Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Post-Transplant Events

An early CT-diagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality

Bone Marrow Transplantation volume 44, pages 51–56 (2009)Cite this article

Abstract

Empirical antifungal therapy is frequently used in allogeneic transplant patients who have persistent febrile neutropenia and can be associated with high cost, toxicity and breakthrough infections. There are limited reports of strategies for early diagnosis of invasive fungal infection (IFI) and, to our knowledge, no reports of treatment strategies based only on high-resolution computerized tomography (HRCT) scans. We used an early treatment strategy for IFI in 99 consecutive patients undergoing allogeneic transplantation. Patients received caspofungin if they had antibiotic-resistant neutropenic fever for more than 72 h and a positive HRCT scan. Fifty-three of 99 patients (54%) had antibiotic-resistant neutropenic fever at 72 h and would have received parenteral antifungal treatment if an empirical approach had been used. The HRCT-based strategy reduced the use of parenteral antifungal agents to 17/99 patients (17%), a 68% reduction. No subsequent diagnoses of IFI occurred within 100 days in patients with a negative HRCT. Only one patient died from IFI within 100 days. These data suggest that this non-empirical strategy may be feasible and that caspofungin may be effective in this setting. A randomized controlled trial is warranted to further assess these results.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T et al. 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Inf Dis 2002; 34: 730–751.

    Article  Google Scholar 

  2. Link H, Bohme A, Cornely OA, Hoffken K, Kellner O, Kern WV et al. Antimicrobial therapy of unexplained fever in neutropenic patients—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), study group interventional therapy of unexplained fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Ann Hematol 2003; 82 (Suppl 2):S105–S117.

    Article  CAS  Google Scholar 

  3. Mahfouz T, Anaissie E . Prevention of fungal infections in the immunocompromised host. Curr Opin Investig Drugs 2003; 4: 974–990.

    CAS  PubMed  Google Scholar 

  4. Prentice AG, Glasmacher A, Hobson RP, Schey S, Barnes RA, Donnelly JP et al. Guidelines on the Management of Invasive Fungal Infection During Therapy for Haematological Malignancy. British Committee for Standards in Haematology, 2007.

  5. Morrissey CO, Bardy PG, Slavin MA, Ananda-Rajah MR, Chen SC, Kirsa SW et al. Diagnostic and therapeutic approach to persistent or recurrent fevers of unknown origin in adult stem cell transplantation and haematological malignancy. Intern Med J 2008; 38: 477–495.

    Article  CAS  Google Scholar 

  6. Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C, Walsh TJ et al. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J Infect Dis 2004; 190: 641–649.

    Article  CAS  Google Scholar 

  7. Sulahian A, Touratier S, Ribaud P . False positive test for Aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam. N Engl J Med 2003; 349: 2366–2367.

    Article  CAS  Google Scholar 

  8. Thomas KE, Owens CM, Veys PA, Novelli V, Costoli V . The radiological spectrum of invasive aspergillosis in children: a 10 year review. Pediatr Radiol 2003; 33: 453–460.

    Article  Google Scholar 

  9. Herbert PA, Bayer AS . Fungal pneumonia (part 4): invasive pulmonary aspergillosis. Chest 1981; 80: 220–225.

    Article  CAS  Google Scholar 

  10. Kami M, Kishi Y, Hamaki T, Kawabata M, Kashima T, Masumoto T et al. The value of the chest computed tomography halo sign in the diagnosis of invasive pulmonary aspergillosis. An autopsy-based retrospective study of 48 patients. Mycoses 2002; 45: 287–294.

    Article  CAS  Google Scholar 

  11. Kim MJ, Lee KS, Kim J, Jung KJ, Lee HG, Kim TS . Crescent sign in invasive pulmonary aspergillosis: frequency and related CT and clinical factors. J Comput Assist Tomogr 2001; 25: 305–310.

    Article  CAS  Google Scholar 

  12. Mori M, Galvin JR, Barloon TJ, Gingrich RD, Stanford W . Fungal pulmonary infections after bone marrow transplantation: evaluation with radiography and CT. Radiology 1991; 178: 721–726.

    Article  CAS  Google Scholar 

  13. Caillot D, Couaillier JF, Bernard A, Casanovas O, Denning DW, Mannone L et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computerised tomography scans in patients with neutropenia. J Clin Oncol 2001; 19: 253–259.

    Article  CAS  Google Scholar 

  14. Weisser M, Rausch C, Droll A, Simcock M, Sendi P, Steffen I et al. Galactomannan does not precede major signs on a pulmonary computerised tomographic scan suggestive of invasive aspergillosis in patients with haematological malignancies. Clin Infect Dis 2005; 41: 1143–1149.

    Article  CAS  Google Scholar 

  15. Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E et al. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis 2005; 41: 1242–1250.

    Article  CAS  Google Scholar 

  16. Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F et al. Empirical versus pre-emptive antifungal therapy in high-risk febrile neutropenic patients: a prospective randomised study. Blood ASH Annu Meet Abstr 2006; 108: 2019.

    Google Scholar 

  17. Hebert H, Klingspor L, Klingebiehl T, Loeffler J, Tollemar J, Ljungman P et al. PCR-based liposomal amphotericin B treatment following allogeneic stem cell transplantation is a safe treatment strategy: preliminary results of a prospective study. Blood ASH Annu Meet Abstr 2004; 104: 192.

    Google Scholar 

  18. Oshima K, Kanda Y, Asano-Mori Y, Nishimoto N, Arai S, Nagai S et al. Presumptive treatment strategy for aspergillosis in allogeneic haematopoietic stem cell transplant recipients. J Antimicrob Chemo 2007; 60: 350–355.

    Article  CAS  Google Scholar 

  19. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002; 347: 2020–2029.

    Article  CAS  Google Scholar 

  20. Ascioglu S, Rex JH, de Paux B, Bennett JE, Bille J, Crokaert F et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002; 34: 7–14.

    Article  CAS  Google Scholar 

  21. Madureira A, Bergeron A, Lacroix C, Robin M, Rocha V, Peffault de Latour R et al. Breakthrough invasive aspergillosis in allogeneic haematopoietic stem cell transplant recipients treated with caspofungin. Int J Antimicrob Agents 2007; 30: 551–554.

    Article  CAS  Google Scholar 

  22. Viscoli C, Herbrecht R, Akan H, Baila C, Doyen A, Gallamini A et al. Caspofungin (C) as first-line therapy of invasive aspergillosis (IA) in haematological patients (pts): a study of the EORTC Infectious Diseases Group. Trends Med Mycol 2007a; 012.

  23. Candoni A, Mestroni R, Damiani D, Tiribelli M, Michelutti A, Silvestri F et al. Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies. Eur J Haematol 2005; 75: 227–233.

    Article  CAS  Google Scholar 

  24. Petrovic J, Ngai A, Bradshaw S, Williams-Diaz A, Taylor A, Sable C et al. Efficacy and safety of caspofungin in solid organ transplant recipients. Transplant Proc 2007; 39: 3117–3120.

    Article  CAS  Google Scholar 

  25. Groetzner J, Kaczmarek I, Wittwer T, Strauch J, Meiser B, Wahlers T et al. Caspofungin as first-line therapy for the treatment of invasive aspergillosis after thoracic organ transplantation. J Heart Lung Transplant 2007; 27: 1–5.

    Article  Google Scholar 

  26. Maertens J, Raad I, Petrikkos G, Boogaerts M, Sellesgerg D, Petersen FB et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis 2005; 41: 1242–1250.

    Article  CAS  Google Scholar 

  27. Maertens J, Glasmacher A, Herbrecht R, Thiebaut A, Cordonnier C, Segal BH et al. Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. Cancer 2006; 107: 2888–2897.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Haemato-oncology, Royal Marsden Hospital, Sutton, Surrey, UK

    F L Dignan, S O Evans, M E Ethell, B E Shaw, F E Davies, C E Dearden, J G Treleaven, G J Morgan & M N Potter

  2. Anthony Nolan Trust, London, UK

    B E Shaw

  3. Department of Microbiology, Royal Marsden Hospital, Sutton, Surrey, UK

    U B G Riley

Authors
  1. F L Dignan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S O Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M E Ethell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B E Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F E Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C E Dearden
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J G Treleaven
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. U B G Riley
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G J Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M N Potter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F L Dignan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dignan, F., Evans, S., Ethell, M. et al. An early CT-diagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality. Bone Marrow Transplant 44, 51–56 (2009). https://doi.org/10.1038/bmt.2008.427

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.427

Keywords

This article is cited by

Search

Advanced search

Quick links