TY - JOUR
T1 - Mutations conferring ganciclovir resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis
AU - Jabs, D. A.
AU - Martin, B. K.
AU - Forman, M. S.
AU - Dunn, J. P.
AU - Davis, J. L.
AU - Weinberg, D. V.
AU - Biron, K. K.
AU - Baldanti, F.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with acquired immunodeficiency syndrome. In a prospective study of 210 patients with CMV retinitis, 26 were identified as having either a phenotypic or a genotypic ganciclovir-resistant isolate from either blood or urine cultures. For blood culture isolates with an IC50 >6.0 μm for ganciclovir, the sensitivity and specificity for detecting a UL97 mutation were 95% and 98%, respectively, whereas for an IC50 >8.0 μM they were 79% and 99%, respectively. Although there were trade-offs between the 2 thresholds for blood culture isolates, for urine culture isolates an IC50 >8.0 μM appeared to be better at identifying genotypic resistance. UL97 mutations identified in both the blood and urine cultures of individual patients were identical in 87.5% of cases. High-level ganciclovir resistance (IC50, >30 μM) typically, but not invariably, was associated with a mutation in both the UL97 and UL54 genes.
AB - Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with acquired immunodeficiency syndrome. In a prospective study of 210 patients with CMV retinitis, 26 were identified as having either a phenotypic or a genotypic ganciclovir-resistant isolate from either blood or urine cultures. For blood culture isolates with an IC50 >6.0 μm for ganciclovir, the sensitivity and specificity for detecting a UL97 mutation were 95% and 98%, respectively, whereas for an IC50 >8.0 μM they were 79% and 99%, respectively. Although there were trade-offs between the 2 thresholds for blood culture isolates, for urine culture isolates an IC50 >8.0 μM appeared to be better at identifying genotypic resistance. UL97 mutations identified in both the blood and urine cultures of individual patients were identical in 87.5% of cases. High-level ganciclovir resistance (IC50, >30 μM) typically, but not invariably, was associated with a mutation in both the UL97 and UL54 genes.
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U2 - 10.1086/317931
DO - 10.1086/317931
M3 - Article
C2 - 11120934
AN - SCOPUS:0035863450
VL - 183
SP - 333
EP - 337
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 2
ER -