CMV after solid organ transplantation: Difference between revisions
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+ | ==Clinical Manifestations== |
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+ | *Tends to reactivate in the transplanted organ, but can have colitis |
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+ | ===CMV Syndrome=== |
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+ | *Detectable CMV viremia, plus at least two of: |
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+ | **Fever ≥38ºC for 2+ days |
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+ | **New or increased malaise or fatigue |
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+ | **Leukopenia or neutropenia on 2 separate measurements |
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+ | **5% atypical lymphocytes |
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+ | **Thrombocytopenia |
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+ | **Hepatic aminotransferases ≥2 times the upper limit of normal (except non-liver transplant recipients) |
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+ | *Treated with [[Is treated by::ganciclovir]] 5 mg/kg IV q12h or [[Is treated by::valganciclovir]] 900 mg PO bid, depending on severity of illness |
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+ | *Second-line treatment includes [[Is treated by::foscarnet]] and [[Is treated by::cidofovir]] |
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+ | *Expect a 1-log decrease in viral level after 2 weeks |
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+ | *Duration is for a minimum of 2 weeks, until resolution of symptoms, and until viral load falls below the negative cutoff |
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+ | *While being treated, check CBC and creatinine weekly to monitor for toxicity |
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+ | ===Refractory Disease=== |
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+ | *Refractory CMV infection: viral load increases >1 log after 2 weeks of appropriate therapy |
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+ | *Probable refractory CMV infection: viral load persists or increases <1 log after 2 weeks of appropriate therapy |
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+ | *Lack of clinical improvement after 2 weeks is also concerning |
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+ | *The causes of refractory disease include: |
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+ | **Over-immunosuppression resulting in a severe deficiency of CMV-specific T cells |
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+ | **Subtherapeutic antiviral drug levels |
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+ | **Antiviral resistance |
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+ | ***Ganciclovir resistance occurs in 0-3% of patients, and foscarnet resistance in less |
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+ | ***Risk factors include prolonged subtherapeutic levels, D+/R– serostatus, heavy immunosuppression, and lung transplantation |
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+ | ***If suspected, send testing for UL97 kinase (ganciclovir) ± UL54 DNA polymerase (ganciclovir & foscarnet) |
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+ | ==Prevention== |
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+ | **Prophylaxis: easier to coordinate, higher drug costs, greater drug toxicity (myelosuppression) |
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+ | **Preemptive therapy: harder to coordinate, viral load thresholds not well-defined, higher laboratory costs, lower drug toxicity |
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{| class="wikitable" |
{| class="wikitable" |
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+ | ! colspan="2" |Serostatus |
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− | ! Serostatus !! Risk profile !! Approach !! Prophylaxis regimen |
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+ | ! rowspan="2" |Risk profile |
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+ | ! rowspan="2" |Approach |
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+ | ! rowspan="2" |Prophylaxis regimen |
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+ | !D |
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+ | !R |
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+ | | + |
+ | |– |
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+ | |- |
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+ | | + |
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+ | |- |
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+ | |– |
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+ | |- |
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+ | |– |
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+ | |– |
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+ | |Low |
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+ | |Clinical monitoring; consider PET if other risk factors for CMV |
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− | == |
+ | ==Further Reading== |
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+ | *Cytomegalovirus in solid organ transplant recipients— Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. ''Clin Transplant''. 2019;33:e13512. doi: [https://doi.org/10.1111/ctr.13512 10.1111/ctr.13512] |
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[[Category:Immunocompromised hosts]] |
[[Category:Immunocompromised hosts]] |
Latest revision as of 20:42, 11 September 2020
Clinical Manifestations
- Tends to reactivate in the transplanted organ, but can have colitis
CMV Syndrome
- Detectable CMV viremia, plus at least two of:
- Fever ≥38ºC for 2+ days
- New or increased malaise or fatigue
- Leukopenia or neutropenia on 2 separate measurements
- 5% atypical lymphocytes
- Thrombocytopenia
- Hepatic aminotransferases ≥2 times the upper limit of normal (except non-liver transplant recipients)
Management
- Treated with ganciclovir 5 mg/kg IV q12h or valganciclovir 900 mg PO bid, depending on severity of illness
- Second-line treatment includes foscarnet and cidofovir
- Expect a 1-log decrease in viral level after 2 weeks
- Duration is for a minimum of 2 weeks, until resolution of symptoms, and until viral load falls below the negative cutoff
- While being treated, check CBC and creatinine weekly to monitor for toxicity
Refractory Disease
- Refractory CMV infection: viral load increases >1 log after 2 weeks of appropriate therapy
- Probable refractory CMV infection: viral load persists or increases <1 log after 2 weeks of appropriate therapy
- Lack of clinical improvement after 2 weeks is also concerning
- The causes of refractory disease include:
- Over-immunosuppression resulting in a severe deficiency of CMV-specific T cells
- Subtherapeutic antiviral drug levels
- Antiviral resistance
- Ganciclovir resistance occurs in 0-3% of patients, and foscarnet resistance in less
- Risk factors include prolonged subtherapeutic levels, D+/R– serostatus, heavy immunosuppression, and lung transplantation
- If suspected, send testing for UL97 kinase (ganciclovir) ± UL54 DNA polymerase (ganciclovir & foscarnet)
Prevention
- Two approaches are used, either ongoing antimicrobial prophylaxis following transplantation, or close monitoring of viral load with preemptive treatment (PET) of subclinical viremia
- Prophylaxis: easier to coordinate, higher drug costs, greater drug toxicity (myelosuppression)
- Preemptive therapy: harder to coordinate, viral load thresholds not well-defined, higher laboratory costs, lower drug toxicity
- Approach and duration depends on risk profile and organ transplanted
- Intermediate and high risk patients should get either prophylaxis or PET
- Prophylaxis (rather than PET) is preferred in lung, heart, and pancreas transplantations
- Low risk should either be monitored for symptoms or be followed with PET (if there is other concern for CMV disease, such as frequent transfusions)
- Intermediate and high risk patients should get either prophylaxis or PET
- Antimicrobial of choice is valganciclovir 900 mg po daily, starting within 10 days of transplantation
Serostatus | Risk profile | Approach | Prophylaxis regimen | |
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D | R | |||
+ | – | High | Either prophylaxis or PET; prophylaxis preferred for lung, heart, and pancreas | 3-6 months for most organs; 6 months for kidney; 6-12 months for lung |
+ | + | Intermediate | Either prophylaxis or PET; prophylaxis preferred for lung, heart, and pancreas | 3 months for most organs; 6 months for lung |
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– | – | Low | Clinical monitoring; consider PET if other risk factors for CMV |
Further Reading
- Cytomegalovirus in solid organ transplant recipients— Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33:e13512. doi: 10.1111/ctr.13512
- The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid organ Transplantation. Transplantation. 2018;102:900–931. DOI: 10.1097/TP.0000000000002191