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Fungal Necrotizing Skin and Soft Tissue Infections

  • Fungal Infections of Skin and Subcutaneous Tissue (A Bonifaz and M Pereira, Section Editors)
  • Published:
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Abstract

Purpose of Review

This review summarizes the medical literature regarding fungal necrotizing skin and soft tissue infections (NSTI). The available epidemiologic, microbiologic, treatment, and outcome data are presented by the most common causal organisms of this disease process.

Recent Findings

With the exception of cutaneous mucormycosis, which often progresses to necrotizing infection, clinical data for other fungal NSTI are largely limited to case reports and small case series. Fungal NSTI are rare but some data suggests that incidence may be increasing. These infections occur in both immunocompromised and immunocompetent hosts, especially following trauma. Mortality varies by host factors, organism, and extent of disease. Foundations of treatment include targeted antifungal therapy and aggressive surgical debridement.

Summary

Fungal NSTI is a rarely described clinical entity associated with a high mortality. More study is needed to better understand the epidemiology and optimal management of these infections.

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References

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  1. • Stevens DL, Bryant AE. Necrotizing Soft-Tissue Infections. New England Journal of Medicine. 2017;377(23):2253–65. https://doi.org/10.1056/NEJMra1600673A general review of bacterial necrotizing soft tissue infections with a focus on epidemiology, diagnostic and treatment strategies.

    Article  Google Scholar 

  2. Bonne SL, Kadri SS. Evaluation and Management of Necrotizing Soft Tissue Infections. Infect Dis Clin North Am. 2017;31(3):497–511. https://doi.org/10.1016/j.idc.2017.05.011.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Khamnuan P, Chongruksut W, Jearwattanakanok K, Patumanond J, Yodluangfun S, Tantraworasin A. Necrotizing fasciitis: risk factors of mortality. Risk Manag Healthc Policy. 2015;8:1–7. https://doi.org/10.2147/RMHP.S77691.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Naseer U, Steinbakk M, Blystad H, Caugant DA. Epidemiology of invasive group A streptococcal infections in Norway 2010-2014: A retrospective cohort study. Eur J Clin Microbiol Infect Dis. 2016;35(10):1639–48. https://doi.org/10.1007/s10096-016-2704-y.

    Article  PubMed  CAS  Google Scholar 

  5. Glass GE, Sheil F, Ruston JC, Butler PE. Necrotising soft tissue infection in a UK metropolitan population. Ann R Coll Surg Engl. 2015;97(1):46–51. https://doi.org/10.1308/003588414x14055925058553.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Bocking N, Matsumoto CL, Loewen K, Teatero S, Marchand-Austin A, Gordon J, et al. High Incidence of Invasive Group A Streptococcal Infections in Remote Indigenous Communities in Northwestern Ontario, Canada. Open Forum Infect Dis. 2017;4(1):ofw243. https://doi.org/10.1093/ofid/ofw243.

    Article  PubMed  Google Scholar 

  7. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis. 2007;44(5):705–10. https://doi.org/10.1086/511638.

    Article  PubMed  CAS  Google Scholar 

  8. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg. 1995;221(5):558–63; discussion 63-5. https://doi.org/10.1097/00000658-199505000-00013.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Willis RN, Guidry CA, Horn CB, Gilsdorf D, Davies SW, Dietch ZC, et al. Predictors of Monomicrobial Necrotizing Soft Tissue Infections. Surg Infect (Larchmt). 2015;16(5):533–7. https://doi.org/10.1089/sur.2014.189.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Singh G, Ray P, Sinha SK, Adhikary S, Khanna SK. Bacteriology of Necrotizing Infections of Soft Tissues. Australian and New Zealand Journal of Surgery. 1996;66(11):747–50. https://doi.org/10.1111/j.1445-2197.1996.tb00735.x.

    Article  PubMed  CAS  Google Scholar 

  11. Moore SA, Levy BH, Prematilake C, Dissanaike S. The Prediction Predicament: Rethinking Necrotizing Soft Tissue Infections Mortality. Surg Infect (Larchmt). 2015;16(6):813–21. https://doi.org/10.1089/sur.2015.002.

    Article  PubMed  PubMed Central  Google Scholar 

  12. •• Horn CB, Wesp BM, Fiore NB, Rasane RK, Torres HA, Turnbull IR, et al. Fungal Infections Increase the Mortality Rate Three-Fold in Necrotizing Soft-Tissue Infections. Surgical Infections. 2017;18(7):793–8. https://doi.org/10.1089/sur.2017.164The largest retrospective case series specifically designed to estimate the rates of fungal involvement within necrotizing soft tissue infections as isolated from initial intraoperative cultures.

    Article  PubMed  Google Scholar 

  13. •• Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–53. https://doi.org/10.1086/432579The first large-scale systematic review of mucormycosis which serves as a baseline specifically detailing the epidemiology and outcomes of this disease between 1940 and 2003.

    Article  PubMed  Google Scholar 

  14. Bitar D, Van Cauteren D, Lanternier F, Dannaoui E, Che D, Dromer F, et al. Increasing incidence of zygomycosis (mucormycosis), France, 1997-2006. Emerg Infect Dis. 2009;15(9):1395–401. https://doi.org/10.3201/eid1509.090334.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis. 2009;48(3):265–73. https://doi.org/10.1086/595846.

    Article  PubMed  CAS  Google Scholar 

  16. • Rammaert B, Lanternier F, Zahar JR, Dannaoui E, Bougnoux ME, Lecuit M, et al. Healthcare-associated mucormycosis. Clin Infect Dis. 2012;54 Suppl 1:S44–54. https://doi.org/10.1093/cid/cir867A review of mucormycosis within healthcare settings also detailing case clusters and outbreaks with a notably large proportion of cutaneous disease.

    Article  PubMed  Google Scholar 

  17. Skiada A, Rigopoulos D, Larios G, Petrikkos G, Katsambas A. Global epidemiology of cutaneous zygomycosis. Clin Dermatol. 2012;30(6):628–32. https://doi.org/10.1016/j.clindermatol.2012.01.010.

    Article  PubMed  Google Scholar 

  18. •• Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DCM, et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clin Microbiol Infect. 2019;25(1):26–34. https://doi.org/10.1016/j.cmi.2018.07.011A recent systematic review of 851 cases of mucormycosis reported between 2000 and 2017 with the aim to update understanding of the epidemiology, associated underlying comorbidities, microbiology and outcomes of this disease process.

    Article  PubMed  CAS  Google Scholar 

  19. Giuliano A, Lewis F Jr, Hadley K, Blaisdell FW. Bacteriology of necrotizing fasciitis. Am J Surg. 1977;134(1):52–7. https://doi.org/10.1016/0002-9610(77)90283-5.

    Article  PubMed  CAS  Google Scholar 

  20. Morgan MS. Diagnosis and management of necrotising fasciitis: a multiparametric approach. J Hosp Infect. 2010;75(4):249–57. https://doi.org/10.1016/j.jhin.2010.01.028.

    Article  PubMed  CAS  Google Scholar 

  21. Wong CH, Chang HC, Pasupathy S, Khin LW, Tan JL, Low CO. Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am. 2003;85(8):1454–60.

    Article  PubMed  Google Scholar 

  22. • Warkentien T, Rodriguez C, Lloyd B, Wells J, Weintrob A, Dunne JR, et al. Invasive mold infections following combat-related injuries. Clin Infect Dis. 2012;55(11):1441–9. https://doi.org/10.1093/cid/cis749A case series of post-traumatic, combat associated necrotizing soft tissue infections due to invasive molds.

    Article  PubMed  PubMed Central  Google Scholar 

  23. • Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–50. https://doi.org/10.1093/cid/civ933The most recent IDSA practice guidelines for the treatment of Candidiasis in general with treatment implications for patients with invasive cutaneous disease.

    Article  PubMed  Google Scholar 

  24. Buchanan PJ, Mast BA, Lottenberg L, Kim T, Efron PA, Ang DN. Candida albicans necrotizing soft tissue infection: a case report and literature review of fungal necrotizing soft tissue infections. Ann Plast Surg. 2013;70(6):739–41. https://doi.org/10.1097/SAP.0b013e31823fac60.

    Article  PubMed  CAS  Google Scholar 

  25. Johnin K, Nakatoh M, Kadowaki T, Kushima M, Koizumi S, Okada Y. Fournier's gangrene caused by Candida species as the primary organism. Urology. 2000;56(1):153. https://doi.org/10.1016/s0090-4295(00)00527-6.

    Article  PubMed  CAS  Google Scholar 

  26. Perkins TA, Bieniek JM, Sumfest JM. Solitary Candida albicans Infection Causing Fournier Gangrene and Review of Fungal Etiologies. Rev Urol. 2014;16(2):95–8.

    PubMed  PubMed Central  Google Scholar 

  27. Eisen DB, Brown E. Necrotizing fasciitis following a motor vehicle accident with Candida species as the sole organisms. Can J Plast Surg. 2004;12(1):43–6. https://doi.org/10.1177/229255030401200103.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jordan A, Sharma P, Moss C, Durrani A, Price R. Cervico-facial necrotising fasciitis due to Candida albicans. European Journal of Plastic Surgery. 2013;36(7):453–6. https://doi.org/10.1007/s00238-013-0837-0.

    Article  Google Scholar 

  29. Loulergue P, Mahe V, Bougnoux ME, Poiree S, Hot A, Lortholary O. Fournier's gangrene due to Candida glabrata. Med Mycol. 2008;46(2):171–3. https://doi.org/10.1080/13693780701636567.

    Article  PubMed  Google Scholar 

  30. Gassiep I, Douglas J, Playford EG. First report of monomicrobial Candida parapsilosis necrotizing fasciitis. Transpl Infect Dis. 2016;18(5):752–5. https://doi.org/10.1111/tid.12571.

    Article  PubMed  CAS  Google Scholar 

  31. Baer S, Baddley JW, Gnann JW, Pappas PG. Cryptococcal disease presenting as necrotizing cellulitis in transplant recipients. Transpl Infect Dis. 2009;11(4):353–8. https://doi.org/10.1111/j.1399-3062.2009.00399.x.

    Article  PubMed  CAS  Google Scholar 

  32. Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006;20(3):507–44, v-vi. https://doi.org/10.1016/j.idc.2006.07.001.

    Article  PubMed  Google Scholar 

  33. Molina-Leyva A, Ruiz-Carrascosa JC, Leyva-Garcia A, Husein-Elahmed H. Cutaneous Cryptococcus laurentii infection in an immunocompetent child. Int J Infect Dis. 2013;17(12):e1232–3. https://doi.org/10.1016/j.ijid.2013.04.017.

    Article  PubMed  Google Scholar 

  34. Narayan S, Batta K, Colloby P, Tan CY. Cutaneous cryptococcus infection due to C. albidus associated with Sezary syndrome. Br J Dermatol. 2000;143(3):632–4. https://doi.org/10.1111/j.1365-2133.2000.03724.x.

    Article  PubMed  CAS  Google Scholar 

  35. Hoang JK, Burruss J. Localized cutaneous Cryptococcus albidus infection in a 14-year-old boy on etanercept therapy. Pediatr Dermatol. 2007;24(3):285–8. https://doi.org/10.1111/j.1525-1470.2007.00404.x.

    Article  PubMed  Google Scholar 

  36. • Ho SW, Ang CL, Ding CS, Barkham T, Teoh LC. Necrotizing Fasciitis Caused by Cryptococcus gattii. Am J Orthop (Belle Mead NJ). 2015;44(12):E517–22 A case report of Cryptococcal necrotizing soft tissue infection and review of the literature largely inclusive of cases described to date.

    Google Scholar 

  37. Marcus JR, Hussong JW, Gonzalez C, Dumanian GA. Risk factors in necrotizing fasciitis: a case involving Cryptococcus neoformans. Ann Plast Surg. 1998;40(1):80–3.

    Article  CAS  PubMed  Google Scholar 

  38. Richardson TE, Lee NE, Cykowski MD, Chang SA, Powell SZ. Necrotizing fasciitis as the initial presentation of disseminated infection with fluconazole-resistant Cryptococcus neoformans. JMM Case Rep. 2014;1(4):e003608-e. https://doi.org/10.1099/jmmcr.0.003608-0.

    Article  Google Scholar 

  39. Capoor MR, Khanna G, Malhotra R, Verma S, Nair D, Deb M, et al. Disseminated cryptococcosis with necrotizing fasciitis in an apparently immunocompetent host: a case report. Med Mycol. 2008;46(3):269–73. https://doi.org/10.1080/13693780701675797.

    Article  PubMed  Google Scholar 

  40. Adachi M, Tsuruta D, Imanishi H, Ishii M, Kobayashi H. Necrotizing fasciitis caused by Cryptococcus neoformans in a patient with pemphigus vegetans. Clin Exp Dermatol. 2009;34(8):e751–3. https://doi.org/10.1111/j.1365-2230.2009.03472.x.

    Article  PubMed  CAS  Google Scholar 

  41. Basaran O, Emiroglu R, Arikan U, Karakayali H, Haberal M. Cryptococcal necrotizing fasciitis with multiple sites of involvement in the lower extremities. Dermatol Surg. 2003;29(11):1158–60. https://doi.org/10.1046/j.1524-4725.2003.29357.x.

    Article  PubMed  Google Scholar 

  42. Gave AA, Torres R, Kaplan L. Cryptococcal myositis and vasculitis: an unusual necrotizing soft tissue infection. Surg Infect (Larchmt). 2004;5(3):309–13. https://doi.org/10.1089/sur.2004.5.309.

    Article  PubMed  Google Scholar 

  43. Yoneda T, Itami Y, Hirayama A, Saka T, Yoshida K, Fujimoto K. Cryptococcal necrotizing fasciitis in a patient after renal transplantation--a case report. Transplant Proc. 2014;46(2):620–2. https://doi.org/10.1016/j.transproceed.2013.11.034.

    Article  PubMed  CAS  Google Scholar 

  44. Begon E, Bachmeyer C, Thibault M, Boulet E, Staub G, Trouillet G, et al. Necrotizing fasciitis due to Cryptococcus neoformans in a diabetic patient with chronic renal insufficiency. Clin Exp Dermatol. 2009;34(8):935–6. https://doi.org/10.1111/j.1365-2230.2008.03045.x.

    Article  PubMed  CAS  Google Scholar 

  45. Doorenbos-Bot AC, Hooymans JM, Blanksma LJ. Periorbital necrotising fasciitis due to Cryptococcus neoformans in a healthy young man. Doc Ophthalmol. 1990;75(3-4):315–20. https://doi.org/10.23937/2378-3656/1410271.

    Article  PubMed  CAS  Google Scholar 

  46. Hoshino T, Omura K, Kimura S, Takahashi H, Kamei K, Ohkusu M. A case of disseminated cryptococcosis with necrotizing fasciitis in a non-HIV patient. Acute Med Surg. 2017;4(4):454–7. https://doi.org/10.1002/ams2.298.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Van Grieken SA, Dupont LJ, Van Raemdonck DE, Van Bleyenbergh P, Verleden GM. Primary cryptococcal cellulitis in a lung transplant recipient. J Heart Lung Transplant. 2007;26(3):285–9. https://doi.org/10.1016/j.healun.2006.11.603.

    Article  PubMed  Google Scholar 

  48. Huang KC, Tu YK, Lee KF, Huang TJ, Wen-Wei HR. Disseminated cryptococcosis presented as necrotizing fasciitis of a limb. J Trauma. 2007;63(2):E44–6. https://doi.org/10.1097/01.ta.0000246581.83536.68.

    Article  PubMed  Google Scholar 

  49. Spellberg B, Edwards J, Ibrahim A. Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management. Clinical Microbiology Reviews. 2005;18(3):556–69. https://doi.org/10.1128/cmr.18.3.556-569.2005.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. • Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of Mucormycosis. Clinical Infectious Diseases. 2012;54(suppl_1):S16–22. https://doi.org/10.1093/cid/cir865A review of mucormycosis with particular attention to the pathophysiology of this disease process and implications for novel approaches to therapy.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Lanternier F, Dannaoui E, Morizot G, Elie C, Garcia-Hermoso D, Huerre M, et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005-2007). Clin Infect Dis. 2012;54(Suppl 1):S35–43. https://doi.org/10.1093/cid/cir880.

    Article  PubMed  CAS  Google Scholar 

  52. • Lelievre L, Garcia-Hermoso D, Abdoul H, Hivelin M, Chouaki T, Toubas D, et al. Posttraumatic mucormycosis: a nationwide study in France and review of the literature. Medicine (Baltimore). 2014;93(24):395–404. https://doi.org/10.1097/MD.0000000000000221An analysis of post-traumatic, cutaneous mucormycosis from the RetroZygo study as well as a review of the literature regarding subsequently described cases.

    Article  Google Scholar 

  53. Skiada A, Petrikkos G. Cutaneous zygomycosis. Clinical Microbiology and Infection. 2009;15:41–5. https://doi.org/10.1111/j.1469-0691.2009.02979.x.

    Article  PubMed  Google Scholar 

  54. Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis. 2000;30(6):851–6. https://doi.org/10.1086/313803.

    Article  PubMed  CAS  Google Scholar 

  55. Maertens J, Demuynck H, Verbeken EK, Zachee P, Verhoef GE, Vandenberghe P, et al. Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant. 1999;24(3):307–12. https://doi.org/10.1038/sj.bmt.1701885.

    Article  PubMed  CAS  Google Scholar 

  56. Boelaert JR, Van Cutsem J, de Locht M, Schneider YJ, Crichton RR. Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int. 1994;45(3):667–71. https://doi.org/10.1038/ki.1994.89.

    Article  PubMed  CAS  Google Scholar 

  57. de Locht M, Boelaert JR, Schneider YJ. Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating spores of Rhizopus microsporus. Biochem Pharmacol. 1994;47(10):1843–50. https://doi.org/10.1016/0006-2952(94)90314-x.

    Article  PubMed  Google Scholar 

  58. Boelaert JR, Fenves AZ, Coburn JW. Deferoxamine therapy and mucormycosis in dialysis patients: report of an international registry. Am J Kidney Dis. 1991;18(6):660–7.

    Article  CAS  PubMed  Google Scholar 

  59. Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005;191(8):1350–60. https://doi.org/10.1086/428780.

    Article  PubMed  Google Scholar 

  60. Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect. 2011;17(12):1859–67. https://doi.org/10.1111/j.1469-0691.2010.03456.x.

    Article  PubMed  CAS  Google Scholar 

  61. Neblett Fanfair R, Benedict K, Bos J, Bennett SD, Lo YC, Adebanjo T, et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med. 2012;367(23):2214–25. https://doi.org/10.1056/NEJMoa1204781.

    Article  PubMed  CAS  Google Scholar 

  62. Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis. 2008;47(4):503–9. https://doi.org/10.1086/590004.

    Article  PubMed  Google Scholar 

  63. • Patterson TF, Thompson GR III, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60. https://doi.org/10.1093/cid/ciw326The most recent IDSA practice guidelines for the treatment of invasive Aspergillosis with treatment receommendations for patients with cutaneous disease in general.

    Article  PubMed  PubMed Central  Google Scholar 

  64. 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(7):909–17. https://doi.org/10.1086/339202.

    Article  PubMed  Google Scholar 

  65. van Burik JA, Colven R, Spach DH. Cutaneous aspergillosis. J Clin Microbiol. 1998;36(11):3115–21. https://doi.org/10.1097/MD.0000000000001018.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Falsey AR, Goldsticker RD, Ahern MJ. Fatal subcutaneous aspergillosis following necrotizing fasciitis: a case report. Yale J Biol Med. 1990;63(1):9–13. https://doi.org/10.1007/BF00192441.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Rieder J, Lechner M, Lass-Floerl C, Rieger M, Lorenz I, Piza H, et al. Successful management of Aspergillus liver abscess in a patient with necrotizing fasciitis. Dig Dis Sci. 2007;52(6):1548–53. https://doi.org/10.1007/s10620-006-9402-z.

    Article  PubMed  Google Scholar 

  68. Yuen JC, Puri SK, Feng Z. Scalp necrotizing fasciitis with osteomyelitis of the skull from Aspergillus. J Craniofac Surg. 2002;13(6):762–4. https://doi.org/10.1097/00001665-200211000-00009.

    Article  PubMed  Google Scholar 

  69. Johnson MA, Lyle G, Hanly M, Yeh KA. Aspergillus: a rare primary organism in soft-tissue infections. Am Surg. 1998;64(2):122–6.

    PubMed  CAS  Google Scholar 

  70. Mathew M, Priya P, Mathew S. Scrotal Aspergillosis Associated with Fournier’s Gangrene in a Patient with Cirrhosis. Iranian Journal of Pathology. 2012;7(1):53–7.

    Google Scholar 

  71. Rath S, Kar S, Sahu SK, Sharma S. Fungal periorbital necrotizing fasciitis in an immunocompetent adult. Ophthalmic Plast Reconstr Surg. 2009;25(4):334–5. https://doi.org/10.1097/iop.0b013e3181ab7518.

    Article  PubMed  Google Scholar 

  72. Abdul Kadir N, Ahmad SS, Abdul Ghani S, Paramananda M. A case of acute periorbital necrotizing fasciitis. Journal of Acute Disease. 2016;5(2):174–6. https://doi.org/10.1016/j.joad.2015.10.005.

    Article  Google Scholar 

  73. Voloshin DK, Lacomis D, McMahon D. Disseminated histoplasmosis presenting as myositis and fasciitis in a patient with dermatomyositis. Muscle Nerve. 1995;18(5):531–5. https://doi.org/10.1002/mus.880180509.

    Article  PubMed  CAS  Google Scholar 

  74. Tsai YH, Wang CH, Hsueh PR, Jean SS, Chen FL, Lee WS. Breakthrough invasive Trichosporon asahii infection in an uremic patient with systemic calciphylaxis complicating necrotizing fasciitis during echinocandin therapy for C. tropicalis. J Microbiol Immunol Infect. 2019. https://doi.org/10.1016/j.jmii.2019.04.002.

    Article  Google Scholar 

  75. Sato E, Togawa A, Masaki M, Shirahashi A, Kumagawa M, Kawano Y, et al. Community-acquired Disseminated Exophiala dermatitidis Mycosis with Necrotizing Fasciitis in Chronic Graft-versus-host Disease. Internal Medicine. 2019;advpub. https://doi.org/10.2169/internalmedicine.1706-18.

  76. Pushker N, Chra M, Bajaj MS, Ghose S, Naik N, Kashyap S, et al. Necrotizing periorbital Fusarium infection--an emerging pathogen in immunocompetent individuals. J Infect. 2002;44(4):236–9. https://doi.org/10.1053/jinf.2002.1005.

    Article  PubMed  CAS  Google Scholar 

  77. Walsh TJ, Gamaletsou MN, McGinnis MR, Hayden RT, Kontoyiannis DP. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis). Clin Infect Dis. 2012;54(Suppl 1):S55–60. https://doi.org/10.1093/cid/cir868.

    Article  PubMed  Google Scholar 

  78. Ambrosioni J, Bouchuiguir-Wafa K, Garbino J. Emerging invasive zygomycosis in a tertiary care center: epidemiology and associated risk factors. Int J Infect Dis. 2010;14(Suppl 3):e100–3. https://doi.org/10.1016/j.ijid.2009.11.024.

    Article  PubMed  Google Scholar 

  79. Verweij PE, Brandt ME. Aspergillus, Fusarium, and Other Opportunistic Moniliaceous Fungi. In: Murray PR, Baron EJ, editors. Manual of clinical microbiology. Washington, D.C.: ASM Press; 2007.

    Google Scholar 

  80. Cruciani M, Mengoli C, Loeffler J, Donnelly P, Barnes R, Jones BL, et al. Polymerase chain reaction blood tests for the diagnosis of invasive aspergillosis in immunocompromised people. Cochrane Database Syst Rev. 2015;9:Cd009551. https://doi.org/10.1002/14651858.CD009551.pub2.

    Article  Google Scholar 

  81. • Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50(3):291–322. https://doi.org/10.1086/649858The most recent IDSA practice guidelines for the treatment of Cryptococcal disease with treatment implications for patients with cutaneous infection due to these organisms.

    Article  PubMed  Google Scholar 

  82. • Cornely OA, Arikan-Akdagli S, Dannaoui E, Groll AH, Lagrou K, Chakrabarti A, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clinical Microbiology and Infection. 2014;20:5–26. https://doi.org/10.1111/1469-0691.12371The most recent ESCMID and ECMM practice guidelines for the management of mucromycosis with treatment guidance for cutaneous disease.

    Article  PubMed  CAS  Google Scholar 

  83. • Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102(3):433–44. https://doi.org/10.3324/haematol.2016.152900The most recent ECIL-6 practice guidelines for invasive fungal infections within patients with leukemia and HSCT with treatment guidance for cutaneous disease.

    Article  PubMed  PubMed Central  Google Scholar 

  84. • Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, et al. Executive Summary: Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2014;59(2):147–59. https://doi.org/10.1093/cid/ciu444The most recent IDSA practice guidelines for the management of soft tissue infections with a review and management recommendations of fungal soft tissue infections in general.

    Article  PubMed  Google Scholar 

  85. Espinel-Ingroff A, Chakrabarti A, Chowdhary A, Cordoba S, Dannaoui E, Dufresne P, et al. Multicenter Evaluation of MIC Distributions for Epidemiologic Cutoff Value Definition To Detect Amphotericin B, Posaconazole, and Itraconazole Resistance among the Most Clinically Relevant Species of Mucorales. Antimicrob Agents Chemother. 2015;59(3):1745–50. https://doi.org/10.1128/aac.04435-14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Caramalho R, Maurer E, Binder U, Araújo R, Dolatabadi S, Lass-Flörl C, et al. Etest cannot be recommended for in vitro susceptibility testing of mucorales. Antimicrob Agents Chemother. 2015;59(6):3663–5. https://doi.org/10.1128/AAC.00004-15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Brugiere O, Dauriat G, Mal H, Marrash-Chalha R, Fournier M, Groussard O, et al. Pulmonary mucormycosis (zygomycosis) in a lung transplant recipient: recovery after posaconazole therapy. Transplantation. 2005;80(9):1361–2. https://doi.org/10.1097/01.tp.0000168343.47569.1c.

    Article  PubMed  Google Scholar 

  88. Garbino J, Uçkay I, Amini K, Puppo M, Richter M, Lew D. <em>Absidia</em> posttraumatic infection: successful treatment with posaconazole. Journal of Infection. 2005;51(3):e135–e8. https://doi.org/10.1016/j.jinf.2004.11.002.

    Article  CAS  Google Scholar 

  89. van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42(7):e61–5. https://doi.org/10.1086/500212.

    Article  PubMed  Google Scholar 

  90. Dolton MJ, Ray JE, Chen SC, Ng K, Pont L, McLachlan AJ. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration. Antimicrob Agents Chemother. 2012;56(11):5503–10. https://doi.org/10.1128/aac.00802-12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Krishna G, Ma L, Martinho M, Preston RA, O'Mara E. A new solid oral tablet formulation of posaconazole: a randomized clinical trial to investigate rising single- and multiple-dose pharmacokinetics and safety in healthy volunteers. J Antimicrob Chemother. 2012;67(11):2725–30. https://doi.org/10.1093/jac/dks268.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Marty FM, Ostrosky-Zeichner L, Cornely OA, Mullane KM, Perfect JR, Thompson GR 3rd, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828–37. https://doi.org/10.1016/s1473-3099(16)00071-2.

    Article  PubMed  CAS  Google Scholar 

  93. Reed C, Bryant R, Ibrahim AS, Edwards J Jr, Filler SG, Goldberg R, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47(3):364–71. https://doi.org/10.1086/589857.

    Article  PubMed  CAS  Google Scholar 

  94. Kyvernitakis A, Torres HA, Jiang Y, Chamilos G, Lewis RE, Kontoyiannis DP. Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis. Clinical Microbiology and Infection. 2016;22(9):811.e1–8. https://doi.org/10.1016/j.cmi.2016.03.029.

    Article  CAS  Google Scholar 

  95. Pagano L, Cornely OA, Busca A, Caira M, Cesaro S, Gasbarrino C, et al. Combined antifungal approach for the treatment of invasive mucormycosis in patients with hematologic diseases: a report from the SEIFEM and FUNGISCOPE registries. Haematologica. 2013;98(10):e127–e30. https://doi.org/10.3324/haematol.2012.083063.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15. https://doi.org/10.1056/NEJMoa020191.

    Article  PubMed  CAS  Google Scholar 

  97. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007;44(1):2–12. https://doi.org/10.1086/508774.

    Article  PubMed  CAS  Google Scholar 

  98. Maertens JA, Raad II, Marr KA, Patterson TF, Kontoyiannis DP, Cornely OA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760–9. https://doi.org/10.1016/s0140-6736(15)01159-9.

    Article  CAS  PubMed  Google Scholar 

  99. Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162(2):81–9. https://doi.org/10.7326/m13-2508.

    Article  PubMed  Google Scholar 

  100. Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39(6):797–802. https://doi.org/10.1086/423380.

    Article  PubMed  CAS  Google Scholar 

  101. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis. 2007;44(4):531–40. https://doi.org/10.1086/510592.

    Article  PubMed  Google Scholar 

  102. Cohen-Ludmann C, Kerob D, Feuilhade M, Chaine B, Guermazi A, Janier M, et al. Zygomycosis of the Penis Due to Rhizopus oryzae Successfully Treated With Surgical Debridement and a Combination of High-Dose Liposomal and Topical Amphotericin B. JAMA Dermatology. 2006;142(12):1650–66. https://doi.org/10.1001/archderm.142.12.1657.

    Article  Google Scholar 

  103. Di Pentima MC, Chan S, Powell J, Napoli JA, Walter AW, Walsh TJ. Topical amphotericin B in combination with standard therapy for severe necrotizing skin and soft-tissue mucormycosis in an infant with bilineal leukemia: case report and review. J Pediatr Hematol Oncol. 2014;36(7):e468–70. https://doi.org/10.1097/mph.0000000000000166.

    Article  PubMed  Google Scholar 

  104. Rodriguez CJ, Tribble DR, Malone DL, Murray CK, Jessie EM, Khan M, et al. Treatment of Suspected Invasive Fungal Infection in War Wounds. Military Medicine. 2018;183(suppl_2):142–6. https://doi.org/10.1093/milmed/usy079.

    Article  PubMed  Google Scholar 

  105. Spellberg B, Ibrahim AS, Chin-Hong PV, Kontoyiannis DP, Morris MI, Perfect JR, et al. The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J Antimicrob Chemother. 2012;67(3):715–22. https://doi.org/10.1093/jac/dkr375.

    Article  PubMed  CAS  Google Scholar 

  106. John BV, Chamilos G, Kontoyiannis DP. Hyperbaric oxygen as an adjunctive treatment for zygomycosis. Clin Microbiol Infect. 2005;11(7):515–7. https://doi.org/10.1111/j.1469-0691.2005.01170.x.

    Article  PubMed  CAS  Google Scholar 

  107. Tragiannidis A, Groll AH. Hyperbaric oxygen therapy and other adjunctive treatments for zygomycosis. Clin Microbiol Infect. 2009;15(Suppl 5):82–6. https://doi.org/10.1111/j.1469-0691.2009.02986.x.

    Article  PubMed  Google Scholar 

  108. Abzug MJ, Walsh TJ. Interferon-gamma and colony-stimulating factors as adjuvant therapy for refractory fungal infections in children. Pediatr Infect Dis J. 2004;23(8):769–73.

    Article  PubMed  Google Scholar 

  109. Gil-Lamaignere C, Simitsopoulou M, Roilides E, Maloukou A, Winn RM, Walsh TJ. Interferon- gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J Infect Dis. 2005;191(7):1180–7. https://doi.org/10.1086/428503.

    Article  PubMed  CAS  Google Scholar 

  110. Hubel K, Dale DC, Engert A, Liles WC. Current status of granulocyte (neutrophil) transfusion therapy for infectious diseases. J Infect Dis. 2001;183(2):321–8. https://doi.org/10.1086/317943.

    Article  PubMed  CAS  Google Scholar 

  111. Chamilos G, Lewis RE, Kontoyiannis DP. Lovastatin has significant activity against zygomycetes and interacts synergistically with voriconazole. Antimicrob Agents Chemother. 2006;50(1):96–103. https://doi.org/10.1128/aac.50.1.96-103.2006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Bellanger AP, Tatara AM, Shirazi F, Gebremariam T, Albert ND, Lewis RE, et al. Statin Concentrations Below the Minimum Inhibitory Concentration Attenuate the Virulence of Rhizopus oryzae. J Infect Dis. 2016;214(1):114–21. https://doi.org/10.1093/infdis/jiw090.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Grimaldi D, Pradier O, Hotchkiss RS, Vincent JL. Nivolumab plus interferon-gamma in the treatment of intractable mucormycosis. Lancet Infect Dis. 2017;17(1):18. https://doi.org/10.1016/s1473-3099(16)30541-2.

    Article  PubMed  Google Scholar 

  114. Parks T, Wilson C, Curtis N, Norrby-Teglund A, Sriskandan S. Polyspecific Intravenous Immunoglobulin in Clindamycin-treated Patients With Streptococcal Toxic Shock Syndrome: A Systematic Review and Meta-analysis. Clin Infect Dis. 2018;67(9):1434–6. https://doi.org/10.1093/cid/ciy401.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Madsen MB, Hjortrup PB, Hansen MB, Lange T, Norrby-Teglund A, Hyldegaard O, et al. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT): a randomised, blinded, placebo-controlled trial. Intensive Care Med. 2017;43(11):1585–93. https://doi.org/10.1007/s00134-017-4786-0.

    Article  PubMed  CAS  Google Scholar 

  116. Kadri SS, Swihart BJ, Bonne SL, Hohmann SF, Hennessy LV, Louras P, et al. Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score-Matched Analysis From 130 US Hospitals. Clin Infect Dis. 2017;64(7):877–85. https://doi.org/10.1093/cid/ciw871.

    Article  PubMed  Google Scholar 

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Bartram, L., Aaron, J.G. Fungal Necrotizing Skin and Soft Tissue Infections. Curr Fungal Infect Rep 13, 146–156 (2019). https://doi.org/10.1007/s12281-019-00355-5

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