Emergence and persistence of multiple antiviral-resistant CMV strains in a highly immunocompromised child.
BACKGROUND
The emergence of human cytomegalovirus (CMV) antiviral resistance plays a significant role in disease progression in immunocompromised patients who have received antiviral therapy.


OBJECTIVE
To determine the pattern of antiviral-resistant CMV strains in a highly immunocompromised child.


METHODS
Retrospective specimens of blood and urine were analysed using PCR-sequencing to identify antiviral-resistant CMV strains containing UL97 or UL54 mutations.


RESULTS
CMV strains resistant to antiviral agents contributed to disease in a bone marrow transplant recipient with X-linked severe combined immunodeficiency (SCID) treated with ganciclovir (GCV) and foscarnet (FOS). Retrospective analyses detected GCV-resistant CMV (L595S) in a specimen taken after disease progression. This GCV-resistant CMV strain persisted for 1 year, after which time it was no longer detected even though the patient continued to receive GCV. A FOS-resistant strain (T700A) then emerged even though no FOS had been administered in the preceding year.


CONCLUSIONS
The detection of antiviral-resistant CMV did not follow the patterns found in other patients tested for antiviral resistance, including emergence of a FOS-resistant strain in the absence of antiviral-selective pressure. These findings indicate the patient's underlying immunosuppressive condition should be considered for diagnosis and management of resistant CMV.
Iwasenko
Jenna M
JM
Virology Research, POWH and UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW, Australia.
Scott
Gillian M
GM
Ziegler
John B
JB
Rawlinson
William D
WD
D000998:Antiviral Agents / Q000494:pharmacology*; D002648:Child; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology / Q000821:virology*; D016903:Drug Monitoring; D024921:Drug Resistance, Multiple, Viral; D017245:Foscarnet / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016867:Immunocompromised Host; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies; D053632:X-Linked Combined Immunodeficiency Diseases / Q000150:complications
D000998:Antiviral Agents; D017245:Foscarnet; D015774:Ganciclovir