# Presentation: 681161

## Mortality Due to Invasive Mycoses

- McNeil MM, et al. *Clin Infect Dis *2001;33:641-7

**United States, 1980-1997**

## Invasive Aspergillosis Mortality Review of Literature after 1995

**Invasive Aspergillosis Mortality ****Review of Literature after 1995**

- Review of 1941 Patients from 50 Studies

- Lin S-J et al, *Clin Infect Dis* 2001; 32:358-66

## 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* 2000;30:696-709

## 
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			

**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****	****	****	**

**Invasive Aspergillosis:  Disease Spectrum, Treatment Practices, & Outcome**

- Patterson TF, et al. *Medicine*, 2000;79:250-60

## 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 *2001;33:95-106; Patterson TF, et al. *ICAAC *2000;abstract 1324.

## Treatment of Invasive Aspergillosis:  Unmet Medical Needs*

**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* 1995;86(suppl 1):849a; Maertens J, et al. *ECCMID* 2001;abstract O248;
- Leenders ACAP et al. *Br J Haem* 1998;103:205

## Efficacy of Empirical L-AmB vs Amphotericin B Deoxycholate in Neutropenic Patients*

**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%)****	****	**

**Walsh TJ et al, *****New Eng J Med*****, 1999;340:764-71**

***Proven or probable breakthrough fungal infection**

## 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