Pulmonary Cryptococcosis

ABSTRACT

Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus gattii accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B + / - flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections.

Cryptococcus - cryptococcosis - pulmonary - pneumonia - HIV - epidemiology - clinical presentation - therapy

REFERENCES

• 1 Jarvis J N, Harrison T S. HIV-associated cryptococcal meningitis.  AIDS. 2007;  21 , In press
• 2 Aberg J A, Mundy L M, Powderly W G. Pulmonary cryptococcosis in patients without HIV infection.  Chest. 1999;  115 734-740
• 3 Chang W C, Tzao C, Hsu H H et al.. Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients.  Chest. 2006;  129 333-340
• 4 Duperval R, Hermans P E, Brewer N S, Roberts G D. Cryptococcosis, with emphasis on the significance of isolation of Cryptococcus neoformans from the respiratory tract.  Chest. 1977;  72 13-19
• 5 Hage C A, Wood K L, Winer-Muram H T, Wilson S J, Sarosi G, Knox K S. Pulmonary cryptococcosis after initiation of anti-tumor necrosis factor-alpha therapy.  Chest. 2003;  124 2395-2397
• 6 Kerkering T M, Duma R J, Shadomy S. The evolution of pulmonary cryptococcosis: clinical implications from a study of 41 patients with and without compromising host factors.  Ann Intern Med. 1981;  94 611-616
• 7 Lui G, Lee N, Ip M et al.. Cryptococcosis in apparently immunocompetent patients.  QJM. 2006;  99 143-151
• 8 Pappas P G, Perfect J R, Cloud G A et al.. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.  Clin Infect Dis. 2001;  33 690-699
• 9 Rozenbaum R, Goncalves A J. Clinical epidemiological study of 171 cases of cryptococcosis.  Clin Infect Dis. 1994;  18 369-380
• 10 Vilchez R A, Irish W, Lacomis J, Costello P, Fung J, Kusne S. The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center.  Medicine (Baltimore). 2001;  80 308-312
• 11 Nadrous H F, Antonios V S, Terrell C L, Ryu J H. Pulmonary cryptococcosis in nonimmunocompromised patients.  Chest. 2003;  124 2143-2147
• 12 Okongo M, Morgan D, Mayanja B, Ross A, Whitworth J. Causes of death in a rural, population-based human immunodeficiency virus type 1 (HIV-1) natural history cohort in Uganda.  Int J Epidemiol. 1998;  27 698-702
• 13 French N, Gray K, Watera C et al.. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults.  AIDS. 2002;  16 1031-1038
• 14 Corbett E L, Churchyard G J, Charalambos S et al.. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus.  Clin Infect Dis. 2002;  34 1251-1258
• 15 Wasser L, Talavera W. Pulmonary cryptococcosis in AIDS.  Chest. 1987;  92 692-695
• 16 Chayakulkeeree M, Perfect J R. Cryptococcosis.  Infect Dis Clin North Am. 2006;  20 507-544 v-vi
• 17 Speed B, Dunt D. Clinical and host differences between infections with the two varieties of Cryptococcus neoformans .  Clin Infect Dis. 1995;  21 28-34 discussion 35-26
• 18 Krumholz R A. Pulmonary cryptococcosis: a case due to Cryptococcus albidus .  Am Rev Respir Dis. 1972;  105 421-424
• 19 Burnik C, Altintas N D, Ozkaya G et al.. Acute respiratory distress syndrome due to Cryptococcus albidus pneumonia: case report and review of the literature.  Med Mycol. 2007;  45 469-473
• 20 Lynch III J P, Schaberg D R, Kissner D G, Kauffman C A. Cryptococcus laurentii lung abscess.  Am Rev Respir Dis. 1981;  123 135-138
• 21 Casadevall A, Steenbergen J N, Nosanchuk J D. “Ready made” virulence and “dual use” virulence factors in pathogenic environmental fungi: the Cryptococcus neoformans paradigm.  Curr Opin Microbiol. 2003;  6 332-337
• 22 Lazera M S, Salmito Cavalcanti M A, Londero A T, Trilles L, Nishikawa M M, Wanke B. Possible primary ecological niche of Cryptococcus neoformans .  Med Mycol. 2000;  38 379-383
• 23 Randhawa H S, Kowshik T, Preeti Sinha K et al.. Distribution of Cryptococcus gattii and Cryptococcus neoformans in decayed trunk wood of Syzygium cumini trees in north-western India.  Med Mycol. 2006;  44 623-630
• 24 Kwon-Chung K J, Bennett J E. Epidemiologic differences between the two varieties of Cryptococcus neoformans .  Am J Epidemiol. 1984;  120 123-130
• 25 Chen S, Sorrell T, Nimmo G et al.. Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group.  Clin Infect Dis. 2000;  31 499-508
• 26 Chen S C, Currie B J, Campbell H M et al.. Cryptococcus neoformans var. gattii infection in northern Australia: existence of an environmental source other than known host eucalypts.  Trans R Soc Trop Med Hyg. 1997;  91 547-550
• 27 Jenney A, Pandithage K, Fisher D A, Currie B J. Cryptococcus infection in tropical Australia.  J Clin Microbiol. 2004;  42 3865-3868
• 28 Ellis D H, Pfeiffer T J. Natural habitat of Cryptococcus neoformans var. gattii .  J Clin Microbiol. 1990;  28 1642-1644
• 29 Pfeiffer T J, Ellis D H. Environmental isolation of Cryptococcus neoformans var. gattii from Eucalyptus tereticornis .  J Med Vet Mycol. 1992;  30 407-408
• 30 Lindberg J, Hagen F, Laursen A, Stenderup J, Boekhout T. Cryptococcus gattii risk for tourists visiting Vancouver Island, Canada.  Emerg Infect Dis. 2007;  13 178-179
• 31 Galanis E, MacDougall L, Li M, Kidd S, Lee M, Morshed M. Clinical and epidemiological aspects of locally acquired Cryptococcus gattii human infections, an emerging fungal pathogen in British Colombia, Canada. 17th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) Munich; Abstract O170 April 2007
• 32 Goldman D L, Khine H, Abadi J et al.. Serologic evidence for Cryptococcus neoformans infection in early childhood.  Pediatrics. 2001;  107 E66-71
• 33 Wickes B L, Mayorga M E, Edman U, Edman J C. Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the alpha-mating type.  Proc Natl Acad Sci U S A. 1996;  93 7327-7331
• 34 Hung J J, Ou L S, Lee W I, Huang J L. Central nervous system infections in patients with systemic lupus erythematosus.  J Rheumatol. 2005;  32 40-43
• 35 Ross J J, Katz J D. Cryptococcal meningitis and sarcoidosis.  Scand J Infect Dis. 2002;  34 937-939
• 36 Chen G H, McDonald R A, Wells J C, Huffnagle G B, Lukacs N W, Toews G B. The gamma interferon receptor is required for the protective pulmonary inflammatory response to Cryptococcus neoformans .  Infect Immun. 2005;  73 1788-1796
• 37 Herring A C, Lee J, McDonald R A, Toews G B, Huffnagle G B. Induction of interleukin-12 and gamma interferon requires tumor necrosis factor alpha for protective T1-cell-mediated immunity to pulmonary Cryptococcus neoformans infection.  Infect Immun. 2002;  70 2959-2964
• 38 Goldman D L, Lee S C, Mednick A J, Montella L, Casadevall A. Persistent Cryptococcus neoformans pulmonary infection in the rat is associated with intracellular parasitism, decreased inducible nitric oxide synthase expression, and altered antibody responsiveness to cryptococcal polysaccharide.  Infect Immun. 2000;  68 832-838
• 39 Salyer W R, Salyer D C, Baker R D. Primary complex of Cryptococcus and pulmonary lymph nodes.  J Infect Dis. 1974;  130 74-77
• 40 Baker R D. The primary pulmonary lymph node complex of cryptococcosis.  Am J Clin Pathol. 1976;  65 83-92
• 41 Garcia-Hermoso D, Janbon G, Dromer F. Epidemiological evidence for dormant Cryptococcus neoformans infection.  J Clin Microbiol. 1999;  37 3204-3209
• 42 Fessel W J. Cryptococcal meningitis after unusual exposures to birds.  N Engl J Med. 1993;  328 1354-1355
• 43 MacDougall L, Fyfe M. Emergence of Cryptococcus gattii in a novel environment provides clues to its incubation period.  J Clin Microbiol. 2006;  44 1851-1852
• 44 Feigin D S. Pulmonary cryptococcosis: radiologic-pathologic correlates of its three forms.  AJR Am J Roentgenol. 1983;  141 1262-1272
• 45 Zinck S E, Leung A N, Frost M, Berry G J, Muller N L. Pulmonary cryptococcosis: CT and pathologic findings.  J Comput Assist Tomogr. 2002;  26 330-334
• 46 Chechani V, Kamholz S L. Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS.  Chest. 1990;  98 1060-1066
• 47 Chuck S L, Sande M A. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome.  N Engl J Med. 1989;  321 794-799
• 48 Cameron M L, Bartlett J A, Gallis H A, Waskin H A. Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome.  Rev Infect Dis. 1991;  13 64-67
• 49 Meyohas M C, Roux P, Bollens D et al.. Pulmonary cryptococcosis: localized and disseminated infections in 27 patients with AIDS.  Clin Infect Dis. 1995;  21 628-633
• 50 Eng R H, Bishburg E, Smith S M, Kapila R. Cryptococcal infections in patients with acquired immune deficiency syndrome.  Am J Med. 1986;  81 19-23
• 51 Zuger A, Louie E, Holzman R S, Simberkoff M S, Rahal J J. Cryptococcal disease in patients with the acquired immunodeficiency syndrome: diagnostic features and outcome of treatment.  Ann Intern Med. 1986;  104 234-240
• 52 Dismukes W E. Cryptococcal meningitis in patients with AIDS.  J Infect Dis. 1988;  157 624-628
• 53 Clark R A, Greer D, Atkinson W, Valainis G T, Hyslop N. Spectrum of Cryptococcus neoformans infection in 68 patients infected with human immunodeficiency virus.  Rev Infect Dis. 1990;  12 768-777
• 54 Kovacs J A, Kovacs A A, Polis M et al.. Cryptococcosis in the acquired immunodeficiency syndrome.  Ann Intern Med. 1985;  103 533-538
• 55 Driver J A, Saunders C A, Heinze-Lacey B, Sugar A M. Cryptococcal pneumonia in AIDS: is cryptococcal meningitis preceded by clinically recognizable pneumonia?.  J Acquir Immune Defic Syndr Hum Retrovirol. 1995;  9 168-171
• 56 Murray J F. Pulmonary complications of HIV-1 infection among adults living in sub-Saharan Africa.  Int J Tuberc Lung Dis. 2005;  9 826-835
• 57 Murray J, Sonnenberg P, Shearer S C, Godfrey-Faussett P. Human immunodeficiency virus and the outcome of treatment for new and recurrent pulmonary tuberculosis in African patients.  Am J Respir Crit Care Med. 1999;  159 733-740
• 58 Batungwanayo J, Taelman H, Bogaerts J et al.. Pulmonary cryptococcosis associated with HIV-1 infection in Rwanda: a retrospective study of 37 cases.  AIDS. 1994;  8 1271-1276
• 59 Bernicker E H, Atmar R L, Schaffner D L, Greenberg S B. Unanticipated diagnoses found at autopsy in an urban public teaching hospital.  Am J Med Sci. 1996;  311 215-220
• 60 Lucas S B, Hounnou A, Peacock C et al.. The mortality and pathology of HIV infection in a west African city.  AIDS. 1993;  7 1569-1579
• 61 Lanjewar D N, Duggal R. Pulmonary pathology in patients with AIDS: an autopsy study from Mumbai.  HIV Med. 2001;  2 266-271
• 62 Wong M L, Back P, Candy G, Nelson G, Murray J. Cryptococcal pneumonia in African miners at autopsy.  Int J Tuberc Lung Dis. 2007;  11 528-533
• 63 Grant A D, Djomand G, Smets P et al.. Profound immunosuppression across the spectrum of opportunistic disease among hospitalized HIV-infected adults in Abidjan, Cote d'Ivoire.  AIDS. 1997;  11 1357-1364
• 64 Grant A D, Sidibe K, Domoua K et al.. Spectrum of disease among HIV-infected adults hospitalised in a respiratory medicine unit in Abidjan, Cote d'Ivoire.  Int J Tuberc Lung Dis. 1998;  2 926-934
• 65 Hajjeh R A, Conn L A, Stephens D S et al.. Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. Cryptococcal Active Surveillance Group.  J Infect Dis. 1999;  179 449-454
• 66 Chen K Y, Ko S C, Hsueh P R, Luh K T, Yang P C. Pulmonary fungal infection: emphasis on microbiological spectra, patient outcome, and prognostic factors.  Chest. 2001;  120 177-184
• 67 Yang C J, Hwang J J, Wang T H et al.. Clinical and radiographic presentations of pulmonary cryptococcosis in immunocompetent patients.  Scand J Infect Dis. 2006;  38 788-793
• 68 Dromer F, Mathoulin S, Dupont B, Laporte A. Epidemiology of cryptococcosis in France: a 9-year survey (1985-1993). French Cryptococcosis Study Group.  Clin Infect Dis. 1996;  23 82-90
• 69 Brouwer A E, Siddiqui A A, Kester M I et al.. Immune dysfunction in HIV-seronegative, Cryptococcus gattii meningitis.  J Infect. 2007;  54 e165-e168
• 70 Lee K H, Chang U I, Kim H W et al.. Acute respiratory failure associated with cryptococcal pneumonia and disseminated cryptococcosis in an AIDS patient.  Korean J Intern Med. 2006;  21 39-42
• 71 Miller Jr W T, Edelman J M, Miller W T. Cryptococcal pulmonary infection in patients with AIDS: radiographic appearance.  Radiology. 1990;  175 725-728
• 72 Clark R A, Greer D L, Valainis G T, Hyslop N E. Cryptococcus neoformans pulmonary infection in HIV-1-infected patients.  J Acquir Immune Defic Syndr. 1990;  3 480-484
• 73 Visnegarwala F, Graviss E A, Lacke C E et al.. Acute respiratory failure associated with cryptococcosis in patients with AIDS: analysis of predictive factors.  Clin Infect Dis. 1998;  27 1231-1237
• 74 Wu T T, Wang H C, Yang P C, Kuo S H, Luh K T. Pulmonary cryptococcosis: manifestations in the era of acquired immunodeficiency syndrome.  J Formos Med Assoc. 1999;  98 621-626
• 75 Gal A A, Koss M N, Hawkins J, Evans S, Einstein H. The pathology of pulmonary cryptococcal infections in the acquired immunodeficiency syndrome.  Arch Pathol Lab Med. 1986;  110 502-507
• 76 Malabonga V M, Basti J, Kamholz S L. Utility of bronchoscopic sampling techniques for cryptococcal disease in AIDS.  Chest. 1991;  99 370-372
• 77 Similowski T, Datry A, Jais P, Katlama C, Rosenheim M, Gentilini M. AIDS-associated cryptococcosis causing adult respiratory distress syndrome.  Respir Med. 1989;  83 513-515
• 78 Murray R J, Becker P, Furth P, Criner G J. Recovery from cryptococcemia and the adult respiratory distress syndrome in the acquired immunodeficiency syndrome.  Chest. 1988;  93 1304-1306
• 79 Perla E N, Maayan S, Miller S N, Ramaswamy G, Eisenberg H. Disseminated cryptococcosis presenting as the adult respiratory distress syndrome.  N Y State J Med. 1985;  85 704-706
• 80 Loerinc A M, Bottone E J, Finkel L J, Teirstein A S. Primary cryptococcal pneumonia mimicking Pneumocystis carinii pneumonia in a patient with AIDS.  Mt Sinai J Med. 1988;  55 181-186
• 81 Shelburne III S A, Darcourt J, White Jr A C et al.. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy.  Clin Infect Dis. 2005;  40 1049-1052
• 82 Lortholary O, Fontanet A, Memain N, Martin A, Sitbon K, Dromer F. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France.  AIDS. 2005;  19(10) 1043-1049
• 83 Trevenzoli M, Cattelan A M, Rea F et al.. Mediastinitis due to cryptococcal infection: a new clinical entity in the HAART era.  J Infect. 2002;  45 173-179
• 84 Jenny-Avital E R, Abadi M. Immune reconstitution cryptococcosis after initiation of successful highly active antiretroviral therapy.  Clin Infect Dis. 2002;  35 e128-e133
• 85 Vilchez R A, Linden P, Lacomis J, Costello P, Fung J, Kusne S. Acute respiratory failure associated with pulmonary cryptococcosis in non-AIDS patients.  Chest. 2001;  119 1865-1869
• 86 Hammerman K J, Powell K E, Christianson C S et al.. Pulmonary cryptococcosis: clinical forms and treatment. A Center for Disease Control cooperative mycoses study.  Am Rev Respir Dis. 1973;  108 1116-1123
• 87 Mitsuoka S, Kanazawa H. Images in thorax: an unique case of primary pulmonary cryptococcosis with extensive chest wall invasion.  Thorax. 2005;  60 86
• 88 Robinson II G R. Images in clinical medicine: severe cryptococcal pneumonia.  N Engl J Med. 1995;  332 1752
• 89 Emmons III W W, Luchsinger S, Miller L. Progressive pulmonary cryptococcosis in a patient who is immunocompetent.  South Med J. 1995;  88 657-660
• 90 Zhu L P, Shi Y Z, Weng X H, Muller F M. Case reports: pulmonary cryptococcosis associated with cryptococcal meningitis in non-AIDS patients.  Mycoses. 2002;  45 111-117
• 91 Reichman N, Elias M, Raz R, Flatau E. Cryptococcal meningitis following cryptococcal pneumonia in an immunocompetent.  Harefuah. 1999;  137 291-292, 350
• 92 Lindell R M, Hartman T E, Nadrous H F, Ryu J H. Pulmonary cryptococcosis: CT findings in immunocompetent patients.  Radiology. 2005;  236 326-331
• 93 Khoury M B, Godwin J D, Ravin C E, Gallis H A, Halvorsen R A, Putman C E. Thoracic cryptococcosis: immunologic competence and radiologic appearance.  AJR Am J Roentgenol. 1984;  142 893-896
• 94 Gordonson J, Birnbaum W, Jacobson G, Sargent E N. Pulmonary cryptococcosis.  Radiology. 1974;  112 557-561
• 95 Cheong W Y, Thomas A, Tan K P. Pulmonary cryptococcosis.  Singapore Med J. 1988;  29 223-231
• 96 Patz Jr E F, Goodman P C. Pulmonary cryptococcosis.  J Thorac Imaging. 1992;  7 51-55
• 97 Murayama S, Sakai S, Soeda H et al.. Pulmonary cryptococcosis in immunocompetent patients: HRCT characteristics.  Clin Imaging. 2004;  28 191-195
• 98 Roebuck D J, Fisher D A, Currie B J. Cryptococcosis in HIV negative patients: findings on chest radiography.  Thorax. 1998;  53 554-557
• 99 Lacomis J M, Costello P, Vilchez R, Kusne S. The radiology of pulmonary cryptococcosis in a tertiary medical center.  J Thorac Imaging. 2001;  16 139-148
• 100 Friedman E P, Miller R F, Severn A, Williams I G, Shaw P J. Cryptococcal pneumonia in patients with the acquired immunodeficiency syndrome.  Clin Radiol. 1995;  50 756-760
• 101 Sider L, Westcott M A. Pulmonary manifestations of cryptococcosis in patients with AIDS: CT features.  J Thorac Imaging. 1994;  9 78-84
• 102 Wallace J M, Hannah J B. Pulmonary disease at autopsy in patients with the acquired immunodeficiency syndrome.  West J Med. 1988;  149 167-171
• 103 Baughman R P, Rhodes J C, Dohn M N, Henderson H, Frame P T. Detection of cryptococcal antigen in bronchoalveolar lavage fluid: a prospective study of diagnostic utility.  Am Rev Respir Dis. 1992;  145 1226-1229
• 104 Saag M S, Graybill R J, Larsen R A et al.. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America.  Clin Infect Dis. 2000;  30 710-718
• 105 Feldmesser M, Harris C, Reichberg S, Khan S, Casadevall A. Serum cryptococcal antigen in patients with AIDS.  Clin Infect Dis. 1996;  23 827-830
• 106 Aberg J A. Pulmonary cryptococcosis in normal hosts: treat or observe?.  Chest. 2003;  124 2049-2051
• 107 Sarosi G A. Cryptococcal lung disease in patients without HIV infection.  Chest. 1999;  115 610-611
• 108 Meyohas M C, Meynard J L, Bollens D et al.. Treatment of non-meningeal cryptococcosis in patients with AIDS. Centre d'Informations et de Soins de l'Immunodeficience Humaine de l'Est Parisien.  J Infect. 1996;  33 7-10
• 109 Dromer F, Mathoulin S, Dupont B, Brugiere O, Letenneur L. 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. 1996;  22(Suppl 2) S154-S160
• 110 Aberg J A, Price R W, Heeren D M, Bredt B. A pilot study of the discontinuation of antifungal therapy for disseminated cryptococcal disease in patients with acquired immunodeficiency syndrome, following immunologic response to antiretroviral therapy.  J Infect Dis. 2002;  185 1179-1182
• 111 Vibhagool A, Sungkanuparph S, Mootsikapun P et al.. Discontinuation of secondary prophylaxis for cryptococcal meningitis in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy: a prospective, multicenter, randomized study.  Clin Infect Dis. 2003;  36 1329-1331
• 112 Mussini C, Pezzotti P, Miro J M et al.. Discontinuation of maintenance therapy for cryptococcal meningitis in patients with AIDS treated with highly active antiretroviral therapy: an international observational study.  Clin Infect Dis. 2004;  38 565-571
• 113 Larsen R A, Bozzette S A, Jones B E et al.. Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in patients with AIDS.  Clin Infect Dis. 1994;  19 741-745
• 114 Denning D W, Tucker R M, Hanson L H, Hamilton J R, Stevens D A. Itraconazole therapy for cryptococcal meningitis and cryptococcosis.  Arch Intern Med. 1989;  149 2301-2308
• 115 Perfect J R, Marr K A, Walsh T J et al.. Voriconazole treatment for less-common, emerging, or refractory fungal infections.  Clin Infect Dis. 2003;  36 1122-1131
• 116 Pitisuttithum P, Negroni R, Graybill J R et al.. Activity of posaconazole in the treatment of central nervous system fungal infections.  J Antimicrob Chemother. 2005;  56 745-755
• 117 Nunez M, Peacock Jr J E, Chin Jr R. Pulmonary cryptococcosis in the immunocompetent host: therapy with oral fluconazole: a report of four cases and a review of the literature.  Chest. 2000;  118 527-534