Yıl: 2012 Cilt: 46 Sayı: 3 Sayfa Aralığı: 359 - 365 Metin Dili: Türkçe

Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi

Öz:
Günümüzde, tüm dünyada çoğul ilaç direncine sahip gram-pozitif bakterilerin etken olduğu enfeksiyonların oranı giderek artmaktadır. Ayrıca, enterokok suşları arasında glikopeptid antibiyotiklere direncin ortaya çıkması ve giderek yayılması, bu bakterilerin etken olduğu enfeksiyonların tedavisinde kullanılabilecek yeni antimikrobiyallerin geliştirilmesini zorunlu hale getirmiştir. Oksazolidinon grubu antibiyotik olan linezolid ve bir ikinci kuşak yarı sentetik lipoglikopeptid antibiyotik olan dalbavansin, sıklıkla rastlanan antimikrobiyal maddelere dirençli gram-pozitif patojenlerle gelişen enfeksiyonların tedavisi için başlıca seçenekleri oluşturmaktadır. Bu çalışmanın amacı, linezolid ve dalbavansinin vankomisine dirençli enterokok (VRE) suşlarına karşı in vitro antimikrobiyal aktivitesini belirlemektir. 2006-2007 yılları arasında İstanbul Üniversitesi İstanbul Tıp Fakültesi kliniklerinde yatan hastaların rektal sürüntü örneklerinden izole edilmiş toplam 100 VRE suşu, çalışma kapsamına alınmıştır. Tüm suşlar, geleneksel yöntemlerle cins düzeyinde tanımlanmıştır. Mikrodilüsyon yöntemiyle yapılan duyarlılık deneylerinde vankomisinin minimum inhibitör konsantrasyonu (MİK) ≥ 32 μg/ml olarak saptanmıştır. Linezolid ve dalbavansin duyarlılığının belirlenmesinde de mikrodilüsyon yöntemi uygulanmıştır. Kalite kontrolü için her bir deney serisinde, Staphylococcus aureus ATCC 29213 ve Enterococcus faecalis ATCC 29212 referans suşları kullanılmıştır. Linezolide dirençli suşlarda tür düzeyinde tanımlama, 16S rRNA’nın dizilenmesiyle yapılmış; direnç mekanizmaları ise 23S rRNA’nın dizilenmesiyle araştırılmıştır. İncelenen suşlar için, linezolid ve dalbavansin MİK50, MİK90 ve MİK aralıkları sırasıyla 4, 4, 1-6 μg/ml ve 32, 64, 0.25-128 μg/ml olarak bulunmuştur. Linezolide duyarlılık, orta duyarlılık ve direnç oranları ise, aynı sırayla %32, %66 ve %2 olarak saptanmıştır. Linezolide dirençli iki suş Enterococcus faecium olarak tanımlanmış ve sonuçlar Pasteur Enstitüsünde doğrulanmıştır. Bu, Türkiye’de ilk linezolide ve vankomisine dirençli E.faecium suşu bildirimidir. Her iki suşun 23S rRNA geninde G2576T mutasyonu saptanmıştır. Dalbavansin için henüz “Clinical and Laboratory Standards Institute (CLSI)” tarafından bir duyarlılık sınır değeri belirtilmediği için, duyarlılık ve direnç oranları saptanamamıştır. Belirlenen MİK değerlerine göre, linezolid VRE suşlarına karşı en etkili antibiyotik olarak belirlenmiş, dalbavansin ise vankomisinden daha etkili bulunmuştur. Ayrıca, çalışmamızın sonuçları yatan hasta örneklerinden izole edilen VRE suşlarında, linezolid direncinin rutin olarak izlenmesinin gerekliliğini de göstermiştir.
Anahtar Kelime:

In vitro activity of linezolid and dalbavancin against vancomycin-resistant enterococci

Öz:
The incidence of infections caused by multidrug resistant gram-positive bacteria is increasing worlwide. In addition, emergence and dissemination of glycopeptide resistance in enterococci has accelerated the need for the development of new antimicrobial agents for treatment. Linezolid which is an oxazolidinone and dalbavancin which is a second-generation, semi-synthetic lipoglycopeptid are important therapeutic options for infections caused by antimicrobial-resistant gram-positive pathogens. The aim of this study was to investigate the in-vitro antimicrobial activity of linezolid and dalbavancin against vancomycin- resistant enterococci (VRE). A total of 100 VRE strains, isolated from rectal swabs of patients hospitalized in Istanbul University Faculty of Istanbul Medicine between 2006-2007 were included in the study. All strains were identified as Enterococcus spp. by conventional methods and had minimum inhibitory concentrations (MICs) of ≥ 32 μg/ml for vancomycin. Vancomycin, linezolid and dalbavancin susceptibility testing was performed by broth microdilution method. For the quality control of the tests, S.aureus ATCC 29213 and E.faecalis ATCC 29212 were included in each run. Molecular identification of linezolid-resistant strains (n= 2) were done by 16S rRNA sequencing and resistance mechanisms were tested by 23S rRNA sequencing. Against VRE strains, MIC50, MIC90 and MIC ranges of linezolid and dalbavancin were found as 4, 4, 1-16 μg/ml and 32, 64, 0.25-128 μg/ml, respectively. Linezolid susceptibility, intermediate susceptibility and resistance rates were found as 32%, 66% and 2% in the same order. Linezolid-resistant two strains were identified as E.faecium, and this data was confirmed by Pasteur Institute. Both of those isolates had G2576T mutations in 23S rRNA genes. Because susceptibility breakpoint for dalbavancin has not been established by Clinical and Laboratory Standards Institute (CLSI) yet, susceptibility and resistance rates for dalbavancin were not indicated. According to the MIC results, linezolid was found to be the most effective antibiotic against VRE strains, and dalbavancin was found more effective than vancomycin. Additionally, our results showed that routine susceptibility testing of VRE strains isolated from hospitalized patients to linezolid was required.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Bibliyografik
  • 1. Woodford N. Novel agents for the treatment of resistant gram-positive infections. Expert Opin Investig Drugs 2003; 12(2): 117-37.
  • 2. Climo MW, Archer GL, Monroe S. Vancomycin-resistant gram-positive pathogens: potential approaches for prevention and control, pp: 169-85. In: Wenzel RP (ed), Prevention and Control of Nosocomial Infections, 2003, 4th ed. Lippincott Williams and Wilkins, Philadelphia.
  • 3. Livermore DM. Linezolid in vitro: mechanism and antibacterial spectrum. J Antimicrob Chemother 2003; 51(Suppl 2): ii9-16.
  • 4. Malabarba A, Goldstein BP. Origin, structure, and activity in-vitro and in-vivo of dalbavancin. J Antimicrob Chemother 2005; 55(Suppl 2): ii15-20.
  • 5. Goldstein BP, Draghi DC, Sheehan DJ, Hogan P, Sahm DF. Bactericidal activity and resistance development profiling of dalbavancin. Antimicrob Agents Chemother 2007; 51(4): 1150-4.
  • 6. Teixeira LM, Facklam RR. Enterococcus, pp: 422-33. In: Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH (eds), Manual of Clinical Microbiology, 2003, 8th ed. ASM Press, Washington, DC.
  • 7. Ruoff KL. Aerococcus, Abiorophia, and other infrequently isolated aerobic catalase-negative, gram-positive cocci, pp: 34-44. In: Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH (eds), Manual of Clinical Microbiology, 2003, 8th ed. ASM Press, Washington, DC.
  • 8. Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard, Document M7-A7. 2006, CLSI, Wayne, PA.
  • 9. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 15th informational supplement, Document M100-S15. 2005, CLSI, Wayne, PA.
  • 10. Edwards U, Rogall T, Blöcker H, Emde M, Böttger EC. Isolation and direct complete nucleotide determination of entire genes. Characterization of a gene coding for 16S ribosomal RNA. Nucleic Acids Res 1989; 17(19): 7843-53.
  • 11. Zheng D, Alm EW, Stahl DA, Raskin L. Characterization of universal small-subunit rRNA hybridization probes for quantitative molecular microbial ecology studies. Appl Environ Microbiol 1996; 62(12): 4504-13.
  • 12. Prystowsky J, Siddiqui F, Chosay J, et al. Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycin-resistant enterococci. Antimicrob Agents Chemother 2001; 45(7): 2154-6.
  • 13. Lodise TP, McKinnon PS, Tam VH, Rybak MJ. Clinical outcomes for patients with bacteremia caused by vancomycin- resistant enterococcus in a level 1 trauma center. Clin Infect Dis 2002; 34(7): 922-9.
  • 14. Borgmann S, Schulte B, Wolz C, et al. Discrimination between epidemic and non-epidemic glycopeptideresistant E.faecium in a post-outbreak situation. J Hosp Infect 2007; 67(1): 49-55.
  • 15. Babcock HM, Ritchie DJ, Christiansen E, Starlin R, Little R, Stanley S. Successful treatment of vancomycinresistant Enterococcus endocarditis with oral linezolid. Clin Infect Dis 2001; 32(9): 1373-5.
  • 16. Patel R. Rouse MS, Piper KE, Steckelberg JM. Linezolid therapy of vancomycin-resistant Enterococcus faecium experimental endocarditis. Antimicrob Agents Chemother 2001; 45(2): 621-3.
  • 17. Streit JM, Fritsche TR, Sader HS, Jones RN. Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates. Diagn Microbiol Infect Dis 2004; 48(2): 137-43.
  • 18. Streit JM, Sader HS, Fritsche TR, Jones RN. Dalbavancin activity against selected populations of antimicrobial- resistant gram-positive pathogens. Diagn Microbiol Infect Dis 2005; 53(4): 307-10.
  • 19. Gales AC, Sader HS, Jones RN. Antimicrobial activity of dalbavancin tested against gram-positive clinical isolates from Latin American medical centers. Clin Microbiol Infect 2005; 11(2): 95-100.
  • 20. Jones RN, Ross JE, Bell JM, et al. Zyvox annual appraisal of potency and spectrum program: linezolid surveillance program results for 2008. Diagn Microbiol Infect Dis 2009; 65(4): 404-13.
  • 21. Farrell DJ, Mende RE, Ross JE, Jones RN. Linezolid surveillance program results for 2008 (LEADER Program for 2008). Diagn Microbiol Infect Dis 2009; 65(4): 392-403.
  • 22. Tunger A, Aydemir S, Uluer S, Cilli F. In vitro activity of linezolid & quinupristin/dalfopristin against grampositive cocci. Indian J Med Res 2004; 120(6): 546-52.
  • 23. Bae HG, Sung H, Kim MN, Lee EJ, Koo Lee S. First report of a linezolid- and vancomycin-resistant Enterococcus faecium strain in Korea. Scand J Infect Dis 2006; 38(5): 383-6.
  • 24. Krawczyk B, Samet A, Bronk M, Hellmann A, Kur J. Emerging linezolid-resistant, vancomycin resistant Enterococcus faecium from a patient of a haematological unit in Poland. Pol J Microbiol 2004; 53(3): 193-6.
  • 25. Scheetz MH, Knechtel SA, Postelnick MJ, Malczynski M, Qi C. Differences in clinical outcomes in patients with vancomycin-resistant enterococci according to linezolid susceptibility. Pharmacotherapy 2010; 30(12): 1221-8.
  • 26. Swoboda S, Fritz S, Martignoni ME, et al. Varying linezolid susceptibility of vancomycin-resistant Enterococcus faecium isolates during therapy: a case report. J Antimicrob Chemother 2005; 56(4): 787-9.
  • 27. Schulte B, Heininger A, Autenrieth IB, Wolz C. Emergence of increasing linezolid-resistance in enterococci in a post-outbreak situation with vancomycin-resistant Enterococcus faecium. Epidemiol Infect 2008; 136(8): 1131-3.
  • 28. Biedenbach DJ, Bell JM, Sader HS, Turnidge JD, Jones RN. Activities of dalbavancin against a worldwide collection of 81.673 gram-positive bacterial isolates. Antimicrob Agents Chemother 2009; 53(3): 1260-3.
  • 29. Cornaglia G, Rossolini GM. Forthcoming therapeutic perspectives for infections due to multidrug-resistant gram-positive pathogens. Clin Microbiol Infect 2009; 15(3): 218-23.
APA AKTAŞ G, BOZDOĞAN B, DERBENTLİ Ş (2012). Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi. Mikrobiyoloji Bülteni, 46(3), 359 - 365.
Chicago AKTAŞ GÜLSEREN,BOZDOĞAN Bülent,DERBENTLİ Şengül Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi. Mikrobiyoloji Bülteni 46, no.3 (2012): 359 - 365.
MLA AKTAŞ GÜLSEREN,BOZDOĞAN Bülent,DERBENTLİ Şengül Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi. Mikrobiyoloji Bülteni, vol.46, no.3, 2012, ss.359 - 365.
AMA AKTAŞ G,BOZDOĞAN B,DERBENTLİ Ş Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi. Mikrobiyoloji Bülteni. 2012; 46(3): 359 - 365.
Vancouver AKTAŞ G,BOZDOĞAN B,DERBENTLİ Ş Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi. Mikrobiyoloji Bülteni. 2012; 46(3): 359 - 365.
IEEE AKTAŞ G,BOZDOĞAN B,DERBENTLİ Ş "Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi." Mikrobiyoloji Bülteni, 46, ss.359 - 365, 2012.
ISNAD AKTAŞ, GÜLSEREN vd. "Linezolid ve dalbavansinin vankomisine dirençli enterokok suşlarına karşı in vitro aktivitesi". Mikrobiyoloji Bülteni 46/3 (2012), 359-365.