Tavşanda metisiline dirençli staphylococcus aureus ile oluşturulmuş deneysel menenjit modelinde seftarolin, seftobiprol, televansin ile vankomisinin bakteriyolojik etkinliklerinin karşılaştırılması
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Dosyalar
Tarih
2016
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Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Bu çalışmada tavşanda metisiline dirençli S. aureus kökeni ile (MRSA) oluşturulmuş deneysel menenjit modelinde seftarolin ve vankomisinin antibakteriyel etkinliklerinin karşılaştırılması amaçlandı.
Yöntem: Menenjit, standart ATCC 43300 MRSA kökeninin Yeni Zelanda tavşanlarının sisterna magnaları içine doğrudan inokülasyonu ile oluşturuldu. Tavşanlar 28 saatlik enkübasyon süresinin ardından kontrol, seftarolin ve vankomisin olmak üzere üç gruba ayrıldı. Seftarolin grubuna 10 mg/kg seftarolin (Astra Zeneca, Cambridge, Britanya) günde iki kez, vankomisin grubuna 20 mg/kg vankomisin (Koçak Farma, İstanbul, Türkiye) günde iki kez verildi, kontrol grubuna ilaç verilmedi. Tedaviye başlandıktan sonra sıfırıncı, 24. ve 73. saatlerde alınan BOS örneklerinden kantitatif kültür yapıldı. Yirmidördüncü ve 73. saatte alınan serum ve BOS örneklerinde biyolojik yöntemle ilaç seviyesi ölçümü yapıldı. Seftarolin ilaç düzeyi için, K. rhizophilia ATCC 9341 kökeni, vankomisin ilaç düzeyi için ise B. subtilis ATCC 6633 kökeni kullanıldı. Steril insan serumunda 0,2,4,6,8,12 ve 24. saatlerde in vitro zamana karşı öldürme verileri araştırıldı.
Bulgular: Yirmisekiz saatlik enkübasyon süresinin sonunda 47 tavşandan 30’u menenjit kriterlerini sağlıyordu. Alınan BOS örneklerindeki bakteri miktarları logaritma 10 cinsinden hesaplandığında enkübasyon süresinin sonunda kontrol grubunda 3,968±0,521 kob/mL, seftarolin grubunda 3,974±0,603 kob/mL, vankomisin grubunda 3,967±0,527 kob/mL bakteri vardı (p>0,05). Deney sırasında 24. saatte sağ kalan tavşanlar açısından gruplar arasında anlamlı fark yoktu (p>0,05). Deney sonunda seftarolin ve vankomisin grupları ile kontrol grubu arasında sağkalım açısından anlamlı fark varken (p<0.05), iki tedavi grubu arasında anlamlı fark yoktu (p>0,05). Tedavinin 24. saatinde BOS’daki bakteri miktarı tedavi gruplarında kontrol grubuna göre istatistiksel olarak anlamlı şekilde düştü (kontrol: 3,682±3,543 kob/mL, seftarolin: -2,608±3,279kob/mL, vankomisin: -2,167±3,612 kob/mL). Seftarolin ve vankomisin grupları arasında anlamlı fark yoktu. BOS’da saptanabilir düzeyin üzerinde seftarolin (≥0,12 mg/L) saptanan tavşanlarda, seftarolinin BOS’a geçiş oranı %38.3 ile %70 arasında değişmekteydi (ortalama %51±15). Vankomisin (saptanabilir düzey: ≥0,5 mg/L) grubunda BOS’a geçiş oranı ise, ölçülebilen iki tavşanda %14,7 ve %35,5 idi. İn vitro zamana karşı öldürme verilerinde seftarolin vankomisine kıyasla daha kuvvetli bakterisidal etki göstermiş olsa da 24. saatin sonunda aradaki farkın nispeten kapandığı ve vankomisinin de en azından x10 MIC düzeyinde insan serumunu steril hale getirmeyi başardığı saptandı.
Sonuç: Bu bulgular MRSA ile oluşturulmuş tavşan menenjiti modelinde seftarolinin antibakteriyel etkinliğinin en az vankomisin kadar olduğunu düşündürmektedir.
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.
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.
Açıklama
Anahtar Kelimeler
Menenjit, Metisiline Dirençli Staphylococcus Aureus, MRSA, Seftarolin, Vankomisin, Hayvan Modeli, Tavşan, Bioassay, Meningitis, Methicillin Resistant Staphylococcus Aureus, MRSA, Ceftaroline, Vancomycin, Animal Model, Rabbit, Bioassay
