Mortality Due to Invasive Mycoses

1
Mortality Due to Invasive Mycoses
United States, 1980-1997
McNeil MM, et al. Clin Infect Dis 200133641-7
2
Invasive Aspergillosis Mortality Review of
Literature after 1995
Review of 1941 Patients from 50 Studies
Lin S-J et al, Clin Infect Dis 2001 32358-66
3
IDSA Practice Guidelines for Aspergillus

• Early management
• Prompt, aggressive diagnosis (BIII)
• Therapy initiated on suspicion of diagnosis
  (BIII)
• Antifungal therapy
• Intravenous therapy initiated (BIII)
• AmB deoxycholate at maximum doses (1-1.5 mg/kg/d)
  (BIII)
• Lipid AmB impaired renal function or intolerance
  (AII)
• Itraconazole oral therapy, sequential use
  (CIII)
• Adjunctive therapy Surgery, combinations,
  immunotherapy (CIII)
• New therapies and diagnostic tools needed to
  improve prognosis

Stevens DA et al, Clin Infect Dis 200030696-709
4
Invasive Aspergillosis Disease Spectrum,
Treatment Practices, Outcome

• Underlying Disease (n) Complete/Partial
  Responses ()
• Overall (595) 37
• Severe Immunosuppression (363) 28
• Allo BMT (151) 13
• Hematological Malignancy (212) 39
• Less Severe Immunosuppression (232) 51
• Site of Infection
• Pulmonary (330) 40
• Disseminated (without CNS) (114) 18
• Central Nervous System (34) 9

Patterson TF, et al. Medicine, 200079250-60
5
Trial Design for Invasive Mycoses

• Limitations in trials for invasive mycoses
• Relative infrequency
• Difficult diagnosis (surrogate markers, high
  resolution imaging)
• Host factors (underlying conditions, disease
  presentation)
• Trial issues (slow enrollment, expensive,
  difficult, use of approved comparators,
  definitions/endpoints)
• Large, prospective randomized trials for invasive
  aspergillosis 2
• Ellis, 1998 (87 pts) Liposomal AmB 1 vs 4
• Bowden, 1998 (103 pts) ABCD vs D-AmB

Rex JH et al, CID 20013395-106 Patterson TF,
et al. ICAAC 2000abstract 1324.
6
Treatment of Invasive Aspergillosis Unmet
Medical Needs

• Hiemenz, 1995 ABLC (n) Control (n)
• Historical Control 42 (151) 23 (122)
• Maertens, 2001 Caspofungin Control
• Historical Control 41 (56) 17 (206)
• Leenders, 1998 L-AmB D-AmB
• Open, Randomized 52 (25) 29 (28)
• Includes suspected infections

Complete Partial Responses
Hiemenz JW, et al. Blood 199586(suppl 1)849a
Maertens J, et al. ECCMID 2001abstract
O248 Leenders ACAP et al. Br J Haem 1998103205
7
Efficacy of Empirical L-AmB vs Amphotericin B
Deoxycholate in Neutropenic Patients

• L-AmB (343) AmB Deoxycholate (344)
• Aspergillus 12 15
• Candida 3 12
• Fusarium 1 1
• Zygomycetes 1 0
• Other 0 2
• Total 17 (5.0) 30 (8.7)

Proven or probable breakthrough fungal infection
Walsh TJ et al, New Eng J Med, 1999340764-71
8
Invasive Mycoses Present and Future

• Epidemiology
• Increasing number of patients at risk
• Changing patterns of disease
• Major cause of morbidity and mortality
• Improved prognosis
• Prompt diagnosis
• Host factors
• Antifungal therapy
• Early, aggressive induction antifungal therapy
• New approaches and new agents needed