key: cord-0773035-00gjgwta authors: nan title: Introduction to the Guidelines date: 2004-10-25 journal: Am J Transplant DOI: 10.1111/j.1600-6135.2004.00615.x sha: 8e8342f1f8fc7d1713564beecd3d83d509fc8f07 doc_id: 773035 cord_uid: 00gjgwta nan The transformation of organ transplantation from an interesting experiment in human immunobiology to the most practical means of rehabilitating patients with a variety of forms of end organ dysfunction may be the outstanding clinical accomplishment of the biomedical revolution that has occurred over the last three decades. Indeed, the rate of one year graft survival at many centers for nonpulmonary allografts approaches and even exceeds 90%, with the comparable statistic for lung allografts being ∼75%. Despite this success, 50-75% of transplant patients will have evidence of microbial invasion in the first year posttransplant, with the consequences of such invasion being quite diverse, encompassing the following: direct consequences, in which the microbial invasion results in a variety of clinical infectious disease syndromes such as mononucleosis, pneumonia, gastroenteritis, hepatitis, etc. and indirect consequences, in which cytokines, chemokines, and growth factors elaborated by the transplant recipient in response to microbial replication and invasion contribute to the net state of immunosuppression, the pathogenesis of acute and chronic allograft injury, and even, in some cases, the development of malignancy. Given this array of clinical effects of infection in the transplant patient, the prevention (rather than the treatment of established clinical disease) has become a primary goal of practitioners of transplant infectious disease, and it is with this goal in mind that these guidelines have been prepared (1) . In this analysis, the evidence-based rating systems for both the strength of recommendations and assessment of the quality of the evidence established by the Infectious Disease Society of America (Tables 1 and 2 ) are employed (2) . These guidelines should be regarded in two ways, as the present state of the art and as an outline of a research agenda for the coming decade. As one approaches these guidelines certain general principles merit particular attention. 1 What is to be prevented by a particular intervention must be clearly defined; that is, are you concerned just with the prevention of clinical infectious disease syndromes, or are you also interested in the prevention of indirect consequences of infection. For example, a variety of regimens have been brought forth in an effort to prevent the direct manifestations of cytomegalovirus (CMV) infection, with significant success. What is perhaps even more interesting are three separate reports suggesting that antiviral prophylaxis may have value in decreasing the incidence of acute and chronic allograft injury (1,3-5). 2 The risk of infection in the solid organ transplant patient is largely determined by the interaction of three factors: technical/anatomic mishaps that involve the transplant procedure itself, and such perioperative aspects of care as the management of vascular access, drains, and the endotracheal tube; environmental exposures (Table 3) ; and the patient's net state of immunosuppression (Table 4 ). In the case of technical/anatomic mishaps, the best way to prevent infection is to correct the anatomic abnormality under coverage of appropriate antimicrobial therapy; antimicrobial therapy by itself will just extend the incubation period at the price of inducing resistance (1,6). 3 When one is considering therapy in the transplant patient, the concept of the therapeutic prescription is very useful. This has two major components, an immunosuppressive component to prevent and treat rejection; and an antimicrobial component to make it safe. Thus, the nature of the antimicrobial program being administered must be closely linked to the nature and intensity of the immunosuppressive program required. 'One size does not fit all' (1,6). 4 There are three modes in which antimicrobial agents can be administered to the transplant recipient: a therapeutic mode, in which antimicrobial agents are administered in the treatment of established clinical infection (not the primary focus of these guidelines); a prophylactic mode, in which antimicrobial agents are administered to an entire population before an event in order to prevent the occurrence of an infection important enough to justify this intervention: and a preemptive mode, in which antimicrobial agents are administered to a subpopulation noted to be at particular risk of clinically important infection on the basis of clinical, epidemiologic, or laboratory markers. These guidelines will focus both on preventive strategies (prophylactic and preemptive) and also on the diagnosis and management of established infection. 5 Infection in the post-transplant period has a very stereotyped temporal pattern, a timetable; that is, although such clinical syndromes as pneumonia can occur at any time point post-transplant, the etiology will be very different at different time points. Figure 1 delineates the timetable for organ transplants in the absence of antimicrobial intervention. When preventative antimicrobial therapy fails to protect, a common clinical effect is to extend the incubation period. For example, in the case of CMV infection, in the absence of prophylaxis CMV induced clinical disease is most common 1-3 months post-transplant; when prophylaxis is used, but fails, it is common for the disease to occur 4-8 months post-transplant (depending on the nature of the prophylaxis and the immunosuppressive regimen) (6,7). The timetable is useful in three ways: in the differential diagnosis of a patient with a possible infectious disease syndrome; as an infection control device, as exceptions to the timetable are usually due to an unusual environmental hazard, often within the hospital; and, most important in the context of these guidelines, this timetable is the ba- Dose, duration, and temporal sequence of immunosuppressive therapy Metabolic abnormalities Protein-calorie malnutrition Uremia Hyperglycemia 4. Infection with immunomodulating viruses Cytomegalovirus Epstein-Barr virus Human herpesvirus-6 Hepatitis B virus Hepatitis C virus Infection in organ-transplant recipients Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficency Virus Prevention of primary cytomegalovirus disease in organ transplant recipients Legendre CM et al Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled study Infection in the organ transplant recipient The therapeutic prescription for the organ transplant recipient: the linkage of immunosuppression and antimicrobial strategies