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The past decade has witnessed an explosive rise in the rate of bacteremia and intravascular catheter infection. Although gram-negative organisms continue to account for up to one third of these infections, gram-positive organisms have become increasingly prevalent pathogens. Virulent antibiotic-resistant bacterial strains have emerged and present a formidable treatment challenge. Simultaneously, management of catheter infection has evolved. Although patients who develop fungemia, gram-negative bacteremia, or sepsis syndrome are best treated by catheter removal in addition to antimicrobial therapy, an increasing body of evidence suggests that many gram-positive bacterial catheter infections can be treated by use of antimicrobial agents without catheter removal. Advances in catheter design and immunotherapy for sepsis syndrome also hold promise. Despite these innovations, determining the initial need for catheter placement, adherence to meticulous sterile surgical technique during insertion, and subsequent fastidious catheter maintenance remain the mainstays of preventing these potentially disastrous infections.

PURPOSE: To study the histopathologic findings, clinical course, and therapeutic outcome of patients who developed a lymphoproliferative disorder after undergoing solid organ transplantation. PATIENTS AND METHODS: A series of 26 patients who developed a lymphoproliferative disorder after solid organ transplant during a 27-year period were studied. RESULTS: The 26 patients ranged in age from 6 to 68 years (median 42 years). The lymphoproliferative disorder was diagnosed from 1 to 211 months (median 80 months) after transplantation. The type of transplant was kidney (n = 21), heart or heart-lung (n = 4), or liver (n = 1). Most patients received azathioprine and prednisone, in addition to antilymphocyte globulin or cyclosporine, for post-transplant immunosuppression. Eight patients had lymphoma that could be classified according to the international Working Formulation (IWF-F, IWF-G, IWF-H). Sixteen patients had polymorphic lymphoma, and 2 patients were classified as having polymorphic lymphoid hyperplasia. Patients were staged by the Ann Arbor staging system. Nine patients had stage I disease, 4 stage II, 6 stage III, and 7 stage IV. Central nervous system, lung, or marrow involvement was present in 27%, 23%, and 14% of patients, respectively. In the 17 patients studied, immunophenotype was monoclonal B-cell (n = 12), malignant T-cell (n = 2), or polyclonal B-cell (n = 3). The initial therapeutic approach was generally a reduction in immunosuppression, but, thereafter, the approach to therapy varied. In patients with localized disease, surgical excision and/or involved field radiotherapy were utilized as applicable. For patients with more extensive disease, other approaches such as high-dose acyclovir, combination chemotherapy, or alpha interferon were utilized. Overall, 15 of 26 patients (58%) responded to systemic therapy or were rendered disease-free either by surgery or radiation, including 8 (31%) with a complete remission (CR). Only 3 of 9 patients responded to chemotherapy, whereas 4 of 13 patients responded to acyclovir (including 3 patients who experienced CR). Remission duration ranged from 8 to 122 months (median 32+ months). Twenty-one of 26 patients (81%) have died. Survival ranged from less than 1 to 122 months (median 14 months). CONCLUSION: The outcome of patients with post-solid organ transplant lymphoproliferative disorders is poor, and the optimal approach to therapy is not clear. Newer therapeutic approaches are thus needed to improve the outcome of these patients.

The use of biologic reagents directed against invading microbes and deleterious, aspects of the host response is presently under intense investigation. The development and use of these reagents have contributed significantly to our understanding of the host response to infection, and they probably represent the first true foray into the area of immunotherapeutic manipulation. Thus, the effects of the administration of anti-endotoxin and antitumor necrosis factor-[alpha] monoclonal antibodies and the interleukin-1 receptor antagonist are being examined in large-scale clinical trials, and tumor necrosis factor-binding protein and bactericidal/permeability-increasing Protein also may undergo clinical testing. Much controversy has already arisen regarding the manner in which these therapeutic reagents Will be best utilized. The enormous amount of information that has already been obtained concerning the use of these reagents assuredly will contribute significantly to our understanding of the diagnosis and treatment of serious infection and will set the stage for the development and appropriate testing of additional new diagnostic and therapeutic reagents during the current decade.

Over the past 10 years, the care of the kidney transplant patient has been modified. This modification has included changes in drugs used to suppress graft rejection, treatment and prevention of infections, indications for transplant and modifications of the surgical technique, and improvements in anesthesia and intensive care. A study was undertaken at one hospital to evaluate the effect of these changes on both the rate and cause of rejection of the transplanted kidney. Outcomes of patients treated during the 1970s and those treated during the 1980s were compared. During the 1970s there were 1,012 patients who received kidneys; in the 1980s 1,384. There were 355 recipients who were diabetic in the 1970s and 628 diabetic recipients in the 1980s. The source of the kidney was a living donor for 617 of the 1970s patients and for 740 of the 1980s patients. Overall patient survival increased significantly. At one year, patient survival was 94 percent in the 1980s, compared with 86 percent in the 1970s; five-year survival was 84 percent versus 69 percent; 10-year survival was 68 percent versus 57 percent. Survival of the transplanted kidney also increased during the 1980s. These increases in occurred in spite of a higher percentage of recipients who were diabetic and who received a cadaver organ. The gains observed in the 1980s in graft survival were due mainly to a lower incidence of acute organ rejection and fewer infections. The two leading causes of poor outcomes, chronic rejection and death due to cardiovascular (heart and blood-vessel problems), showed little if any improvement. These are the two areas of challenge for the 1990s. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infection with cytomegalovirus (CMV) is a major cause of illness and death in patients whose immune systems are not functioning adequately. This immune compromised state may be acquired, as in AIDS (acquired immune deficiency syndrome), or may result from chemotherapy to treat cancer or to suppress organ rejection in transplant patients. The symptoms of CMV are usually related to pneumonitis (lung inflammation) and include fever, malaise, lethargy, low white blood cell count and difficulty breathing. CMV may involve the gastrointestinal (GI) tract, where it can produce ulcers with massive bleeding or perforation of the bowel, and has an 83 percent mortality. A study was undertaken of the GI tracts of organ transplant patients who developed CMV infection to determine the incidence and signs of CMV disease in this area. There were 93 patients who had tissue-invasive CMV disease; 14 had primary CMV disease of the GI tract. The average age of these 14 patients was 42.2 years; they were all treated with a new antiviral drug, ganciclovir guanine (DHPG). Most of the patients had symptoms of abdominal pain; other symptoms included fever, diarrhea, GI bleeding, malaise, nausea, loss of appetite and loss of weight. In 13 of the 14 patients, the disease was identified before severe complications developed; the 14th patient had intestinal perforation and died of bacterial sepsis (blood poisoning). Thirteen patients improved with DHPG treatment, although four patients required further DHPG treatment for recurrence of CMV disease. There were no toxic side effects of DHPG observed. These findings indicate that this type of patient population can benefit from treatment with DHPG; further studies are needed to fully determine DHPG's impact on patient and transplant organ survival. (Consumer Summary produced by Reliance Medical Information, Inc.)

A state of balance must exist between a transplanted organ and the person receiving it. This balance begins with the actual transplant, and is continued throughout the process of controlling transplant rejection by incremental adjustments in immune suppression medications. Infection remains one of the major complications of organ transplant, and a significant cause of morbidity and death. An important challenge for the future is to be able to separate the elements of immune suppression so that those that complicate graft acceptance can be controlled without reducing the patient's natural defenses against infection. This ideal immune suppression would involve very selective host tolerance to transplant donor antigens. Progress has been made in treating fungal and bacterial infections, but viral infections remain a threat to transplant patients. Infection with cytomegalovirus (a herpes type virus) has had an impact on organ transplant. These infections, which are initially mild and involve complaints of fever, malaise, lethargy and muscle pains, can evolve into fatal illness. Cytomegalovirus infections (CMV) usually occur in the first few months after transplant, the time corresponding to peak immune suppression treatment. Diagnosis is based on physical signs and symptoms. Recent improvements in diagnostic testing are permitting early diagnosis. Prophylaxis and treatment of CMV infection involve the use of antiviral agents specifically directed toward CMV. Administration of acyclovir after transplant may reduce the incidence CMV disease. Acyclovir is not particularly effective in treating CMV disease. Gancyclovir may be effective, but it must be given intravenously. Another new drug is trisodium phosphonoformate, which may be useful if drug resistance occurs. This drug is toxic to the kidney and must be used with caution. (Consumer Summary produced by Reliance Medical Information, Inc.)