial Infection?

Difficult question!


Difficult question!• Incubation period unknown


Difficult question!• Incubation period unknown• Role of colonization


Difficult question!• Incubation period unknown• Role of colonization• Community associated infections


Is there a correlation between:environmental Aspergillus

concentrations and incidence of invasive Aspergillosis?

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




• Inclusion: allogenic HSCT, acute leukemia





• Inclusion: allogenic HSCT, acute leukemia

• Probable and definite IA case definition

• Systematic air and surface sampling


Results

• 64 hospital-acquired IA cases identified

• No clusters or seasonal variation


Results



• Incidence rate: 0 – 2.59 per 1000 pt-days


Results



• 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


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



• Construction project




• Construction project– 9 cases in 35 patients on unit without

HEPA filtration– 1 case in 20 patients on unit with HEPA

filtration


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



• Proven, probable, possible categories



• Proven, probable, possible categories• Ascioglu S, Clin Inf Dis 2002;34,7



• Proven, probable, possible categories• Ascioglu S, Clin Inf Dis 2002;34,7

• Recent revision: DePauw B, Clin Inf Dis 2008;46,1813

Microbiological Surveillance

0

1

2

3

4

5

6

7

Jan Mar May July Sept Nov Jan Mar

Month of culture

# of clinical cultures

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

Epidemic curve

0

1

2

3

4

1st 2nd 3rd 4th 1st 2nd 3rd

Quarter

# meeting case definition

Proven

Probable

Possible

Summary

• Incidence of IA is increasing

Summary


• IA is a healthcare-associated infection

Summary



• Implementation of protective measures can

be successful

Summary



• Implementation of protective measures can

be successful

• Systematic, ongoing surveillance for IA is

needed

Thank you!

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

Hospital-acquired Invasive Aspergillosis: How Big is the Problem? Michael Phillips, MD NYU Medical...

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