Daptomycin versus Vancomycin in Treatment of Methicillin-Resistant Staphylococcus aureus Meningitis in an Experimental Rabbit Model

Abstract

In this study, we aimed to compare the antibacterial activities of daptomycin and vancomycin in the treatment of methicillinresistant Staphylococcus aureus (MRSA) meningitis (induced by MRSA strain ATCC 43300) in an experimental rabbit meningitis model. After an 8-h period of treatment, bacterial counts decreased significantly in both treatment groups compared to the control group (P < 0.05). However, there was no statistically significant difference between treatment groups. Our results suggest that the antibacterial activity of daptomycin is similar to vancomycin for treatment in the experimental MRSA meningitis model in rabbits. Staphylococcus aureus can cause community-acquired and nosocomial bacterial meningitis and is associated with significant mortality. Methicillin-resistant S. aureus (MRSA) is one of the major etiologic agents in hospital-acquired central nervous system infections. Since the available treatment options are limited, therapy of MRSA meningitis is problematic (1). The aim of this study was to compare the efficacies of vancomycin and daptomycin in MRSA meningitis in an experimental rabbit meningitis model.Bacterial strain. S. aureus ATCC 43300 (vancomycin MIC, 1 mg/liter; daptomycin MIC, 0.064 mg/liter [measured in duplicate using the Etest; AB Biodisk, Solna, Sweden]) was used as the infecting bacterial strain (2).The bacterial solution was prepared in 0.9% NaCl at a concentration of 10 6 CFU/ml as described elsewhere (2, 3). Antimicrobial agents. The drugs used were vancomycin (Lilly, Indianapolis, IN) and daptomycin (Novartis Pharma AG, Basel, Switzerland).Rabbit meningitis model. New Zealand White rabbits weighing 2.5 to 3.0 kg were anesthetized by intramuscular injections of ketamine (35 mg/kg of body weight) and xylazine (5 mg/kg) before each intraventricular intervention, including induction of meningitis and cerebrospinal fluid (CSF) sampling (2). The duration of anesthesia was 10 to 15 min. Then, 0.5 ml of the bacterial solution of MRSA was injected directly into the cisterna magna of each rabbit by using a 22-gauge spinal needle (Hayat Ticaret, Istanbul, Turkey).Animals were not anesthetized after the primary inoculation or between the CSF sampling procedures. In addition, they were kept in their cages, except during intraventricular interventions.Sixteen hours after the inoculation, meningitis criteria were determined. CSF white cell counts of more than 1,000/mm 3 (counted by using a Thoma slide) and a bacterial count of Ն10 3 CFU/ml were accepted as the indications of meningitis. Then, rabbits were separated into three groups: the daptomycin (D) group received one dose of 15 mg/kg daptomycin, and the vancomycin (V) group received 20 mg/kg vancomycin two times (4 h apart) through a peripheral ear vein. The control (C) group did not receive any drug treatment (4).Quantitative bacterial cultures were prepared from CSF samples, which were obtained at the beginning and at 8 hours after treatment. CSF and serum drug levels were measured by a bioassay technique in samples obtained at ...

Use of the Antimicrobial Peptide Sublancin with Combined Antibacterial and Immunomodulatory Activities To Protect against Methicillin-Resistant Staphylococcus aureus Infection in Mice

“…Methicillin-resistant S. aureus ATCC43300 was the test organism used throughout this study. This particular MRSA strain has been widely used to assess antibacterial activities of antimicrobial substances or to establish several animal infection models. − The bacteria were grown in LB broth at 37 °C with 120 rpm shaking for 18 h. Sublancin was generated in our laboratory using a highly efficient expression system involving B. subtilis 800 as described previously . The amino acid sequence of sublancin was GLGK­A­Q­C­A­A­L­W­L­Q­C­A­S­G­G­T­I­G­C­G­G­G­A­V­A­C­Q­N­Y­R­QFCR, and its relative molecular mass was 3879.8 Da.…”

Bacterial Meningitis: Insights Into Pathogenesis and Evaluation of New Treatment Options: A Perspective from Experimental Studies

“…In rabbits with staphylococcal meningitis, daptomycin was at least as effective as vancomycin to clear the infection [129,130].…”

The direct anti-MRSA effect of emodin via damaging cell membrane

“…Generally, new anti-MRSA active compounds are obtained from bioseparation, chemical synthesis, or structural modification of existing antibiotics, such as daptomycin and linezolid (Bardak-Ozcem et al 2013;Tanaka et al 2013;Nguyen et al 2014). Active components from natural plants generally have low toxicity and good security features compared to synthetic drugs.…”