1887

Abstract

Purpose. Previous epidemiological and cost studies of fungal meningitis have largely focused on single pathogens, leading to a poor understanding of the disease in general. We studied the largest and most diverse group of fungal meningitis patients to date, over the longest follow-up period, to examine the broad impact on resource utilization within the United States.

Methodology. The Truven Health Analytics MarketScan database was used to identify patients with a fungal meningitis diagnosis in the United States between 2000 and 2012. Patients with a primary diagnosis of cryptococcal, Coccidioides, Histoplasma, or Candida meningitis were included in the analysis. Data concerning healthcare resource utilization, prevalence and length of stay were collected for up to 5 years following the original diagnosis.

Results. Cryptococcal meningitis was the most prevalent type of fungal meningitis (70.1 % of cases over the duration of the study), followed by coccidioidomycosis (16.4 %), histoplasmosis (6.0 %) and candidiasis (7.6 %). Cryptococcal meningitis and candidiasis patients accrued the largest average charges ($103 236 and $103 803, respectively) and spent the most time in the hospital on average (70.6 and 79 days). Coccidioidomycosis and histoplasmosis patients also accrued substantial charges and time in the hospital ($82 439, 48.1 days; $78 609, 49.8 days, respectively).

Conclusion. Our study characterizes the largest longitudinal cohort of fungal meningitis in the United States. Importantly, the health economic impact and long-term morbidity from these infections are quantified and reviewed. The healthcare resource utilization of fungal meningitis patients in the United States is substantial.

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2017-12-15
2019-09-21
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References

  1. Gottfredsson M, Perfect JR. Fungal meningitis. Semin Neurol 2000; 20: 307– 322 [CrossRef] [PubMed]
    [Google Scholar]
  2. Ransohoff RM, Engelhardt B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 2012; 12: 623– 635 [CrossRef] [PubMed]
    [Google Scholar]
  3. Williamson PR, Jarvis JN, Panackal AA, Fisher MC, Molloy SF et al. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. Nat Rev Neurol 2017; 13: 13– 24 [CrossRef] [PubMed]
    [Google Scholar]
  4. Leal AL, Faganello J, Fuentefria AM, Boldo JT, Bassanesi MC et al. Epidemiological profile of cryptococcal meningitis patients in Rio Grande do Sul, Brazil. Mycopathologia 2008; 166: 71– 75 [CrossRef] [PubMed]
    [Google Scholar]
  5. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG et al. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009; 23: 525– 530 [CrossRef] [PubMed]
    [Google Scholar]
  6. Banerjee U, Datta K, Majumdar T, Gupta K. Cryptococcosis in India: the awakening of a giant?. Med Mycol 2001; 39: 51– 67 [PubMed] [Crossref]
    [Google Scholar]
  7. Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS–100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 1995; 8: 515– 548 [PubMed]
    [Google Scholar]
  8. Robinson PA, Bauer M, Leal MA, Evans SG, Holtom PD et al. Early mycological treatment failure in AIDS-associated cryptococcal meningitis. Clin Infect Dis 1999; 28: 82– 92 [CrossRef] [PubMed]
    [Google Scholar]
  9. van der Horst CM, Saag MS, Cloud GA, Hamill RJ, Graybill JR et al. 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 1997; 337: 15– 21 [CrossRef] [PubMed]
    [Google Scholar]
  10. Pyrgos V, Seitz AE, Steiner CA, Prevots DR, Williamson PR. Epidemiology of cryptococcal meningitis in the US: 1997-2009. PLoS One 2013; 8: e56269 [CrossRef] [PubMed]
    [Google Scholar]
  11. Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017; 17: 873– 881 [CrossRef] [PubMed]
    [Google Scholar]
  12. Friedman GD, Jeffrey Fessel W, Udaltsova NV, Hurley LB. Cryptococcosis: the 1981–2000 epidemic. Mycoses 2005; 48: 122– 125 [CrossRef] [PubMed]
    [Google Scholar]
  13. Mirza SA, Phelan M, Rimland D, Graviss E, Hamill R et al. The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992-2000. Clin Infect Dis 2003; 36: 789– 794 [CrossRef] [PubMed]
    [Google Scholar]
  14. Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 2001; 33: 690– 699 [CrossRef] [PubMed]
    [Google Scholar]
  15. Dodds Ashley E, Drew R, Johnson M, Danna R, Dabrowski D et al. Cost of invasive fungal infections in the era of new diagnostics and expanded treatment options. Pharmacotherapy 2012; 32: 890– 901 [CrossRef] [PubMed]
    [Google Scholar]
  16. Stockamp NW, Thompson GR. Coccidioidomycosis. Infect Dis Clin North Am 2016; 30: 229– 246 [CrossRef] [PubMed]
    [Google Scholar]
  17. Bouza E, Dreyer JS, Hewitt WL, Meyer RD. Coccidioidal meningitis. An analysis of thirty-one cases and review of the literature. Medicine 1981; 60: 139– 172 [PubMed] [Crossref]
    [Google Scholar]
  18. Bronnimann DA, Adam RD, Galgiani JN, Habib MP, Petersen EA et al. Coccidioidomycosis in the acquired immunodeficiency syndrome. Ann Intern Med 1987; 106: 372– 379 [CrossRef] [PubMed]
    [Google Scholar]
  19. Rouhani AA. Infectious disease/CDC update. Update on emerging infections: news from the centers for disease control and prevention. Ann Emerg Med 2016; 67: 131– 134 [CrossRef] [PubMed]
    [Google Scholar]
  20. Nguyen C, Barker BM, Hoover S, Nix DE, Ampel NM et al. Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis. Clin Microbiol Rev 2013; 26: 505– 525 [CrossRef] [PubMed]
    [Google Scholar]
  21. Chiller TM, Galgiani JN, Stevens DA. Coccidioidomycosis. Infect Dis Clin North Am 2003; 17: 41– 57 [CrossRef] [PubMed]
    [Google Scholar]
  22. Kirkland TN, Fierer J. Coccidioidomycosis: a reemerging infectious disease. Emerg Infect Dis 1996; 2: 192– 199 [CrossRef] [PubMed]
    [Google Scholar]
  23. Blair JE. Coccidioidal meningitis: update on epidemiology, clinical features, diagnosis, and management. Curr Infect Dis Rep 2009; 11: 289– 295 [PubMed] [Crossref]
    [Google Scholar]
  24. Bercovitch RS, Catanzaro A, Schwartz BS, Pappagianis D, Watts DH et al. Coccidioidomycosis during pregnancy: a review and recommendations for management. Clin Infect Dis 2011; 53: 363– 368 [CrossRef] [PubMed]
    [Google Scholar]
  25. Powell BL, Drutz DJ, Huppert M, Sun SH. Relationship of progesterone- and estradiol-binding proteins in Coccidioides immitis to coccidioidal dissemination in pregnancy. Infect Immun 1983; 40: 478– 485 [PubMed]
    [Google Scholar]
  26. Holmquist L, Russo CA, Elixhauser A. Meningitis-related hospitalizations in the United States, 2006. HCUP Statistical Brief #57, July 2008 In Healthcare Cost and Utilization Project (HCUP) Statistical Briefs Rockville, MD: Agency for Healthcare Research and Quality; 2006
    [Google Scholar]
  27. Vincent T, Galgiani JN, Huppert M, Salkin D. The natural history of coccidioidal meningitis: VA-Armed Forces cooperative studies, 1955-1958. Clin Infect Dis 1993; 16: 247– 254 [PubMed] [Crossref]
    [Google Scholar]
  28. Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Geertsma F et al. 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of Coccidioidomycosis. Clin Infect Dis 2016; 63: e112-146 [CrossRef]
    [Google Scholar]
  29. Johnson RH, Einstein HE. Coccidioidal meningitis. Clin Infect Dis 2006; 42: 103– 107 [CrossRef] [PubMed]
    [Google Scholar]
  30. Bradsher RW. Histoplasmosis and blastomycosis. Clin Infect Dis 1996; 22: S102– S111 [CrossRef] [PubMed]
    [Google Scholar]
  31. Schuster JE, Wushensky CA, di Pentima MC. Chronic primary central nervous system histoplasmosis in a healthy child with intermittent neurological manifestations. Pediatr Infect Dis J 2013; 32: 794– 796 [CrossRef] [PubMed]
    [Google Scholar]
  32. Zarrin M, Mahmoudabadi AZ. Central nervous system fungal infections; a review article. Jundishapur J Microbiol 2010; 3: 41– 47
    [Google Scholar]
  33. Duncan RA, von Reyn CF, Alliegro GM, Toossi Z, Sugar AM et al. Idiopathic CD4+ T-lymphocytopenia–four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med 1993; 328: 393– 398 [CrossRef] [PubMed]
    [Google Scholar]
  34. Weidenheim KM, Nelson SJ, Kure K, Harris C, Biempica L et al. Unusual patterns of Histoplasma capsulatum meningitis and progressive multifocal leukoencephalopathy in a patient with the acquired immunodeficiency virus. Hum Pathol 1992; 23: 581– 586 [PubMed] [Crossref]
    [Google Scholar]
  35. Anaissie E, Fainstein V, Samo T, Bodey GP, Sarosi GA. Central nervous system histoplasmosis. An unappreciated complication of the acquired immunodeficiency syndrome. Am J Med 1988; 84: 215– 217 [PubMed] [Crossref]
    [Google Scholar]
  36. Wright SH, Czaja AJ, Katz RS, Soloway RD. Systemic mycosis complicating high dose corticosteroid treatment of chronic active liver disease. Am J Gastroenterol 1980; 74: 428– 432 [PubMed]
    [Google Scholar]
  37. Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine 1990; 69: 244– 260 [CrossRef] [PubMed]
    [Google Scholar]
  38. Wilson LS, Reyes CM, Stolpman M, Speckman J, Allen K et al. The direct cost and incidence of systemic fungal infections. Value Health 2002; 5: 26– 34 [CrossRef] [PubMed]
    [Google Scholar]
  39. Hariri OR, Minasian T, Quadri SA, Dyurgerova A, Farr S et al. Histoplasmosis with deep CNS involvement: case presentation with discussion and literature review. J Neurol Surg Rep 2015; 76: e167-172 [CrossRef] [PubMed]
    [Google Scholar]
  40. Black KE, Baden LR. Fungal infections of the CNS: treatment strategies for the immunocompromised patient. CNS Drugs 2007; 21: 293– 318 [PubMed] [Crossref]
    [Google Scholar]
  41. Chadwick DW, Hartley E, MacKinnon DM. Meningitis caused by Candida tropicalis. Arch Neurol 1980; 37: 175– 176 [PubMed] [Crossref]
    [Google Scholar]
  42. Fernandez M, Moylett EH, Noyola DE, Baker CJ. Candidal meningitis in neonates: a 10-year review. Clin Infect Dis 2000; 31: 458– 463 [CrossRef] [PubMed]
    [Google Scholar]
  43. Nguyen MH, Yu VL. Meningitis caused by Candida species: an emerging problem in neurosurgical patients. Clin Infect Dis 1995; 21: 323– 327 [CrossRef] [PubMed]
    [Google Scholar]
  44. Sánchez-Portocarrero J, Martín-Rabadán P, Saldaña CJ, Pérez-Cecilia E. Candida cerebrospinal fluid shunt infection. Report of two new cases and review of the literature. Diagn Microbiol Infect Dis 1994; 20: 33– 40 [CrossRef] [PubMed]
    [Google Scholar]
  45. Poon WS, Ng S, Wai S. CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a randomised study. Acta Neurochir Suppl 1998; 71: 146– 148 [PubMed]
    [Google Scholar]
  46. Henao N. Infections of the central nervous system by Candida. J Infect Dis Immun 2011; 3: 79– 84
    [Google Scholar]
  47. Lee BE, Cheung PY, Robinson JL, Evanochko C, Robertson CM. Comparative study of mortality and morbidity in premature infants (birth weight, < 1,250 g) with candidemia or candidal meningitis. Clin Infect Dis 1998; 27: 559– 565 [PubMed] [Crossref]
    [Google Scholar]
  48. Holmquist L. Meningitis-related hospitalizations in the United States, 2006: Statistical Brief #57. In Russo C, Elixhaurser A. (editors) Healthcare Cost and Utilization Project (HCUP) Statistical Briefs Rockville, MD: Agency for Healthcare Research and Quality; 2008
    [Google Scholar]
  49. Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 2010; 36: 1– 53 [Crossref]
    [Google Scholar]
  50. Bicanic T, Harrison TS. Cryptococcal meningitis. Br Med Bull 2004; 72: 99– 118 [CrossRef] [PubMed]
    [Google Scholar]
  51. Bratton EW, El Husseini N, Chastain CA, Lee MS, Poole C et al. Approaches to antifungal therapies and their effectiveness among patients with cryptococcosis. Antimicrob Agents Chemother 2013; 57: 2485– 2495 [CrossRef] [PubMed]
    [Google Scholar]
  52. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 2007; 20: 133– 163 [CrossRef] [PubMed]
    [Google Scholar]
  53. Twarog M, Thompson GR. Coccidioidomycosis: recent updates. Semin Respir Crit Care Med 2015; 36: 746– 755 [CrossRef] [PubMed]
    [Google Scholar]
  54. Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev 2007; 20: 115– 132 [CrossRef] [PubMed]
    [Google Scholar]
  55. Enoch DA, Ludlam HA, Brown NM. Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol 2006; 55: 809– 818 [CrossRef] [PubMed]
    [Google Scholar]
  56. Centers for Disease Control and Prevention (CDC) Characteristics associated with HIV infection among heterosexuals in urban areas with high AIDS prevalence – 24 cities, United States, 2006–2007. MMWR Morb Mortal Wkly Rep 2011; 60: 1045– 1049 [PubMed]
    [Google Scholar]
  57. Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 2010; 36: 1– 53 [CrossRef] [PubMed]
    [Google Scholar]
  58. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009; 53: 24– 34 [CrossRef] [PubMed]
    [Google Scholar]
  59. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994; 47: 1245– 1251 [PubMed] [Crossref]
    [Google Scholar]
  60. Charlson ME, Pompei P, Ales KL, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373– 383 [PubMed] [Crossref]
    [Google Scholar]
  61. Brenier-Pinchart MP, Leclercq P, Mallié M, Bettega G. Candida meningitis possibly resulting from a harpoon injury. Eur J Clin Microbiol Infect Dis 1999; 18: 454– 455 [CrossRef] [PubMed]
    [Google Scholar]
  62. Zunt JR. Infections of the central nervous system in the neurosurgical patient. Handb Clin Neurol 2010; 96: 125– 141 [CrossRef] [PubMed]
    [Google Scholar]
  63. Zunt JR. Central nervous system infection during immunosuppression. Neurol Clin 2002; 20: 1– 22 [CrossRef] [PubMed]
    [Google Scholar]
  64. Jacobs CS, Etherton MR, Lyons JL. Fungal infections of the central nervous system. Curr Infect Dis Rep 2014; 16: 449 [CrossRef] [PubMed]
    [Google Scholar]
  65. Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med 1974; 80: 176– 181 [PubMed] [Crossref]
    [Google Scholar]
  66. Dismukes WE, Cloud G, Gallis HA, Kerkering TM, Medoff G et al. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med 1987; 317: 334– 341 [CrossRef] [PubMed]
    [Google Scholar]
  67. Merry M, Boulware DR. Cryptococcal meningitis treatment strategies affected by the explosive cost of flucytosine in the United States: a cost-effectiveness analysis. Clin Infect Dis 2016; 62: 1564– 1568 [CrossRef] [PubMed]
    [Google Scholar]
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