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Changing Epidemiology: The Importance of Broad Spectrum Therapeutics . Cornelia Lass-Flörl Innsbruck Medical University. Candidiasis. Aspergillosis. Incidence of Fatal Invasive Mycoses in USA. Mc Neil et al 2001 Clin Infect Dis 33;641. Incidence of Invasive Mycoses .

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changing epidemiology the importance of broad spectrum therapeutics

Changing Epidemiology: The Importance of Broad Spectrum Therapeutics

Cornelia Lass-Flörl

Innsbruck Medical University

incidence of fatal invasive mycoses in usa

Candidiasis

Aspergillosis

Incidence of Fatal Invasive Mycoses in USA

Mc Neil et al 2001 Clin Infect Dis 33;641

incidence of invasive mycoses
Incidence of Invasive Mycoses

Incidence per 100.000 population

Pfaller, ICAAC M 1805, 2006

slide4

The medically most important opportunistic mycoses in Europe are caused by Aspergillus spp. and Candida spp.

Aspergillus spp.A.fumigatus is the most common etiologic agent (80-90%), other species are A.flavus (10-15%), A.terreus (2-5%), A.niger (1-2%).

Candida spp.C. albicans, with an increasing incidence of

C. glabrata , C. tropicalis and C. krusei.

Kullberg et al. Epidemiology of opportunistic invasive mycosis.

Europ. J Med. Research, 2002

nosocomial bloodstream infections in us hospitals 1995 2002
Nosocomial Bloodstream Infections in US Hospitals: 1995-2002

BSI=blood stream infection.

Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE) study.

Wisplinghoff H, et al. Clin Infect Dis. 2004;39:309-317.

incidence distribution of candidemia 1999 2003 in san martino hospital icu
Incidence & Distribution of Candidemia (1999-2003) in San Martino Hospital ICU

Number of isolates (% of species)

Bassetti M et al. BMC Infectious Diseases 2006:1-6.

candida glabrata
Sub-optimal fluconazole dosing

Pan-azole resistance

Over 10 years, the frequency of C. glabrata increased in

Canada, 13-24%

Europe, 11-13%

USA, 14-28%

Least common in Latin America (7.5%)

Candida glabrata

Pfaller 2006, Bhatti 2006, Pfaller 2007

biofilms and candida parapsilosis
2nd most common species in blood, related to catheters and glucose solutions

Causes biofilms which usually require removal of catheters etc, as antifungal drugs are ineffective in eradicating biofilms

Biofilms and Candida parapsilosis

Pfaller 2006, Pfaller 2007

evolution of isolation of candida species in relation to fluconazole consumption

C. albicans

C. glabrata

C. tropicalis

C. parapsilosis

C. krusei

Other species

Evolution of Isolation of Candida Species in Relation to Fluconazole Consumption

Sendid B et al. BMC Infectious Diseases 2006:61-9.

invasive aspergillosis in transplant recipients
Invasive Aspergillosis in Transplant Recipients

Singh & Paterson. Clin Microbiol Rev. 2005 18:44-69.

invasive proven mould infections lki

Asp.spp

A.terreus

zygomycosis

Invasive Proven Mould Infections, LKI

Lass-Flörl, 2005, additional unpublished data added

slide15

27% of proven infections are due to zygomycetes

Lass-Flörl et al,submitted, 2007

zygomycosis
Vulnerable populations

Malignancy

Bone marrow transplantation

Solid organ transplantation

Corticosteroid exposure

GvHD

CMV reactivity

neutropenia

Diabetes mellitus

Initial presentation with sinusitis

Occurrence as breakthrough prior VRC prophylaxis

56% mortality

Zygomycosis

others…

Fusarium sp.

Penicillium sp.

Trichosporon sp.

Marr, CID 2002

Steinbach, J Infect 2004

Roden, et al. Clin Inf Dis 2005;41:634-53.

Kontoyiannis et al. JID, 2005; 191:1350-60.

Siwek et al. CID 2004; 39:584-87.

antifungal mics g ml against clinical isolates of zygomycetes
Antifungal MICs (µg/ml) againstClinical Isolates of Zygomycetes

Sun QN et al. AAC 2002; 46: 1581–1582.

environment as a risk factor fungus at home
Environment as a Risk FactorFungus at Home
  • Hospital construction is known to increase cases of IA
  • HEPA filtration is known to decrease cases of IA
  • Aspergillus may be found in patient showers… genetically identical to the one from the patient!
  • Highest concentration of Aspergillus fumigatus is at home
  • Protective environment for pts with allo-BMT now included in the new draft CDC guidelines for isolation

Williamson, Thorax 1997;52:229.

Taskinen, Acta Paediatr 1999; 88:1373.

Oren, Am J Hematol 2001; Anaissie, CID 2002.

variables that account for the current trends in the epidemiology
Variables that Account for the Current Trends in the Epidemiology
  • Increasing number of susceptible hosts: transplant type
  • Center to center differences, patient selection
  • Greater laboratory expertise in detection & identification of fungi
  • Use of new transplant modalities for hematopietic stem cell transplantation
  • Changing surgical techniques: evolution in organ transplant practices
  • Use of corticosteroid-sparing regimens and overall conservative approach to immunosuppression
  • Use of novel immunosuppressive agents
  • Antimicrobial prophylactic practices
  • Underlying Diseases
  • Poor diagnostic tools

Singh 2001; Denning 2005, Kontoyiannis 2005, Lass-Flörl 2005

slide21
…turning risk factors and local epidemiology into useful information!

Thank you for your attention!