How effective is beta glucan test in early diagnosis of invasive fungal infection in patient with hematologic malignancy?

Yıl 2015, , 102 - 107, 26.12.2015

Mehmet Kürşat Keskin Fahir Özkalemkaş Nizameddin Koca Vildan Özkocaman Beyza Ener Rıdvan Ali Tülay Özçelik Hakan Yorulmaz Ahmet Tunalı

https://doi.org/10.5505/aot.2015.49091

Öz

INTRODUCTION: Invasive fungal infections (IFI) are commonly seen in immunosuppressive patients. Early diagnosis is key to optimizing antifungal treatment success. Betaglucan (BG) assay can detect most of the fungal pathogens except mucormycosis and Cryptococcus. In this study we aimed to evaluate the value of BG as a diagnostic tool in patients with hematological malignancy and IFI.METHODS: Forty-six hematological malignancy patients under induction and consolidation chemotherapy that expected to have neutropenia for more than 14 days with no clinical and radiological signs of IFI are included in this study. Blood Galactomannan (GM) and BG levels were measured 2 times in a week during the hospitalization period. Method A (proven + probable groups vs non IFI) and Method B (proven + probable + possible groups vs. non IFI) variables were determined to assess the sensitivity, specifity and predictive values.RESULTS: In method A; BG test's sensitivity, specifity, positive predictive value (PPV), negative predictive value (NPV) was determined as 68.75%, 84.1%, 52.4%, 91.4% respectively. In method B (proven + probable + possible groups vs. non IFI) BG test sensitivity, specifity, PPV, NPV was determined as 60%, 88.9%, 71.4%, and 82.8% respectively.DISCUSSION AND CONCLUSION: Depending on our data and present literature; we conclude that BG and GM is a non-invasive contributory test for the diagnosis of IFI The current treatment of the symptomatic extremity

Anahtar Kelimeler

Invasive Fungal Infections, Beta glucan, galactomannan, sensitivity, specifity

Hematolojik kanserli hastalarda Invaziv fungal enfeksiyonun erken tanısındabeta glukan testi ne kadar etkilidir?

Öz

GİRİŞ ve AMAÇ: İnvaziv fungal enfeksiyonlar (IFE) sıklıkla immün süpresif hastalarda görülmektedir. Antifungal tedavi başarısı için erken tanı anahtar öneme sahiptir. Betaglucan (BG) testi mucormikoz ve kriptokoklar dışında birçok mantar patojeni tespit edebilir. Bu çalışmada betaglucan düzeyinin hematolojik kanserli ve IFE'li hastalarda tanısal bir araç olarak değerlendirmeyi amaçladık.YÖNTEM ve GEREÇLER: Indüksiyon veya konsolidasyon tedavisi alan, klinik ve radyolojik IFE bulguları olmayan 14 günden uzun süreli nötropeni beklentisi olan 46 hasta çalışmaya dahil edildi. Hastanede yattıkları süre içerisinde haftada 2 defa kan galaktmannan (GM) ve BG düzeyleri ölçüldü. Sensitivite, spesifite ve öngörğlen değerlerin yorumlanması için Metod A (kanıtlanmış + muhtemel grup vs non-IFE) ve Metod B (kanıtlanmış + muhtemel +olası grup vs non-IFE ) değişkenleri tanımlandı.BULGULAR: Metod A'da; BG testinin sensitivitesi, spesifitesi, pozitif öngörülen değer (PÖD), Negatif öngörülen değer (NÖD) sırasıyla %68.75, %84.1, %52.4, %91.4 olarak tespit edildi. Metod B'de; BG testinin sensitivitesi, spesifitesi, PÖD, NÖD sırasıyla %60, %88.9, %71.4, %82.8 olarak tespit edildi.Hiçbir hastada ameliyat içi istenmeyen durum olmadı. Cerrahi gruptaki 3 hastaya embolizasyon uygulandı. Postoperatif takiplerde 1 hastada enfeksiyon, 2 hastada nüks saptandı.TARTIŞMA ve SONUÇ: Bizim verilerimiz ve mevcut literature dayanarak BG ve GM'nin IFE tanısına katkı sağlayan non-invaziv test olduğu sonucuna vardık.

Anahtar Kelimeler

İnvaziv fungal enfeksiyonlar, beta glukan, galaktomannan, sensitivite, spesifite

Kaynakça

• Segal BH. Aspergillosis. N Engl J Med 2009; 360: 1870-1884.
• Lin SJ, Schranz J, Teutsch SM. Aspergillosis case- fatality rate: systematic review of the literature. Clin Infect Dis 2001; 32: 358-366.
• Kaiser L, Huguenin T, Lew PD et al. Invasive aspergillosis. Clinical features of 35 proven cases at a single institution. Medicine (Baltimore) 1998; 77: 188-194.
• Wingard JR, Hiemenz JW, Jantz MA. How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation. Blood 2012; 120: 1791-1800.
• Wingard JR. Have novel serum markers supplanted tissue diagnosis for invasive fungal infections in acute leukemia and transplantation? Best Pract Res Clin Haematol 2012; 25: 487-491.
• Upton A, Kirby KA, Carpenter P et al. Invasive aspergillosis transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis 2007; 44: 531-540. hematopoietic cell
• Pagano L, Caira M, Candoni A et al. Invasive aspergillosis in patients with acute myeloid leukemia: Haematologica 2010; 95: 644-650. registry study.
• Miceli MH, Maertens J. Role of Non-Culture-Based Tests, with an Emphasis on Galactomannan Testing for the Diagnosis of Invasive Aspergillosis. Semin Respir Crit Care Med. 2015 Oct;36(5): 650-61.
• Mikulska M, Furfaro E, Viscoli C. Non-cultural methods for the diagnosis of invasive fungal disease. Expert Rev Anti Infect Ther. 2015 Jan;13(1): 103- 17.
• Ceesay MM, Desai SR, Berry L, Cleverley J, Kibbler CC, Pomplun S, Nicholson AG, Douiri A, Wade J, Smith M, Mufti GJ, Pagliuca A. A comprehensive galactomannan, targeted β-d-glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients. Br J Haematol. 2015 Jan;168(2): 219-29.
• Buchheidt D, Baust C, Skladny H et al. Detection of Aspergillus species in blood and bronchoalveolar lavage samples from immunocompromised patients by means of 2-step polymerase chain reaction: clinical results. Clin fect Dis 2001; 33: 428-435.
• Farina C, Lombardi G, Andreoni S, Manso E, Perin S, Panellis D, Fazii P, Conte M, Sanna S, Pini P, Blasi E. Routine use of a protease zymogen-based colorimetric assay for the detection of Beta-glucan and its role in clinical practice. Int J Immunopathol Pharmacol. 2014 Oct-Dec;27(4): 661-8.
• Lamoth F, Cruciani M, Mengoli C et al. beta-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis 2012; 54: 633-643.
• Ostrosky-Zeichner L, Alexander BD, Kett DH et al. Multicenter clinical evaluation of the (1-->3) beta- D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005; 41: 654- 659.
• Pickering JW, Sant HW, Bowles CA et al. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol 2005; 43: 5957-5962.
• Kawazu M, Kanda Y, Nannya Y et al. Prospective comparison of the diagnostic potential of real-time PCR, immunosorbent assay for galactomannan, and a (1-- >3)-beta-D-glucan test in weekly screening for invasive aspergillosis in patients with hematological disorders. J Clin Microbiol 2004; 42: 2733-2741.
• Odabasi Z, Mattiuzzi G, Estey E et al. Beta-D- glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis 2004; 39: 199-205.
• Obayashi T, Negishi K, Suzuki T, Funata N. Reappraisal of the serum (1-->3)-beta-D-glucan assay for the diagnosis of invasive fungal infections- -a study based on autopsy cases from 6 years. Clin Infect Dis 2008; 46: 1864-1870.
• Senn L, Robinson JO, Schmidt S et al. 1,3-Beta-D- glucan antigenemia for early diagnosis of invasive fungal infections in neutropenic patients with acute leukemia. Clin Infect Dis 2008; 46: 878-885.
• Pazos C, Ponton J, Del Palacio A. Contribution of (1->3)-beta-D-glucan diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. J Clin Microbiol 2005; 43: 299-305.