Considerations for Using Ketoconazole in Solid Organ Transplant Recipients Receiving Cyclosporine Immunosuppression

1996 ◽  
Vol 6 (3) ◽  
pp. 148-154
Author(s):  
Scott A Chapman ◽  
Kathleen D Lake ◽  
Diane F Solbrack ◽  
Sherry K Milfred ◽  
Peter S Marshall ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Organ Transplant ◽  
Cost Savings ◽  
Solid Organ ◽  
Close Monitoring ◽  
Transplant Recipients ◽  
Potential Cost ◽  
Patients At Risk ◽  
Solid Organ Transplant Recipients ◽  
Cytochrome P 450

Drug interactions involving cyclosporine following transplantation are a challenging issue for the transplant clinician. This is especially true when ketoconazole is the second agent used in conjunction with cyclosporine. Because both agents are metabolized by the cytochrome P-450 IIIA4 enzyme system, cyclosporine levels rise dramatically in the presence of ketoconazole. Many other agents interact with ketoconazole, either by competitive enzyme inhibition in the liver and gastrointestinal tract, or by reducing the absorption of ketoconazole by agents that increase the pH of the gastrointestinal tract. Despite the potential cost savings when using ketoconazole to reduce cyclosporine doses, adverse effects associated with ketoconazole put patients at risk when using this combination. Close monitoring of cyclosporine levels is imperative when adding ketoconazole to cyclosporine, and once the dosage adjustments are complete, the addition of a third drug that interacts with either cyclosporine or ketoconazole could result in an unexpected rejection episode or toxic cyclosporine side effect.

scholarly journals HUMORAL AND CELLULAR IMMUNOGENICITY and SAFETY UP TO 4 MONTHS AFTER VACCINATION WITH BNT162B2 mRNA COVID-19 VACCINE IN HEART AND LUNG TRANSPLANTED YOUNG ADULTS

2021 ◽  
Author(s):  
Nicola Cotugno ◽  
Chiara Pighi ◽  
Elena Morrocchi ◽  
Alessandra Ruggiero ◽  
Donato Amodio ◽  
...  
Keyword(s):  
T Cells ◽  
Young Adults ◽  
Cd4 T Cells ◽  
Organ Transplant ◽  
Solid Organ ◽  
Close Monitoring ◽  
Transplant Recipients ◽  
Short Term ◽  
Solid Organ Transplant Recipients

Background: Immunizations among vulnerable population, including solid organ transplant recipients (SOT), present suboptimal responses at vaccination and over time. We investigated safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 34 SOT young adults as compared to 36 healthy controls (HC). Methods: immunogenicity was measured through the analysis of anti SARS-CoV2 IgG Antibodies and antigen specific CD4 T cells (CD40L+), detected by flow cytometry before vaccination, 21 days after priming (T21), 7 days after booster dose (T28) and 2-4 months after priming (T120). Baseline T and B cell immune phenotype was deeply investigated. The safety profile was investigated by close monitoring and self-reported diary. Results: Anti-S and anti-Trimeric Ab responses were significantly lower in SOT vs HC at T21 (p<0.0001) and at T28 (p<0.0001). Ten out of 34 SOT (29%) at T28 and 3 out of 33 (9%) at T120 had undetectable SARS-CoV-2 IgG. The analysis of SARS-CoV-2 specific CD4 T cells showed lower CD40L expression after in vitro stimulation in SOT compared to HC. Lower frequencies of memory B cells were found in patients not responding to vaccination. Lack of seroconversion was higher in patients treated with mycophenolate (p=0.0005). The vaccination was safe and well tolerated. Only short-term adverse events, were reported and no hospitalization or graft rejection were observed after vaccinations. Conclusions: These data show that SOT have a suboptimal immune response following mRNA vaccinations as compared to HC. Alternative strategies should be investigated to improve the immunization against SARS-CoV-2 in these patients.

scholarly journals Serologic Evidence for Reactivation of Cryptococcosis in Solid-Organ Transplant Recipients

2007 ◽  
Vol 14 (12) ◽  
pp. 1550-1554 ◽  
Author(s):  
D. C. Saha ◽  
D. L. Goldman ◽  
X. Shao ◽  
A. Casadevall ◽  
S. Husain ◽  
...  
Keyword(s):  
Latent Infection ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Before And After ◽  
Patients At Risk ◽  
Serologic Evidence ◽  
Solid Organ Transplant Recipients

ABSTRACT Cryptococcosis is a significant infection with a high mortality in solid-organ transplant recipients. Nonetheless, the pathogenesis of this disease is poorly understood. It has been hypothesized that cryptococcosis may result from either primary infection or reactivation of a latent infection. Sera were obtained from transplant recipients prior to transplantation and at the time they developed cryptococcosis. Control sera were obtained before and after transplant from patients who did not develop cryptococcosis. Sera were tested for antibodies against Cryptococcus neoformans by using an immunoblot assay. Antibody responses were also compared with those observed in sera from rats with experimental pulmonary cryptococcosis. In all, 52% of the transplant recipients who developed cryptococcosis exhibited serologic evidence of cryptococcal infection before transplantation. These patients developed cryptococcosis significantly earlier after transplant than patients without preexisting reactivity did (5.6 ± 3.4 months compared to 40.6 ± 63.8 months, respectively [P = 0.0011]). The results from our study suggest that a substantial proportion of transplant-associated cryptococcosis cases result from the reactivation of a latent infection. These findings also highlight the potential utility of serologic studies in identifying patients at risk for the development of cryptococcosis after transplantation.

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