Affiliation:
1. Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences
2. School of Medicine, Wayne State University, Detroit, Michigan 48201
Abstract
ABSTRACT
Daptomycin exhibits in vitro bactericidal activity against clinically significant gram-positive bacteria. We employed pharmacodynamic modeling to determine a once-daily dosing regimen of daptomycin that correlates to pharmacodynamic endpoints for different resistant gram-positive clinical strains. An in vitro pharmacodynamic model with an initial inoculum of 6 log
10
CFU/ml was used to simulate daptomycin regimens ranging in dose from 0 to 9 mg/kg of body weight/day, with corresponding exposures reflecting free-daptomycin concentrations in serum. Bacterial density was profiled over 48 h for two methicillin-resistant
Staphylococcus aureus
(MRSA-67 and -R515), two glycopeptide intermediate-resistant
S. aureus
(GISA-992 and -147398), and two vancomycin-resistant
Enterococcus faecium
(VREF-12366 and -SF12047) strains. A sigmoid dose-response model was used to estimate the effective dose required to achieve 50% (ED
50
) and 80% (ED
80
) bacterial density reduction at 48 h. Daptomycin MICs for study isolates ranged from 0.125 to 4 μg/ml. Model fitting resulted in an
r
2
of >0.80 for all tested isolates. Control growths at 48 h ranged from 7.3 to 8.5 log
10
CFU/ml. Sigmoid relationships were not superimposable between categorical resistant species: ED
50
and ED
80
values were 1.9 and 3.1, 4.2 and 5.6, and 5.4 and 6.8 mg/kg for MRSA, GISA, and VREF isolates, respectively. Doses required to achieve ED
50
and ED
80
values correlated with MIC differences between tested organisms. Corresponding area under the concentration-time curve from 0 to 24 h/MIC exposure ratios demonstrated a wide range of ED
80
values among the tested isolates. Doses ranging between 3 and 7 mg/kg produced significant bactericidal activity (ED
80
) against these multidrug-resistant
S. aureus
and
E. faecium
isolates.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference22 articles.
1. Analysis of Vancomycin Population Susceptibility Profiles, Killing Activity, and Postantibiotic Effect against Vancomycin-Intermediate
Staphylococcus aureus
2. In Vitro Activities of Daptomycin, Arbekacin, Vancomycin, and Gentamicin Alone and/or in Combination against Glycopeptide Intermediate-Resistant
Staphylococcus aureus
in an Infection Model
3. Centers for Disease Control and Prevention. 1998. Summary of notifiable diseases United States. Morb. Mortal. Wkly. Rep. 47: 19.
4. Centers for Diseases Control and Prevention. 1997. Interim guidelines for prevention and control of staphylococcal infection associated with reduced susceptibility to vancomycin. Morb. Mortal. Wkly. Rep. 46: 626-628 635.
5. Garrett, D. O., E. Jochimsen, K. Murfitt, B. Hill, S. McAllister, P. Nelson, R. V. Spera, R. K. Sall, F. C. Tenover, J. Johnston, B. Zimmer, and W. R. Jarvis. 1999. The emergence of decreased susceptibility to vancomycin in Staphylococcus epidermidis. Infect. Control Hosp. Epidemiol.20:167-170.
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