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Invasive fungal infections in solid organ transplant recipients
Invasive fungal infections and chronic obstructive pulmonary disease
Information on how to access prescribing information and adverse event reporting can be found towards the bottom of the page.
Invasive fungal infections in solid organ transplant recipients
Invasive fungal infections are a serious complication for patients undergoing solid organ transplantation (SOT).1–3
Invasive mould infections such as invasive aspergillosis and mucormycosis are a significant cause of morbidity and mortality, and their incidence in SOT patients is rising, which can be attributed to different factors:1,4–6
Increase in number of transplants
Increase in number of transplants
Increase in number of transplants
Use of newer immunosuppressive treatments, which increase susceptibility to opportunistic infections
Emergence of donor-derived infections developing post-transplant, due to a new reliance on previously excluded donor groups
Receiving a solid organ transplant is a risk factor for an invasive mould infection1,4,7
Invasive aspergillosis is the most common mould infection and the second most common invasive fungal infection after candidiasis, accounting for up to 25% of all cases2
Mucormycosis is also emerging as an important invasive mould infection8
Incidence of aspergillosis varies by type of transplant1,4,7
Mucormycosis is also emerging as an important invasive mould infection8
Mucormycosis is also emerging as an important invasive mould infection8
In mucormycosis, incidence rates range from 0.4–16.0% depending on the transplant procedure and geographical area.8
Within the ICU
The risk of invasive aspergillosis also exists in patients admitted to the Intensive Care Unit (ICU). In a study of critically ill patients diagnosed with invasive aspergillosis, 10% had undergone SOT.9
A secondary study of transplant patients in the ICU diagnosed with invasive pulmonary aspergillosis found that around half (~46%) contracted the infection during their ICU stay (following transplantation).10 Prognosis for these patients is poor, with mortality rates of up to 68%.10
Risk factors are varied
Risk factors for invasive aspergillosis in SOT patients vary by type of transplant and time of infection.11
|
Type of transplant |
Risk factors for early infection |
Risk factors for late infection (>3 months post-transplant) |
|---|---|---|
|
Liver transplant |
Re-transplantation Kidney failure, especially post-transplant Haemodialysis Fulminant hepatic failure Complicated surgery or re-operation |
More than 6g of accumulative prednisone in the third month after transplantation Post-transplant renal failure Post-transplant haemodialysis Leukopenia (<500/mm3) Chronic graft dysfunction |
|
Lung transplant |
Bronchial anastomotic ischaemia or bronchial stent placement Acute rejection Single-lung transplant Aspergillus colonisation before or during first year post-transplant |
Chronic graft dysfunction |
|
Heart transplant |
Aspergillus colonisation of the respiratory tract Re-operation Post-transplant haemodialysis Hypogammaglobulinaemia (Immunoglobulin G <400 mg/dL) |
Intensive care unit readmission Kidney transplantation >2 acute rejection episodes |
|
Kidney transplant |
Graft lost and haemodialysis Post-transplant haemodialysis Prolonged high corticosteroid doses |
|
|
Cytomegalovirus infection |
||
Adapted from Gavaldà J et al. 2014.
Treatment option considerations
For SOT patients with invasive mould infections, antifungal treatment should be initiated promptly.11 The primary options are azoles (CRESEMBA® and voriconazole) or amphotericin B. Posaconazole or itraconazole can also be used as salvage therapy.12
Treatments for invasive mould disease have important considerations for the SOT population:12—17
PK linearity, which could affect need for therapeutic drug monitoring
Contraindications for coadministration with certain immunosuppressants
Presence of cyclodextrin in IV formulations
Potential renal toxicity or failure, which could impact SOT patients
Real-world experience from clinical practice
Two real-world studies performed in Spain have shown that CRESEMBA® is effective and well tolerated in SOT recipients13,18,a
In the SOTIS study, clinical response with CRESEMBA® was 61% at week 6 and 63% at week 1218
In the ISASOT study, CRESEMBA® was well tolerated by the majority of patientsb, and the rate of clinical cure with CRESEMBA® at the end of treatment was 44%13
These results were similar to those reported in the SECURE clinical trial12,16
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How can CRESEMBA® help your patients?
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ICU, intensive care unit; IPA, invasive pulmonary aspergillosis; ISASOT, Safety and Effectiveness of Isavuconazole Treatment for Fungal Infections in Solid Organ Transplant Recipients; IV, intravenous; PK, pharmacokinetic; SOT, solid organ transplant; SOTIS, Solid Organ Transplantation and Isavuconazole; TDM, therapeutic drug monitoring.
a. SOTIS was a retrospective, multicentre study in adult SOT patients with proven or probable invasive mould disease (n=81). ISASOT was a non-comparative, single-centre, prospective observational study in adult SOT patients (n=53).
b. Mild gamma-glutamyl transferase elevation was the most frequent adverse event (34%). Six patients (11.3%) prematurely discontinued treatment due to: mild hepatotoxicity (n=2), fatigue (n=2), gastrointestinal intolerance (n=1) and myopathy (n=1).13
Prescribing Information
Click here for CRESEMBA® (isavuconazole) and VFEND (voriconazole) prescribing information
References:
Husain S and Camargo JF. Clin Transplant 2019;33:e13544.
Lemonovich Tl. Infect Dis Clin N Am 2018;32:687–701.
Anesi JA and Baddley JW. Infect Dis Clin North Am 2016;30:277–296.
Aguilar C et al. F1000Res 2018;7:661.
Pappas PG et al. Clin Infect Dis 2010;50:1101–1111.
Welte T et al. Infection 2019;47:919–927.
Bongomin F et al. J Fungi (Basel) 2017;3(4).
Garcia-Vidal C et al. J Antimicrob Chemother 2019;74(Suppl 2):ii16–ii20.
Taccone FS et al. Crit Care 2015;19(1):7.
Klein J et al. Transpl Infect Dis 2022;24:e13746.
Gavaldà J et al. Clin Microbiol Infect 2014;20(Suppl. 7):27–48.
Neofytos D et al. BMC Infect Dis 2021;21(1):296.
Fernandez-Ruiz M et al. Transplantation 2023;107(3):762–773.
VFEND GB Summary of Product Characteristics.
Noxafil Summary of Product Characteristics.
AmBisome Summary of Product Characteristics.
CRESEMBA GB Summary of Product Characteristics.
Monforte A et al. Microbiol Spectr 2022;10(1):e0178421.
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