Antiviral resistance in CMV: Difference between revisions
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+ | ==Background== |
+ | |||
+ | * Inherent resistance to [[acyclovir]] |
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+ | * Acquired resistance to [[ganciclovir]], [[foscarnet]], [[cidofovir]], and [[letermovir]] is possible |
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+ | |||
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!Gene |
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+ | ==Clinical Manifestations== |
− | * |
+ | *CMV viral load increasing or failing to decrease after 2 weeks of appropriate antiviral therapy |
− | * |
+ | *Failure to improve clinically after 2 weeks of appropriate antiviral therapy |
− | == |
+ | ==Diagnosis== |
− | * |
+ | *Genotyping for resistance alleles |
− | == |
+ | ==Management== |
− | * |
+ | *Decrease immunosuppression, if possible |
− | * |
+ | *If switching to foscarnet or cidofovir, monitor closely for renal toxicity |
[[Category:Infectious diseases]] |
[[Category:Infectious diseases]] |
Latest revision as of 20:28, 6 August 2020
Background
- Inherent resistance to acyclovir
- Acquired resistance to ganciclovir, foscarnet, cidofovir, and letermovir is possible
Gene | Product | Mutations | Resistance | Notes |
---|---|---|---|---|
UL97 | kinase | M460V, H520Q, A594V, L595S, C603W, L595F | high-level ganciclovir | most common (0-3% of transplant recipients) |
M460I, C592G, L595W | low-level ganciclovir | |||
L405P, M460T, V466G, A594T/P/G/E, L595S, E596G, G598S, K599T, C603W/R/S, C607Y/F, Δ591-594, Δ591-607, Δ595, Δ595-603, Δ600, Δ601, Δ601-603 | ganciclovir | |||
V353A, L397R, T409M, H411Y/N/L | maribavir | |||
UL54 | DNA polymerase | D301N, N408D/K, N410K, F412C/V, D413A/E, L501I, T503I, K513E/N, L516R, I521T, P522A/S, L545S, A987G | ganciclovir and cidofovir | |
N495K, D588E, E756D/Q, T700A, V715M, T838A | foscarnet | |||
L776M, V781I, V787L, L802M, A809V | foscarnet and ganciclovir | |||
D588N, E756K, V812L, T813S, A834P, G841A, Δ981-2 | foscarnet, ganciclovir, and cidofovir | |||
K805Q | cidofovir | |||
UL56 | terminase complex | mutations in the codon range 231-369 | letermovir | |
UL51 | terminase complex | letermovir | ||
UL89 | terminase complex | letermovir |
Clinical Manifestations
- CMV viral load increasing or failing to decrease after 2 weeks of appropriate antiviral therapy
- Failure to improve clinically after 2 weeks of appropriate antiviral therapy
Diagnosis
- Genotyping for resistance alleles
Management
- Decrease immunosuppression, if possible
- If switching to foscarnet or cidofovir, monitor closely for renal toxicity