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Perché è Difficile Diagnosticare e Trattare l’Aspergillosi Invasiva?

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Presentation on theme: "Perché è Difficile Diagnosticare e Trattare l’Aspergillosi Invasiva?"— Presentation transcript:

1 Perché è Difficile Diagnosticare e Trattare l’Aspergillosi Invasiva?

2 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

3 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

4 INFECTION!INFECTION!

5 INFECTION!INFECTION!

6 fungi bacteria viruses

7 EUKARYOTIC ORGANISM!! MRS. FUNGUS cell membrane -ergosterol cell wall cholesterol

8 ASPERGILLUS FIRST DESCRIPTION “brush-shaped structure” 1729 MICHELI catholic priest

9

10 ASPERGILLUS IS EVERYWHERE moss soil decaying material environment

11 According to Odds

12 DEFENSE SYSTEMS Mucosa / Skin Granulocytes Commensal flora Humoral immunity T-cell function removes viruses, fungi and tumor cells antibody production micro-organisms in the gut against bacteria – pus formation against bacteria – pus formation border control of our body border control of our body

13 day 40 100 DEFENSE SYSTEMS Mucosa / Skin Granulocytes Commensal flora Humoral immunity T-cell function

14 day 40 100 Mucosa Granulocytes Commensal flora Humoral immunity T-cell function / Skin COURSE OF DEFENSE SYSTEMS ASPERGILLUS INFECTIONS

15 INFECTIOUS AGENTS IN RELATION TO THE COURSE OF DEFENSE SYSTEMS Garcia-Vidal et al. Clin Infect Dis 2008; 47:1041-1050 time ASPERGILLUS

16 BASIC RISK FACTORS FOR FUNGAL INFECTIONS immuno- suppression immuno- suppression epidemiologic exposure epidemiologic exposure Adapted from RH Rubin, Boston

17 OPPORTUNISTS! money shops

18 xxxxx

19 TRENDS INCIDENCE INVASIVE FUNGAL INFECTIONS Pagano et al. Haematologica 2006; 91:1068-1075 0 10 20 30 40 50 60 70 80 87-8892-9397-982002-2003 number of cases ASPERGILLUS

20 INVASIVE FUNGAL DISEASE AFTER NON-MYELOABLATIVE ALLO-BMT Fukuda et al. Blood 2003; 102:827-833 22% non-relapse mortality 39% mould-related 9% mould-related deaths n = 163

21 MORTALITY OF INVASIVE ASPERGILLOSIS Variation due to: timing of intervention timely diagnosis patients’ defense system treatment given

22 MORTALITY OF INVASIVE ASPERGILLOSIS Variation due to: timing of intervention timely diagnosis patients’ defense system treatment given 97% 42%

23 GROWTH OF ASPERGILLUS 1-2 cm per 24 hours

24 MAKE YOUR CHOICE!

25 ONE WEEK LATER….

26 INFECTION -- DISEASE

27 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

28 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

29 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

30 WELCOME TO MYCOLOGY ASPERGILLUS spore hyphae spores

31 ADMISSION TO THE HUMAN BODY

32 Caso MK - 5

33 EVOLUTION OF AN INFECTION AND MORTALITY FUNGAL BURDEN TRADITIONAL DIAGNOSIS TRADITIONAL DIAGNOSIS 97% 42%

34 97% 42% AWAY FROM EMPIRISM? FUNGAL BURDEN diagnostics TRADITIONAL DIAGNOSIS TRADITIONAL DIAGNOSIS NEW TOOLS NEW TOOLS

35 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 DAYS 55 patients FIRST TEST POSITIVE FOR ASPERGILLOSIS IN HEMATOLOGICAL MALIGNANCIES Florent et al. J Infect Dis 2006;193:741-747 culture histology culture histology CT serology

36 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

37 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

38 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

39 Empirical anti- fungals fungals 100% 75% 50% ADMINISTRATION OF ANTIMICROBIALS IN RELATION TO THE COURSE OF NEUTROPENIA antibacterials <100 GRANULOCYTES 1000 500 >1000 0 10 20 30 days

40 ESTIMATING TIME FOR INTERVENTIONAspergillus day 1 5 7 12 // 28 > 42 day 1 5 7 12 // 28 > 42 antigenantigen Persisting fever + very high risk or a suggestive symptom or a suspected sign or any positive test infiltrateinfiltrate

41 TACTICS ITALIAN: -strong defense -efficient attack BRAZILIAN: -no defense -intuitive attack

42 TOPICS Behavior of AspergillusBehavior of Aspergillus -characteristics -characteristics Principles of managementPrinciples of management-detection-treatment when and what when and what

43 PACE OF DEVELOPMENT OF NEW ANTIFUNGAL AGENTS 1950 19601970198019902000 Adapted from Rex & Edwards, 1997 AmBisome fluconazole Amphocil Abelcet itraconazole ketoconazole miconazole 5-flucytosine terbinafine Amphotericin B Nystatin Griseofulvin isavuconazole caspofungin anidulafungin micafungin voriconazole posaconazole

44 0 10 20 30 40 50 60 %response RESULTS FIRST LINE TREATMENT OF INVASIVE ASPERGILLOSIS Herbrecht et al N Engl J Med 2002; 347:408-415 Cornely et al. Clin Infect Dis 2007; 44:1289-1297 Viscoli et al. J Chemother 2007; 19, suppl 5:36 EORTC IFICG VoriconazoleAmpho B Lipo-AmB Caspofungin

45 OUTCOME OF ASPERGILLOSIS IN RELATION TO INITIAL ANTIFUNGAL THERAPY Nivoix, Y et al. Clin Infect Dis 2008; 47:1176-1184 n = 289 SURVIVALSURVIVAL SURVIVALSURVIVAL n = 62 n = 51 n = 127 70% 47% P=0.016

46 40 30 20 10 0 OUTCOME OF THERAPY FOR ASPERGILLOSIS ARISING DURING AML IN DAILY PRACTICE Pagano et al. SEIFEM 2008 140 cases voriconazole L-AmB caspofungincombo 28% 27% 21% 16% First line therapy N° of patients treated

47 OUTCOME OF THERAPY FOR ASPERGILLOSIS ARISING DURING AML IN DAILY PRACTICE Pagano et al. SEIFEM 2008 140 cases voriconazole L-AmB caspofungincombo 18%24%32%23% 40 30 20 10 0 N° of patients treated Aspergillosis attributable mortality

48 CORTICOSTEROIDS AND SURVIVAL OF ASPERGILLOSIS IN HSCT Cordonnier et al. Clin Infect Dis 2006;42:955-963 low dose corticosteroids high dose SURVIVALSURVIVAL 51 patients with aspergillosis 41 allo HSCT 10 auto

49 RELATION OUTCOME OF FUNGAL INFECTIONS AND GRANULOCYTE COUNT n = 63 INCREASING GRANULOCYTES Response 86% DECREASING GRANULOCYTES Response 36%

50 RELATION OUTCOME OF FUNGAL INFECTIONS AND STATE OF UNDERLYING DISEASE n = 63 SUCCESSFUL OUTCOME REFRACTORY UNDERLYING DISEASE 8%8% REMISSION 61%

51 EVOLUTION OF ASPERGILLUS INFECTIONS AMONGST PATIENTS WITH ACUTE LEUKEMIA EVOLUTION OF ASPERGILLUS INFECTIONS AMONGST PATIENTS WITH ACUTE LEUKEMIA Pagano et al. Clin Infect Dis 2007; 44:1524-1525 0 3 6 9 12 15 1987-1998 1999-20032006 Incidence (%) attributable mortality 60% 50% 40% 30% 20% 10% new anti- fungals new anti- fungals serological tests CT-scan serological tests CT-scan

52 CRUCIAL ELEMENTS IN AVOIDANCE OF DISASTERS  Knowledge on behavior of the offender  High awareness  Early recognition  Early treatment

53 ASPERGILLUS IS EVERYWHERE ***** IT IS AN OPPORTUNIST ***** EARLY DIAGNOSIS REQUIRES CONTINUOUS, SPECIFIC SCREENING ***** ANTIFUNGALS MAY KEEP A PATIENT ALIVE but CURE NEEDS RECOVERY OF THE IMMUNE SYSTEM CONCLUSIONS

54 Grazie, Ben! Buona conferenza a tutti voi!


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