Heart transplantation infection

Heart transplantation represents the final option for refractory, end-stage HF patients who have exhausted medical and device therapies. Heart transplantation is not a cure, but should be considered a trade between a life-threatening syndrome and the risks associated with the operation and long-term immunosuppression. Assessment of appropriate candidates includes comorbid illnesses, psychosocial behavior, available financial and social support, and patient willingness to adhere to lifelong therapy and close medical follow-up.1 Overall, the transplant recipient s quality of life may be improved, but not all patients receive this benefit. Posttransplant survival continues to improve due to advances in immunosuppression, treatment and prevention of infection, and optimal management of patient comorbidities. 

Cytomegalovirus (CMV) Cytomegalovirus immune globulin (IV) Consult the manufacturer s dosing recommendations. Prophylaxis of CMV infection in bone marrow, kidney, liver, lung, pancreas, heart transplant recipients. 

Attenuation of primary CMV infection associated with renal, lung, liver, pancreas and heart transplantation recipients who are CMV-negative and receive an organ from a CMV-positive donor... 

A 30-year-old male has had a heart transplant and is being maintained on the immunosuppressant, cyclosporine. He develops a Candida infection and is treated with ketoconazole. Why is this poor therapy ... 

Glucocorticoids inhibit the formation of antibodies. Of 111 consecutive heart transplant recipients taking oral prednisone (mean 13.8 months), 57% developed hypogammaglobulinemia (IgG below 7 g/1) (266). Those with severe hypogammaglobulinemia (IgG below 3.5 g/1) were at increassed risk of opportunistic infections compared with those with IgG concentrations over 3.5 g/1 (55 versus 5%, OR = 23). Parenteral glucocorticoid pulse therapy... 

In heart transplantation, induction with daclizumab produced favorable results with a lower incidence of acute rejection 18% in the daclizumab-treated patients compared with 63% in the group receiving CSA, MMF, and prednisone with no induction therapy (P = 0.04). The time to occurrence of the first rejection episode also was significantly longer in the daclizumab-treated patients. There were no adverse reactions to daclizumab and no significant differences between the groups in the incidence of infection or cancer dnr-ing follow-up. Data for basiliximab in heart transplant recipients are lacking. 

Systemic fungal infections are a major cause of morbidity and mortality in the immunocompromised patient. Fungal infections account for 20% to 30% of fatal infections in patients with acute leukemia, 10% to 15% of fatal infections in patients with lymphoma, and 5% of fatal infections in patients with solid tumors. The frequency of fungal infections among transplant recipients ranges from 0% to 20% for kidney and bone marrow transplant recipients to 10% to 35% for heart transplant recipients and 30% to 40% for liver transplant recipients. ... 

Montoya JG, Giraldo LE, Efron B, et al Infectious complications among 620 consecutive heart transplant recipients at Stanford University Medical Center. Clin Infect Dis 2001 33 629-640. 

FIGURE 3.5 Adenovirus pneumonia in a heart transplant patient who developed ARDS and respiratory failure. Infected cells within necrotizing exudate show intranuclear reactivity with antibody to adenovirus antigen. Some cells show inclusions with a clear halo around them, making a differential diagnosis from CMV difficult on H E stain. (Immunoperoxidase staining with DAB and hematoxylin counterstain x400.)... 

Six renal transplant patients given norfloxacin 400 mg twice daily for 3 to 23 days for urinary tract infections, and 4 heart transplant patients given norfloxacin 400 mg for 7 to 140 days had no changes in their serum ciclosporin levels. However, two reports describe rises, one marked, in serum ciclosporin levels in a heart transplant patient and a kidney transplant patient given norfloxacin. A comparative study in 5 children (mean age, 8 years) found that while receiving norfloxacin 5 to 10 mg/kg daily their daily dose of ciclosporin was 4.5 mg/kg daily compared with a control group of 6 children not taking norfloxacin who needed 7.4 mg/kg dai-ly.2 ... 

Aguado JM, Herrero JA, Gavalda J, Torre-Cisneros J, Blanes M, Rufi G, Moreno A, Gurgui A, Hayek Lumbreras C and tiie Spanish Transplantation Infection Study Groiq), GESI-TRA. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Transplantation (1997) 63, 1276-86. 

Munoz P, Palomo J, Munos R, Rodr ez-Creixems M, Pelaez T, Bouza E. Tuberculosis in heart transplant recipients. Clin Infect Dis (1995) 21, 398-402. 

However, in one clinical study in heart transplant patients taking ciclosporin, mycophenolate, and corticosteroids, use of daclizumab with another antilymphocyte (such as mnromonab-CD3 or antithymocyte immunoglobniin) appeared to be associated with a higher incidence of fatal infection 8 of 40 patients died, compared with 2 of 37 who received an antilymphocyte and placebo. The manufacturer suggests that concurrent use of daclizumab with another antilymphocyte antibody in patients receiving intensive immunosuppression may be a factor leading to fatal infection. Caution may be warranted, and more study is needed. 

Cardiovascular A 50-year-old recipient of an orthotopic heart transplant died after acute allograft failure and hepatitis C viral infection death was attributed to cardio-toxicity from peginterferon alfa-2b [8" ]. 

Systematic reviews In a systematic review of 10 randomized trials in 952 heart transplant recipients, a ciclosporin-based immunosuppressive regimen caused more hypertension, hyperlipidemia, gingival hyperplasia, and hirsutism than tacrolimus [7 ]. There were no significant differences with regard to acute rejection, diabetes mellitus, renal dysfunction, infection, malignancy, or neurotoxicity. 

Studies by Desmard and co-workers have shown that CO-RM-3 is a potential treatment for Pseudomonas aeruginosa infection. Infected mice treated with CO-RM-3 show increased survival rates. Clark and coworkers have shown that administration of CO-RM-3 to mice that have had a heart transplant enables them to survive longer than ones that receive no CO-RM-3. In addition to this, i-CO-RM-3 is a solution of CO-RM-3 that has been allowed to release one CO thermally and this solution shows no improvement compared to the control, suggesting the effect is due to the action of CO. There are however some problems with i-CO-RM-3. Only one CO from CO-RM-3 is released thermally and the exact... 

Bourke P, Castro P, Rabagliati R, Beltran C, Verdejo H, Winter JL, et al. Zygomycosis over-infection during voriconazole therapy for aspergillosis in a heart transplant patient, successfully treated with liposomal amphotericin and posaconazole. Transpl Infect Dis 2012 14(5) E56-9. 

A retrospective study evaluated oral valganciclovir CMV prophylaxis in 146 heart transplant recipients, who received 900 mg of oral valganciclovir twice daily for 2 weeks after the transplant and then 900 mg once daily for the next 6months [23 j. Twenty-one patients (14.4%) developed leucopenia. Sixteen patients developed CMV infection despite valganciclovir prophylaxis (eight patients tested positive for CMV in the first 6 months following transplant, and eight patients from 6 to 12 months). 

Doesch AO, Repp J, Hofmann N, Erbel G, Frankenstein L, Gleissner CA, et al. Effects of oral valganciclovir prophylaxis for cytomegalovirus infection in heart transplant patients. Dmg Des Devel Ther 2012 6 289-95. 

Infectious complications persist as a major cause of death, especially within the first year of heart transplantation (Hosenpud et al. 2000). Within the first month of transplantation, infections are usually of nosocomial bacterial origin, including Pseudomonas aeruginosa. Staphylococcus aureus. Enterococci, and Enterobacteriaceae. These organisms can cause pneumonia, urinary tract and wound infections. Later infections are commonly caused by viruses and opportunistic fungi (e.g., Pneumocystis, Candida, and Aspergillus) (Miniati and Robbin 2002). 

More specifically in heart transplant recipients, bleeding, leaks, and frank rupture can occur at the anastomosis sites the most critical of which is the aortic anastomosis, particularly if there is a marked difference in diameter between the donor and recipient aorta (Knisely et al. 1999 Reitz et al. 1982) (Fig. 2.2.3). In addition, acute or chronic breakdown at the aortic anastomosis can lead to aortic dehiscence, dissection, and pseudoaneurysm formation (Henry et al. 1989 Knollmann et al. 2000a Knosalla et al. 1996). Pseudoaneurysms can also form at two additional sites in the cardiac transplant patient at the cannulation sites used for cardiopulmonary bypass and at the endomyocardial biopsy sites in the right ventricle, taken to look for rejection (Knisely et al. 1999). Although most of these complications occur in the immediate post-operative period, some can occur months to years later (Knisely et al. 1999). Aortic dissection, when it occurs in the heart transplant patient (l%-2%), usually involves the recipient s native aorta, although rare cases of dissection involving the donor s aorta have been reported (ScHELLEMANS et al. 2004). Dissection can occur in the immediate peri-operative period usually due to mismatches in donor-recipient vessel size or years later when they may he due to infection or accelerated atherosclerosis (Schellemans et al. 2004). 

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