Nancy L. Stitt, RN, BSN

Disclosures

April 03, 2003

Pathogens Associated With Opportunistic Infections

Over the years, with the use of prophylactic antimicrobial therapy, there has been an expansion of the list of potential pathogens for posttransplant infection. However, the more familiar organisms still predominate.[14] The frequency and type of infections posttransplantation differ by type of organ transplanted. As previously noted, the risk of infection can be linked and determined by the interaction of 3 factors: (1) the patient's net state of immunosuppression, (2) environmental exposures, and (3) surgical factors such as technical error or anatomic abnormalities. The net result is that more than 50% of allograft recipients have evidence of active infection during the first 6 months posttransplantation, and infection remains the most common cause of death at all stages of the posttransplant course.[15] The following section will review the major categories of pathogens: bacterial, viral, fungal, and parasitic.

It is important to note the increased documentation in the literature of case studies that report episodes of emerging infections. Clinicians are urged to review the literature for these case studies and to be vigilant for the potential development of these infections in their centers. In addition, with the introduction of newer diagnostic techniques that make early diagnosis possible, clinicians have the opportunity to initiate more precise, preemptive therapy.

Time Line of Infections in the Organ Transplant Recipient

The relationship between immunotherapy and infection requires a therapeutic approach that is based on familiarity with the time line of the various posttransplant infections. This time line is useful for differential diagnosis and provides a framework for decision making regarding preventive strategies. Understanding the general time frame in which infections occur can assist the transplant team in anticipating and ultimately preventing infections. There are 3 general time frames during which infection can occur in the posttransplant period: first month, second through sixth month, and beyond the sixth month. These time frames are influenced by surgical factors, the type and level of immunosuppression, and geographical location and environmental exposure of transplant centers.[16]

Most infections that occur in the first month after transplantation are similar to infections that occur in the general surgical patient and are related to surgical and/or technical complications. The high level of immunosuppression during this first month exacerbates these infections in transplant recipients, but the net state of immunosuppression has not been prolonged enough to favor the development of opportunistic infections.[17] Infections during this time include bacterial and Candida wound infections, nosocomial pneumonia, UTI, intravascular device-related bacteremias, and infections secondary to biliary, chest, and other drainage catheters. Infections common in the hospital and intensive care unit (ICU) environments during the first month also include C. difficile-associated colitis and VRE. The most common viral infection seen in the first weeks posttransplantation is reactivation of human herpes simplex virus (HSV). Prophylaxis with acyclovir has significantly decreased the incidence of this infection.

Beyond the first 6 months, patients commonly experience community acquired infections such as influenza virus infection, UTI, and pneumococcal pneumonia. An opportunistic viral infection seen during this period is the reactivation of varicella zoster virus (VZV), manifested as HZV. Two groups of patients are at risk for persistent infection in this late posttransplant period: (1) patients who have had frequent acute rejection and required increased immunosuppression and/or the additional use of antilymphocyte agents such as OKT3 or antilymphocyte globulin, and (2) patients who have had chronic rejection and are maintained at a higher level of immunosuppression. The latter group includes those patients with chronic viral infections and the presence of viral-viral interactions. Viruses such as hepatitis B virus, hepatitis C virus, CMV, human herpesvirus (HHV)-6, HHV-8, and Epstein-Barr virus (EBV) interact, thus potentiating immunomodulation and contributing to an increased net state of immunosuppression and risk for fungal and bacterial infections, as well as the development of posttransplant lymphoproliferative disorder (PTLD) and Kaposi's sarcoma.[18]

The time line of posttransplant infection that has emerged over the past 20 years should serve only as a guideline for patient care. Clinicians need to individualize both immunosuppressive and antimicrobial regimens according to the unique needs and epidemiologic exposure of each patient.[19] It is also important to emphasize that the time line of posttransplant infections begins anew after therapy for each acute rejection episode. Simultaneous or sequential infections with multiple pathogens and emerging infections create a significant challenge for the transplant clinician. The reliance on empiric therapy based on algorithms may need reexamination with an eye on preemptive, evidence-based therapy. New generation antimicrobial testing (antigenemia testing methods and polymerase chain reaction [PCR] will lead to early diagnosis and shift the paradigm from 'therapy based on algorithm' (empiric therapy) to 'preemptive therapy based on a measurement'.[20]

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