Fluconazole versus micafungin for initial antifungal prophylaxis against Candida in pancreas transplant recipients: A comparative study of two consecutive periods
Corresponding Author
Francisco López-Medrano
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Correspondence
Francisco López-Medrano, Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Centro de Actividades Ambulatorias, 2ª planta, bloque D, Avda. de Córdoba, s/n. Postal code 28041, Madrid, Spain.
Email: [email protected]
Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Supervision (equal), Validation (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorMaría Muñoz de la Espada
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal)
Search for more papers by this authorMaría Asunción Pérez-Jacoiste Asín
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Data curation (equal), Methodology (equal)
Search for more papers by this authorMario Fernández-Ruiz
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorJuan María Herrero-Martínez
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Data curation (equal)
Search for more papers by this authorJesús Alonso-Carrillo
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Data curation (equal)
Search for more papers by this authorRafael San Juan
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Search for more papers by this authorIsabel Rodríguez-Goncer
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Validation (equal), Visualization (equal)
Search for more papers by this authorAmado Andrés
Department of Medicine, Universidad Complutense, Madrid, Spain
Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Validation (equal), Visualization (equal)
Search for more papers by this authorEsther González
Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Validation (equal)
Search for more papers by this authorAlejandro Manrique
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorIago Justo
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Investigation (equal), Validation (equal)
Search for more papers by this authorAlberto Marcacuzco
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorCarmelo Loinaz
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorCarlos Jiménez
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorCarlos Lumbreras
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Department of Internal Medicine, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Formal analysis (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorJosé María Aguado
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Contribution: Conceptualization (equal), Investigation (equal), Validation (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorCorresponding Author
Francisco López-Medrano
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Correspondence
Francisco López-Medrano, Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Centro de Actividades Ambulatorias, 2ª planta, bloque D, Avda. de Córdoba, s/n. Postal code 28041, Madrid, Spain.
Email: [email protected]
Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Supervision (equal), Validation (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorMaría Muñoz de la Espada
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal)
Search for more papers by this authorMaría Asunción Pérez-Jacoiste Asín
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Data curation (equal), Methodology (equal)
Search for more papers by this authorMario Fernández-Ruiz
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorJuan María Herrero-Martínez
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Data curation (equal)
Search for more papers by this authorJesús Alonso-Carrillo
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Data curation (equal)
Search for more papers by this authorRafael San Juan
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Search for more papers by this authorIsabel Rodríguez-Goncer
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Validation (equal), Visualization (equal)
Search for more papers by this authorAmado Andrés
Department of Medicine, Universidad Complutense, Madrid, Spain
Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Validation (equal), Visualization (equal)
Search for more papers by this authorEsther González
Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Validation (equal)
Search for more papers by this authorAlejandro Manrique
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorIago Justo
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Investigation (equal), Validation (equal)
Search for more papers by this authorAlberto Marcacuzco
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorCarmelo Loinaz
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorCarlos Jiménez
Department of General Surgery, Digestive Tract and Abdominal Organ Transplantation, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Department of Surgery, Universidad Complutense, Madrid, Spain
Contribution: Formal analysis (equal), Validation (equal)
Search for more papers by this authorCarlos Lumbreras
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Department of Internal Medicine, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
Contribution: Conceptualization (equal), Formal analysis (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorJosé María Aguado
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
Department of Medicine, Universidad Complutense, Madrid, Spain
Contribution: Conceptualization (equal), Investigation (equal), Validation (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorFrancisco López-Medrano and María Muñoz de la Espada equally contributed to this work.
Funding information
This work was supported by the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation—co-financed by the European Development Regional Fund ‘A way to achieve Europe’ and the European Social Fund ‘The ESF invests in your future’. MFR holds a research contract ‘Miguel Servet’ (CP 18/00073) and IRG holds a research training contract ‘Río Hortega’ (CM19/00163), both from the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation
Abstract
Background
Invasive fungal infection, particularly intraabdominal candidiasis, exerts a negative impact on the outcome of pancreas transplant recipients (PTRs). Optimal antifungal prophylaxis in this context remains unclear.
Methods
We performed a single-centre retrospective study to compare the incidence of invasive candidiasis during the first 6 post-transplant months in a cohort of 218 PTRs over two periods in which different agents for antifungal prophylaxis were used: fluconazole (Fluco-Px) from March 1995 to June 2012, and micafungin followed by fluconazole (Mica-Px) from July 2012 to December 2018.
Results
A total of 152 and 66 PTRs received Fluco-Px and Mica-Px. Mean age was 39.7 ± 7.8 years, 56.4% (123/218) were males, and 85.3% (186/218) underwent simultaneous pancreas–kidney transplantation. Invasive candidiasis occurred in 21.7% (33/152) of PTRs under Fluco-Px compared to 24.2% (16/66) of those under Mica-Px (p-value = .681). Median time from transplantation to infection was 8 days (interquartile range [IQR]: 6–16) under Fluco-Px versus 6.5 (IQR: 3.3–15.8) under Mica-Px (p-value = .623). Non-albicans Candida species comprised 27.5% (11/40) and 25.0% (4/16) of episodes under Fluco-Px and Mica-Px respectively (p-value = .849). Surgical site infection was the most common form in both groups (82.5% [33/40] and 87.5% [14/16]; p-value = .954). Multivariable analysis identified cold ischaemia time of the pancreas and kidney grafts, surgical reintervention and insulin requirement after transplantation as risks factor for invasive candidiasis.
Conclusion
This retrospective study did not reveal a significant benefit from the initial use of micafungin-based antifungal prophylaxis over fluconazole among PTRs in terms of invasive candidiasis.
CONFLICT OF INTEREST
All authors report no conflicts of interest relevant to this work.
REFERENCES
- 1Boggi U, Vistoli F, Andres A, et al. First World Consensus Conference on pancreas transplantation: Part II - recommendations. Am J Transplant. 2021; 21(Suppl 3): 17-59. doi:10.1111/ajt.16750
- 2Herrero-Martínez JM, Lumbreras C, Manrique A, et al. Epidemiology, risk factors and impact on long-term pancreatic function of infection following pancreas-kidney transplantation. Clin Microbiol Infect. 2013; 19: 1132-1139. doi:10.1111/1469-0691.12165
- 3Berger N, Wirmsberger R, Kafka R, et al. Infectious complications following 72 consecutive enteric-drained pancreas transplants. Transpl Int. 2006; 19: 549-557. doi:10.1111/j.1432-2277.2006.00293.x
- 4van Delden C, Stampf S, Hirsch HH, et al. Burden and timeline of infectious diseases in the first year after solid organ transplantation in the Swiss Transplant Cohort Study. Clin Infect Dis. 2020; 71: e159-e169. doi:10.1093/cid/ciz1113
- 5Shaikh SA, Zimmerman A, Nolan A, et al. The incidence of fungal infections in pancreas transplant recipients in the absence of systemic antifungal prophylaxis. Clin Transplant. 2019; 33:e13691. doi:10.1111/ctr.13691
- 6Flateau C, Aït-Ammar N, Angebault C, et al. Risk factors for intra-abdominal fungal infection after simultaneous pancreas-kidney transplantation: a single-center retrospective experience. Transpl Infect Dis. 2021; 23:e13486. doi:10.1111/tid.13486
- 7Benedetti E, Gruessner AC, Troppmann C, et al. Intra-abdominal fungal infections after pancreatic transplantation: incidence, treatment, and outcome. J Am Coll Surg. 1996; 183: 307-316.
- 8Wasmann RE, Muilwijk EW, Burger DM, et al. Clinical pharmacokinetics and pharmacodynamics of micafungin. Clin Pharmacokinet. 2018; 57: 267-286. doi:10.1007/s40262-017-0578-5
- 9Gioia F, Gomez-Lopez A, Alvarez ME, et al. Pharmacokinetics of echinocandins in suspected candida peritonitis: a potential risk for resistance. Int J Infect Dis. 2020; 101: 24-28. doi:10.1016/j.ijid.2020.09.019
- 10Scott LJ. Micafungin: a review of its use in the prophylaxis and treatment of invasive Candida infections. Drugs. 2012; 72: 2141-2165. doi:10.2165/11209970-000000000-00000
- 11Jiménez-Romero C, Manrique A, Meneu JC, et al. Compative study of bladder versus enteric drainage in pancreas transplantation. Transplant Proc. 2009; 41: 2466-2468. doi:10.1016/j.transproceed.2009.06.164
- 12Donnelly 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: 1367-1376. doi:10.1093/cid/ciz1008
- 13Andes DR, Safdar N, Baddley JW, et al. The epidemiology and outcomes of invasive Candida infections among organ transplant recipients in the United States: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Transpl Infect Dis. 2016; 18: 921-931. doi:10.1111/tid.12613
- 14Akhtar MZ, Jones A, Sideso E, et al. Management of a ruptured mycotic pseudo-aneurysm following pancreas-kidney transplantation. Ann Transplant. 2011; 16: 122-125. doi:10.12659/aot.882229
- 15Snider JF, Hunter DW, Kuni CC, et al. Pancreatic transplantation: radiologic evaluation of vascular complications. Radiology. 1991; 178: 749-753. doi:10.1148/radiology.178.3.1994413
- 16Fujita S, Fujikawa T, Mekeel KL, et al. Successful endovascular treatment of a leaking pseudoaneurysm without graft loss after simultaneous pancreas and kidney transplantation. Transplantation. 2006; 82: 717-718. doi:10.1097/01.tp.0000234930.24555.12
