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Pharmacokinetics and Pharmacodynamics of Antibiotics in Transplant Patients

  • Kelly E. Schoeppler
  • Scott W. Mueller
  • Gerard R. BarberEmail author
Chapter

Abstract

Transplant infectious diseases are among the most challenging sectors of present-day medicine. Solid organ and hematopoietic stem cell transplants are being performed with increasing frequency, and the threat of infection is ever-present due to a degree of dependence upon potent immunosuppressive agents that ensure sustained engraftment. Accordingly, antibacterial agents will be employed as well. The responses of these patients to bacterial infection can be very different when compared to the immunocompetent host. This lack of intact immune status presents a markedly different patient population and often requires a different approach to the prophylaxis or treatment of infection. Segments of patient populations within transplant medicine, such as cystic fibrosis or elderly patients, pose physiologic challenge to optimizing medication regimens as they also can be taking other medications indicated for chronic underlying conditions that precede or develop following transplantation. Consideration for changes in the pharmacokinetics of antimicrobials is critical in achieving adequate serum concentrations while minimizing toxicity. Clinicians must be mindful of drug interactions of antibacterials to immunosuppressive agents as well as these other medications. Despite the fact that ultimately the dynamics of these drug interactions can be crucial and influence the success or failure of the transplanted organ, methodologically solid pharmacokinetic drug interaction trials are lacking for many commonly used antibacterials. A keen awareness of the pharmacokinetic and pharmacodynamic activities of medications within the transplant recipient is crucial. For example, the anticipated changes of a drug’s concentration or potency with new or sustained exposure to another agent, the relevance of objective measurements of drug concentrations, and the employment of novel routes of administration such as aerosolization to preferentially target pulmonary exposure while minimizing systemic activities must be recognized. There has been considerable interest regarding the influence of several antibacterials on immunomodulation. This chapter will discuss these issues within the context of stewardship and optimization citing the most recent evidence, trends, and controversy. For now, among recipients of solid organ and hematopoietic stem cell transplantation, the drug classes of antimicrobials and immunosuppressives remain inextricably woven.

Keywords

Therapeutic drug monitoring (TDM) Volume of distribution (Vd) Bioavailability (F) Area under the concentration curve (AUC) Minimum inhibitory concentration (MIC) Drug interactions Aerosolized Immunomodulation Investigational 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kelly E. Schoeppler
    • 1
  • Scott W. Mueller
    • 2
  • Gerard R. Barber
    • 3
    Email author
  1. 1.Department of Pharmacy ServicesUniversity of Colorado Health, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical SciencesAuroraUSA
  2. 2.Department of Clinical PharmacyUniversity of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado HealthAuroraUSA
  3. 3.Department of Pharmacy ServicesUniversity of Colorado Hospital, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical SciencesAuroraUSA

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