Staphylococcus aureus ventriculitis treated with single-dose intraventricular vancomycin or daptomycin (LY146032): bacterial and antibiotic kinetics in hydrocephalic rabbits

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 ,Ig or 120 jg) or daptomycin (7.5 jig). Results Ventriculitis is a serious complication of shunt placement for hydrocephalus, plaguing 2.7 to 27% of these procedures (25,32). Staphylococci are the most common organisms isolated from shunt infections (8,9,14,22,25,32,36). Experimental investigation of the treatment for staphylococcal ventriculitis is surprisingly lacking, and all treatment guidelines are empiric and based on clinical experience. Problems with studies of clinical ventriculitis include a lack of data on quantitative bacterial concentrations in cerebrospinal fluid (CSF) and wide variations in intraventricular antibiotic concentrations for a given dose (1,14,15,34,36,39).Vancomycin is the most common antibiotic given by the intraventricular route at our institution and is often used in the treatment of staphylococcal ventriculitis (1,2,9,10,26,31,41). Daptomycin (LY146032) (Eli Lilly & Co., Indianapolis, Ind.) is a new lipopeptide antibiotic which interrupts cell wall synthesis in gram-positive cocci at a different site of action than glycopeptide (vancomycin) and beta-lactam (cephalosporins, penicillins) antibiotics do (7,20,35). Therefore, we focused our study on the role of intraventricular vancomycin in the treatment of Staphylococcus aureus ventriculitis but compared its efficacy with that of daptomycin.The purposes of this study were as follows: (i) to establish a model of S. aureus ventriculitis in hydrocephalic rabbits, (ii) to determine the efficacies of single-dose intraventricular vancomycin and daptomycin treatment in this model, (iii) to determine the pharmacokinetics of intraventricular vancomycin and daptomycin in the CSF in vivo, (iv) to determine the penetrations of intraventricular vancomycin and daptomycin into the periventricular white matter (PVWM), and (v) to compare in vivo results from the model against established in vitro test methods. * Corresponding author. MATERIALS AND METHODSA beta-hemolytic, methicillin-resistant S. aureus strain was selected for study because it is a common pathogen, virulent in the rabbit, and treated clinically with vancomycin (22). MIC and MBC tests were performed by broth microdilution in cation-supplemented Mueller-Hinton broth (MHB) (16). The MIC testing was performed with S. aureus in cation-supplemented MHB at a concentration of approximately 105 CFU/ml. An Eppendorf digital pipette (Brinkmann

Activity of Daptomycin against Listeria monocytogenes Isolates from Cerebrospinal Fluid

“…It is, therefore, essential that new antimicrobial agents be investigated with reference to their activity against meningitis pathogens. In animal studies of meningitis due to S. aureus (5,7) and Streptococcus pneumoniae (2), daptomycin was more efficacious than vancomycin. However, daptomycin MICs for the S. aureus and S. pneumoniae strains used were 0.25 (7), 1.0 (5), and 0.06 (2), respectively, which are much lower than the daptomycin MIC 50 for L. monocytogenes.…”

Treatment of external ventricular drain-associated ventriculitis caused by Enterococcus faecalis with intraventricular daptomycin

“…5 On the other hand, a study involving a rabbit model of Staphylococcus aureus ventriculitis demonstrated that intraventricular daptomycin achieved greater bactericidal activity, more rapid killing kinetics and a longer half-life in the ventricles than intraventricular vancomycin. 6 Many years' experience of managing patients with EVD-associated ventriculitis by instilling antibiotics into the ventricles encouraged us to treat the patient described in this report with intraventricular daptomycin. This present experience suggests that intraventricular daptomycin is an effective therapy of patients with EVD-associated ventriculitis caused by enterococci; it may be equally appropriate as treatment for patients with ventriculitis caused by other Gram-positive bacteria and those with CSF shunt infections.…”

A review of daptomycin for injection (Cubicin) in the treatment of complicated skin and skin structure infections

“…Daptomycin killed more Staphylococcus aureus more rapidly than vancomycin in this model (Haworth et al 1990). …”