Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease

  • J. W. Baddley
  • J. R. Perfect
  • R. A. Oster
  • R. A. Larsen
  • G. A. Pankey
  • H. Henderson
  • D. W. Haas
  • C. A. Kauffman
  • R. Patel
  • A. K. Zaas
  • P. G. Pappas
Article

Abstract

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.

References

  1. 1.
    Levitz SM (1991) The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis 13(6):1163–1169PubMedGoogle Scholar
  2. 2.
    Chayakulkeeree M, Perfect JR (2006) Cryptococcosis. Infect Dis clin North Am 20(3):507–544 v–viPubMedCrossRefGoogle Scholar
  3. 3.
    Pappas PG, Perfect JR, Cloud GA et al (2001) Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 33(5):690–699PubMedCrossRefGoogle Scholar
  4. 4.
    Dromer F, Mathoulin S, Dupont B, Brugiere O, Letenneur L (1996) Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. French Cryptococcosis Study Group. Clin Infect Dis 22 [Suppl 2]:S154–S160PubMedGoogle Scholar
  5. 5.
    Saag MS, Graybill RJ, Larsen RA et al (2000) Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis 30(4):710–718PubMedCrossRefGoogle Scholar
  6. 6.
    Saag MS, Powderly WG, Cloud GA et al (1992) Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group. N Engl J Med 326(2):83–89PubMedGoogle Scholar
  7. 7.
    Van der Horst CM, Saag MS, Cloud GA et al (1997) Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. N Engl J Med 337(1):15–21PubMedCrossRefGoogle Scholar
  8. 8.
    Dismukes WE (1993) Management of cryptococcosis. Clin Infect Dis 17 [Suppl 2]:S507–S512PubMedGoogle Scholar
  9. 9.
    Bennett JE, Dismukes WE, Duma RJ et al (1979) A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal [sic] meningitis. N Engl J Med 301(3):126–131PubMedGoogle Scholar
  10. 10.
    Dismukes WE, Cloud G, Gallis HA et al (1987) Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med 317(6):334–341PubMedGoogle Scholar
  11. 11.
    Kerkering TM, Duma RJ, Shadomy S (1981) The evolution of pulmonary cryptococcosis: clinical implications from a study of 41 patients with and without compromising host factors. Ann Intern Med 94(5):611–616PubMedGoogle Scholar
  12. 12.
    Aberg JA, Mundy LM, Powderly WG (1999) Pulmonary cryptococcosis in patients without HIV infection. Chest 115(3):734–740PubMedCrossRefGoogle Scholar
  13. 13.
    Aberg JA (2003) Pulmonary cryptococcosis in normal hosts: treat or observe? Chest 124(6):2049–2051PubMedCrossRefGoogle Scholar
  14. 14.
    Woodring JH, Ciporkin G, Lee C, Worm B, Woolley S (1996) Pulmonary cryptococcosis. Semin Roentgenol 31(1):67–75PubMedCrossRefGoogle Scholar
  15. 15.
    Nadrous HF, Antonios VS, Terrell CL, Ryu JH (2003) Pulmonary cryptococcosis in nonimmunocompromised patients. Chest 124(6):2143–2147PubMedCrossRefGoogle Scholar
  16. 16.
    Kontoyiannis DP, Peitsch WK, Reddy BT et al (2001) Cryptococcosis in patients with cancer. Clin Infect Dis 32(11):E145–E150PubMedCrossRefGoogle Scholar
  17. 17.
    Ascioglu S, Rex JH, de Pauw B et al (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34(1):7–14PubMedCrossRefGoogle Scholar
  18. 18.
    Larsen RA, Leal MA, Chan LS (1990) Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial. Ann Intern Med 113(3):183–187PubMedGoogle Scholar
  19. 19.
    Bicanic T, Meintjes G, Wood R et al (2007) Fungal burden, early fungicidal activity, and outcome in cryptococcal meningitis in antiretroviral-naive or antiretroviral-experienced patients treated with amphotericin B or fluconazole. Clin Infect Dis 45(1):76–80PubMedCrossRefGoogle Scholar
  20. 20.
    Brouwer AE, Rajanuwong A, Chierakul W et al (2004) Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial. Lancet 363(9423):1764–1767PubMedCrossRefGoogle Scholar
  21. 21.
    Perfect JR (1989) Cryptococcosis. Infect Dis Clin North Am 3(1):77–102PubMedGoogle Scholar
  22. 22.
    Singh N, Husain S, De Vera M, Gayowski T, Cacciarelli TV (2004) Cryptococcus neoformans infection in patients with cirrhosis, including liver transplant candidates. Medicine 83(3):188–192PubMedCrossRefGoogle Scholar
  23. 23.
    Park WB, Choe YJ, Lee KD et al (2006) Spontaneous cryptococcal peritonitis in patients with liver cirrhosis. Am J Med 119(2):169–171PubMedCrossRefGoogle Scholar
  24. 24.
    El-Serag HB, Anand B, Richardson P, Rabeneck L (2003) Association between hepatitis C infection and other infectious diseases: a case for targeted screening? Am J Gastroenterol 98(1):167–174PubMedCrossRefGoogle Scholar
  25. 25.
    Robinson PA, Bauer M, Leal MA et al (1999) Early mycological treatment failure in AIDS-associated cryptococcal meningitis. Clin Infect Dis 28(1):82–92PubMedCrossRefGoogle Scholar
  26. 26.
    Singh N, Alexander BD, Lortholary O et al (2008) Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen. Clin Infect Dis 46(2):e12–e18PubMedCrossRefGoogle Scholar
  27. 27.
    Dromer F, Mathoulin-Pelissier S, Launay O, Lortholary O (2007) Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med 4(2):e21PubMedCrossRefGoogle Scholar
  28. 28.
    Vilchez RA, Irish W, Lacomis J, Costello P, Fung J, Kusne S (2001) The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center. Medicine 80(5):308–312PubMedCrossRefGoogle Scholar
  29. 29.
    Vilchez RA, Linden P, Lacomis J, Costello P, Fung J, Kusne S (2001) Acute respiratory failure associated with pulmonary cryptococcosis in non-aids patients. Chest 119(6):1865–1869PubMedCrossRefGoogle Scholar
  30. 30.
    Chang WC, Tzao C, Hsu HH et al (2006) Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients. Chest 129(2):333–340PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • J. W. Baddley
    • 1
  • J. R. Perfect
    • 2
  • R. A. Oster
    • 3
  • R. A. Larsen
    • 4
  • G. A. Pankey
    • 5
  • H. Henderson
    • 6
  • D. W. Haas
    • 7
  • C. A. Kauffman
    • 8
  • R. Patel
    • 9
  • A. K. Zaas
    • 2
  • P. G. Pappas
    • 1
  1. 1.Division of Infectious Diseases and International Health, Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Division of Infectious Diseases, Department of MedicineDuke University Medical CenterDurhamUSA
  3. 3.Biostatistics and Bioinformatics Unit, Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Division of Infectious Diseases, Department of MedicineUniversity of Southern California Keck School of MedicineLos AngelesUSA
  5. 5.Division of Infectious Diseases, Department of MedicineOchsner ClinicNew OrleansUSA
  6. 6.Division of Infectious Diseases, Department of MedicineUniversity of Mississippi Medical CenterJacksonUSA
  7. 7.Department of MedicineVanderbilt University Medical CenterNashvilleUSA
  8. 8.Department of MedicineUniversity of Michigan and Veterans Affairs, Ann Arbor Healthcare SystemAnn ArborUSA
  9. 9.Division of Infectious Diseases, Department of MedicineMayo ClinicRochesterUSA

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