A retrospective analysis on mucormycosis in patients with hematological diseases: a single center experience from Turkey
Abstract
Aim: Mucormycosis is an acute, invasive, devastating and highly fatal fungal infection, affecting particularly immunocompromised patients; fortunately, it is rare. This study aimed to describe the attitude of mucormycosis in patients with a hematological disease, and to evaluate the risk factors associated with mortality.
Material and Method: We retrospectively assessed the demographic and clinical data of patients who were diagnosed with mucormycosis in Erciyes University Hematology and Bone Marrow Transplantation Center, between 2010 and 2020. The study was included 34 patients with a history of either hematological malignancy or hematopoietic stem cell transplantation.
Results: Twenty-seven patients had proven infection, and the others had possible infection. The most frequent underlying disease was acute leukemia. Seven-teen patients had a history of allogeneic transplantation, and frequency of mucormycosis was 3.5% among allogeneic transplant recipients. The most frequent site of infection was the rhino-orbital region (85.3%). Forty-seven percent of patients presented with acute orbital symptoms. Fifteen patients were on a mucor-active antifungal (posaconazole and liposomal Amphotericin B) prophylaxis or treatment at the time of diagnosis. All patients received liposomal Amphotericin B and seven patients received posaconazole additionally as initial therapy. Surgical debridement was performed in 91.1% of patients. The two-year mucor-related mortality rate was 44.1%. The survival curves were significantly lower in patients with concomitant fungal pneumonia, allogeneic transplantation and also in patients who were receiving mucor-active antifungal drugs at the time of diagnosis.
Conclusion: Mucormycosis remains a significant problem for hematology clinicians despite the expanding use of antifungal prophylaxis. Moreover, breakthrough infections indicate rising danger regarding resistant agents. We also highlight that, most of the patients receiving broad-spectrum antifungal prophylaxis are more fragile and more complicated patients, which put them at increased baseline risk for mucormycosis, and deserve more attention.
Keywords
Invasive fungal infection mucormycosis hematological malignancy hematopoietic stem cell transplantation
References
- Kontoyiannis DP, Lewis RE, editors. Agents of Mucormycosis and Entomophthoramycosis. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Philadelphia: Churchill Livingstone Elsevier; 2010.
- Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi 2019; 5: 26.
- Lanternier F, Dannaoui E, Morizot G, et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005–2007). Clin Infect Dis 2012; 54: S35-S43.
- Skiada A, Pavleas I, Drogari-Apiranthitou M. Epidemiology and diagnosis of mucormycosis: an update. J Fungi 2020;6:265.
- Stemler J, Hamed K, Salmanton‐García J, et al. Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature. Mycoses 2020; 63: 1060-8.
- Cuenca‐Estrella M, Bernal‐Martinez L, Isla G, Gomez‐Lopez A, Alcazar‐Fuoli L, Buitrago M. Incidence of zygomycosis in transplant recipients. Clin Microbiol Infect 2009;15: 37-40.
- Roques M, Chretien ML, Favennec C, et al. Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis. Mycoses 2016; 59: 383-90.
- Hoenigl M, Strenger V, Buzina W, et al. European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) host factors and invasive fungal infections in patients with haematological malignancies. J Antimicrob cChemother 2012; 67: 2029-33.
- Kontoyiannis DP, Marr KA, Park BJ et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50: 1091-100.
- Park BJ, Pappas PG, Wannemuehler KA, et al. Invasive non-Aspergillus mold infections in transplant recipients, United States, 2001–2006. Emerg Infect Dis 2011; 17: 1855.
- Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41: 634-53.
- Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 2020; 71: 1367-76.
- Garcia-Vidal C, Upton A, Kirby KA, Marr KA. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis 2008; 47: 1041-50.
- Wingard JR. The changing face of invasive fungal infections in hematopoietic cell transplant recipients. Curr Opin Oncol 2005; 17: 89-92.
- Kontoyiannis DP, Lionakis MS, Lewis RE, 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: 1350-60.
- Maertens J. Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies. Eur J Haematol 2007; 78: 275-82.
- Siwek GT, Dodgson KJ, de Margarida MS, et al. Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis 2004; 39: 584-7.
- Abidi MZ, Sohail MR, Cummins N, et al. Stability in the cumulative incidence, severity and mortality of 101 cases of invasive mucormycosis in high‐risk patients from 1995 to 2011: a comparison of eras immediately before and after the availability of voriconazole and echinocandin‐amphotericin combination therapies. Mycoses 2014; 57: 687-98.
- Rausch CR, DiPippo AJ, Bose P, Kontoyiannis DP. Breakthrough fungal infections in patients with leukemia receiving isavuconazole. Clin Infect Dis 2018; 67: 1610-3.
- Axell-House DB, Wurster S, Jiang Y et al. Breakthrough mucormycosis developing on mucorales-active antifungals portrays a poor prognosis in patients with hematologic cancer. J Fungi 2021; 7: 217.
- Hardak E, Fuchs E, Geffen Y, Zuckerman T, Oren I. Clinical spectrum, diagnosis and outcome of rare fungal infections in patients with hematological malignancies: experience of 15-year period from a single tertiary medical center. Mycopathologia 2020; 185: 347-55.
- Koehler P, Mellinghoff SC, Stemler J, et al. Quantifying guideline adherence in mucormycosis management using the EQUAL score. Mycoses 2020; 63: 343-51.
- Prakash H, Ghosh AK, Rudramurthy SM, et al. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Medical Mycology 2019; 57: 395-402.
- Nucci M, Engelhardt M, Hamed K. Mucormycosis in South America: a review of 143 reported cases. Mycoses 2019; 62: 730-8.
- Dolatabadi S, Ahmadi B, Rezaei-Matehkolaei, A et al. Mucormycosis in Iran: a six-year retrospective experience. J Mycologie Medicale 2018; 28: 269-73.
- Vaughan C, Bartolo A, Vallabh N, Leong SC. A meta‐analysis of survival factors in rhino‐orbital‐cerebral mucormycosis—has anything changed in the past 20 years? Clin Otolaryngol 2018; 43: 1454-64.
- Ketenci I, Ünlü Y, Kaya H, et al. Rhinocerebral mucormycosis: experience in 14 patients. J Laryngol Otol 2011; 125: e3.
- Skiada A, Lass-Floerl C, Klimko N, Ibrahim A, Roilides E, Petrikkos G. Challenges in the diagnosis and treatment of mucormycosis. Medical Mycology 2018; 56: S93-S101.
- Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev 2011; 24: 247-80.
- 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: S55-S60.
- Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019; 19: e405-e21.
- Vehreschild JJ, Koehler P, Lamoth F et al. Future challenges and chances in the diagnosis and management of invasive mould infections in cancer patients. Medical Mycology 2021; 59: 93-101.
- 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: 503-9.
- Tissot F, Agrawal S, Pagano L, 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: 433.
- Skiada A, Pagano L, Groll A 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: 1859-67
Abstract
References
- Kontoyiannis DP, Lewis RE, editors. Agents of Mucormycosis and Entomophthoramycosis. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Philadelphia: Churchill Livingstone Elsevier; 2010.
- Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi 2019; 5: 26.
- Lanternier F, Dannaoui E, Morizot G, et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005–2007). Clin Infect Dis 2012; 54: S35-S43.
- Skiada A, Pavleas I, Drogari-Apiranthitou M. Epidemiology and diagnosis of mucormycosis: an update. J Fungi 2020;6:265.
- Stemler J, Hamed K, Salmanton‐García J, et al. Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature. Mycoses 2020; 63: 1060-8.
- Cuenca‐Estrella M, Bernal‐Martinez L, Isla G, Gomez‐Lopez A, Alcazar‐Fuoli L, Buitrago M. Incidence of zygomycosis in transplant recipients. Clin Microbiol Infect 2009;15: 37-40.
- Roques M, Chretien ML, Favennec C, et al. Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis. Mycoses 2016; 59: 383-90.
- Hoenigl M, Strenger V, Buzina W, et al. European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) host factors and invasive fungal infections in patients with haematological malignancies. J Antimicrob cChemother 2012; 67: 2029-33.
- Kontoyiannis DP, Marr KA, Park BJ et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50: 1091-100.
- Park BJ, Pappas PG, Wannemuehler KA, et al. Invasive non-Aspergillus mold infections in transplant recipients, United States, 2001–2006. Emerg Infect Dis 2011; 17: 1855.
- Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41: 634-53.
- Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 2020; 71: 1367-76.
- Garcia-Vidal C, Upton A, Kirby KA, Marr KA. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis 2008; 47: 1041-50.
- Wingard JR. The changing face of invasive fungal infections in hematopoietic cell transplant recipients. Curr Opin Oncol 2005; 17: 89-92.
- Kontoyiannis DP, Lionakis MS, Lewis RE, 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: 1350-60.
- Maertens J. Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies. Eur J Haematol 2007; 78: 275-82.
- Siwek GT, Dodgson KJ, de Margarida MS, et al. Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis 2004; 39: 584-7.
- Abidi MZ, Sohail MR, Cummins N, et al. Stability in the cumulative incidence, severity and mortality of 101 cases of invasive mucormycosis in high‐risk patients from 1995 to 2011: a comparison of eras immediately before and after the availability of voriconazole and echinocandin‐amphotericin combination therapies. Mycoses 2014; 57: 687-98.
- Rausch CR, DiPippo AJ, Bose P, Kontoyiannis DP. Breakthrough fungal infections in patients with leukemia receiving isavuconazole. Clin Infect Dis 2018; 67: 1610-3.
- Axell-House DB, Wurster S, Jiang Y et al. Breakthrough mucormycosis developing on mucorales-active antifungals portrays a poor prognosis in patients with hematologic cancer. J Fungi 2021; 7: 217.
- Hardak E, Fuchs E, Geffen Y, Zuckerman T, Oren I. Clinical spectrum, diagnosis and outcome of rare fungal infections in patients with hematological malignancies: experience of 15-year period from a single tertiary medical center. Mycopathologia 2020; 185: 347-55.
- Koehler P, Mellinghoff SC, Stemler J, et al. Quantifying guideline adherence in mucormycosis management using the EQUAL score. Mycoses 2020; 63: 343-51.
- Prakash H, Ghosh AK, Rudramurthy SM, et al. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Medical Mycology 2019; 57: 395-402.
- Nucci M, Engelhardt M, Hamed K. Mucormycosis in South America: a review of 143 reported cases. Mycoses 2019; 62: 730-8.
- Dolatabadi S, Ahmadi B, Rezaei-Matehkolaei, A et al. Mucormycosis in Iran: a six-year retrospective experience. J Mycologie Medicale 2018; 28: 269-73.
- Vaughan C, Bartolo A, Vallabh N, Leong SC. A meta‐analysis of survival factors in rhino‐orbital‐cerebral mucormycosis—has anything changed in the past 20 years? Clin Otolaryngol 2018; 43: 1454-64.
- Ketenci I, Ünlü Y, Kaya H, et al. Rhinocerebral mucormycosis: experience in 14 patients. J Laryngol Otol 2011; 125: e3.
- Skiada A, Lass-Floerl C, Klimko N, Ibrahim A, Roilides E, Petrikkos G. Challenges in the diagnosis and treatment of mucormycosis. Medical Mycology 2018; 56: S93-S101.
- Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev 2011; 24: 247-80.
- 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: S55-S60.
- Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019; 19: e405-e21.
- Vehreschild JJ, Koehler P, Lamoth F et al. Future challenges and chances in the diagnosis and management of invasive mould infections in cancer patients. Medical Mycology 2021; 59: 93-101.
- 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: 503-9.
- Tissot F, Agrawal S, Pagano L, 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: 433.
- Skiada A, Pagano L, Groll A 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: 1859-67
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