Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Vankomisin Dirençli Enterokok ile Oluşturulmuş Deneysel Menenjit Modelinde Daptomisin ve Linezolidin Etkinliklerinin Karşılaştırılması
Efficacy of Daptomisin Versus Linezolid in the Treatment of Vancomycin Resistant Enterococcus Meningitis in an Experimental Rabbit Model
Sema SARIa, Ediz TÜTÜNCÜb , İrem Gül SANCAKc , İrfan ŞENCANb
a Niğde Ömer Halisdemir Üniversitesi Eğitim ve Araştırma Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji (Erişkin) ABD, Yoğun Bakım BD, Niğde, Türkiye
bDışkapı Yıldırım Beyazıt Eğitim Araştırma ve Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Kliniği, Ankara, Türkiye
c Ankara Üniversitesi Veteriner Fakültesi, Cerrahi ABD, Ankara, Türkiye
Turkiye Klinikleri J Med Sci. 2023;43(3):261-8
doi: 10.5336/medsci.2022-92253
Article Language: TR
Full Text
ÖZET
Amaç: Akut bakteriyel menenjitlerin yüksek mortalite ve morbidite oranları ile acil tedavi endikasyonları olup uygun tedavi, uygun dozda ve uygun sürede verilmelidir. Vankomisin dirençli enterokok [vancomycin resistant enterococcus (VRE)] taşıyıcılığı giderek artan oranlarda görülmeye başlanmıştır ve postoperatif menenjit etkeni olarak da karşımıza çıkmaktadır. Ancak VRE menenjitinde optimal tedavi rejimi bulunmayıp, vaka bazında değerlendirilmektedir. Bu çalışmada, deneysel menenjit modelinden yola çıkılarak VRE menenjitinde tedavi planı oluşturulmasına katkı sağlanması amaçlanmıştır. Gereç ve Yöntemler: Çalışmamızda Yeni Zelanda tavşanlarında VRE menenjit modeli oluşturulduktan sonra daptomisin ve linezolidin etkinliği kontrol grubu ile karşılaştırılmıştır. Daptomisin 15 mg/kg tek doz, linezolid 20 mg/kg dozunda 12 saat arayla 2 doz olarak uygulanmıştır. Kontrol grubuna antibiyotik verilmemiştir. Gruplar, beyin omurilik sıvısı (BOS) hücre sayımı, kültür, protein, glikoz ve eş zamanlı kan şekerleri açısından karşılaştırılmıştır. Bulgular: BOS pleositozu ve biyokimyasında her iki grupta benzer gerilemeler olmakla birlikte tedavinin 24. saatinde daptomisin grubunda tavşanların %22'sinde üreme devam ederken, linezolid ve kontrol grubunda üreme olmamıştır. Sonuç: Çalışmamızda daptomisin ve linezolid grubu arasında istatistiksel olarak anlamlı fark saptanmamıştır. VRE menenjiti için yerleşik bir tedavi rejimi olmaması nedeniyle çalışmamızdaki antibiyotiklerin etkinliğinin standart rejimle kıyaslanması imkânı olmamıştır. Mevcut bulgularla önerilebilecek optimal bir tedavi rejimi bulunmamaktadır. Yeni tedavi seçenekleri, kombinasyon tedavileri ya da intratekal, intraventriküler uygulamalar üzerine ileri araştırmalar yapılması gerekmektedir.

Anahtar Kelimeler: Menenjit; vankomisin dirençli enterokok; linezolid; daptomisin
ABSTRACT
Objective: Acute bacterial meningitis, which has a high rate of mortality and morbidity, has emergency therapy indication. Optimal therapy must be applied at optimal duration and optimal dosage. Carriage of vancomycin resistant enterococcus (VRE) are increasingly seen and we see VRE as the cause of postoperative meningitis. However, in VRE meningitis, there is no optimal treatment regimen and the disease is evaluated on a case-by-case basis. In this study, it is aimed to contribute to a treatment plan for VRE meningitis based on the experimental meningitis model. Material and Methods: In our study, after creating a VRE experimental meningitis model, daptomycin and linezolid activity was compared with control group. Daptomycin was given 15 mg/kg at one dose, linezolid was given 20 mg/kg at 2 doses every 12 hours. Groups were compared with each other for cerebrospinal fluid (CSF) cell count, culture, protein, glucose, simultaneous blood glucose. Results: In both groups, CSF pleocytosis and biochemical response were similar. In the daptomycin group 24th hour of the treatment, CSF culture was positive in 22% of the rabbits, whereas no growth was observed in linezolid and control groups. Conclusion: As a result, there is no statistically significant difference observed between daptomycin and linezolid groups. There is not a standard treatment regimen for VRE meningitis, so we couldn't compare the antibiotics that we use in our study with the standard regimen. Due to the lack of an established treatment regimen for VRE meningitis, it was not possible to compare the efficacy of antibiotics in our study with the standard regimen. Further research should be conducted on new antibiotics, combination therapies and intrathecal-intraventricular practices.

Keywords: Meningitis; vancomycin resistant enterococcus; linezolid; daptomycin
REFERENCES:
  1. Tülek N, Fışkın NT. Akut bakteriyel menenjitler. Topçu Willke A, Söyletir G, Doğanay M, editörler. Enfeksiyon Hastalıkları ve Mikrobiyolojisi. 3. Baskı. İstanbul: Nobel Tıp Kitapevleri; 2008. p.1390-422.
  2. Srinivas D, Veena Kumari HB, Somanna S, Bhagavatula I, Anandappa CB. The incidence of postoperative meningitis in neurosurgery: an institutional experience. Neurol India. 2011;59(2):195-8. [Crossref]  [PubMed] 
  3. Tunkel AR, van de Beek D, Scheld WM. Acute meningitis. Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Elsevier Churchill-Livingstone; 2015. p.1097-137. [Crossref] 
  4. Gültekin M. Enterokoklar: mikrobiyoloji, epidemiyoloji ve patogenez. Ulusoy S, Usluer G, Ünal S, editörler. Önemli ve Sorunlu Gram-Pozitif Bakteri İnfeksiyonları. 2. Baskı. Ankara: Bilimsel Tıp Kitabevi; 2012. p.189-219.
  5. Arias CA, Murray BE. Enterococcus species, streptococcus gallolyticus group, and leuconostoc species. In: Mandell GL, Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Elsevier Churchill-Livingstone; 2015. p.2328-39. [Crossref] 
  6. Durmaz G. Enterokoklar. Topçu Willke A, Söyletir G, Doğanay M, editörler. Enfeksiyon Hastalıkları ve Mikrobiyolojisi. 3. Baskı. İstanbul: Nobel Tıp Kitapevleri; 2008. p.2057-65
  7. Pintado V, Cabellos C, Moreno S, Meseguer MA, Ayats J, Viladrich PF. Enterococcal meningitis: a clinical study of 39 cases and review of the literature. Medicine (Baltimore). 2003;82(5):346-64. [Crossref]  [PubMed] 
  8. Bilgehan H. Klinik Mikrobiyolojik Tanı. 3. Baskı. İzmir: Fakülteler Kitabevi; 2009.
  9. Dacey RG, Sande MA. Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob Agents Chemother. 1974;6(4):437-41. [Crossref]  [PubMed]  [PMC] 
  10. Wang JS, Muzevich K, Edmond MB, Bearman G, Stevens MP. Central nervous system infections due to vancomycin-resistant enterococci: case series and review of the literature. Int J Infect Dis. 2014;25:26-31. [Crossref]  [PubMed] 
  11. Çay Ü, Alabaz D, Özgür Gündeşlioğlu Ö, Kibar F, Çetin C, Oktay K. Experience with enterococcal meningitis/ventriculitis in children. Pediatr Int. 2022;65(1):e15398. [Crossref]  [PubMed] 
  12. Gerber P, Stucki A, Acosta F, Cottagnoud M, Cottagnoud P. Daptomycin is more efficacious than vancomycin against a methicillin-susceptible Staphylococcus aureus in experimental meningitis. J Antimicrob Chemother. 2006;57(4):720-3. [Crossref]  [PubMed] 
  13. Arias CA, Murray BE. Emergence and management of drug-resistant enterococcal infections. Expert Rev Anti Infect Ther. 2008;6(5):637-55. [Crossref]  [PubMed] 
  14. Tan TQ. Update on the use of linezolid: a pediatric perspective. Pediatr Infect Dis J. 2004;23(10):955-6. [Crossref]  [PubMed] 
  15. Keep JM, Steel JD, Whittem JH. A clinical, pathological and experimental study of a meningitic syndrome in dogs. Aust Vet J. 1950;26(12):330-7. [Crossref]  [PubMed] 
  16. Hartmann C, Peter C, Hermann E, Ure B, Sedlacek L, Hansen G, et al. Successful treatment of vancomycin-resistant Enterococcus faecium ventriculitis with combined intravenous and intraventricular chloramphenicol in a newborn. J Med Microbiol. 2010;59(Pt 11):1371-4. [Crossref]  [PubMed] 
  17. Mueller SW, Kiser TH, Anderson TA, Neumann RT. Intraventricular daptomycin and intravenous linezolid for the treatment of external ventricular-drain-associated ventriculitis due to vancomycin-resistant Enterococcus faecium. Ann Pharmacother. 2012;46(12):e35. [Crossref]  [PubMed] 
  18. Cottagnoud P, Gerber CM, Acosta F, Cottagnoud M, Neftel K, Tauber MG. Linezolid against penicillin-sensitive and -resistant pneumococci in the rabbit meningitis model. The Journal of Antimicrobial Chemotherapy. 2000;46(6):981-5. [Crossref]  [PubMed] 
  19. Cottagnoud P, Pfister M, Acosta F, Cottagnoud M, Flatz L, Kühn F, et al. Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant pneumococci in experimental meningitis. Antimicrob Agents Chemother. 2004;48(10):3928-33. [Crossref]  [PubMed]  [PMC] 
  20. Egermann U, Stanga Z, Ramin A, Acosta F, Stucki A, Gerber P, et al. Combination of daptomycin plus ceftriaxone is more active than vancomycin plus ceftriaxone in experimental meningitis after addition of dexamethasone. Antimicrob Agents Chemother. 2009;53(7):3030-3. [Crossref]  [PubMed]  [PMC] 
  21. Vivas M, Force E, Garrigós C, Tubau F, Platteel AC, Ariza J, et al. Experimental study of the efficacy of daptomycin for the treatment of cephalosporin-resistant pneumococcal meningitis. J Antimicrob Chemother. 2014;69(11):3020-6. [Crossref]  [PubMed] 
  22. Vivas M, Force E, Tubau F, El Haj C, Ariza J, Cabellos C. Effect of dexamethasone on the efficacy of daptomycin in the therapy of experimental pneumococcal meningitis. Int J Antimicrob Agents. 2015;46(1):28-32. [Crossref]  [PubMed] 
  23. Bardak-Ozcem S, Turhan T, Sipahi OR, Arda B, Pullukcu H, Yamazhan T, et al. Daptomycin versus vancomycin in treatment of methicillin-resistant Staphylococcus aureus meningitis in an experimental rabbit model. Antimicrob Agents Chemother. 2013;57(3):1556-8. [Crossref]  [PubMed]  [PMC] 
  24. Calik S, Turhan T, Yurtseven T, Sipahi OR, Buke C. Vancomycin versus linezolid in the treatment of methicillin-resistant Staphylococcus aureus meningitis in an experimental rabbit model. Med Sci Monit. 2012;18(11):SC5-8. [Crossref]  [PubMed]  [PMC] 
  25. Cabellos C, Garrigós C, Taberner F, Force E, Pachón-Iba-ez ME. Experimental study of the efficacy of linezolid alone and in combinations against experimental meningitis due to Staphylococcus aureus strains with decreased susceptibility to beta-lactams and glycopeptides. J Infect Chemother. 2014;20(9):563-8. [Crossref]  [PubMed] 
  26. Sipahi OR, Bardak-Ozcem S, Turhan T, Arda B, Ruksen M, Pullukcu H, et al. Vancomycin versus linezolid in the treatment of methicillin-resistant Staphylococcus aureus meningitis. Surg Infect (Larchmt). 2013;14(4):357-62. [Crossref]  [PubMed] 

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