- Posttransplant infections are a significant cause of morbidity and, in some cases, mortality for transplant recipients. Types of infections vary depending on the time since transplantation (Table 17-3).1
- CMV infection from reactivation of CMV in a seropositive recipient or new infection from a CMV-positive organ can lead to a wide range of presentations from a mild viral syndrome to allograft dysfunction, invasive disease in multiple organ systems, and even death. CMV-seronegative patients who receive a CMV-seropositive organ are at substantial risk, particularly in the first year.
- Because of the potential progression and severity of untreated disease, treatment is indicated in viremic transplant patients without tissue diagnosis of invasive disease. Seroconversion with a positive IgM titer or a fourfold increase in IgM or IgG titer suggests acute infection; however, many centers now use polymerase chain reaction–based diagnostic techniques from blood samples, and treatment is usually administered in the patient with evidence of viremia. Common treatment options include oral valganciclovir, 450–900 mg PO bid, or IV ganciclovir, 2.5–5.0 mg/kg bid for 3–4 weeks or until clearance of the virus. Both drugs are adjusted for renal function. Hyperimmune globulin is also used with ganciclovir for patients with organ involvement.
- Foscarnet and cidofovir are more toxic alternatives and should be reserved for ganciclovir-resistant cases.
- Hepatitis B and C: Chronic hepatitis B or hepatitis C or cirrhosis were once considered contraindications to nonhepatic transplant because immunosuppression increases viral replication in organ transplant recipients. However, advances in medical treatment have created opportunities for a substantial number of patients to be effectively treated prior to transplantation.2
- Hepatitis B reactivation can cause fulminant hepatic failure even in patients with no evidence of viral DNA replication prior to transplantation. In liver transplantation, the risk of recurrent hepatitis B virus infection can be reduced by the administration of hepatitis B immunoglobulin during and after transplantation. Lamivudine therapy initiated before transplantation to lower viral load leads to decreased likelihood of recurrent hepatitis B virus.
- Hepatitis C progresses slowly in nonhepatic transplants, and the effect of immunosuppression on mortality because of liver disease remains to be determined. Hepatitis C nearly always recurs in untreated liver transplant recipients whose original disease was due to hepatitis C. Therapy for hepatitis C virus with directed antiviral therapy can achieve a sustained virologic response and clearance of the virus.
- EBV plays a role in the development of PTLD. This life-threatening lymphoma is treated by withdrawal or reduction in immunosuppression and aggressive chemotherapy.
- Other viruses: The role other viruses, such as human herpesvirus (HHV)-6, HHV-7, HHV-8, and polyomavirus (BK and JC), play in causing posttransplant infections is an area of active investigation. Notably, BK virus is known to cause interstitial nephritis, resulting in renal allograft loss and occasionally ureteral stricture, resulting in obstruction. Because BK virus nephropathy results primarily from reactivation of latent BK in the transplanted organ, this is rarely seen in nonrenal transplant recipients.
- Fungal and parasitic infections, such as Cryptococcus, Mucor, aspergillosis, and Candida spp., result in increased mortality after transplantation. A high degree of suspicion is imperative to diagnose and treat these infections. The role of prophylaxis with oral fluconazole has not been established.
- Renal disease: Chronic allograft dysfunction is the leading cause of allograft loss in renal transplant recipients. Chronic CNI (CsA or tacrolimus) nephrotoxicity may also lead to chronic kidney disease and end-stage renal disease (ESRD), requiring dialysis or transplantation in recipients of other solid organ transplants. The incidence of ESRD secondary to CNI toxicity in recipients of solid organ transplants is at least 10%, and the incidence of significant chronic kidney disease approaches 50%.
- Malignancy occurs in transplant patients with an overall incidence 3–4 times higher than the general population (age-matched). Cancers with an increased risk of fivefold or greater compared with the general population are Kaposi sarcoma, non-Hodgkin lymphoma, and skin, lip, vulvar, anal, and liver cancer, illustrating the oncogenic potential of associated viral infections and the role of normal immune function in surveillance and clearance of malignant cells.
- Skin and lip cancers are the most common de novo malignancies (40%–50%) seen in transplant recipients, with an incidence 10–250 times that of the general population. Risk factors include immunosuppression, UV radiation, and human papillomavirus infection. These cancers develop at a younger age, and they are more aggressive in transplant patients. Protective clothing, sunscreens, and avoiding sun exposure are recommended. Examination of the skin is the principal screening test and early diagnosis offers the best prognosis.
- PTLD accounts for one-fifth of all malignancies after transplantation, with an incidence of approximately 1%. This is 30- to 50-fold higher than in the general population, and the risk increases with the use of antilymphocyte therapy for induction or rejection. The majority of these neoplasms are large-cell non-Hodgkin lymphomas of the B-cell type. PTLD results from EBV-induced B-cell proliferation in the setting of chronic immunosuppression. The EBV-seronegative recipient of a seropositive organ is at greatest risk. The presentation is often atypical and should always be considered in the patient with new symptoms. Diagnosis requires a high index of suspicion followed by a tissue biopsy. Treatment includes reduction or withdrawal of immunosuppression and chemotherapy.
|Time Period||Infectious Complication||Etiology|
|<1 mo after transplant||Nosocomial pneumonia, wound infection, urinary tract infection, catheter-related sepsis, biliary, chest, or other drainage catheter infection||Bacterial or fungal infections|
|1–6 mo after transplant||Opportunistic infections||Cytomegalovirus|
West Nile virus
Varicella-zoster virus (VZV)
|Reactivation of preexisting infections||Mycobacteria spp.|
|>6 mo after transplant||Community-acquired infections||Bacterial|
|Chronic progressive infection||Reactivated VZV (zoster)|
|Opportunistic infections||P. jirovecii|
West Nile virus
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