Infections after Transplant

The contract between this chapter and the reader.

1. 1. Explain the net state of immunosuppression and the infection timeline.
2. 2. Recognise the early, middle, and late infection periods.
3. 3. Diagnose, prevent, and treat CMV infection.
4. 4. Recognise BK nephropathy and its management.
5. 5. Distinguish BK nephropathy from rejection.
6. 6. Prevent Pneumocystis pneumonia.
7. 7. Recognise the other important post-transplant infections.
8. 8. Apply the standard prophylaxis.
9. 9. Balance immunosuppression against infection.

A sixty-second reading. Each bullet stands alone.

• Infection risk after transplant reflects the net state of immunosuppression and the patient's exposures.
• The early period (first month) brings nosocomial and surgical infections, like any major operation.
• The middle period (one to six months), at peak immunosuppression, brings opportunistic infections — CMV, BK, and Pneumocystis.
• The late period (beyond six months) brings community-acquired infections, with late opportunistic infection if heavily immunosuppressed.
• Cytomegalovirus is the most important viral infection, with risk highest in a seronegative recipient of a seropositive donor.
• CMV is prevented by prophylaxis or preemptive PCR monitoring and treated with ganciclovir or valganciclovir.
• BK polyomavirus reactivates under immunosuppression and can cause BK nephropathy.
• BK nephropathy is managed by reducing immunosuppression — the opposite of rejection, which it mimics.
• BK is screened for by plasma PCR, progressing from viruria to viremia to nephropathy.
• Pneumocystis pneumonia is prevented by co-trimoxazole prophylaxis.
• Other important infections include fungal infections, tuberculosis, and EBV (causing PTLD).
• Standard prophylaxis includes co-trimoxazole and CMV prophylaxis by serostatus.
• A serious infection signals over-immunosuppression and prompts reducing immunosuppression.

The medical core. An expert should agree post-transplant infection is fully covered here.

Why it matters at the bedside

The same immunosuppression that protects the graft disarms the patient against infection — so infection is the price of transplantation's success, and managing it is a constant balancing act. Two things make it tractable: a predictable timeline that tells you what to expect when, and a short list of signature pathogens — CMV, BK, Pneumocystis — that prophylaxis and vigilance can largely defeat.

The net state of immunosuppression and the timeline

• Infection risk is the product of two things: the net state of immunosuppression (how suppressed the patient is, summing all the drugs and their intensity) and their epidemiologic exposures (community, donor-derived, latent). From this comes the classic post-transplant timeline — a roughly predictable sequence of infection types as immunosuppression peaks and then wanes.

The early period

• In the first month, infections look like those of any major operation: wound and surgical-site infection, line and catheter infection, urinary infection, and occasional donor-derived infection. The graft recipient is immunosuppressed but opportunistic infection has not yet had time to emerge; the threats are nosocomial and surgical.

The middle period: opportunistic

• From one to six months, at the peak of immunosuppression, the opportunistic infections appear: cytomegalovirus, BK polyomavirus, Pneumocystis, and fungal infections, alongside reactivation of latent infection such as tuberculosis. This is the window that prophylaxis is designed to cover — and prophylaxis reshapes the picture, deferring some infections rather than abolishing them.

The late period

• Beyond six months, with immunosuppression lower, the pattern returns toward community-acquired infections — respiratory viruses, pneumonia, urinary infection. But a patient kept heavily immunosuppressed (for example, after treatment of chronic rejection) remains at risk of late opportunistic infection, and CMV can appear late once prophylaxis is stopped.

Cytomegalovirus

• CMV is the single most important viral infection, and risk is stratified by serostatus — a seronegative recipient of a seropositive donor (D+/R-) is highest risk, having no prior immunity. It presents as asymptomatic viremia, a febrile illness with leukopenia, or tissue-invasive disease (colitis, pneumonitis, hepatitis), and has indirect effects including a predisposition to rejection. It is prevented by either universal prophylaxis (valganciclovir) or preemptive PCR-guided treatment, and disease is treated with ganciclovir or valganciclovir, with immunosuppression reduced.

BK polyomavirus

• BK polyomavirus lies latent in the urothelium and reactivates under immunosuppression, ascending from viruria to viremia to BK nephropathy — a destructive interstitial nephritis of the graft. It is detected by screening plasma BK PCR (catching viremia before nephropathy) and confirmed on biopsy by SV40 staining. There is no reliably effective antiviral, so the treatment is to reduce immunosuppression and let immunity clear the virus.

BK versus rejection

• BK nephropathy is the great mimic of rejection: both inflame the graft and raise the creatinine — but their treatments are opposite. Rejection is treated by increasing immunosuppression; BK by reducing it. Escalating immunosuppression for what is actually BK feeds the virus and destroys the graft, which is the cardinal reason to screen for BK and stain SV40 before treating presumed rejection (the trap met in the rejection and chronic-dysfunction chapters).

Pneumocystis

• Pneumocystis jirovecii pneumonia — hypoxia and dyspnea with diffuse infiltrates — is a feared but almost entirely preventable infection: routine co-trimoxazole prophylaxis for the first months after transplant (and longer with heavy immunosuppression) abolishes most cases. Its appearance usually means prophylaxis was missing.

Other infections

• Beyond the big three: fungal infections (Candida, Aspergillus, Cryptococcus, endemic mycoses), tuberculosis reactivation (screened and treated before transplant), Epstein-Barr virus (which drives post-transplant lymphoproliferative disorder — its own chapter), herpesviruses (HSV, VZV), viral hepatitis, and less common opportunists such as Nocardia, Listeria, and Toxoplasma. Urinary tract infection is common throughout.

Prophylaxis and the balance

• Standard prophylaxis carries much of the load: co-trimoxazole for Pneumocystis (and incidentally toxoplasma, Nocardia, and urinary infection), CMV prophylaxis (valganciclovir) directed by serostatus, antifungal prophylaxis in selected patients, and the pre-transplant work of treating latent tuberculosis and completing vaccination. Underlying all of it is the balance: a serious infection is a signal of over-immunosuppression, and the response — the opposite of rejection — is to reduce immunosuppression while treating the pathogen.

Five fully-built tables.

Table A — The infection timeline

Table B — Cytomegalovirus

Table C — BK polyomavirus

Table D — Other key infections

Table E — Standard prophylaxis

Visualise & Map

Numbered rules. These numbers are the cross-reference handle for the cases and flowcharts.

Clinical Reasoning

Five cases. Each stops you at a decision before it answers it.

Exhaustive. Every rule in the chapter is here.

Safety & Evidence

Panel A — Red flags

Panel B — NEVER DO

Anti-patterns clinicians fall into. Each becomes a Level 22 distractor.

The grade reflects strength of evidence, not importance.

Patient Decisions

Outcomes as natural frequencies. Figures are representative; the direction of effect is given where precise numbers are uncertain.

Apply & Test

Copy-paste chart notes that map to the real decisions in this chapter.

Template 1 — Post-transplant infection assessment note

• Time since transplant and period: early / middle / late.
• Net state of immunosuppression and prophylaxis status (co-trimoxazole, CMV): ___.
• Workup: cultures; CMV PCR; BK PCR; SV40 (if biopsy); imaging ___.
• Likely pathogen / diagnosis: ___.
• Action: pathogen-directed treatment; immunosuppression reduced (severity): ___.

Template 2 — Prophylaxis plan note

• CMV serostatus (D/R) and strategy: prophylaxis (valganciclovir) / preemptive PCR ___.
• Co-trimoxazole (Pneumocystis) started: yes/no; duration ___.
• Antifungal prophylaxis (if indicated): ___.
• Pre-transplant: latent TB treated; vaccinations complete (Chapter 4): ___.
• BK screening schedule (plasma PCR): ___.

Pre-rounds compression. Rules only.

Active recall. At least one card per objective.

Micro-teaching for rounds. Two scenarios, five steps each.

Nine items, each anchored in this chapter. At least one per objective.