Chapter 126. Infections in Transplant Recipients (Part 11) pptx

Chapter 126. Infections in Transplant Recipients (Part 11) Middle-Period Infections T. gondii (Chap. 207) residing in the heart of a seropositive donor may be transmitted to a seronegative recipient. Thus serologic screening for T. gondii infection is important before and in the months after cardiac transplantation. Rarely, active disease can be introduced at the time of transplantation. The overall incidence of toxoplasmosis is so high in the setting of heart transplantation that some prophylaxis is always warranted. Although alternatives are available, the most frequently used agent is TMP-SMX, which prevents infection with Pneumocystis as well as with Nocardia and several other bacterial pathogens. CMV also has been transmitted by heart transplantation. CNS infections can be caused by Toxoplasma, Nocardia, and Aspergillus. L. monocytogenes meningitis should be considered in heart transplant recipients with fever and headache. CMV infection is associated with poor outcomes after heart transplantation. The virus is usually cultivable 1–2 months after transplantation, causes early signs and laboratory abnormalities (usually fever and atypical lymphocytosis or leukopenia and thrombocytopenia) at 2–3 months, and can produce severe disease (e.g., pneumonia) at 3–4 months. Seropositive recipients usually develop cultivable virus faster than patients whose primary CMV infection is a consequence of transplantation. Between 40 and 70% of patients develop symptomatic CMV disease in the form of (1) CMV pneumonia, the most likely form to be fatal; (2) CMV esophagitis and gastritis, sometimes accompanied by abdominal pain with or without ulcerations and bleeding; and (3) the CMV syndrome, consisting of CMV in the blood along with fever, leukopenia, thrombocytopenia, and hepatic enzyme abnormalities. Ganciclovir is efficacious in the treatment of CMV infection; prophylaxis with ganciclovir or possibly with other antiviral agents, as described for renal transplantation, may reduce the overall incidence of CMV-related disease. When prophylaxis is stopped, late-onset disease may occur. In fact, because of the expanded use of prophylaxis, this scenario is increasingly common, particularly in patients with ongoing GVHD. Late Infections EBV infection usually presents as a lymphoma-like proliferation of B cells late after heart transplantation, particularly in patients maintained on intense immunosuppressive therapy. A subset of heart and heart-lung transplant recipients may develop early fulminant EBV-LPD (within 2 months). Treatment includes the reduction of immunosuppression (if possible), the use of glucocorticoid and calcineurin inhibitor–sparing regimens, and the consideration of therapy with anti– B cell antibodies (rituximab and possibly others). Immunomodulatory and antiviral agents continue to be studied, and aggressive chemotherapy is a last resort, as discussed earlier for HSCT recipients. KSHV-associated disease, including Kaposi's sarcoma and primary effusion lymphoma, has been reported in heart transplant recipients. Treatment with rapamycin (sirolimus) may prevent both rejection and outgrowth of KSHV-infected cells. Antitumor therapy is discussed in Chap. 81. Prophylaxis for Pneumocystis infection is required for these patients (see "Lung Transplantation, Late Infections," below). Lung Transplantation Early Infections It is not surprising that lung transplant recipients are predisposed to the development of pneumonia. The combination of ischemia and the resulting mucosal damage, together with accompanying denervation and lack of lymphatic drainage, probably contributes to the high rate of pneumonia (66% in one series). The prophylactic use of high doses of broad-spectrum antibiotics for the first 3–4 days after surgery may decrease the incidence of pneumonia. Gram-negative pathogens (Enterobacteriaceae and Pseudomonas species) are troublesome in the first 2 weeks after surgery (the period of maximal vulnerability). Pneumonia can also be caused by Candida (possibly as a result of colonization of the donor lung), Aspergillus, and Cryptococcus. Mediastinitis may occur at an even higher rate among lung transplant recipients than among heart transplant recipients and most commonly develops within 2 weeks of surgery. In the absence of prophylaxis, pneumonitis due to CMV (which may be transmitted as a consequence of transplantation) usually presents between 2 weeks and 3 months after surgery, with primary disease occurring later than reactivation disease. Middle-Period Infections The incidence of CMV infection, either reactivated or primary, is 75–100% if either the donor or the recipient is seropositive for CMV. CMV-induced disease appears to be most severe in recipients of lung and heart-lung transplants. Whether this severity relates to the mismatch in lung antigen-presenting and host immune cells or is attributable to other (nonimmunologic) factors is not known. More than half of lung transplant recipients with symptomatic CMV disease have pneumonia. Difficulty in distinguishing the radiographic picture of CMV infection from other infections and organ rejection further complicates therapy. CMV can also cause bronchiolitis obliterans in lung transplants. The development of pneumonitis related to HSV has led to the prophylactic use of acyclovir. Such prophylaxis may also decrease rates of CMV disease, but ganciclovir is more active against CMV and is also active against HSV. The prophylaxis of CMV infection with IV ganciclovir—or increasingly with valganciclovir, the oral alternative—is recommended for lung transplant recipients. Antiviral alternatives are discussed in the earlier section on hematopoietic stem cell transplantation. Although the overall incidence of serious disease is decreased during prophylaxis, late disease may occur when prophylaxis is stopped—a pattern observed increasingly in recent years. With recovery from peritransplantation complications and, in many cases, a decrease in immunosuppression, the recipient is often better equipped to combat late infection. . Chapter 126. Infections in Transplant Recipients (Part 11) Middle-Period Infections T. gondii (Chap. 207) residing in the heart of a seropositive donor. particularly in patients maintained on intense immunosuppressive therapy. A subset of heart and heart-lung transplant recipients may develop early fulminant EBV-LPD (within 2 months). Treatment includes. scenario is increasingly common, particularly in patients with ongoing GVHD. Late Infections EBV infection usually presents as a lymphoma-like proliferation of B cells late after heart transplantation,