Infection after solid-organ transplantation

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Infection risk reflects the net state of immunosuppression: induction and maintenance drugs, recent rejection therapy, leukopenia, hypogammaglobulinaemia, mucosal or surgical barriers, graft function, metabolic disease and cumulative pathogen exposure. The transplanted organ shapes presentation. Lung recipients have direct environmental exposure, liver and intestinal recipients have complex anastomotic and abdominal sources, and kidney recipients have urinary instrumentation and BK polyomavirus risk.

A timeline prevents diagnostic anchoring when used flexibly. During the first postoperative month, technical and nosocomial problems predominate. Between one and six months, maximal immune suppression permits reactivation and classical opportunists, although prophylaxis shifts their onset. Later, the pattern depends on graft stability: a well recipient resembles the wider community, whereas chronic rejection, augmented therapy or persistent viral replication creates continued opportunistic susceptibility.

The central management tension is infection control without precipitating rejection or drug toxicity. Azoles and macrolides can markedly raise calcineurin- and mTOR-inhibitor concentrations; rifamycins can lower them; diarrhoea and kidney injury also destabilise exposure. Antimicrobial treatment, trough monitoring and any immunosuppression reduction should therefore be designed together by transplant, infection, microbiology and pharmacy teams.

Key points

In the first month, prioritise donor-derived, surgical, device-associated and healthcare-acquired infection, including wound, anastomotic, urinary, pulmonary, bloodstream and intra-abdominal sources.
From roughly one to six months, viral reactivation and opportunists become prominent: CMV, EBV, BK polyomavirus, Pneumocystis, Aspergillus, Candida, nocardia, toxoplasma and tuberculosis depend on organ, serostatus and prophylaxis.
After six months, stable recipients mainly acquire community infections, while chronic graft dysfunction or intensified immunosuppression sustains late opportunistic risk.
Timing is a map, not a rule: prophylaxis delays disease, rejection therapy moves the patient back into a high-risk phase and donor or geographic exposures create exceptions.
First-line assessment combines cultures, graft-function tests, medication levels and syndrome-directed imaging; add quantitative viral testing and tissue sampling according to the immune defect.
Treat severe undifferentiated infection promptly with the locally approved, source-based regimen informed by previous colonisation and prophylaxis; narrow when cultures or molecular results define the cause.
Never adjust tacrolimus, ciclosporin, mycophenolate or corticosteroids casually during infection; antimicrobial interactions, rejection risk and immune restoration require transplant-pharmacy and transplant-team control.
CMV QNAT is the standard blood monitoring method, but proven tissue-invasive disease may require histology with viral demonstration; isolated DNAaemia is not synonymous with organ disease.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Donor and recipient pathogens

Latent CMV, EBV, toxoplasma, tuberculosis, fungi and other organisms may reactivate from recipient tissues or arrive with the donated organ.

Surgical and healthcare exposure

Anastomoses, drains, urinary devices, ventilation, prolonged admission and broad antibiotics favour bacterial, Candida and resistant healthcare-associated infection early after transplantation.

Community and environmental acquisition

Respiratory viruses, foodborne pathogens, Legionella, mould spores, cryptococcus, nocardia and travel-associated infections remain possible, with severity amplified by immune suppression.

Latent viral reactivation

T-cell suppression releases CMV, EBV, BK polyomavirus, hepatitis viruses, HSV and VZV from immune control, sometimes producing graft-specific disease.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
T-cell impairment
Calcineurin inhibition, antiproliferative therapy, corticosteroids and lymphocyte-depleting agents weaken control of intracellular pathogens, herpesviruses, fungi and malignant EBV-driven B-cell proliferation.
2
Barrier and anatomical defects
Operative wounds, devascularised tissue, leaks, strictures and indwelling devices allow colonising organisms to enter deep tissue and create sources drugs cannot sterilise alone.
3
Virus-graft interaction
CMV and BK replication can directly injure tissue, amplify alloimmune inflammation and complicate the distinction between infection, rejection and immunosuppressant toxicity.
4
Drug-mediated ecological pressure
Antibacterial, antiviral and antifungal prophylaxis suppresses susceptible pathogens but delays disease, selects resistance and leaves organisms outside its spectrum unaffected.
5
Reduced inflammatory signalling
Immunosuppressive medicines can attenuate fever, leukocytosis and local inflammation, allowing advanced disease before ordinary clinical thresholds are reached.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Early postoperative sourceRed flag

Wound change, line symptoms, urinary obstruction, bile leak, anastomotic pain, collection or ventilator-associated disease within the first month points toward surgical and healthcare pathogens.

CMV syndrome or tissue diseaseRed flag

Fever, malaise, leukopenia and thrombocytopenia suggest CMV syndrome; diarrhoea, hepatitis, pneumonitis, retinitis or other organ dysfunction raises tissue-invasive disease.

Subacute pulmonary infectionRed flag

Progressive dry cough, exertional desaturation or nodular CT change may represent Pneumocystis, mould, nocardia, CMV or mycobacteria despite a quiet chest examination.

Graft-specific deteriorationRed flag

A creatinine rise, cholestatic tests, reduced lung function or new cardiac impairment can be infection, rejection, obstruction or toxicity and rarely separates clinically without targeted investigation.

EBV-driven proliferative disease

Unexplained fever, lymphadenopathy, tonsillar enlargement, weight loss, graft dysfunction or extranodal masses should prompt EBV and post-transplant lymphoproliferative disorder assessment.

Red flags requiring action

Hypotension, rising lactate, confusion, oliguria or increasing oxygen need requires immediate sepsis treatment even when fever and CRP are modest.
New graft pain, falling urine output, cholestasis, cardiac dysfunction or deteriorating spirometry may represent infection, rejection, obstruction or vascular compromise and needs same-day transplant assessment.
Severe headache, altered behaviour, seizure or focal neurology raises concern for cryptococcosis, nocardiosis, mould infection, toxoplasmosis, bacterial infection or post-transplant lymphoproliferative disorder.
Haemoptysis, pleuritic pain, nodules, cavities or diffuse hypoxaemia requires rapid CT-based evaluation for mould, Pneumocystis, nocardia, CMV and bacterial disease.
Diarrhoea with dehydration, abdominal pain or graft-drug toxicity can rapidly destabilise calcineurin-inhibitor exposure and renal function.
Recent rejection treatment, lymphocyte-depleting therapy, lapse of prophylaxis or donor-derived infection warning resets risk regardless of the calendar time since transplant.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line sepsis and graft panelFirst stepFirst line
Why
Define severity, recover bacteria and detect organ or graft dysfunction before therapy reduces diagnostic yield.
Interpretation and limitations
Take peripheral and relevant line cultures, FBC, renal and liver profiles, CRP, lactate, glucose and urinalysis or urine culture as appropriate. Add graft-specific tests and compare with the recipient's baseline.
02
Medication and exposure review
Why
Estimate net immune suppression and identify toxicity, interaction, non-adherence or loss of prophylaxis.
Interpretation and limitations
Record organ and transplant date, donor and recipient serostatus, rejection episodes, prophylaxis, immunosuppressant doses, trough levels, prior organisms, travel and donor alerts. Interpret levels with sampling time, diarrhoea and interacting medicines.
03
CMV quantitative nucleic-acid testing
Why
Detect and trend CMV DNAemia for surveillance, pre-emptive therapy, treatment response and resistance assessment.
Interpretation and limitations
Use the same calibrated whole-blood or plasma assay longitudinally and follow the centre-specific threshold. Low or absent DNA in blood does not exclude every compartmental tissue disease.
04
Syndrome-directed CT and sampling
Why
Reveal infiltrates, collections, anastomotic complications or focal lesions and secure pathogen-specific material.
Interpretation and limitations
Use CT chest for significant respiratory disease and contrast abdominal imaging for graft or surgical features. Bronchoalveolar lavage, drainage fluid or tissue should undergo broad bacterial, fungal, mycobacterial and molecular testing selected with microbiology.
05
Tissue diagnosis
Why
Distinguish invasive viral or fungal disease, rejection, drug injury and post-transplant lymphoproliferative disorder when blood tests are insufficient.
Interpretation and limitations
Histopathology with organism-specific stain, immunohistochemistry, culture or molecular detection is the reference approach for proven organ-invasive disease; plan biopsy safety and specimen allocation before the procedure.
06
BK polyomavirus plasma qPCR
Why
Identify and monitor BK DNAaemia in kidney recipients and support investigation of otherwise unexplained graft dysfunction.
Interpretation and limitations
Use a UKAS-accredited calibrated plasma assay and trends rather than an isolated threshold. Persistent dysfunction despite immunosuppression reduction may require graft biopsy to distinguish BK nephropathy from rejection.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Acute or chronic rejection

Graft dysfunction, fever and inflammatory change overlap with infection; drug levels, donor-specific antibodies, imaging and biopsy may be needed before immunosuppression is intensified.

Immunosuppressant toxicity

Calcineurin inhibitors cause kidney and neurological toxicity, antiproliferatives cause diarrhoea and cytopenia, and mTOR inhibitors can cause pneumonitis that resembles infection.

Post-transplant lymphoproliferative disorder

EBV-associated or EBV-negative lymphoid proliferation can cause fever, nodes, gastrointestinal lesions, masses, cytopenias and graft dysfunction, requiring tissue diagnosis.

Vascular or mechanical complication

Thrombosis, obstruction, leak, ischaemia and anastomotic failure can produce pain, organ dysfunction and inflammation and may secondarily become infected.

Drug fever or inflammation

Medication reactions, gout, thrombosis and other inflammatory disorders may create fever, but infection must be sampled and treated first when physiology is unsafe.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01UNSTABLEResuscitate and cover likely sourcesFirst stepA transplant recipient has shock, organ dysfunction, hypoxaemia or another severe infection phenotype.

1Perform ABCDE, obtain cultures and urgent laboratory tests, then start the locally approved source-based intravenous regimen without waiting for transfer or specialist arrival.
2Use prior susceptibility, current prophylaxis, organ type, time after transplant and healthcare exposure to identify resistant Gram-negative, enterococcal, staphylococcal and fungal gaps.
3Contact the implanting or responsible transplant service, microbiology and critical care; arrange drainage, device removal or surgical assessment when anatomy drives sepsis.
4Continue essential corticosteroid coverage and ask the transplant team to direct any reduction of antiproliferative or calcineurin therapy.

02TIMELINEMatch pathogens to immune phaseThe patient is stable enough for a structured diagnostic search after immediate threats are addressed.

1Within one month, inspect wound, drains, lines and anastomoses and investigate donor-derived or nosocomial infection before attributing illness to a late opportunist.
2From one to six months, test for CMV and organ-specific viruses and investigate Pneumocystis, mould, nocardia, mycobacteria and toxoplasma according to symptoms, serostatus and prophylaxis.
3After six months, start with community syndromes but move back to an opportunistic framework after rejection treatment, chronic high-dose immunosuppression or prophylaxis failure.
4Reconcile the timeline with geography, donor information, prior colonisation and the exact immune defect rather than ordering every opportunistic assay indiscriminately.

03CMVTreat infection and tissue diseaseCMV DNAemia crosses the centre threshold, CMV syndrome develops or organ-invasive disease is established.

1Use oral valganciclovir for a stable patient with reliable absorption, adjusting the dose to creatinine clearance and monitoring blood counts closely.
2Use intravenous ganciclovir for severe, life-threatening or tissue-invasive disease when absorption is doubtful, with renal and marrow adjustment.
3Recheck viral load after two weeks and then no more frequently than the specialist schedule, continuing until symptoms resolve and virological stopping criteria are met.
4Investigate underexposure, adherence, absorption and UL97 or UL54 resistance when the viral load fails to fall appropriately despite at least two weeks of correctly dosed treatment.

04BK VIRUSProtect the kidney graftA kidney recipient develops BK DNAaemia, unexplained graft dysfunction or biopsy features of BK polyomavirus nephropathy.

1Confirm the plasma qPCR trend, review creatinine and immunosuppressant exposure and exclude bacterial urinary infection, obstruction, toxicity and rejection.
2Ask the transplant team to reduce immunosuppressive burden cautiously, usually by reducing an antiproliferative agent and/or calcineurin exposure according to graft risk.
3Arrange graft biopsy when dysfunction persists or worsens and histology will change management, including examination for concurrent rejection and SV40 large-T-antigen staining.
4Do not substitute fluoroquinolones, cidofovir, leflunomide or immunoglobulin for specialist immune adjustment because no isolated antiviral treatment has robust recommended efficacy.

05PREVENTIONMaintain layered prophylaxisA recipient is newly transplanted, leaves hospital, receives rejection therapy or has prophylaxis interrupted.

1Verify CMV donor-recipient serostatus and use valganciclovir prophylaxis or centre-defined surveillance according to organ, T-cell-depleting therapy and BTS guidance.
2Continue Pneumocystis prophylaxis for the organ-specific interval and restart or extend it after intensified immunosuppression when the transplant protocol requires.
3Update inactivated vaccines through the transplant programme, avoid live vaccines during significant immunosuppression and vaccinate close household contacts appropriately.
4Teach food, water, soil, animal, respiratory-exposure and travel precautions without imposing unnecessary isolation; provide a direct route for same-day advice.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Provides immediate coverage for likely surgical, healthcare or community bacteria while previous colonisation and the anatomical source are clarified.

Empirical antibacterial therapy

Give the hospital's transplant- and source-specific intravenous sepsis regimen at full loading doses, then adjust for renal or hepatic function and extracorporeal support after cultures are obtained when safe.

No universal combination fits every graft; incorporate local resistance, recent prophylaxis and allergy, then narrow quickly to reduce kidney injury, interactions and Clostridioides difficile risk.

BTS-recommended oral treatment when absorption is reliable; 900 mg once daily is the licensed prophylactic dose for selected normal-renal-function solid-organ recipients.

Valganciclovir

For CMV infection or disease, give 900 mg orally twice daily in an adult with normal renal function for at least 2 weeks, then continue to specialist clinical and virological stopping criteria.

Use Cockcroft-Gault creatinine clearance for product-specific adjustment, monitor FBC at least fortnightly during prophylaxis and more closely during treatment, and address neutropenia, thrombocytopenia, reproductive toxicity and adherence.

Preferred CMV treatment when disease is severe, gastrointestinal absorption is unreliable or oral delivery cannot be assured.

Intravenous ganciclovir

Give 5 mg/kg intravenously every 12 hours initially for severe CMV disease in an adult with normal renal function, using actual specialist dosing and renal adjustment.

Monitor neutrophils, platelets and renal function frequently; avoid simultaneous underdosing and excessive marrow toxicity, and obtain resistance advice for inadequate viral-load response.

First-choice Pneumocystis prevention with additional activity against toxoplasma, nocardia and common urinary pathogens.

Co-trimoxazole prophylaxis

A common adult transplant regimen is 480 mg orally once daily or 960 mg three times weekly; the transplant protocol selects dose and duration for organ, renal function and rejection therapy.

Check sulfonamide hypersensitivity, FBC, potassium and renal function; interactions and marrow toxicity may require an alternative such as atovaquone or inhaled pentamidine under specialist direction.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Graft loss

Direct infection, haemodynamic injury, obstruction, rejection triggered by immune adjustment and antimicrobial toxicity can cause irreversible deterioration of the transplanted organ.

Disseminated opportunistic disease

CMV, moulds, cryptococcus, nocardia, mycobacteria and toxoplasma may spread to brain, eye, lung, skin, bone or bloodstream with subtle initial signs.

Antiviral resistance

Prolonged or inadequately dosed ganciclovir exposure can select CMV UL97 and later UL54 mutations, producing refractory replication and cross-resistance patterns.

Post-transplant lymphoproliferation

Poor EBV immune control permits clonal B-cell expansion ranging from early proliferations to aggressive lymphoma, threatening graft and patient survival.

Treatment interaction injury

Anti-infectives can precipitate calcineurin toxicity, rejection from low exposure, marrow suppression, electrolyte disturbance or renal failure unless prescribing and monitoring are integrated.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Trend physiology, graft-specific function, urine output and the symptomatic organ daily during acute illness; compare values with the recipient's stable baseline rather than the laboratory reference range alone.
Review every culture, viral load, pathology and imaging result with microbiology or virology and document whether treatment is empirical, pre-emptive or targeted.
Measure tacrolimus, ciclosporin or mTOR-inhibitor trough concentrations at the interval set by the transplant team whenever infection, diarrhoea, kidney injury or an interacting antimicrobial changes exposure.
During valganciclovir or ganciclovir, follow FBC and renal function closely and recalculate dose promptly; apparent virological resistance may instead be underdosing from an incorrect clearance estimate.
After immunosuppression reduction, monitor both pathogen load and rejection or sensitisation risk so microbial improvement is not purchased with avoidable graft injury.
At discharge, reconcile antimicrobial duration, prophylaxis, immunosuppressants, pending results, vaccination and the named transplant team responsible for follow-up.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The clock can reset

High-dose corticosteroids or lymphocyte-depleting rejection therapy recreates early opportunistic risk years after transplantation and may require renewed prophylaxis.

DNAemia is not tissue disease

A quantitative viral result supports risk and response assessment, while symptoms, organ tests and sometimes biopsy establish whether replication is causing organ injury.

Interactions threaten both outcomes

Raising calcineurin exposure can cause kidney or neurological toxicity, whereas enzyme induction can produce subtherapeutic levels and rejection; both may accompany otherwise effective anti-infective treatment.

Diarrhoea has several owners

CMV, norovirus, Clostridioides difficile, other pathogens, mycophenolate toxicity and graft-related disease can overlap, so stool tests, endoscopy and medication review may all be required.

Prophylaxis changes presentation

A protected patient can develop disease after prophylaxis ends or with non-adherence, malabsorption, resistance or an organism outside the drug's spectrum.

11Common pitfallsFrequent interpretation and management errors.

01
Assuming every illness between one and six months is CMV and overlooking a collection, line infection, pulmonary embolus or graft complication.
02
Using the transplant anniversary rather than recent rejection treatment, prophylaxis and current lymphocyte or neutrophil impairment to estimate risk.
03
Stopping all immunosuppression during sepsis without transplant input, thereby creating adrenal crisis, rejection or sensitisation risk.
04
Starting an azole, macrolide or rifamycin without an immediate calcineurin-inhibitor interaction and trough-monitoring plan.
05
Calling BK nephropathy from viruria alone or treating DNAaemia with an unproven antiviral instead of coordinated immunosuppression reduction.
06
Allowing referral back to the transplant centre to delay local cultures, resuscitation, active antimicrobials or urgent anatomical source control.