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ASPERGILLUS CINSI MANTARLAR VE İNVAZİV ASPERGİLLOZ: MİKOLOJİ, PATOGENEZ, LABORATUVAR TANIMI, ANTİFUNGALLERE DİRENÇ VE DUYARLILIK DENEYLERİ

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Abstract (2. Language): 
Aspergillus species has become one of the most important airborne pathogen in developed countries, causing a significant increase in fatal pulmonary invazive aspergillosis. In spite of the recent progress in the study of laboratory diagnosis and antifungal treatments invazive aspergillosis tends to occur in immunologically debilitated individuals with an overall mortality of >50% and a mortality approaching 100% in allogenic bone marrow transplant patients. This paper briefly reviews the current state of knowledge regarding Aspergillus species and invazive aspergillosis focusing on the mycology, pathogenesis, laboratory diagnosis, antifungal agents and susceptibility tests.
Abstract (Original Language): 
Aspergillus türleri, ölümcül invaziv akciğer aspergillozunda önemli artışa yol açarak gelişmiş ülkelerde en önemli hava kaynaklı patojenlerden biri haline gelmiştir. Laboratuvar tanımı ve antifungallerle ile ilgili çalışmalardaki gelişmelere karşın invaziv aspergilloz bağışıklığı zayıflamış bireylerde >%50 mortalite ve allojenik kemik iliği transplantasyonu yapılmış hastalarda >%100 mortalite ile seyretme eğilimindedir. Bu yazıda mikoloji, patogenez, laboratuvar tanımı, antifungal maddeler ve duyarlılık deneylerine yoğunlaşılarak Aspergillus türleri ve Aspergillozla ilgili bugünkü bilgiler gözden geçirilmektedir.

REFERENCES

References: 

1. Chazalet V, Debeaupuis JP, Sarfati J, Lortholary J,
Ribaud P, Shah P, Cornet M, Vu Thien H, Gluckman E,
Brücker G, Latgé JP. Molecular typing of environmental
and patient isolates of Aspergillus fumigatus from various
hospital settings. J Clin Microbiol 1998; 36: 1494-1500.
2. Hosphental DR, Kwon-Chung KJ, Bennett JE.
Concentrations of airborne Aspergillus compared to the
incidence of invazive aspergillosis: lack of correlation.
Med Mycol 1998; 36: 165-168.
3. Latgé JP. Aspergillus fumigatus and aspergillosis. Clin
Microbiol Rev 1999; 2: 310-350.
4. Bennett JW. Mycotoxins, mycotoxicoses,
mycotoxycology and Mycopathologia. Mycopathologia
1987; 100: 3-5.
5. Risk estimation for ochratoxin A in European cpuntries.
IARC Sci Publ 1991; 115: 321-325.
6. Vesonder R, Haliburton J, Stubblefield R, Gilmore W,
Peterson S. Aspergillus flavus and aflatoxins B1, B2, and
M1 in corn associated with equine death. Arch Environ
Contam Toxicol 1991; 1: 151-153.
7. Lopez-Diaz TM, Flannigan B. Production of patulin and
cytochalasin E by Aspergillus clavatus during malting of
barley and wheat. Int J Food Microbiol 1997; 2: 129-136.
8. Unat EK, Yücel A. Tıp mikolojisi. Unat E, Yücel A,
Altaş K, Samastı M (ed). Unat’ın Tıp Parazitolojisi’nde.
İnsanın Ökaryonlu Parazitleri ve Bunlarla Bulaşan
Hastalıkları’nda. Beşinci baskı. İstanbul, Cerrahpaşa Tıp
Fak. Vakfı Yayınları; 15; 1995 : 831-39.
9. Kwon Chung KJ, Bennett JE. Medical Mycology.
Philadelphia; Lea and Fabinger, 1992.
10. Richardson MD, Warnock DW. Aspergillosis. In: Fungal
Infection. Diagnosis and Management. 2nd ed. London:
Blackwell Science; 1997; 113-130.
11. Verschraegen CF, van Besien KW, Dignani C, Hester JP,
Andersson BS, Anaissie E. Invazive Aspergillus sinusitis
during bone marrow transplantation. Scand J Infect Dis
1997; 4: 436-438.
12. Barnes AJ, Oppenheim BA, Chang J, Mongenstern GR,
Scarffe JH. Early investigation and initiation of therapy
for invazive pulmonary aspergillosis in leukaemic and
bone marrow transplant patients. Mycoses 1999; 5-6:
403-408.
13. Groll AH, Kurz M, Schneider W, Witt V, Schmidt H,
Schneider M, Schwabe D. Five-year-survey of invazive
aspergillosis in a pediatric cancer centre. Epidemiology,
mamnagement and long-term survival. Mycoses 1999; 7-
8: 431-442.
14. Lortholary O, Aşcıoğlu S, Moreau P, Herbrecht R,
Marinus A, Casassus I, De Pauw B, Denning DW.
Invazive aspergillosis as an opportunistic infection in
nonallografted patients with multiple myeloma: a
European Organization for Research and Treatment of
Cancer/ Invazive Fungal Infections Cooperative Group
and the Intergroupe Français du Myelome. Clin Infect
Dis 2000; 1: 41-46.
Temmuz-Eylül 2003 ASPERGILLUS CİNSİ MANTARLAR; KANTARCIOĞLU VE YÜCEL
155
15. Manuel R, Kibber C. The epidemiology and prevention
of invazive aspergillosis. J Hospital Infect 1998; 39: 95-
109.
16. Caillot D, Mannone L, Cuisenier B, Couallier JF. Role of
early diagnosis and aggressive surgery in the
management of invazive pulmonary aspergillosis in
neutropenic patients. Clin Microbiol Infect 2001; (Suppl
2): 54-61.
17. Sulahian A, Boutboul F, Ribaud P, Leblanc T, Lacroix T,
Derouin F. Value of antigen detection using an enzyme
immunoassay in the diagnosis and prediction of invazive
aspergillosis in two adult pediatric hematology units
during a 4-year prospective study. Cncer 2001; 2: 311-
318.
18. Raper KB, Fennell DI. Aspergillus. Baltimore, The
Williams and Wilkins Company, 1965.
19. Samson RA, Pitt JI, eds. Modern concepts in Penicillium
and Aspergillus classification. New York: Plenum Press,
1990.
20. Samson RA, Hoekstra ES, Frisvad JC, Filtenborg O.
Introduction to Food-borne Fungi. 4th ed. Baarn:
Centraalbureau voor Schimmelcultures, 1995.
21. Denning DW. Invazive aspergillosis. Clin Infect Dis
1998; 26: 781-805.
22. Özyaral O, Germeyan H, Johansson Bozok C. İstanbul’da
ev tozu küfleri üzerine çalışmalar I. Yatak tozu küf
florasının saptanması. Mikrobiyol Bült 1988; 22: 51-60.
23. Yücel A, Kantarcıoğlu A.S. Müzelerdeki eserlerin
bozulmasında mikropların rolü. Kültür Bakanlığı
Yayınları; 2004. Yayımlar Dairesi Başkanlığı Başvuru
Eserleri Dizisi; 47. Ankara, Türk Tarih Kurumu
Basımevi, 1997.
24. Şimşekli Y, Asan A, Gücin F. Bursa İli’nin çeşitli
semtlerinde ev dışı havasında bulunan Penicillium,
Aspergillus türleri ve mevsimsel dağılımları. Kükem
Dergisi 1998; 1: 13-20.
25. Leenders ACAP, van Belkum A, Behrendt M, Luijendijk
AD, Verbrugh HA. Density and molecular epidemiology
of Aspergillus in air and relationship to outbreaks of
Aspergillus infection. J Clin Microbiol 1999; 37: 1752-
1757.
26. Interdisciplinary forum on aspergillosis (Göttingen,
Germany). Mycology Newsletter 2000; 1: 9-16.
27. Kantarcıoğlu A.S. Cerrahpaşa Tıp Fakültesi
Mikrobiyoloji ve Klinik Mikrobiyoloji Derin Mikoz
laboratuvarında 01 Nisan 1999 -27 Mart 2001 arasında
ayrılan maya ve küflerin tür dağılımları. 2. Ulusal Mantar
Hastalıkları ve Klinik Mikoloji Kongresi (19-21 Haziran
2001, Ankara)’nde sunulmak üzere kabul edilmiştir.
28. Ghannoum MA, Edwards KE, Edwards JE Jr.
Pathogenesis of fungal infections. Bailliére’s Clinical
Infectious Disesases’de. Ed.F.Meunier. 1995; 2; 1-16.
29. CBS Course of Mycology. Centralbureau voor
Schimmelcultures, Drukkerij, “ERLA”, Amsterdam-
Zuid, The Netherlands, 1980.
30. Klich MA, Pitt JI. A laboratory Guide to Common
Aspergillus species and their Teleomorphs. Australia:
Commonwealth Scientific and Industrial Research
Organization, Division of Food Processing, 1988.
31. Smith GR. Aspergillus fumigatus: A possible relationship
between spore size and virulence for mice. J Gen
Microbiol 1977; 102: 413-415.
32. Annaix V, Bouchara JP, Larcher G, Chabasse D,
Tronchin G. Specific binding of human fibrinogen
fragment D to Aspergillus fumigatus conidia. Infect
Immun 1992; 60: 1747-1755.
33. Bouchara JP, Bouali A, Tronchin G, Robert R, Chabasse
D, Senet JM. Binding of fibrinogen to the pathogenic
Aspergillus species. J Med Vet Mycol 1988; 26: 327-334.
34. Coulot P, Bouchara JP, Renier G, Annaix V,
Planchenault C, Tronchin G, Chabasse D. Specific
interactions of Aspergillus fumigatus with fibrinogen and
its role in cell adhesion. Infect Immun 1994; 62: 2169-
2177.
35. Gill ML, Penalver MC, Lopez-Ribot JL, O’Connor JE,
Martinez JP. Binding of extracellular matrix proteins to
Aspergillus fumigatus conidia. Infect Immun 1996; 64:
5239-5247.
36. Penalver MC, Casanova M, Martinez JP, Gil ML. Cell
wall protein and glycoprotein constituents of Aspergillus
fumigatus that bind to polystrene may be responsible for
the cell surface hydrofphobicity of the mycelium.
Microbiology 1996; 142: 1597-1604.
37. Sturtevant J, Latgé P. Interactions between conidia of
Aspergillus fumigatus and human complement
component C3. Infect Immun 1992; 60: 1913-1918.
38. Tronchin G, Bouchara JP, Ferron M, Larcher G,
Chabasse D. Cell surface properties of Aspergillus
fumigatus conidia correlation between adherence,
agglutination, and rearrangements of the cell wall. Can J
Microbiol 1995; 41: 714-721.
39. Tronchin G, Bouchara JP, Latgé JP, Chabasse D.
Application of a Lowicryl K4M embedding technique for
analysis of fungal adhesins. J Mycol Méd 1992; 3: 74-79.
40. Tronchin G, Esnault K, Reiner G, Filmon R, Chabasse D,
Bouchara JP. Expression and identification of lamininbinding
protein in Aspergillus fumigatus conidia. Infect
Immun 1997; 65: 9-15.
41. Verweij PE, Oakley KL, Morrissey J, Morrissey G,
Denning DW. Efficacy of LY303366 against
amphotericin B-susceptible and –resistant Aspergillus
fumigatus in a murine model invazive aspergillosis.
Antimicrob Agents Chemother 1998; 42: 873-878.
CERRAHPAŞA TIP DERGİSİ Cilt (Sayı) 34 (3)
156
42. Kantarcıoğlu AS, Yücel A. Cryptococcus neoformans’ın
virülens faktörleri. (Cerrahpal Tıp Derg’ne sunulmuştur).
43. Sutton P, Newcombe NR, Waring P, Mullbacher A.
Immunosuppressive activity of gliotoxin, a metabolite
produced by human pathogenic fungi. Infect Immun
1994; 62: 1192-1198.
44. Amitani R, Taylor G, Elezis EN, Llewellyn-Jones C,
Mitchell J, Kuze F, Cole PJ, Wilson R. Purification and
characterization of factors produced by Aspergillus
fumigatus which affect human ciliated respiratory
epithelium. Infect Immun 1995; 63: 3266-3271.
45. Monod M, Fatih A, Jaton-Ogay K, Paris S, Latge JP. The
secreted proteases of pathogenic species of Aspergillus
and their possible role in virulence. Can J Bot 1995; 73:
S1081-S1086.
46. Richard U, Monod M, Odds F, Rüchel R. Virulance of an
aspergillopepsin-deficient mutant of Aspergillus
fumigatus and evidence for another aspartic proteinase
linked to the fungal cell wall. J Med Vet Mycol 1997; 35:
189-196.
47. Birch M, Robson G, Law D, Denning DW. Evidence of
multiple phospholipase activities of Aspergillus
fumigatus. Infect Immun 1996; 64: 751-755.
48. Chris Tomee JF, Wierengha ATJ, Hiemstra PS, Kaufman
HF. Proteases from Aspergillus fumigatus induce release
of proimlammatory cytokines and cell detachment in
airway epithelial cell lines. J Infect Dis 1997; 176: 300-
303.
49. Yücel A, Kantarcıoğlu AS. Candida’ların patojenlik
belirtgenleri. Cerr Tıp Derg 2000; 31: 172-186 .
50. Holdom MD, Hay RJ, Hamilton AJ. The Cu, Zn
superoxide dismutases of Aspergillus flavus, Aspergillus
niger, Aspergillus nidulans, Aspergillus terreus:
purification and biochemical comparison with the
Aspergillus fumigatus, Cu Zn dismutase. Infect Immun
1996; 64: 3326-3332.
51. Wong B, Brauner KL, Tsai RR, Jayasimhulu K.
Increased amounts of the Aspergillus metabolite Dmannitol
in tissue and serum of rats with experimental
aspergillosis. J Infect Dis 1989; 160: 95-103.
52. Roilides E, Unlig K, Venzon D, Pizzo PA, Walsh TJ.
Prevention of corticosteroid-induced suppression of
human polymorphonuclear leukocyte-induced damage of
Aspergillus fumigatus hyphae by granulocyte colonystimulating
factor and gamma interferon. Infect Immun
1993; 61: 4870-4877.
53. Roilides E, Blake C, Holmes A, Pizzo PA, Waslh TJ.
Granulocytomacrophage colony-stimulating factor and
interferon-γ prevent dexa-methasone-induced
immunosuppression of antifungal monocyte activity
against Aspergillus fumigatus hyphae. J Med Vet Mycol
1996; 34: 63-69.
54. De Repetingy L, Petithois S, Bouchira M. Acquired
immunity in experimental murine aspergillosis is
mediated by macrophages. Infect Immun 1003; 61: 3791-
3802.
55. Carlson GL, Birch M, Mughal MM, Denning DW.
Aspergillus wound infection fallowing laparostomy. J
Infect 1996; 33: 119-122.
56. Denning DW. Chronic forms of pulmonary aspergillosis.
Clin Microbiol Infect 2001; (Suppl 2): 25-31.
57. Koneman EW, Allen SD, Janda WM, Schreckenberger
PC, Washington CW Jr (Eds). Diagnostic Microbiology.
Fifth edition. Philadelphia: Lippincott, 1997; 983-1057.
58. Richardson MD. Aspergillus and Penicillium species. In:
Collier L, Balows A, Sussman M (Eds). Topley and
Wilson’s Microbiology and Microbial Infections. v.4
Ajello L, Hay RJ (v. Eds). Medical Mycology. 9th
edition. London: 2000; 281-314.
59. Ruhnke M. Initial diagnosis to differential identification.
In: Vincent JL (ed). The Management of Fungal Infection
in the ICU.The Liposome Company 1999; 23-32.
60. Horvath JA, Dummer S. The use of respiratory-tract
cultures in the diagnosis of invazive pulmonary
aspergillosis. Am J Med 1996; 2: 171-178.
61. Klont RR, Meis JFMG, Verveij PE. Critical assessment
of issues in the diagnosis of invazive aspergillosis. Clin
Microbiol Infect 2001; (Suppl 2): 32-37.
62. Verweij PE, Weemaes CM, Curfs JHA, Bretagne S, Meis
JFMG. Failure to detect circulating Aspergillus markers
in a patient with chronic granulomatous disease and
invazive aspergillosis. J Clin Microbiol 2000; 38: 3900-
3901.
63. Maertens J, Verhaegen J, Lagrou K, Van Eldere J,
Boogaerts M. Screening for circulating galactomannan as
a noninvazive diagnostic tool for invazive aspergillosis in
prolonged neutropenic patients stem cell transplantation
recipients: a prospective validation. Blood 2001; 6: 1604-
1610.
64. Kami M, Ogawa S, Kanda I, Tanaka I, Machida U,
Matsumura T, Sakamaki H, Hirai H. Early diagnosis of
central nervous system aspergillosis using polymerase
chain reaction, latex agglutination test, and enzymelinked
immunosorbent assay. Br J Haematol 1999; 2:
536-537.
65. Manuel RJ, Ainscough S, Prentice HG, Berger LA,
Yeghen T, Potter MN, Kibber C. The diagnosis of
invazive aspergillosis: is early early enough? Abstracts of
11th European Congress of Clinical Microbiology and
Infection Diseases (1-4 April, 2001, Istanbul, Turkey).
Clin Microbiol Infect 2001; (Suppl 1): 33.
66. De Pauw BE. Systemic mycotic infections: management
in cancer patients. Abstracts of 5th Congress of the
European Confederation of Medical Mycology (3-6 June
1999, Dresden, Germany). Mycoses 1999; 42: 147-150.
Temmuz-Eylül 2003 ASPERGILLUS CİNSİ MANTARLAR; KANTARCIOĞLU VE YÜCEL
157
67. Aşcıoğlu S, De Pauw B, Donnelly JP, Collette L.
Reliability of clinical research on invazive fungal
infections: a systematic review of the literature. Med
Mycol 2001; 39: 35-40.
68. Bernhardt H. German work on standardization. Abstracts
of 5th Congress of the European Confederation of
Medical Mycology (3-6 June 1999, Dresden, Germany).
Mycoses 1999; 42: 126.
69. Evans EGV. International perspective of standardization.
Abstracts of 5th Congress of the European Confederation
of Medical Mycology (3-6 June 1999, Dresden,
Germany). Mycoses 1999; 42: 132.
70. Denning DW, Marinus A, Cohen J, Spence D, Hervrecht
R, Pagano L, Kibber C, Kermery V, Offner F, Cordonnier
C, Jehn U, Ellis M, Collette L, Sylvester R. An EORTC
multicentre prospective survey of invazive aspergillosis
haematological patients: diagnosis and therapeutic
outcome. I Invazive Fungal Infections Cooperative
Group. J Infect 1998; 2: 173-180.
71. Yücel A, Kantarcıoğlu S. Çeşitli Aspergillus türleri
üzerine CO2'in etkilerini araştırdığımız deneylerin ilk
sonuçları. Türkiye Parazitoloji Dergisi, 1998; 22: 67-72.
72. Fridkin S, Jarvis W. Epidemiology of nosocomial fungal
infections. Clin Microbiol Rev 1996; 9: 499-511.
73. VandenBergh M, Verweij P, Voss A. Epidemiology of
nosocomial fungal infections: invazive aspergillosis and
the environment. Diagn Microbiol Infect Dis 1999; 34:
221-227.
74. Munoz P, Burillo A, Bouza E. Environmental
surveillance and other control measures in the prevention
of nosocomial fungal infections. Clin Microbiol Infect
2001; (Suppl 2): 38-45.
75. Yücel A. Mikozların tedavisi: Antifungal ilaçlar. Yücel
A, Tabak F, Öztürk R, Mert A. (ed). Günümüzde
Antimikrobik Tedavi’de. İstanbul Bulaşıcı Hastalıklarla
Savaş Derneği Yayın no: 12. İstanbul, 1998; 117-142.
76. Dayan AD, Working PK. Non-clinical studies of the
efficacy, pharmacokinetics and safety of amphotericin B
colloidal dispersion (ABCD). In: Mackenzie DWR (ed).
Amphotericin B Colloidal Dispersion (ABCD) in the
Treatment of Disseminated Fungal Infections. London
1993; 12-26.
77. McGinnis MR, Rinaldi MG. Antifungal drugs:
mechanism of action, drug resistance, susceptibility
testing, and assay of activity in biologic fluids. In: Lorian
V (ed). Antibiotics in Laboratory Medicine. Williams and
Wilkins, Baltimore, 1996; 176-311.
78. Denning DW, Radford SA, Oakley KL, Hall L, Johnson
EM, Warnock DW. Correlation between in vitro
susceptibility testing to itraconazole and in vivo outcome
of Aspergillus infection. J Antimicrob Chemother 1997;
40: 401-414.
79. Denning DW, Venkateswarlu KL, Oakley KL, Anderson
MJ, Manning NJ, Stevens DA, Warnock DW, Kelly SL.
Itraconazole resistance in Aspergillus fumigatus.
Antimicrob Agents Chemother 1997; 6: 1364-1368.
80. Chryssanthou E. In vitro susceptibility of respiratory
isolates of Aspergillus species to itraconazole and
amphotericin B, acquired resistance to itraconazole.
Scand J Infect Dis 1997; 5: 509-512.
81. Dannaoui E, Borel E, Monier MF, Piens MA, Picot S,
Persat F. Acquired itraconazole resistance in Aspergillus
fumigatus. J Antimicrob Chemother 2001; 3: 333-340.
82. Kantarcıoğlu AS. Cerrahpaşa Tıp Fakültesi Mikrobiyoloji
ve Klinik Mikrobiyoloji Derin Mikoz laboratuvarında 01
Nisan 1999 -27 Mart 2001 arasında ayrılan maya ve
küflerin duyarlılık paterni. 2. Ulusal Mantar Hastalıkları
ve Klinik Mikoloji Kongresi (19-21 Haziran 2001,
Ankara)’nde sunulmak üzere kabul edilmiştir.
83. Manavathu EK, Cutright JL, Loebenberg D,
Chandrasekar PH. A comparative study of the in vitro
susceptibilities of clinical and laboratory selected
resistant isolates of Aspergillus spp. to amphotericin B,
itraconazole, voriconazole and posaconazole (SCH
56592). J Antimicrob Chemother 2000; 2: 229-234.
84. Petraitiene R, Petraitis V, Groll AH, Sein T, Piscitelli S,
Candelario M, Field-Ridley A, Avila N, Bacher J, Walsh
TJ. Antifungal activity and pharmacokinetics of
posaconazole (SCH 56592) in treatment and prevention
of experimental invazive pulmonary aspergillosis:
correlation with galactomannan antigenemia. Antimicrob
Agents Chemother 2001; 3: 857-869.
85. Pérez A. Terbinafine: broad new spectrum of indications
in several subcutaneous and systemic mycoses and
parasitic diseases. Abstracts of 5th Congress of the
European Confederation of Medical Mycology (3-6 June
1999, Dresden, Germany). Mycoses 1999; 42: 150-151.
86. Ryder NS. Activity of terbinafine against serious fungal
pathogens. Mycoses 1999; (Suppl 2): 115-119

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