title: Variability in telavancin cross-reactivity among vancomycin immunoassays.
abstract: Telavancin is a semisynthetic lipoglycopeptide with a dual mechanism of action against Gram-positive pathogens. Two brief reports have suggested potential cross-reactivity of telavancin with the vancomycin particle-enhanced turbidometric immunoassay (PETIA). The purpose of this study was to evaluate several commercially available vancomycin immunoassays (fluorescence polarization [FPIA], enzyme-multiplied immunoassays [EMIT], PETIA, and chemiluminescent immunoassay [CMIA]) for cross-reactivity with telavancin. Seven sites were selected to analyze serum samples for vancomycin. Each site received a set of samples (n = 18) which combined drug-free serum with telavancin, 7-OH telavancin metabolite, or vancomycin. Immunoassays demonstrating potential cross-reactivity were further evaluated by sending a duplicate sample set to multiple laboratories. Cross-reactivity was defined as the percent theoretical concentration (reported concentration/theoretical concentration × 100). No cross-reactivity was seen with FPIA or EMIT. Within the theoretical concentration range of 5 to 120 μg/ml of telavancin, the Synchron PETIA system reported vancomycin concentrations ranging from 4.7 to 54.2 μg/ml compared to vancomycin concentrations from 1.1 to 5.6 μg/ml for the Vista PETIA system. The Architect CMIA system reported vancomycin concentrations in the range of 0.27 to 0.97 μg/ml, whereas Advia Centaur XP CMIA reported vancomycin concentrations between 1.6 and 31.6 μg/ml. The Architect CMIA immunoassay had the lowest percent cross-reactivity (0.8 to 5.4%), while the Synchron PETIA immunoassay demonstrated the highest percent cross-reactivity (45.2 to 53.8%). Telavancin samples measured by liquid chromatography-mass spectroscopy were within 93.9 to 122% of theoretical concentrations. Vancomycin concentrations were not measured in any 7-OH telavancin-spiked sample. Vancomycin concentrations measured by liquid chromatography-mass spectroscopy were within 57.2 to 113% of theoretical concentrations. PETIA and CMIA measured vancomycin concentrations in telavancin-spiked samples. Significant variability in percent cross-reactivity was observed for each platform regardless of immunoassay method.
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: McConeghy
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA.
authors.forename: Siyun
authors.initials: S
authors.lastname: Liao
authors.affiliation: Theravance Biopharma US, South San Francisco, California, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Clark
authors.affiliation: Theravance, Inc., South San Francisco, California, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Worboys
authors.affiliation: Theravance Biopharma US, South San Francisco, California, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Barriere
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA kar@uic.edu.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Rodvold
mesh_terms: D000617:Aminoglycosides / Q000097:blood* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000494:pharmacology; D000906:Antibodies / Q000737:chemistry; D016477:Artifacts; D001711:Biotransformation; D003429:Cross Reactions; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007118:Immunoassay / Q000592:standards*; D000077427:Lipoglycopeptides; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014640:Vancomycin / Q000097:blood* / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000906:Antibodies; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin