rehberler eşliğinde antifungal tedavi - · pdf fileullmann, paul verweij, claudio viscoli...
TRANSCRIPT
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Rehberler Eşliğinde Antifungal
Tedavi
Dr. Murat Akova
Hacettepe Üniversitesi Tıp Fakültesi
İnfeksiyon Hastalıkları AD,
Ankara
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Guidelines
Please tear
Courtesy of Ben de Pauw
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Guidelines
Practice vs Praxis
Courtesy of Ben de Pauw
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Hematolojik Kanserli Hastalarda
İnvaziv Fungal İnfeksiyon Sıklığı
0
1
2
3
4
5
6
1999 2000 2001 2002 2003
Yıl
lık
in
fek
siy
on
hızı
Pagano L, et al. Haematologica 2006;91:1068
Aspergillus spp. Diğer küf Candida spp.
Diğer maya Tüm fungal etkenler
n=538 IFI
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Avrupa‟da Kandidemi
Kandida Türlerinin Dağılımı
Tortorano et al., Int J Antimicrob Agents 2006; 27: 359
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“Prospective Antifungal Therapy
(PATH) Alliance” Çalışmasında
Kandidemi
• 2019 hasta
– 1 Temmuz 2004-5 Mart 2008
• C. albicans (%45.6)
• 12. haftada kaba mortalite %35.2
– C. parapsilosis %23.7
– C. krusei %52.9
Horn Dl, et al. Clin Infect Dis 2009;48:1695
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Kandida Türlerinin Dağılımı
“PATH Registry”
Horn Dl, et al. Clin Infect Dis 2009;48:1695
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Kandidemili Hastalarda 12.
Haftada Sağkalım-PATH
Horn Dl, et al. Clin Infect Dis 2009;48:1695
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Hacettepe‟de Kandidemi
• 2001-2011, retrospektif analiz
• 18.426 pozitif kan kültürü
– 858 kandida-pozitif kan kültürü
– 381 izolat, tek hasta, ilk atak
• Kandida en sık üretilen 5. patojen
Alp S, Arıkan-Akdağlı S & Akova M. 2012
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Hacettepe‟de Kandidemi İzolatları
n=381
0
10
20
30
40
50
60
70
80
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
C. albicans C.parapsilosis C.tropicalis C.glabrata Diğerleri
%
Alp S, Arıkan-Akdağlı S & Akova M. 2012
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Kandida Türleri ve Altta Yatan
Hastalıklar Hacettepe 2001-2010
0
20
40
60
80
100Diğer NAC
C. glabrata
C. tropicalis
C. parapsilosis
C.albicans
%
Alp S, Arıkan-Akdağlı S & Akova M. 2012
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Kandidemi İzolatları
Hacettepe 2013
40%
27%
14%
7%
12%
C. albicans
C. parapsilosis
C. glabrata
C. tropicalis
Diğer mayalar
Akdağlı-Arıkan S, 2013
n=75
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İnvaziv Kandidiyazis Tedavisi
IDSA 2009
Flukonazol-S suş olası
Hasta stabil
Evet Hayır
Fluconazole 800 mg IV ekinokandin
Flukonazol-S
Evet Hayır
Pappas G, et al. Clin Infect Dis 2009;48:503
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ESCMID Guideline for the Diagnosis &
Management of Candida Diseases 2012
Authors: Murat Akova, Maiken Arendrup, Sevtap Arikan-Akdagli, Matteo
Bassetti, Jacque Bille, Thierry Calandra, Elio Castagnola, Oliver A.
Cornely, Manuel Cuenca-Estrella, Peter Donnelly, Jorge Garbino, Andreas
Groll, Raoul Herbrecht, William Hope, Henrik Elvang Jensen, Bart-Jan
Kullberg, Cornelia Lass-Flörl, Olivier Lortholary, Wouter Meersseman,
Georgios Petrikkos, Malcolm Richardson, Emmanuel Roilides, Andrew J.
Ullmann, Paul Verweij, Claudio Viscoli
Main Coordinator: Andrew J. Ullmann
Clin Microbiol Infect 2012;18 (Suppl.7):1-77
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2
3
2
2
3
3
1
3
2
2
1
1
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THE TEAM:
Murat Akova, Hacettepe University, Ankara Turkey
Maiken Cavling Arendrup, Statens Serum Institut ,Copenhagen Denmark
Sevtap Arikan-Akdagli, Hacettepe University, AnkaraTurkey
Matteo Bassetti, San Martino University Hospital, Genoa, Genoa Italy
Jacque Bille, Centre Hospitalier Universitaire Vaudois, Lausanne Switzerland
Thierry Calandra, Centre Hospitalier Universitaire Vaudois, Lausanne Switzerland
Elio Castagnola, "G.Gaslini" Children's Hospital, Genova Italy
Oliver A. Cornely, Universität zu Köln, Cologne Germany
Manuel Cuenca-Estrella, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid Spain
Peter Donnelly, Radboud University Nimegen Medical Centre, Nijmegen, Netherlands
Jorge Garbino, University Hospitals Geneva, Geneva Switzerland
Andreas Groll, University Children's Hospital,Westfälische Wilhelms-Universität, Münster Germany
Raoul Herbrecht, Hôpital de Hautepierre, University of Strasbourg France
William Hope, The University of Manchester, Manchester United Kingdom
Henrik Elvang Jensen, University of Copenhagen, Frederiksberg Denmark
Bart-Jan Kullberg, Radboud University, Nijmegen, Netherlands
Cornelia Lass-Flörl, Division of Hygiene & Medical Microbiology, Innsbruck Medical University, Innsbruck
Austria
Olivier Lortholary, Institut Pasteur, Université Paris Descartes, Hôpital Necker Enfants malades, Paris
France
Wouter Meersseman, University Hospital Gasthuisberg, Leuven Belgium
Georgios Petrikkos, National and Kapodistrian University of Athens, Athens Greece
Malcolm Richardson, University Hospital of South Manchester, & The University of South Manchester,
United Kingdom
Emmanuel Roilides, Aristotle University, Thessaloniki Greece
Paul Verweij, Radboud University, Nijmegen, Netherlands
Claudio Viscoli, University of Genoa, Genoa Italy
ESCMID Diagnostic & Management
Guideline for Candida Diseases 2012
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HIV/AIDS
Haematology/Oncology
Paediatrics
ICU (medical & surgical)
Diagnostic procedure
PICU
Olivier Lortholary, Georgios Petrikkos
Murat Akova, Raoul Herbrecht, Andrew
Ullmann, Claudio Viscoli
Elio Castagnola, Andreas Groll, William
Hope, Emmanuel Roilides
Matteo Bassetti, Thierry Calandra, Oliver
Cornely, Jorge Garbino, Bart-Jan Kullberg,
Wouter Meersseman
Maiken Arendrup, Sevtap Arikan-Akdagli,
Jacques Bille, Manuel Cuenca-Estrella, Peter
Donnelly, Henrik Elvang Jensen, Cornelia
Lass-Flörl, Malcolm Richardson, Paul Verweij
Çalışma Grupları
Other non-immunocompromised
(medical & surgical), other
immunocompromised situations
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Allojeneik KHN
Kandida
Profilaksisi
Ullmann AJ, Akova M, Herbrecht R, et al.
Clin Microbiol Infect 2012;18 (suppl.7):53-67
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Otolog KHN ve Kemoterapiye
Bağlı Nötropenik Hastada Kandida
Profilaksisi
Ullmann AJ, Akova M, Herbrecht R, et al. Clin Microbiol Infect 2012;18 (suppl.7):53-67
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Olası Kandidemi İçin Empirik
Tedavi
Ullmann AJ, Akova M, Herbrecht R, et al. Clin Microbiol Infect 2012;18 (suppl.7):53-67
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İnvaziv Kandidiyazis‟te Hedeflenmiş Tedavi
Ullmann AJ, Akova M, Herbrecht R, et al. Clin Microbiol Infect 2012;18 (suppl.7):53-67
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Kronik Dissemine Kandidiyazis
Tedavisi
Ullmann AJ, Akova M, Herbrecht R, et al. Clin Microbiol Infect 2012;18
(suppl.7):53-67
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Kateterle İlişkili Kandidemi
Tedavisi
Ullmann AJ, Akova M, Herbrecht R, et al. Clin Microbiol Infect 2012;18
(suppl.7):53-67
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Kandidemide Tedavi Süresi
• Son pozitif kan kültüründen sonra en
az 14 gün ve hastalığa ilişkin belirti
ve bulguların kaybolması koşuluyla
– Nötropenik olmayan hastalarda BII
– Nötropenik hastalarda CIII
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ECIL-5 19-21 September 2013,
Juan-les-Pins
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İnvaziv Aspergillozis
Tedavisinde Yenilikler
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Akut Lösemili Hastalarda İnvaziv
Aspergillozis
0
10
20
30
40
50
60
1987-88 2002-03 2006
İnsidans Mortalite
Pagano L, et al. Clin Infect Dis 2007; 44: 1524
Daha iyi tedavi
P=.002 (insidans)
↑olası IA
GM-PCR-CT
%
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Kök Hücre Naklinde İnvaziv
Aspergillozis‟ten Sağkalım ve
Prognostik Faktörler
• Non-myeloablatif “conditioning”
• Periferik kök hücre kullanımı
• Erken tanı
P<.0001 P<.01
Upton A, et al. Clin Infect Dis 2007;44:531
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Erişikin Kök Hücre Nakli Yapılan
Hastalarda İnvaziv Fungal
İnfeksiyonlar
„PATH Alliance Registry‟
• Kuzey Amerika‟da 16 merkezde 234
hastada 250 IFI
– %69 allojeneik
– %31 otolog
– IFI dağılımı
– 6 ve 12. haftalarda sağkalım
Neofytos D, et al. Clin Inf Dis 2009;48:265
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İnvaziv Fungal İnfeksiyon Dağılımı
60%
20% 26%
Aspergillus
Zygo ve diğer küf
C. albicans
Non-albicansCandida
Neofytos D, et al. Clin Inf Dis 2009;48:265
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12. Haftada Mortalite
0
20
40
60
80
100
Diğer küf Zigomikoz Kandidiyaz Aspergilloz
% m
ort
ali
ty
Neofytos D, et al. Clin Inf Dis 2009;48:265
Kök Hücre Nakli Tipine Göre
Fark Yok !
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Kök Hücre Alıcılarında IFI
TRANSNET Veritabanı
43%
28%
8%
21%
Invasive aspergillosis
Invasive candidiasis
Zygomycosis
Others
23 ABD transplant merkezi, 2001-2006 875 KHN hastasında 983 IFI
Kontoyiannis DP, et al. Clin Infect Dis 2010;50:1091
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1 Yıllık Sağkalım
Marr K, et al. Clin Infect Dis 2002;34:909
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Standart Tanı Yöntemlerinin
Duyarlılığı
İnf. bölgesi İşlem % yapılma sıklığı % duyarlılık
Pulmoner
Akciğer filmi
BAL kültürü
Balgam
Nasal sürüntü
Biyopsi
98
38
72
56
18
77
62
58
32
87
Serebral Serebral BT
Biyopsi
65
8
88
66
Sino-nasal
Kranial CT
Nasal sürüntü
Biyopsi
50
71
19
86
85
100
Pagano L, et al. Haematologica 2001; 86: 862
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Akciğer BT
Halo belirtisi Hava hilal belirtisi
G0 96% G0
G3 68% G3 31%
G7 22% G7 50%
G14 19% G14 18%
G0 0%
G3 8%
G7 28%
G14 63%
Caillot D, et al. J Clin Oncol 2001;19:253
Non-spesifik
konsolidasyon
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Halo Belirtisinin Özgüllüğü
Pulmoner nokardiyoz
S. aureus P. aeruginosa
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2013 Update of the ECIL Guidelines for
Antifungal Therapy in Leukemia Patients
Invasive aspergillosis
Livio Pagano, Samir Agrawal, Andreas Groll
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İnvaziv Aspergillozis‟te Cerrahi
Tedavi
• Aşağıdaki durumlarda önerilir CIII
– Büyük damara bitişik lezyon
– Tek lezyon nedeniyle hemoptizi
– Lokalize ekstrapulmoner lezyon
• SSS lezyonları dahil
• Olguya göre değerlendirme yapılmalı
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Yanıt Bekleyen Sorular
• Tedavi süresi
• İlaç serum düzeyi tayini
– Özellikle azol türevlerinde tedavi
başarısızlığı ve yan etki durumlarında
• İn vitro duyarlılık
– Filamentöz funguslar rutin test edilmez
– Duyarlılık ve etkinlik arasında ilişki yok
– Tür düzeyinde identifikasyon CIII
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Empirical Antifungal Therapy Integrated Care Pathway
Agrawal S, et al. J Antimicrob Chemother 2011;66(suppl.1):i45
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Diagnostic Driven Antifungal Therapy Integrated Care Pathway
Agrawal S, et al. J Antimicrob Chemother 2011;66(suppl.1):i45
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Which Strategy to Choose?
Incidence
Availability of
Dx tests
PROPHYLAXIS EMPIRICAL PRE-EMPTIVE TARGETED
Non-
Immunosupp.
Immunosuppressed
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Teşekkürler…