Evolving Epidemiology of Fungal Infections in HighRisk Patients

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Evolving Epidemiology of Fungal Infections in
High-Risk Patients
Infectious Diseases Summit Fungal Series

• B. Guery
• Lille

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High risk patient

• Neutropenia
• Immunosuppression
• HIV, transplantation
• Premature
• Diabetic
• ICU
• Trauma, burn, septic shock, IV, TPN..
• Abdominal surgery
• Prolonged antibiotic treatment

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Hematology
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Endogenous fungal pathogens

• Candida sp
• Invasive trichosporonosis
• Trichosporon sp
• Geotrichum capitatum (Blastoschizomyces capitus)

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Endogenous fungal pathogens

• Candida sp
• Mortality
• Prophylaxis
• Treatment
• Invasive trichosporonosis
• Trichosporon sp
• Geotrichum capitatum (Blastoschizomyces capitus)

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Mortality
EORTC
Viscoli et al, CID 1999
Cancer 50 BMT can reach 100
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Mortality

• 262 BSI 164 albicans, 88 non albicans, 10 non
  candida

Kovacicova et al, J Inf Chemother 2000
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Mortality

• ICU retrospective study, C albicans (41) vs C
  glabrata (15) candidemia
• C. glabrata older patients
• Mortality risks factors age, polymicrobial
  infection, ARF
• No difference in mortality

Blot et al, J Hosp Inf 2001
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Conclusions We found multiple common risk
factors for both non-C. albicans and C. albicans
BSIs, however we could not differentiate between
these two groups based on clinical
characteristics alone.
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Endogenous fungal pathogens

• Candida sp
• Mortality
• Prophylaxis
• Treatment
• Invasive trichosporonosis
• Trichosporon sp
• Geotrichum capitatum (Blastoschizomyces capitus)

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• 1095 nosocomial candidemia
• 1994-2000, Taiwan

Chen et al, JAC 2003
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Glabrata-azoles
-Nb patients treated
-Nb patients treated

Virginia
Pennsylvania
Gleason et al, 1997
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Glabrata-azoles

• 3 groups
• Group 1 Empiric or prophylactic FLU
• Group 2 Control hospital patients
• Group 3 SICU patients without FLU
• Mortality differences but inadequate FLU dosage

Fungal isolates obtained during the study


Safran et al, Arch Surg 1997
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300 patients with proven invasive candida
infection
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Age influence
Pfaller et al, J Clin Microb 2002
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Endogenous fungal pathogens

• Candida sp
• Mortality
• Prophylaxis
• Treatment
• Invasive trichosporonosis
• Trichosporon sp
• Geotrichum capitatum (Blastoschizomyces capitus)

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Fluconazole MIC
Cumulative inhibited at MIC (µg/mL)
Pfaller et al, Clin Microb Inf 2004
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Fluconazole MIC
Pfaller et al, Clin Microb Inf 2004
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Endogenous fungal pathogens

• Candida sp
• Non albicans
• Invasive trichosporonosis
• Trichosporon sp
• Geotrichum capitatum (Blastoschizomyces capitus)

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Trichosporon sp, Geotrichum capitatum

• High risk patients
• Acute leukemia 65, neutropenia 88, cytotoxic
  chemotherapy 90
• Fungemia, abcess, interstitial pneumonia,
  endocarditis, meningitis
• Bad prognosis
• Mortality at 30 days 30-75

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Trichosporon sp, Geotrichum capitatum
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Exogenous fungal pathogens

• Aspergillus
• Fumigatus
• Terreus, ustus, flavus
• Other mold
• Scedosporium
• Fusarium
• Mucor

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Walsh TJ, et al. Clin Infect Dis 200846327-60
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Key RecommendationPrimary Therapy of Invasive
Aspergillosis

• Voriconazole is recommended for the primary
  treatment of invasive aspergillosis in most
  patients (AI).

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Key RecommendationPrimary Treatment of Invasive
Aspergillosis

• Alternative Agents
• A randomized trial comparing two dosages of
  liposomal amphotericin B showed similar efficacy
  in both arms, suggesting that liposomal therapy
  could be considered as alternative primary
  therapy in some patients (AI).

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Global Comparative Aspergillosis Study Survival
Benefit of Voriconazole

• Poor efficacy of AmB prior gold standard
• Vori recommended for primary therapy
• Importance of early therapy
• Limited success of rescue therapy

Herbrecht R et al NEJM 2002347408-15
Patterson TF et al. Clin Infect Dis
2005411448-52 Greene RE et al. Clin Infect Dis
200744373-9
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Scedosporium apiospermum pedal mycetoma
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• Immunocompetent
• Keratitis, onychomycosis
• Skin infections (burn, foreign bodies)
• Peritonitis, sinusitis, pneumonia
• Immunocompromised
• Prolonged and profound neutropenia, Severe T cell
  immunodeficiency
• Invasive and disseminated
• Endophtalmitis, pneumonia, skin, fungemia,
  disseminated

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F. dimerum soft-tissue infection of the foot
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• Prognosis
• Related to the immune status
• Survival 50-21 at 30 and 90d

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• Two fungal pathogenic groups
• Mucorales
• Acute onset, rapid evolution
• Entomophthorales
• Indolent, chronically progressive

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Clinical manifestations

• Cerebral zygomycosis
• Originates the paranasal sinuses and extends to
  the brain
• Pulmonary zygomycosis
• High mortality
• Cutaneous zygomycosis
• Through inoculation
• Gastro-intestinal zygomycosis
• Rare, mortality 85
• Disseminated zygomycosis

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Treatment

• High dose amphotericin B
• Liposomal or lipidic formulation
• Duration 6-8 weeks
• Posaconazole
• Salvage
• Surgery
• Crucial, without delay, aggressive
• Adjunctive
• G-CSF, leukocytes transfusion, HBO

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Entomophthorales

• Conidiobolomycosis
• Unilateral nasal obstruction
• Usaually no systemic symptoms
• Basidiobolomycosis
• Nodule, granulomatous lesions
• GI involvement
• Tt not standardized
• Azole, AmB

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Conclusion

• New emerging pathogens
• New treatments
• Immunosuppression
• Treatment
• ICU
• ....
• Treatment difficult, guidelines not always
  available