This presentation explores how infection and use of anti-infective agents may alter drug pharmacokinetics and pharmacodynamics in the post-transplant period. Transplant recipients are inherently immunocompromised due to the use of immunosuppressive drugs, making them more susceptible to infections. Infections, in turn, may alter the pharmacokinetic and pharmacodynamic properties of both immunosuppressive agents and medicines used to manage infections in transplant recipients. Infectious episodes can potentially lead to changes in gut motility, flora and pH affecting drug absorption and enterohepatic recirculation; altered fluid status and plasma protein levels affecting drug distribution; and altered liver enzyme activity and hepatic and kidney function altering drug elimination. Such alterations may subsequently result in either subtherapeutic drug concentrations or toxicity, complicating the management of both the transplant and the infection. Furthermore, use of antibiotics, antivirals, antifungals with immunosuppressive agents can lead to pharmacokinetic or pharmacodynamic drug-drug interactions. Many drug-drug interactions occur secondary to effects on drug metabolizing enzymes or drug transporters. Certain anti-infective and immunosuppressant drug combinations can also increase the risk of drug toxicity including nephrotoxicity. Infections can additionally exacerbate the inflammatory response, leading to changes in immune system function. In some instances, infections may coexist with, or be difficult to distinguishable from, graft rejection and more studies examining infectious outcomes relative to immunosuppressant level targets are needed. Clinicians need to consider the unique challenges presented by infections in transplant recipients and employ strategies such as therapeutic drug monitoring and careful selection of antimicrobial agents to optimize therapeutic outcomes.

The aim of this symposium in to highlight the duality between a required immunosuppression in solid organ transplant recipients and the associated risk of infection. The symposium will first decipher the alteration of drugs PK and PD during infections in transplant patients. Indeed, a lot of pathophysiological modification can change drugs exposure and effect during infections and their mechanism and clinical impact will be highlighted as a first step. Then, the strategies for immunosuppressive dosing adjustment for infection prevention and the latest immunosuppression net state evaluation approach will be presented and the main results on these topics will be discussed. In the second part of the symposium, a comprehensive overview will be provided to the audience regarding therapeutic drug monitoring and dosing adjustments of immunosuppressive and anti-infective drugs in two clinical situations: bacterial infections, in particular when antituberculous drugs has to be used, and viral infections with a special focus on cytomegalovirus and COVID-19 and their treatment interplay with patient’s immunosuppressive therapy.