       Document 0839
 DOCN  M9460839
 TI    Antiviral susceptibility testing of cytomegalovirus from primary culture
       using shell vial assay to detect the late viral antigen.
 DT    9404
 AU    Lipson SM; Tseng LF; Kaplan MH; Biondo FX; Virology Laboratory, North
       Shore University Hospital-Cornell; University Medical College,
       Manhasset, NY 11030.
 SO    Diagn Microbiol Infect Dis. 1993 Nov-Dec;17(4):283-91. Unique Identifier
       : AIDSLINE MED/94155540
 AB    Susceptibility testing of 68 cytomegalovirus (CMV) peripheral blood
       isolates to Ganciclovir (DHPG) and 11 blood isolates to Foscarnet (PFA),
       was performed on primary culture isolates using the shell vial assay
       methodology (SVA-IFA, that is, quantitation of fluorescent focus units,
       FFUs), with an anti-CMV monoclonal antibody to the late viral antigen. A
       positive reaction in monolayer cultures of MRC-5 cells was characterized
       by cytoplasmic fluorescence with inclusions at both or more commonly off
       one end of the elongated fibroblast nucleus. Isolates from conventional
       MRC-5 tube cultures displaying a 1+ (10% cytopathic effect) were
       inoculated into shell vials containing DHPG concentrations of 0, 1.5, 3,
       6, 12, or 24 microliters/ml shell vials containing 400, 500, 800, or
       1200 microM PFA. The optimal readability of monolayers (expressed as
       FFUs per monolayer) occurred at 96 h after treatment with DHPG and at
       36-48 h with PFA. Resistance to DHPG was determined at the concentration
       of antiviral agent necessary to reduce the number of FFUs to 90% or 50%
       of the control [that is, the 90% minimum inhibitory concentration
       (MIC90) or MIC50]. Six of 68 isolates showed an MIC90 > 12 or an MIC50 >
       1.5 microgram/ml, and were considered DHPG resistant. Three of the six
       isolates were from AIDS patients with late-stage disease who had never
       received DHPG therapy. All but one (specimen 2400) DHPG-resistant
       isolates revealed MIC90 values to a PFA concentration of 500 microM,
       which is considered an achievable peak plasma level in patients
       undergoing PFA therapy. The single DHPG- and FPA-resistant isolate was
       obtained from a patient displaying marked clinical resistance to both
       drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Acquired Immunodeficiency Syndrome/BLOOD/*MICROBIOLOGY  Antigens,
       Viral/*ISOLATION & PURIF  Cytomegalovirus/CHEMISTRY/*DRUG
       EFFECTS/ISOLATION & PURIF  Drug Resistance, Microbial
       Foscarnet/*PHARMACOLOGY  Ganciclovir/*PHARMACOLOGY  Human  Microbial
       Sensitivity Tests  Support, Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

