Staphylococcus aureus ventriculitis treated with single-dose intraventricular vancomycin or daptomycin (LY146032):
C S Haworth1, M W Sobieski, W M Scheld
1Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville 22908.
Abstract:
Vancomycin and a new antibiotic, daptomycin (LY146032), were tested in vitro and in vivo against Staphylococcus aureus. In vivo tests were performed with rabbits with kaolin-induced hydrocephalus. Five groups of rabbits were studied: untreated ventriculitis, intraventricular vancomycin only, and ventriculitis treated with intraventricular vancomycin (30 micrograms or 120 micrograms) or daptomycin (7.5 micrograms). Results of this study were as follows. (i) S. aureus demonstrated static growth in cerebrospinal fluid in vitro and in ventriculitis at a maximum titer of 10(5) to 10(6) CFU/ml. (ii) In vitro time kill curves in cerebrospinal fluid matched those in vivo. (iii) Single-dose intraventricular vancomycin did not lower S. aureus concentrations over 8 h, whereas daptomycin did. (iv) Ventriculitis did not significantly alter the clearance of intraventricular vancomycin. (v) Intraventricular half-lives were approximately 2.8 h (maximum) for vancomycin and 4.5 h for daptomycin. (vi) Vancomycin was detectable in the periventricular white matter only in the presence of ventriculitis. Daptomycin was also detectable in the periventricular white matter of rabbits with ventriculitis, but in amounts too small to quantitate. We concluded that daptomycin achieved greater bactericidal activity, more rapid killing kinetics, and a longer half-life in the ventricle than vancomycin did in this model.
Insights
Daptomycin demonstrated superior efficacy against Staphylococcus aureus ventriculitis in rabbits compared to vancomycin. This new antibiotic showed greater bactericidal activity, faster killing, and a longer half-life in the cerebrospinal fluid.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Staphylococcus aureus infections, particularly ventriculitis, pose significant treatment challenges.
- Vancomycin is a standard treatment, but resistance and efficacy concerns necessitate exploring alternatives.
Purpose of the Study:
- To compare the in vitro and in vivo efficacy of vancomycin and daptomycin against Staphylococcus aureus ventriculitis.
- To evaluate pharmacokinetic parameters and tissue penetration of both antibiotics in a rabbit model.
Main Methods:
- In vitro susceptibility testing and time-kill curves in cerebrospinal fluid.
- In vivo study using rabbits with induced Staphylococcus aureus ventriculitis.
- Administration of intraventricular vancomycin or daptomycin and assessment of bacterial load, drug concentrations, and half-lives.
Main Results:
- Daptomycin exhibited greater bactericidal activity and more rapid killing of Staphylococcus aureus in vitro and in vivo compared to vancomycin.
- Intraventricular daptomycin demonstrated a longer half-life (4.5 hours) than vancomycin (2.8 hours) in the cerebrospinal fluid.
- Both antibiotics were detectable in periventricular white matter, with daptomycin present in smaller, unquantifiable amounts.
Conclusions:
- Daptomycin shows promising therapeutic potential for treating Staphylococcus aureus ventriculitis due to its enhanced bactericidal activity and favorable pharmacokinetics.
- Further investigation into daptomycin's efficacy and safety for central nervous system infections is warranted.
