Download PDF
Semin Respir Crit Care Med 2015; 36(05): 692-705
DOI: 10.1055/s-0035-1562896
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mucormycosis: New Developments into a Persistently Devastating Infection

François Danion
1   Service de Maladies Infectieuses et tropicales, APHP-Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Paris, France
,
Claire Aguilar
1   Service de Maladies Infectieuses et tropicales, APHP-Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Paris, France
,
Emilie Catherinot
1   Service de Maladies Infectieuses et tropicales, APHP-Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Paris, France
2   Service de Pneumologie, Hôpital Foch, Suresnes, France
,
Alexandre Alanio
3   Institut Pasteur, Unité de Mycologie Moléculaire, CNRS URA3012, Paris, France
4   Institut Pasteur, Centre National de Référence des Mycoses Invasives et Antifongiques, Paris, France
5   Laboratoire de Parasitologie-Mycologie; AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Université Paris Diderot, Sorbonne, Paris France
,
Susan DeWolf
1   Service de Maladies Infectieuses et tropicales, APHP-Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Paris, France
,
Olivier Lortholary
1   Service de Maladies Infectieuses et tropicales, APHP-Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Paris, France
3   Institut Pasteur, Unité de Mycologie Moléculaire, CNRS URA3012, Paris, France
4   Institut Pasteur, Centre National de Référence des Mycoses Invasives et Antifongiques, Paris, France
,
Fanny Lanternier
1   Service de Maladies Infectieuses et tropicales, APHP-Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Paris, France
› Author Affiliations
Further Information

Publication History

Publication Date:
23 September 2015 (online)

    Permissions and Reprints

Abstract

Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease. Prompt initiation of an effective treatment is essential to decrease mortality. However, mucormycosis and aspergillosis share close clinical and radiological features. Invasive procedures such as bronchial endoscopy and/or lung biopsy are necessary to confirm diagnosis, as no indirect tests are yet validated. Therefore, the challenge is to minimize the delay in diagnosis. When present, the reversed halo sign on CT scan is suggestive of mucormycosis. Quantitative polymerase chain reaction is a new promising approach to detect Mucorales DNA in serum and new molecular tools are available to detect Mucorales in tissues as well as to specify species. Recommendations from ECIL and ECMM/ESCMID have recently been published on management of mucormycosis. The recommended treatment is an amphotericin B lipid formulation in combination with surgery and modification of risk factors. High-dose (10 mg/kg) of liposomal amphotericin B is recommended in case of neurological involvement and posaconazole for maintenance therapy. Place of isavuconazole as well as posaconazole new formulations (tablets and intravenous) in first line treatment have to be defined. Improved radiologic descriptions of mucormycosis and new molecular tools may be key elements to help with rapid diagnosis in the future. Clinical trials are warranted to improve therapeutic success and hopefully survival.

Keywords

mucormycosis - pulmonary mucormycosis - Mucorales - mycosis - review - treatment
 

  • References

  • 1 Hibbett DS, Binder M, Bischoff JF , et al. A higher-level phylogenetic classification of the Fungi. Mycol Res 2007; 111 (Pt 5): 509-547
    CrossrefPubMedGoogle Scholar
  • 2 Paultauf A. Mycosis mucorina. Arch Path Anat 1885; 102: 543
    CrossrefPubMedGoogle Scholar
  • 3 Skiada A, Pagano L, Groll A , et al; European Confederation of Medical Mycology Working Group on Zygomycosis. 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) 1859-1867
    CrossrefPubMedGoogle Scholar
  • 4 Lanternier F, Dannaoui E, Morizot G , et al; French Mycosis Study Group. A global analysis of mucormycosis in France: the RetroZygo Study (2005-2007). Clin Infect Dis 2012; 54 (Suppl. 01) S35-S43
    CrossrefPubMedGoogle Scholar
  • 5 Cornely OA, Arikan-Akdagli S, Dannaoui E , et al; European Society of Clinical Microbiology and Infectious Diseases Fungal Infection Study Group; European Confederation of Medical Mycology. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect 2014; 20 (Suppl. 03) 5-26
    PubMedGoogle Scholar
  • 6 Skiada A, Lanternier F, Groll AH , et al; European Conference on Infections in Leukemia. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica 2013; 98 (4) 492-504
    CrossrefPubMedGoogle Scholar
  • 7 Bitar D, Van Cauteren D, Lanternier F , et al. Increasing incidence of zygomycosis (mucormycosis), France, 1997-2006. Emerg Infect Dis 2009; 15 (9) 1395-1401
    CrossrefPubMedGoogle Scholar
  • 8 Bitar D, Lortholary O, Le Strat Y , et al. Population-based analysis of invasive fungal infections, France, 2001-2010. Emerg Infect Dis 2014; 20 (7) 1149-1155
    CrossrefPubMedGoogle Scholar
  • 9 Chakrabarti A, Chatterjee SS, Das A , et al. Invasive zygomycosis in India: experience in a tertiary care hospital. Postgrad Med J 2009; 85 (1009) 573-581
    CrossrefPubMedGoogle Scholar
  • 10 Kontoyiannis DP, Azie N, Franks B, Horn DL. Prospective Antifungal Therapy (PATH) Alliance(®): focus on mucormycosis. Mycoses 2014; 57 (4) 240-246
    CrossrefPubMedGoogle Scholar
  • 11 Rüping MJGT, Heinz WJ, Kindo AJ , et al. Forty-one recent cases of invasive zygomycosis from a global clinical registry. J Antimicrob Chemother 2010; 65 (2) 296-302
    CrossrefPubMedGoogle Scholar
  • 12 Chakrabarti A, Das A, Mandal J , et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol 2006; 44 (4) 335-342
    CrossrefPubMedGoogle Scholar
  • 13 Xhaard A, Lanternier F, Porcher R , et al. Mucormycosis after allogeneic haematopoietic stem cell transplantation: a French Multicentre Cohort Study (2003-2008). Clin Microbiol Infect 2012; 18 (10) E396-E400
    CrossrefPubMedGoogle Scholar
  • 14 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 (8) 1091-1100
    CrossrefPubMedGoogle Scholar
  • 15 Pappas PG, Alexander BD, Andes DR , et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 2010; 50 (8) 1101-1111
    CrossrefPubMedGoogle Scholar
  • 16 Sun H-Y, Aguado JM, Bonatti H , et al; Zygomycosis Transplant Study Group. Pulmonary zygomycosis in solid organ transplant recipients in the current era. Am J Transplant 2009; 9 (9) 2166-2171
    CrossrefPubMedGoogle Scholar
  • 17 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 (10) 1855-1864
    CrossrefPubMedGoogle Scholar
  • 18 Lewis RE, Georgiadou SP, Sampsonas F, Chamilos G, Kontoyiannis DP. Risk factors for early mortality in haematological malignancy patients with pulmonary mucormycosis. Mycoses 2014; 57 (1) 49-55
    CrossrefPubMedGoogle Scholar
  • 19 Garcia-Hermoso D, Alanio A, Lortholary O, Dromer F. Agents of systemic and subcutaneous mucormycosis and entomophthoromycosis. In: Manual Clinical Microbiology. 11th ed. Washington, DC: ASM Press; 2015: 2087-2108
    CrossrefGoogle Scholar
  • 20 Legouge C, Caillot D, Chrétien M-L , et al. The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia?. Clin Infect Dis 2014; 58 (5) 672-678
    CrossrefPubMedGoogle Scholar
  • 21 Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis 2012; 54 (Suppl. 01) S16-S22
    CrossrefPubMedGoogle Scholar
  • 22 Chamilos G, Lewis RE, Lamaris G, Walsh TJ, Kontoyiannis DP. Zygomycetes hyphae trigger an early, robust proinflammatory response in human polymorphonuclear neutrophils through toll-like receptor 2 induction but display relative resistance to oxidative damage. Antimicrob Agents Chemother 2008; 52 (2) 722-724
    CrossrefPubMedGoogle Scholar
  • 23 Roilides E, Kontoyiannis DP, Walsh TJ. Host defenses against Zygomycetes . Clin Infect Dis 2012; 54 (Suppl. 01) S61-S66
    CrossrefPubMedGoogle Scholar
  • 24 Chinn RY, Diamond RD. Generation of chemotactic factors by Rhizopus oryzae in the presence and absence of serum: relationship to hyphal damage mediated by human neutrophils and effects of hyperglycemia and ketoacidosis. Infect Immun 1982; 38 (3) 1123-1129
    PubMedGoogle Scholar
  • 25 Waldorf AR, Ruderman N, Diamond RD. Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus. J Clin Invest 1984; 74 (1) 150-160
    CrossrefPubMedGoogle Scholar
  • 26 Ben-Ami R, Luna M, Lewis RE, Walsh TJ, Kontoyiannis DP. A clinicopathological study of pulmonary mucormycosis in cancer patients: extensive angioinvasion but limited inflammatory response. J Infect 2009; 59 (2) 134-138
    CrossrefPubMedGoogle Scholar
  • 27 Liu M, Spellberg B, Phan QT , et al. The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice. J Clin Invest 2010; 120 (6) 1914-1924
    CrossrefPubMedGoogle Scholar
  • 28 Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res 2007; 67 (8) 3496-3499
    CrossrefPubMedGoogle Scholar
  • 29 Gebremariam T, Liu M, Luo G , et al. CotH3 mediates fungal invasion of host cells during mucormycosis. J Clin Invest 2014; 124 (1) 237-250
    CrossrefPubMedGoogle Scholar
  • 30 Artis WM, Fountain JA, Delcher HK, Jones HE. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes 1982; 31 (12) 1109-1114
    CrossrefPubMedGoogle Scholar
  • 31 Chamilos G, Marom EM, Lewis RE, Lionakis MS, Kontoyiannis DP. Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer. Clin Infect Dis 2005; 41 (1) 60-66
    CrossrefPubMedGoogle Scholar
  • 32 Lee FYW, Mossad SB, Adal KA. Pulmonary mucormycosis: the last 30 years. Arch Intern Med 1999; 159 (12) 1301-1309
    CrossrefPubMedGoogle Scholar
  • 33 Pagano L, Offidani M, Fianchi L , et al; GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Infection Program. Mucormycosis in hematologic patients. Haematologica 2004; 89 (2) 207-214
    PubMedGoogle Scholar
  • 34 Tedder M, Spratt JA, Anstadt MP, Hegde SS, Tedder SD, Lowe JE. Pulmonary mucormycosis: results of medical and surgical therapy. Ann Thorac Surg 1994; 57 (4) 1044-1050
    CrossrefPubMedGoogle Scholar
  • 35 Pagano L, Ricci P, Nosari A , et al. Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature. Gimema Infection Program (Gruppo Italiano Malattie Ematologiche dell'Adulto). Br J Haematol 1995; 89 (3) 500-505
    CrossrefPubMedGoogle Scholar
  • 36 Ferrell BA, Tolle JJ. Invasive endobronchial mucormycosis. Am J Respir Crit Care Med 2014; 190 (8) e28-e28
    CrossrefPubMedGoogle Scholar
  • 37 Thomas R, Christopher DJ, Roy A, Balamugesh T. Pulmonary mucormycosis presenting as endobronchial tumours—case reports. Resp Med Extra 2005; 1 (2) 27-30
    PubMedGoogle Scholar
  • 38 Connor BA, Anderson RJ, Smith JW. Mucor mediastinitis. Chest 1979; 75 (4) 525-526
    CrossrefPubMedGoogle Scholar
  • 39 Vogl TJ, Hinrichs T, Jacobi V, Böhme A, Hoelzer D. Computed tomographic appearance of pulmonary mucormycosis [in German]. Rofo 2000; 172 (7) 604-608
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Kim SJ, Lee KS, Ryu YH , et al. Reversed halo sign on high-resolution CT of cryptogenic organizing pneumonia: diagnostic implications. AJR Am J Roentgenol 2003; 180 (5) 1251-1254
    CrossrefPubMedGoogle Scholar
  • 41 Voloudaki AE, Bouros DE, Froudarakis ME, Datseris GE, Apostolaki EG, Gourtsoyiannis NC. Crescentic and ring-shaped opacities. CT features in two cases of bronchiolitis obliterans organizing pneumonia (BOOP). Acta Radiol 1996; 37 (6) 889-892
    PubMedGoogle Scholar
  • 42 Wahba H, Truong MT, Lei X, Kontoyiannis DP, Marom EM. Reversed halo sign in invasive pulmonary fungal infections. Clin Infect Dis 2008; 46 (11) 1733-1737
    CrossrefPubMedGoogle Scholar
  • 43 Okubo Y, Ishiwatari T, Izumi H , et al. Pathophysiological implication of reversed CT halo sign in invasive pulmonary mucormycosis: a rare case report. Diagn Pathol 2013; 8: 82
    CrossrefPubMedGoogle Scholar
  • 44 Gafter-Gvili A, Paul M, Bernstine H , et al. The role of 18F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia. Leuk Res 2013; 37 (9) 1057-1062
    CrossrefPubMedGoogle Scholar
  • 45 Hot A, Maunoury C, Poiree S , et al. Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections. Clin Microbiol Infect 2011; 17 (3) 409-417
    CrossrefPubMedGoogle Scholar
  • 46 Chamilos G, Macapinlac HA, Kontoyiannis DP. The use of 18F-fluorodeoxyglucose positron emission tomography for the diagnosis and management of invasive mould infections. Med Mycol 2008; 46 (1) 23-29
    CrossrefPubMedGoogle Scholar
  • 47 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) 503-509
    CrossrefPubMedGoogle Scholar
  • 48 Marty FM, Koo S. Role of (1→3)-beta-D-glucan in the diagnosis of invasive aspergillosis. Med Mycol 2009; 47 (Suppl. 01) S233-S240
    CrossrefPubMedGoogle Scholar
  • 49 Millon L, Larosa F, Lepiller Q , et al. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin Infect Dis 2013; 56 (10) e95-e101
    CrossrefPubMedGoogle Scholar
  • 50 Potenza L, Vallerini D, Barozzi P , et al. Mucorales-specific T cells emerge in the course of invasive mucormycosis and may be used as a surrogate diagnostic marker in high-risk patients. Blood 2011; 118 (20) 5416-5419
    CrossrefPubMedGoogle Scholar
  • 51 Lass-Flörl C, Resch G, Nachbaur D , et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis 2007; 45 (7) e101-e104
    CrossrefPubMedGoogle Scholar
  • 52 Schrödl W, Heydel T, Schwartze VU , et al. Direct analysis and identification of pathogenic Lichtheimia species by matrix-assisted laser desorption ionization-time of flight analyzer-mediated mass spectrometry. J Clin Microbiol 2012; 50 (2) 419-427
    CrossrefPubMedGoogle Scholar
  • 53 Bernal-Martínez L, Buitrago MJ, Castelli MV, Rodriguez-Tudela JL, Cuenca-Estrella M. Development of a single tube multiplex real-time PCR to detect the most clinically relevant Mucormycetes species. Clin Microbiol Infect 2013; 19 (1) E1-E7
    CrossrefPubMedGoogle Scholar
  • 54 Lass-Flörl C. Zygomycosis: conventional laboratory diagnosis. Clin Microbiol Infect 2009; 15 (Suppl. 05) 60-65
    PubMedGoogle Scholar
  • 55 Jensen HE, Salonen J, Ekfors TO. The use of immunohistochemistry to improve sensitivity and specificity in the diagnosis of systemic mycoses in patients with haematological malignancies. J Pathol 1997; 181 (1) 100-105
    CrossrefPubMedGoogle Scholar
  • 56 Dannaoui E. Molecular tools for identification of Zygomycetes and the diagnosis of zygomycosis. Clin Microbiol Infect 2009; 15 (Suppl. 05) 66-70
    PubMedGoogle Scholar
  • 57 Alanio A, Garcia-Hermoso D, Mercier-Delarue S , et al; the French Mycosis Study Group. Molecular identification of Mucorales in human tissues: contribution of PCR electrospray-ionization mass spectrometry. Clin Microbiol Infect 2015; 21 (6) 594.e1-5
    PubMedGoogle Scholar
  • 58 Rammaert B, Lanternier F, Poirée S, Kania R, Lortholary O. Diabetes and mucormycosis: a complex interplay. Diabetes Metab 2012; 38 (3) 193-204
    CrossrefPubMedGoogle Scholar
  • 59 Saoulidis S, Simitsopoulou M, Dalakiouridou M , et al. Antifungal activity of posaconazole and granulocyte colony-stimulating factor in the treatment of disseminated zygomycosis (mucormycosis) in a neutropaenic murine model. Mycoses 2011; 54 (5) e486-e492
    CrossrefPubMedGoogle Scholar
  • 60 Almyroudis NG, Sutton DA, Linden P, Rinaldi MG, Fung J, Kusne S. Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature. Am J Transplant 2006; 6 (10) 2365-2374
    CrossrefPubMedGoogle Scholar
  • 61 Vironneau P, Kania R, Morizot G , et al; French Mycosis Study Group. Local control of rhino-orbito-cerebral mucormycosis dramatically impacts survival. Clin Microbiol Infect 2014; 20 (5) O336-O339
    CrossrefPubMedGoogle Scholar
  • 62 Nosari A, Ravini M, Cairoli R , et al. Surgical resection of persistent pulmonary fungus nodules and secondary prophylaxis are effective in preventing fungal relapse in patients receiving chemotherapy or bone marrow transplantation for leukemia. Bone Marrow Transplant 2007; 39 (10) 631-635
    CrossrefPubMedGoogle Scholar
  • 63 Caillot D, Mannone L, Cuisenier B, Couaillier JF. Role of early diagnosis and aggressive surgery in the management of invasive pulmonary aspergillosis in neutropenic patients. Clin Microbiol Infect 2001; 7 (Suppl. 02) 54-61
    CrossrefPubMedGoogle Scholar
  • 64 Almyroudis NG, Sutton DA, Fothergill AW, Rinaldi MG, Kusne S. In vitro susceptibilities of 217 clinical isolates of Zygomycetes to conventional and new antifungal agents. Antimicrob Agents Chemother 2007; 51 (7) 2587-2590
    CrossrefPubMedGoogle Scholar
  • 65 Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards Jr J, Ibrahim AS. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis 2009; 48 (12) 1743-1751
    CrossrefPubMedGoogle Scholar
  • 66 Lewis RE, Albert ND, Liao G, Hou J, Prince RA, Kontoyiannis DP. Comparative pharmacodynamics of amphotericin B lipid complex and liposomal amphotericin B in a murine model of pulmonary mucormycosis. Antimicrob Agents Chemother 2010; 54 (3) 1298-1304
    CrossrefPubMedGoogle Scholar
  • 67 Walsh TJ, Goodman JL, Pappas P , et al. Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study. Antimicrob Agents Chemother 2001; 45 (12) 3487-3496
    CrossrefPubMedGoogle Scholar
  • 68 Syriopoulou V, Daikos GL, Theodoridou M , et al. Two doses of a lipid formulation of amphotericin B for the treatment of Mediterranean visceral leishmaniasis. Clin Infect Dis 2003; 36 (5) 560-566
    CrossrefPubMedGoogle Scholar
  • 69 Cornely OA, Maertens J, Bresnik M , et al; AmBiLoad Trial Study Group. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis 2007; 44 (10) 1289-1297
    CrossrefPubMedGoogle Scholar
  • 70 Lanternier F, Poiree S, Elie C , et al. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis. J Antimicrob Chemother ; in press.
    PubMedGoogle Scholar
  • 71 Kontoyiannis DP, Lewis RE. How I treat mucormycosis. Blood 2011; 118 (5) 1216-1224
    CrossrefPubMedGoogle Scholar
  • 72 van Burik J-AH, 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-e65
    CrossrefPubMedGoogle Scholar
  • 73 Greenberg RN, Mullane K, van Burik J-AH , et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 2006; 50 (1) 126-133
    CrossrefPubMedGoogle Scholar
  • 74 Lebeaux D, Lanternier F, Elie C , et al. Therapeutic drug monitoring of posaconazole: a monocentric study with 54 adults. Antimicrob Agents Chemother 2009; 53 (12) 5224-5229
    CrossrefPubMedGoogle Scholar
  • 75 Kraft WK, Chang PS, van Iersel MLPS, Waskin H, Krishna G, Kersemaekers WM. Posaconazole tablet pharmacokinetics: lack of effect of concomitant medications altering gastric pH and gastric motility in healthy subjects. Antimicrob Agents Chemother 2014; 58 (7) 4020-4025
    CrossrefPubMedGoogle Scholar
  • 76 Krishna G, Ma L, Martinho M, O'Mara E. Single-dose phase I study to evaluate the pharmacokinetics of posaconazole in new tablet and capsule formulations relative to oral suspension. Antimicrob Agents Chemother 2012; 56 (8) 4196-4201
    CrossrefPubMedGoogle Scholar
  • 77 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) 2725-2730
    CrossrefPubMedGoogle Scholar
  • 78 Jung DS, Tverdek FP, Kontoyiannis DP. Switching from posaconazole suspension to tablets increases serum drug levels in leukemia patients without clinically relevant hepatotoxicity. Antimicrob Agents Chemother 2014; 58 (11) 6993-6995
    CrossrefPubMedGoogle Scholar
  • 79 Kersemaekers WM, van Iersel T, Nassander U , et al. Pharmacokinetics and safety study of posaconazole intravenous solution administered peripherally to healthy subjects. Antimicrob Agents Chemother 2015; 59 (2) 1246-1251
    CrossrefPubMedGoogle Scholar
  • 80 Verweij PE, González GM, Wiedrhold NP , et al. In vitro antifungal activity of isavuconazole against 345 Mucorales isolates collected at study centers in eight countries. J Chemother 2009; 21 (3) 272-281
    CrossrefPubMedGoogle Scholar
  • 81 Marty FM, Perfect JR, Cornely OA , et al. An Open-Label Phase 3 Study of Isavuconazole (VITAL): Focus on Mucormycosis [Abstract]. Idsa; 2014. Available at: https://idsa.confex.com/idsa/2014/webprogram/Paper45645.html . Accessed February 24, 2015
    PubMedGoogle Scholar
  • 82 Arikan S, Sancak B, Alp S, Hascelik G, McNicholas P. Comparative in vitro activities of posaconazole, voriconazole, itraconazole, and amphotericin B against Aspergillus and Rhizopus, and synergy testing for Rhizopus . Med Mycol 2008; 46 (6) 567-573
    CrossrefPubMedGoogle Scholar
  • 83 Perkhofer S, Locher M, Cuenca-Estrella M , et al. Posaconazole enhances the activity of amphotericin B against hyphae of Zygomycetes in vitro. Antimicrob Agents Chemother 2008; 52 (7) 2636-2638
    CrossrefPubMedGoogle Scholar
  • 84 Reed C, Bryant R, Ibrahim AS , et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 2008; 47 (3) 364-371
    CrossrefPubMedGoogle Scholar
  • 85 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) 660-667
    CrossrefPubMedGoogle Scholar
  • 86 Spellberg B, Ibrahim AS, Chin-Hong PV , et al. The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J Antimicrob Chemother 2012; 67 (3) 715-722
    CrossrefPubMedGoogle Scholar
  • 87 John BV, Chamilos G, Kontoyiannis DP. Hyperbaric oxygen as an adjunctive treatment for zygomycosis. Clin Microbiol Infect 2005; 11 (7) 515-517
    CrossrefPubMedGoogle Scholar
  • 88 Cornely OA, Maertens J, Winston DJ , et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007; 356 (4) 348-359
    CrossrefPubMedGoogle Scholar
  • 89 Ullmann AJ, Lipton JH, Vesole DH , et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007; 356 (4) 335-347
    CrossrefPubMedGoogle Scholar
  • 90 Roden MM, Zaoutis TE, Buchanan WL , et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41 (5) 634-653
    CrossrefPubMedGoogle Scholar
  • 91 Pagano L, Valentini CG, Posteraro B , et al. Zygomycosis in Italy: a survey of FIMUA-ECMM (Federazione Italiana di Micopatologia Umana ed Animale and European Confederation of Medical Mycology). J Chemother 2009; 21 (3) 322-329
    CrossrefPubMedGoogle Scholar
  • 92 Spellberg B, Kontoyiannis DP, Fredricks D , et al. Risk factors for mortality in patients with mucormycosis. Med Mycol 2012; 50 (6) 611-618
    CrossrefPubMedGoogle Scholar
  • 93 Chakrabarti A, Das A, Sharma A , et al. Ten years' experience in zygomycosis at a tertiary care centre in India. J Infect 2001; 42 (4) 261-266
    CrossrefPubMedGoogle Scholar
  • 94 Saegeman V, Maertens J, Meersseman W, Spriet I, Verbeken E, Lagrou K. Increasing incidence of mucormycosis in University Hospital, Belgium. Emerg Infect Dis 2010; 16 (9) 1456-1458
    CrossrefPubMedGoogle Scholar