Abstract
Background: Emergence of human cytomegalovirus (HCMV) resistance to ganciclovir in solid-organ transplant recipients has been found to be mostly associated with primary HCMV infection. Materials and methods: The case of a donor-positive/recipeent-negative (D+/R-) lung transplant patient developing ganciclovir and cidofovir resistance is described. HCMV infection was monitored by weekly determination of antigenaemia, viraemia and DNAaemia. HCMV-specific CD4 cell immunity was determined by cytokine flow cytometry. The emergence of drug-resistant HCMV strains was documented by sequencing of UL97 and UL54 genes of HCMV directly in blood samples. Results: Following primary HCMV infection, the patient showed repeated reactivations for over a year, eventually resulting in the selection of a ganciclovir-resistant HCMV strain with a mutation in the UL97 gene product (A594V). Determination of HCMV-specific CD4 cell immunity showed a persistently impaired immune response. Subsequent foscarnet treatment allowed only transitory virus clearance from blood owing to renal toxicity. Further ganciclovir treatment induced a new mutation in both UL97 (H520Q) and UL54 (P522S) with final emergence of double resistance to both ganciclovir and cidofovir. The patient eventually died of lung failure. Discussion: Determination of HCMV-specific CD4 cell immunity could be of help in predicting the emergence of drug-resistant strains in D+/R-transplant recipients.
| Original language | English |
|---|---|
| Pages (from-to) | 536-539 |
| Number of pages | 4 |
| Journal | Journal of Antimicrobial Chemotherapy |
| Volume | 53 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2004 |
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Keywords
- CD4 cell response
- DR
- Drug resistance
- HCMV
ASJC Scopus subject areas
- Microbiology
- Pharmacology
Cite this
Human cytomegalovirus double resistance in a donor-positve/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response. / Baldanti, Fausto; Lilleri, Daniele; Campanini, Giulia; Comolli, Giuditta; Ridolfo, Anna Lisa; Rusconi, Stefano; Gerna, Giuseppe.
In: Journal of Antimicrobial Chemotherapy, Vol. 53, No. 3, 03.2004, p. 536-539.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human cytomegalovirus double resistance in a donor-positve/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response
AU - Baldanti, Fausto
AU - Lilleri, Daniele
AU - Campanini, Giulia
AU - Comolli, Giuditta
AU - Ridolfo, Anna Lisa
AU - Rusconi, Stefano
AU - Gerna, Giuseppe
PY - 2004/3
Y1 - 2004/3
N2 - Background: Emergence of human cytomegalovirus (HCMV) resistance to ganciclovir in solid-organ transplant recipients has been found to be mostly associated with primary HCMV infection. Materials and methods: The case of a donor-positive/recipeent-negative (D+/R-) lung transplant patient developing ganciclovir and cidofovir resistance is described. HCMV infection was monitored by weekly determination of antigenaemia, viraemia and DNAaemia. HCMV-specific CD4 cell immunity was determined by cytokine flow cytometry. The emergence of drug-resistant HCMV strains was documented by sequencing of UL97 and UL54 genes of HCMV directly in blood samples. Results: Following primary HCMV infection, the patient showed repeated reactivations for over a year, eventually resulting in the selection of a ganciclovir-resistant HCMV strain with a mutation in the UL97 gene product (A594V). Determination of HCMV-specific CD4 cell immunity showed a persistently impaired immune response. Subsequent foscarnet treatment allowed only transitory virus clearance from blood owing to renal toxicity. Further ganciclovir treatment induced a new mutation in both UL97 (H520Q) and UL54 (P522S) with final emergence of double resistance to both ganciclovir and cidofovir. The patient eventually died of lung failure. Discussion: Determination of HCMV-specific CD4 cell immunity could be of help in predicting the emergence of drug-resistant strains in D+/R-transplant recipients.
AB - Background: Emergence of human cytomegalovirus (HCMV) resistance to ganciclovir in solid-organ transplant recipients has been found to be mostly associated with primary HCMV infection. Materials and methods: The case of a donor-positive/recipeent-negative (D+/R-) lung transplant patient developing ganciclovir and cidofovir resistance is described. HCMV infection was monitored by weekly determination of antigenaemia, viraemia and DNAaemia. HCMV-specific CD4 cell immunity was determined by cytokine flow cytometry. The emergence of drug-resistant HCMV strains was documented by sequencing of UL97 and UL54 genes of HCMV directly in blood samples. Results: Following primary HCMV infection, the patient showed repeated reactivations for over a year, eventually resulting in the selection of a ganciclovir-resistant HCMV strain with a mutation in the UL97 gene product (A594V). Determination of HCMV-specific CD4 cell immunity showed a persistently impaired immune response. Subsequent foscarnet treatment allowed only transitory virus clearance from blood owing to renal toxicity. Further ganciclovir treatment induced a new mutation in both UL97 (H520Q) and UL54 (P522S) with final emergence of double resistance to both ganciclovir and cidofovir. The patient eventually died of lung failure. Discussion: Determination of HCMV-specific CD4 cell immunity could be of help in predicting the emergence of drug-resistant strains in D+/R-transplant recipients.
KW - CD4 cell response
KW - DR
KW - Drug resistance
KW - HCMV
UR - http://www.scopus.com/inward/record.url?scp=1642330769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1642330769&partnerID=8YFLogxK
U2 - 10.1093/jac/dkh065
DO - 10.1093/jac/dkh065
M3 - Article
C2 - 14739146
AN - SCOPUS:1642330769
VL - 53
SP - 536
EP - 539
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 3
ER -