Use of Antifungals in the Year 2008

Transcription

1 Use of Antifungals in the Year 2008 Jose G. Montoya, MD Associate Professor of Medicine Associate Chief for Clinical Affairs Division of Infectious Diseases Stanford University School of Medicine

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7 Diagnosis of Invasive Fungal Infections Microscopy (body fluids, i.e.: BAL) helpful in alerting clinicians about the presence of moldlike or yeast-like structure Pathology (H&E and fungal stains) establishes the invasive nature of the disease Microbiology identifies the fungal organism causing disease Serology serves as a diagnostic aid by identifying Ag or AB Antigens: galactomanan, cryptococcal, histoplasma Antibodies: coccidiodomycosis, blastomycosis

8 voriconazole amphob (lipid) Aspergillus fumigatus caspofungin itraconazole mycelial fungi, hyhae, mould Scedosporium apiospermum Voriconazole AmphoB (lipid)?posaconazole Mucor sp. oriconazole QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture. Aspergillus terreus Fusarium solani Voriconazole + Ampho B +?Terbinafine

9 Therapeutic Options for Invasive Fungal Infections IV amphotericin B conventional lipid formulations amphotec, abelcet, ambisome IV/PO fluconazole IV/PO itraconazole IV/PO voriconazole PO posaconazole IV caspofungin, micafungin, anidulafungin combination therapy

10 Mucormycosis

11 Ampho B Posaconazole?

12 Invasive Aspergillosis

13 Ecthyma gangrenosum as a result of P. aeruginosa bacteremia in patient with F&N. Necrotizing vasculitis. GNR invading walls of small arteries and veins Cutaneous Aspergillosis on a previous IV site in a patient with F&N. Hyphal elements invading dermis and Aspergillus fumigatus isolated from fungal culture.

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16 Evolution of treated IPA in a 56 yo HxTx Patient 1.5-cm nodule 8 days 59 days Montoya JG et al. Clinical Infectious Diseases 2003; 37: S

17 F/U CT on 7-6

18 Caillot D et al. J Clin Oncol 2001;19: pp

19 Montoya JG et al. Clinical Infectious Diseases 2003; 37: S

20 Voriconazole Drug-drug Interactions: Dose Adjustment Concomitant medication Con. med. dose adjustment Monitoring Cyclosporine* Halve dose Cyclosporine blood concentration Tacrolimus* Reduce dose to one third Tacrolimus blood concentration Warfarin* As needed Prothrombin time Sulfonylureas As needed Glucose Omeprazole* Halve dose None Benzodiazepines, statins, vinca alkaloids As needed Clinical effects, toxicity * Studied in volunteers, other interactions predicted

21 2/ 20 BM biopsy reveals AML (M0) 2/23 Induction chemotherapy 2/29 Neutropenia 3/3 Febrile. Cefepime initiated 3/7 Left foot edema. Vancomycin added 3/10 Amphotericin B added 3/13 Develops skin lesions Fever and Neturopenia 68 yo man with AML

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28 Stanford Hospital & Clinics: Antifungal Susceptibility of Candida spp, Jan-Dec 2006 QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

29 Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States Ostrosky-Zeichner L. et al. Antimicrob Agents Chemother. 2003; 47:

30 Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis Mora-Duarte J et al. NEJM 2002;347:

31 Micafungin versus liposomal amphotericin B Kuse et al. Lancet 2007; 369: Micafungin was as eff ective as and caused fewer adverse events than liposomal amphotericin B as first-line treatment of candidaemia and invasive candidosis.

32 Global Response to Treatment for Prespecified Time Points in the Modified Intention-to-Treat Population A successful global response required both clinical success (defined as the resolution of signs and symptoms of invasive candidiasis and no additional systemic antifungal therapy) and microbiologic success (defined as the eradication of candida species present at baseline as determined on follow-up culture, or the presumed eradication if culture data were not available for a patient with a successful clinical response Reboli A et al N Engl J Med (24):

33 Microbiologic and Global Responses at the End of Intravenous Therapy in the Modified Intention-to-Treat Population Reboli A et al N Engl J Med (24):

34 Micafungin versus Caspofungin for Treatment of Candidemia and Other Forms of Invasive Candidiasis (in 595 Adults) international, randomized, double-blind trial comparing 191: micafungin (100 mg daily) 199: micafungin (150 mg daily) 188: caspofungin (70 mg/50 mg daily) primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy Pappas P et al CID 2007; 45:883 93

35 Micafungin versus Caspofungin for Treatment of Candidemia and Other Forms of Invasive Candidiasis Pappas P et al CID 2007; 45:883 93

36 Micafungin versus Caspofungin for Treatment of Candidemia and Other Forms of Invasive Candidiasis micafungin 100 mg daily is as safe and effective as micafungin 150 mg daily conventional dosage of caspofungin 70/50mg in the treatment of candidemia and other forms of invasive candidiasis. Pappas P et al CID 2007; 45:883 93

37 Candidemia

38 Opportunistic Invasive Fungal Infections Opportunistic Fungi Mycelial Aspergillus Scedosporium Zygomycetes (mucorales) Fusarium Yeasts Candida Cryptococcus

39 Candidemia Removal of catheters Eye exam by ophthalmologist Appropriate antifungal therapy

40 Therapeutic Options for Candidemia IV/PO fluconazole IV caspofungin, micafungin, anidulafungin amphotericin B conventional lipid formulations amphotec, abelcet, ambisome IV/PO voriconazole