Ceftaroline versus vancomycin in the treatment of methicillin-resistant staphylococcus aureus (mrsa) in an experimental mrsa meningitis model

Aim: In this study it was aimed to compare the antibacterial activity of ceftarolin and vancomycin in the treatment of methicillin-resistant Staphylococcus aureus meningitis in experimental rabbit meningitis model. Method: Meningitis was induced by direct inoculation of ATCC 43300 MRSA strain into cisterna magna of New Zealand rabbits. After 28 hours of incubation, rabbits were divided into three groups as ceftaroline (S), vancomycin (V), and control (C) groups. The S group received 10 mg/kg ceftaroline (Astra Zeneca, Cambridge, UK) twice a day, the V group received 20 mg/kg vancomycin (Koçak Farma, Istanbul, Turkey) twice a day. The C group did not receive any treatment. Quantitative bacterial cultures were performed in cerebrospinal fluid (CSF) samples, which were obtained at the beginning, 24th and 73th hours of the treatment. CSF and serum drug levels were measured by bioassay technique in samples obtained at the 24th and 73th hour of the treatment. K. rhizophila ATCC 9341 strain was used for ceftaroline drug level, B. subtilis ATCC 6633 strain was used for vancomycin drug level. In vitro time-kill data were investigated at 0, 2, 4, 6, 8, 12 and 24th hours in sterile human serum. Results: After 28 hours of incubation, 30 of 47 rabbits met the criteria of meningitis. There was no difference in the number of bacteria (calculated as log10) between the three groups at the beginning of the treatment (C: 3,968±0,521 cfu/mL, S: 3,974±0,603 cfu/mL, V: 3,967±0,527 cfu/mL, p>0,05). There was no statistically significant difference between the groups in terms of surviving rabbits at 24th hour (p> 0,05). At the end of the experiment, there was a significant difference in survival between the ceftaroline, vancomycin and control groups but not between the two treatment groups (p> 0.05). At the 24th hour of treatment, bacterial count decreased significantly in both treatment groups compared to the control group (C: +3,682±3,543 cfu/mL, S: -2,608±3,279 cfu/mL, V: -2,167±3,612 cfu/mL, p<0.05). However, there was no statistically significant difference between the S and the V groups. The CSF penetration rate of ceftaroline ranged from 38.3% to 70% (mean 51% ± 15%) in the rabbits with over the detection limit of bioassay (≥0,12 mg/L). whereas vancomycin penetration rate was 14.7% and 35.5% in the two rabbits with over the detection limit of bioassay. Although ceftaroline exhibited stronger bactericidal action than vancomycin in in vitro time-kill data, at the end of the 24- hour period the difference remained relatively unchanged and vancomycin was able to sterilize human serum at a level of at x10 MIC. Conclusion: Our results suggest that the antibacterial activity of both ceftaroline and vancomycin are similar in the treatment of MRSA meningitis in experimental rabbit model. Keywords: Meningitis, methicillin resistant Staphylococcus aureus, MRSA, ceftaroline, vancomycin, animal model, rabbit, bioassay