Nephrotoxicity was assessed in 173 critically ill patients receiving intravenous colistin or polymyxin B; it occurred in 60.4% and 41.8%, respectively. Further investigation is necessary to elucidate the reason for the difference in nephrotoxicity observed between the groups and to assess the impact of severity of illness and dosing/administration.
Twelve laboratories collaborated in formulating and testing a standardized plaque reduction assay for cytomegalovirus (CMV) cell-associated clinical isolates. Four characterized and plaque-purified CMV strains, as well as six coded clinical isolates obtained after antiviral therapy, were distributed and tested. Good agreement was obtained for four of the clinical isolates, but a broad distribution of results was obtained for two isolates. Analysis of these results indicates the problems associated with clinical isolates, including the large genetic variability and the highly cell-associated phenotype. This collaborative effort, by addressing these problems, represents a significant step toward the development of a standardized assay.Cytomegalovirus (CMV) is a major opportunistic pathogen in immunocompromised hosts. Long-term therapy with ganciclovir (GCV) and foscarnet (PFA) has been associated with development of clinical resistance and progression of disease (3,4,9,10). Standardized laboratory methods to rapidly and accurately determine the susceptibility of CMV isolates to antiviral drugs are needed. The inherent difficulties in working with CMV include the slow growth of the virus and the fact that CMV clinical isolates are strongly cell associated. Multiple passages in culture are typically required to generate sufficient extracellular virus for titration and testing. Standard susceptibility assays require the inhibition of viral replication in the presence of serial concentrations of drug. The slow growth of CMV has limited the usefulness of standard assays in patient management and in guiding clinical trials. Thus, the ultimate goal is to develop a rapid method that can be used directly on clinical samples to detect resistance mutations (1, 11). As a first step toward this goal, 12 laboratories in the CMV Resistance Working Group of the AIDS Clinical Trials Group (ACTG) have collaborated in formulating and testing a standardized plaque reduction assay to use as a "gold standard." In the first phase of this process, four characterized plaque-purified CMV strains (two laboratory strains and two clinical isolates) were distributed and tested in 12 laboratories using variations of a plaque reduction assay. In the second phase, a consensus assay was used to retest these strains, as well as six additional coded clinical isolates. The inhibition curves were calculated by computer modeling using a PROC NLIN program of SAS. The results are presented in this report.
MATERIALS AND METHODS
Cells and drugs.In phase 1, human diploid fibroblasts from a variety of sources, commercial and in-house, were used. In phase 2, MRHF (human foreskin) cell cultures (Biowhittaker, Walkersville, Md.) were used by all of the laboratories. GCV was provided by Syntex-Roche, and PFA was provided by Astra Pharmaceuticals. The drugs were prepared from common lots by the Viral Quality Assurance Laboratory of the ACTG at Rush-Presbyterian-St. Luke's Medical Center. GCV (4.5 mM) and PFA (20 mM) stocks were filter sterilized, shipped on dry i...
Treatment-induced changes of HIV RNA concentration in blood are generally associated with a corresponding change in seminal HIV RNA: If confirmed in larger studies, potent antiretroviral therapy might reduce the spread of HIV-1.
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