Infections in Solid Organ Transplant Recipients: IDFN on call

It is 12:30 PM and you receive a page from the MICU. A second-year resident has just admitted a renal transplant patient to MICU due to hypotension from profound watery diarrhea. The patient was transplanted 12 days prior and remains in hospital due to delayed graft function and treatment for Klebsiella UTI. The resident is concerned for cytomegalovirus and is asking should empiric treatment be started?

Background:

Solid organ transplantation (SOT) offers a significant state of immune suppression which varies based on the immunosuppressant regimen, the time since transplant, and any history of rejection. This is further modified by any underlying disease states that prompted the end organ failure (e.g., cirrhosis, glomerulonephritis, etc.). Both the adaptive and innate system may be impaired in these patients, exposing to an array of opportunistic infections. Over the course of fellowship, it is important to understand the mechanisms of the immune-suppressant agents commonly used, both institutionally and worldwide.

When approaching these cases, a critical consideration, and the emphasis of the prompt above, is understanding the infectious timeline following SOT. (source of picture below)

In the first month following transplant, we generally see nosocomial infections, including drug resistant bacteria, which may be related to hospitalization or technical aspects of the recent procedure. These are generally pathogens that the patient was exposed to in hospital or colonized with prior. The other major consideration early post-transplant is Donor-Derived infections. This link comes from a published set of guidelines from the American Society of Transplant on infectious complications (a site worth a favorites star on your browser).  The resident is asking about CMV, which is an important complication following transplant. However, CMV does not reactivate this quickly, as it takes time for the full effect of immune-suppression to build. Additionally, if at risk, the patient should be receiving prophylaxis or be on a preemptive test and treat protocol for the initial post-transplant period.

Data to acquire:

When called about infection in a SOT in the first month post-transplant, it’s important to gather information about the host, donor, procedure and course. For the Host, it’s important to understand prior infectious history (colonization, prior infections, additional comorbidities for infection). Donor information is available through UNOS, including screening tests and cultures obtained at procurement. This will not be readily available to you, but the transplant teams and your transplant ID attending should have access. Procedure details of interest include any complications with surgery, particularly with anastomoses. Additionally, it is worth considering the type of induction Immune-suppression provided.  Course includes how the allograft is functioning, any additional complications post-transplant, alterations to “typical protocol/post-transplant course”, and current symptoms.

Transplant ID is complex, and complications shortly following transplant are particularly concerning. Do not hesitate to reach out to attending for support when challenging questions come in for this population, particularly if the patient is critically ill. If you are uncertain of what to do, this is an appropriate time to reach out – as an attending on the transplant service,  I would welcome that call.

Key Treatment Decisions:

Key initial treatment decisions are ensuring appropriate diagnostics are sent and empiric management begun. This will be guided by the clinical syndrome (fever, encephalitis, pneumonia, diarrhea) and influenced by the severity of illness. It is important to consider if empiric treatment choices will interact with the immune-suppression. Common antibacterial interactions include azoles and macrolides, which increase tacrolimus and sirolimus levels, while rifamycins decrease these agents.

Our patient is presenting with a diarrheal illness in the first month post-transplant and following antibiotic exposure. Thus, clostridium difficile testing and empiric therapy should be initiated. Oral vancomycin and IV metronidazole should be chosen as hypotension suggests fulminant disease.  Consideration should be given to early imaging and/or surgical consult, based off exam and hemodynamic response to fluids.

Anticipating next steps:

This particular syndrome appears less likely donor related. Testing for your leading diagnosis of C. difficile should be quickly resulted. However, it is important to ensure your attending is aware the next morning, so they can help you consider any next steps for investigation. Despite any guidance provided over the phone, patients with infections following transplant benefit from ID consultation and a formal consult should be recommended for the next morning.

Written by Jeremy Walker From UAB (@bhamjwalk)

Post uploaded on 7/26/2022

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