Rapid decrease of free vancomycin in dense staphylococcal cultures |
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Authors: | C Ekdahl H Hanberger A Hällgren M Nilsson E Svensson L E Nilsson |
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Institution: | 1. Division of Infectious Diseases, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University of Link?ping, 581 85, Link?ping, Sweden 2. Division of Clinical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University of Link?ping, 581 85, Link?ping, Sweden 3. Division of Clinical Bacteriology, Department of Laboratory Medicine, Sahlgrenska University Hospital, 413 46, G?teborg, Sweden
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Abstract: | Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for
strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (105–108 bacteria/ml) after 24 h of incubation in supplemented Mueller–Hinton broth containing vancomycin. All of the tested strains
except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations
in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin
concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low
inoculum (105 bacteria/ml), the broth MICs were 1–4 μg/ml. In a high inoculum (∼108 bacteria/ml), the broth MICs increased two- to fourfold to 4–8 μg/ml. In dense inocula (∼109–1010 bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of
the bioassay (≤0.5 μg/ml). This reduction of free vancomycin was fast, occurring in initially dense inocula in less than 30 min.
No emergence of resistance was seen. These results show a rapid reduction of free vancomycin in the broth and a simultaneous
increase in broth MICs in high inocula, without development of resistance. This indicates that the dosing regimen of vancomycin
is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis. |
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