J Korean Med Sci.  2012 Jan;27(1):10-15. 10.3346/jkms.2012.27.1.10.

Real-Time Nucleic Acid Sequence-Based Amplification to Predict the Clinical Outcome of Invasive Aspergillosis

Affiliations
  • 1Division of Infectious Diseases, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea. jhyoo@catholic.ac.kr
  • 2Clinical Research Institutes of Medical Science, The Catholic University of Korea College of Medicine, Seoul, Korea.

Abstract

Monitoring the response to therapy for invasive aspergillosis (IA) is essential for the management of patients with hematologic diseases. We evaluated the correlation between the outcome of real-time nucleic acid sequence-based amplification (RTi-NASBA) for Aspergillus 18S rRNA and the clinical outcome of IA. A total of 157 serum samples from 29 patients with IA were tested for RTi-NASBA. The treatment response and mortality were compared with the NASBA outcome (whether the NASBA value was converted to negative or not) at 12 weeks after the start of antifungal therapy. At 12 weeks, there was a moderate correlation between the treatment failure and persistently positive NASBA (kappa = 0.482; P = 0.019). Deaths attributable to IA were more prevalent in patients without negative conversion of NASBA than in those with negative conversion (50% vs 5%; P = 0.013). Significant factors of treatment failure at 12 weeks were the status of hematologic disease (nonremission; P = 0.041) and the NASBA outcome (failure of negative conversion; P = 0.024). Survival was significantly better in patients with negative conversion of NASBA than those with persistently positive values (P = 0.036). This study suggests that the serial monitoring of RTi-NASBA could be useful for prediction of the clinical outcome in hematologic patients with IA.

Keyword

Nucleic Acid Sequence-Based Amplification; Aspergillosis; Treatment Outcome

MeSH Terms

Adolescent
Adult
Aged
Antifungal Agents/therapeutic use
Aspergillosis/*diagnosis/drug therapy/microbiology/mortality
Aspergillus/*genetics/isolation & purification
Base Sequence
Female
Humans
Lung/microbiology
Male
Middle Aged
Predictive Value of Tests
RNA, Ribosomal, 18S/analysis
*Real-Time Polymerase Chain Reaction
Retrospective Studies
Sputum/microbiology
Survival Rate

Figure

  • Fig. 1 Cumulative survival of the patients according to the nucleic acid sequence-based amplification (NASBA) outcome.


Reference

1. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002. 34:909–917.
2. Yoo JH, Lee DG, Choi SM, Choi JH, Park YH, Kim YJ, Kim HJ, Lee S, Kim DW, Lee JW, Min WS, Shin WS, Kim CC. Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea. Bone Marrow Transplant. 2004. 34:497–504.
3. Slobbe L, Polinder S, Doorduijn JK, Lugtenburg PJ, el Barzouhi A, Steyerberg EW, Rijnders BJ. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: an observational study. Clin Infect Dis. 2008. 47:1507–1512.
4. Maschmeyer G, Haas A, Cornely OA. Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. Drugs. 2007. 67:1567–1601.
5. Wheat LJ, Walsh TJ. Diagnosis of invasive aspergillosis by galactomannan antigenemia detection using an enzyme immunoassay. Eur J Clin Microbiol Infect Dis. 2008. 27:245–251.
6. Marr KA, Laverdiere M, Gugel A, Leisenring W. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis. 2005. 40:1762–1769.
7. Caillot D, Couaillier JF, Bernard A, Casasnovas O, Denning DW, Mannone L, Lopez J, Couillault G, Piard F, Vagner O, Guy H. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol. 2001. 19:253–259.
8. Brodoefel H, Vogel M, Hebart H, Einsele H, Vonthein R, Claussen C, Horger M. Long-term CT follow-up in 40 non-HIV immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome. AJR Am J Roentgenol. 2006. 187:404–413.
9. Perlin DS, Zhao Y. Molecular diagnostic platforms for detecting Aspergillus. Med Mycol. 2009. 47:S223–S232.
10. Yoo JH, Choi JH, Choi SM, Lee DG, Shin WS, Min WS, Kim CC. Application of nucleic acid sequence-based amplification for diagnosis of and monitoring the clinical course of invasive aspergillosis in patients with hematologic diseases. Clin Infect Dis. 2005. 40:392–398.
11. Yoo JH, Choi SM, Lee DG, Park SH, Choi JH, Kwon EY, Shin WS. Comparison of the real-time nucleic acid sequence-based amplification (RTi-NASBA) with conventional NASBA, and galactomannan assay for the diagnosis of invasive aspergillosis. J Korean Med Sci. 2007. 22:672–676.
12. Yoo JH, Choi SM, Choi JH, Kwon EY, Park C, Shin WS. Construction of internal control for the quantitative assay of Aspergillus fumigatus using real-time nucleic acid sequence-based amplification. Diagn Microbiol Infect Dis. 2008. 60:121–124.
13. Park C, Kwon EY, Shin NY, Choi SM, Kim SH, Park SH, Lee DG, Choi JH, Yoo JH. Evaluation of nucleic acid sequence based amplification using fluorescence resonance energy transfer (FRET-NASBA) in quantitative detection of Aspergillus 18S rRNA. Med Mycol. 2011. 49:73–79.
14. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE. European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group. the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008. 46:1813–1821.
15. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002. 34:730–751.
16. Patterson SS, Casper ET, Garcia-Rubio L, Smith MC, Paul JH 3rd. Increased precision of microbial RNA quantification using NASBA with an internal control. J Microbiol Methods. 2005. 60:343–352.
17. Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, Walsh TJ, Maertens J, Patterson TF, Perfect JR, Dupont B, Wingard JR, Calandra T, Kauffman CA, Graybill JR, Baden LR, Pappas PG, Bennett JE, Kontoyiannis DP, Cordonnier C, Viviani MA, Bille J, Almyroudis NG, Wheat LJ, Graninger W, Bow EJ, Holland SM, Kullberg BJ, Dismukes WE, De Pauw BE. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008. 47:674–683.
18. Chmura Kraemer H, Periyakoil VS, Noda A. Kappa coefficients in medical research. Stat Med. 2002. 21:2109–2129.
19. Segal BH. Aspergillosis. N Engl J Med. 2009. 360:1870–1884.
20. Latgé JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev. 1999. 12:310–350.
21. Wiederhold NP, Najvar LK, Vallor AC, Kirkpatrick WR, Bocanegra R, Molina D, Olivo M, Graybill JR, Patterson TF. Assessment of serum (1->3)-beta-D-glucan concentration as a measure of disease burden in a murine model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2008. 52:1176–1178.
22. Vallor AC, Kirkpatrick WR, Najvar LK, Bocanegra R, Kinney MC, Fothergill AW, Herrera ML, Wickes BL, Graybill JR, Patterson TF. Assessment of Aspergillus fumigatus burden in pulmonary tissue of guinea pigs by quantitative PCR, galactomannan enzyme immunoassay, and quantitative culture. Antimicrob Agents Chemother. 2008. 52:2593–2598.
23. Park SH, Choi SM, Lee DG, Choi JH, Kim SH, Kwon JC, Yoo JH, Kim HJ, Lee S, Eom KS, Min WS. Serum galactomannan strongly correlates with outcome of invasive aspergillosis in acute leukaemia patients. Mycoses. 2011. 54:523–530.
24. Yoo JH, Lee DG, Choi SM, Shin WS. Evaluation of nucleic acid sequence-based amplification (NASBA) for diagnosis and monitoring of invasive aspergillosis: a preliminary report. Infect Chemother. 2003. 35:99–106.
25. Maertens J, Buvé K, Theunissen K, Meersseman W, Verbeken E, Verhoef G, Van Eldere J, Lagrou K. Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients. Cancer. 2009. 115:355–362.
26. Koo S, Bryar JM, Baden LR, Marty FM. Prognostic features of galactomannan antigenemia in galactomannan-positive invasive aspergillosis. J Clin Microbiol. 2010. 48:1255–1260.
27. Woods G, Miceli MH, Grazziutti ML, Zhao W, Barlogie B, Anaissie E. Serum Aspergillus galactomannan antigen values strongly correlate with outcome of invasive aspergillosis: a study of 56 patients with hematologic cancer. Cancer. 2007. 110:830–834.
28. Hummel M, Spiess B, Cornely OA, Dittmer M, Mörz H, Buchheidt D. Aspergillus PCR testing: results from a prospective PCR study within the AmBiLoad trial. Eur J Haematol. 2010. 85:164–169.
29. Bretagne S. Primary diagnostic approaches of invasive aspergillosis: molecular testing. Med Mycol. 2011. 49:S48–S53.
30. White PL, Bretagne S, Klingspor L, Melchers WJ, McCulloch E, Schulz B, Finnstrom N, Mengoli C, Barnes RA, Donnelly JP, Loeffler J. European Aspergillus PCR Initiative. Aspergillus PCR: one step closer to standardization. J Clin Microbiol. 2010. 48:1231–1240.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr