Infection in Organ Transplantation

J. A. Fishman

Disclosures

American Journal of Transplantation. 2017;17(4):856-879. 

In This Article

Abstract and Introduction

Abstract

The prevention, diagnosis, and management of infectious disease in transplantation are major contributors to improved outcomes in organ transplantation. The risk of serious infections in organ recipients is determined by interactions between the patient's epidemiological exposures and net state of immune suppression. In organ recipients, there is a significant incidence of drug toxicity and a propensity for drug interactions with immunosuppressive agents used to maintain graft function. Thus, every effort must be made to establish specific microbiologic diagnoses to optimize therapy. A timeline can be created to develop a differential diagnosis of infection in transplantation based on common patterns of infectious exposures, immunosuppressive management, and antimicrobial prophylaxis. Application of quantitative molecular microbial assays and advanced antimicrobial therapies have advanced care. Pathogen-specific immunity, genetic polymorphisms in immune responses, and dynamic interactions between the microbiome and the risk of infection are beginning to be explored. The role of infection in the stimulation of alloimmune responses awaits further definition. Major hurdles include the shifting worldwide epidemiology of infections, increasing antimicrobial resistance, suboptimal assays for the microbiologic screening of organ donors, and virus-associated malignancies. Transplant infectious disease remains a key to the clinical and scientific investigation of organ transplantation.

Introduction

The prevention, diagnosis, and management of infectious diseases are major contributors to clinical organ transplantation. The emergence of Transplant Infectious Disease as a specialty has paralleled the expansion of organ transplantation with prolonged allograft and patient survivals and increasingly effective immunosuppressive agents. Recent advances include the availability of international standards for quantitative molecular assays for common viruses, demonstration of links between genetic polymorphisms in immune responses with the risk for specific infections, and newer antimicrobial therapies including those for hepatitis C virus (HCV) as well as the development of some detailed practice guidelines.[1–4] Challenges include the paucity of assays to assess risk for specific infections or graft rejection, increasing antimicrobial resistance, suboptimal screening paradigms for microbiologic evaluation of organ donors, virus-associated malignancies, and shifts in global patterns of infection (e.g. Zika and West Nile [WNV] viruses). Bedside clinical skills remain paramount in immunocompromised hosts who manifest few clinical signs of infection. This review will describe an approach to the management of infection in transplantation.

General Concepts

A wide spectrum of potential pathogens infects immunocompromised hosts; many are infrequent pathogens in normal individuals. Fever and physical signs of infection (e.g. erythema) are diminished; infection may be signaled by more subtle laboratory (e.g. liver function tests) or radiographic abnormalities. Antimetabolites (azathioprine and mycophenolate mofetil) are associated with lower leukocyte counts and lower maximum temperatures. Significant infections such as peritonitis may lack fever or localizing signs. Up to 40% of infections cause no fever, notably in fungal infections, and up to 22% of fevers are noninfectious in origin.[5,6]

Given hepatic metabolism and renal toxicity of calcineurin inhibitors, drug interactions and renal injuries are common. Thus, every effort must be made to establish specific microbiologic diagnoses to optimize the therapy for infection while minimizing antimicrobial resistance and associated toxicities. This may necessitate invasive procedures to obtain samples for histopathology, cell counts, and cultures. Reduction in immunosuppression may be a useful component of antimicrobial therapy but risks graft rejection and increased inflammation in the form of immune reconstitution syndromes.[7] Pathogen-specific immune assays suggest the relative risk of certain infections; however, in the face of intensive immunosuppression, protective immunity, while useful, tends to dissipate.

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