{"id":6905,"date":"2020-08-09T19:11:42","date_gmt":"2020-08-09T16:11:42","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=6905"},"modified":"2020-08-09T19:11:43","modified_gmt":"2020-08-09T16:11:43","slug":"metisiline-dayanikli-stafilokok-aureus-mrsa-dayanikliliginin-hikayesi","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/metisiline-dayanikli-stafilokok-aureus-mrsa-dayanikliliginin-hikayesi\/","title":{"rendered":"MET\u0130S\u0130L\u0130NE DAYANIKLI STAF\u0130LOKOK AUREUS (MRSA): DAYANIKLILI\u011eININ H\u0130KAYES\u0130"},"content":{"rendered":"\n

MRSA Nedir?<\/strong><\/h2>\n\n\n\n

Stafilokok aureus bakterileri, insanlarda g\u00f6r\u00fclen cilt enfeksiyonlar\u0131n\u0131n en yayg\u0131n nedenidir (1). MRSA ise, v\u00fccudun farkl\u0131 k\u0131s\u0131mlar\u0131nda enfeksiyona neden olan ve di\u011fer Stafilokok bakterilerine k\u0131yasla tedavisi daha zor olan bir bakteri \u00e7e\u015fididir (2). Bunun nedeni, bu bakterinin \u015fu anda kullan\u0131mda olan bir\u00e7ok antibiyoti\u011fe kar\u015f\u0131 diren\u00e7li olmas\u0131d\u0131r. Metisilin, eskiden Stafilokok aureus bakterilerinden kaynaklanan enfeksiyonlara kar\u015f\u0131 kullan\u0131lan \u00f6nemli bir antibiyotiktir (3). MRSA, bir\u00e7ok yerde bulunabilir ancak \u00f6zellikle hastanelerde ve sa\u011fl\u0131k hizmeti verilen ba\u015fkayerlerde daha da yayg\u0131nd\u0131r (4).<\/p>\n\n\n\n

MRSA s\u00f6z konusu oldu\u011funda bu bakterinin kolonile\u015fmesi ve enfeksiyon yaratmas\u0131 aras\u0131ndaki fark\u0131n anla\u015f\u0131lmas\u0131 \u00f6nemlidir. Genel n\u00fcfusun %30\u2019unda Stafilokok aureus kolonileri, bu grubun %10\u2019unda da (genel toplumun %3-5 aras\u0131 bir k\u0131sm\u0131nda) MRSA kolonileri bulunmaktad\u0131r (4). Bir insan MRSA kolonisini ta\u015f\u0131yarak hayat\u0131n\u0131 s\u00fcrd\u00fcrebilir. Bu koloniler, ki\u015finin hasta olmas\u0131na neden olmak zorunda de\u011fildir ancak ba\u011f\u0131\u015f\u0131kl\u0131k sistemi zarar g\u00f6rm\u00fc\u015f insanlar i\u00e7in yine de tehdit edici bir durum olu\u015fturabilir (5). Dolay\u0131s\u0131yla halihaz\u0131rda hastanede olan, operasyon ge\u00e7irmi\u015f veya hastal\u0131\u011f\u0131ndan\/g\u00f6rd\u00fc\u011f\u00fc tedaviden dolay\u0131 ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 bask\u0131lanan ki\u015filerin korunmas\u0131 i\u00e7in \u00f6nlem al\u0131nmal\u0131d\u0131r. MRSA, bir yara veya kesikten v\u00fccuda girdi\u011finde tehlike olu\u015fturabilir.<\/p>\n\n\n\n

\"\"
MRSA Kolonisi, https:\/\/www.latimes.com\/local\/lanow\/la-me-ln-mrsa-infection-lapd-20190507-story.html <\/figcaption><\/figure>\n\n\n\n

MRSA enfeksiyonlar\u0131, 1961\u2019de ilk vakalar\u0131 bildirildi\u011finden beri katlanarak artmaktad\u0131r (1). MRSA\u2019ya ad\u0131n\u0131 veren metisilin antibiyoti\u011fi, 1950\u2019lerde penisiline diren\u00e7 g\u00f6steren Stafilokok bakterilerine kar\u015f\u0131 kullan\u0131lmak \u00fczere geli\u015ftirilmi\u015ftir. \u00dcretildi\u011fi zaman, enfeksiyona neden olan Stafilokoklar\u0131n yakla\u015f\u0131k %60\u2019\u0131n\u0131n penisiline diren\u00e7li oldu\u011fu tespit edilmi\u015ftir (1). Bu nedenle\u00a0metisilinin\u00a0kullan\u0131labilir hale gelmesi,\u00a0bu bakterilerle ba\u015f edilebilmesi i\u00e7in \u00e7ok \u00f6nemli bir ad\u0131m gibi g\u00f6z\u00fckm\u00fc\u015ft\u00fcr. Ancak bundan \u00e7ok k\u0131sa bir s\u00fcre sonra bakterilerin bu yeni antibiyoti\u011fe kar\u015f\u0131 da diren\u00e7 geli\u015ftirmeyi ba\u015fard\u0131klar\u0131 ve MRSA\u2019n\u0131n yay\u0131ld\u0131\u011f\u0131 g\u00f6zlemlenmi\u015ftir.\u00a0<\/p>\n\n\n\n

\"\"
Metisilinin kimyasal yap\u0131s\u0131, https:\/\/www.acs.org\/content\/acs\/en\/molecule-of-the-week\/archive\/m\/methicillin.html<\/figcaption><\/figure>\n\n\n\n

MRSA\u2019ya Dayan\u0131kl\u0131l\u0131\u011f\u0131n\u0131 Kazand\u0131ran Nedir?<\/strong><\/h2>\n\n\n\n

MRSA, metisilin gibi beta-laktam antibiyotiklerine kar\u015f\u0131 diren\u00e7 geli\u015ftirmi\u015f bir bakteri t\u00fcr\u00fcd\u00fcr (6). Ancak metisiline dayan\u0131kl\u0131 olan bu bakteriler, penisiline kar\u015f\u0131 g\u00f6sterilen direncin \u00e7o\u011funlu\u011fu gibi beta-laktamaz enzimini \u00fcreterek de\u011fil, PBP2a adl\u0131, penisilin ba\u011flayan bir proteini sentezleyerek dayan\u0131kl\u0131l\u0131k kazanm\u0131\u015flard\u0131r (6). Bu protein, ba\u015fka bir t\u00fcrden S. aureus\u2019a ge\u00e7mi\u015f bir genin \u00fcr\u00fcn\u00fc olarak tespit edilmi\u015ftir (6). Beta-laktam antibiyotikleri, bakterilerin h\u00fccre duvar\u0131nda bulunan peptidoglikan maddesinin sentezini engelleyerek bakterilere kar\u015f\u0131 \u00fcst\u00fcnl\u00fck elde edilmesini sa\u011flamaktad\u0131r. Peptidoglikan sentezindeki \u00e7apraz ba\u011flar\u0131n olu\u015fumunu da penisilin ba\u011flayan proteinler (PBP\u2019ler) ger\u00e7ekle\u015ftirmektedir. Penisilin ve metisilin gibi beta-laktam antibiyotikleri de bakterilerin peptidoglikan \u00fcretimi i\u00e7in gereken bu\u00a0fonksiyonu\u00a0ger\u00e7ekle\u015ftirmelerini \u00f6nlemek i\u00e7in PBP\u2019lerin transpeptidaz b\u00f6lgelerine ba\u011flanarak onlar\u0131 etkisiz hale getirmeyi ama\u00e7lamaktad\u0131r (7). MRSA\u2019n\u0131n ay\u0131rt edici \u00f6zelli\u011fi ise DNA\u2019s\u0131nda\u00a0\u201cmecA\u201d\u00a0genini bulundurmas\u0131d\u0131r (6). Bu genom b\u00f6lgesinin, S. sciuri t\u00fcr\u00fcnden ge\u00e7ti\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir (8). PBP2a proteininin sentezini,\u00a0mec b\u00f6lgesine ba\u011fl\u0131 olan ba\u015fka genler ve \u00e7e\u015fitli kontrol mekanizmalar\u0131 denetlemektedir. Tahmin edilebilece\u011fi gibi, bu genin kodlad\u0131\u011f\u0131 proteinin sentezini engelleyebilecek y\u00f6ntemler, bakterinin metisiline kar\u015f\u0131 geli\u015ftirdi\u011fi direnci de olumsuz etkileyerek bir tedavi potansiyeli olu\u015fturabilir. Hatta bu direncin pH seviyesi, s\u0131cakl\u0131k gibi fakt\u00f6rlerden bile etkilendi\u011fi kaydedilmi\u015ftir.\u00a0<\/p>\n\n\n\n

MRSA\u2019n\u0131n kulland\u0131\u011f\u0131 mec gen b\u00f6lgesinin antibiyotik direncine etkisi ve bu direncin \u015fiddetinin belirlenmesi \u00e7ok karma\u015f\u0131k bir ara\u015ft\u0131rma konusudur. Ara\u015ft\u0131rmalar, sadece mec b\u00f6lgesinin ve bu geni kontrol eden b\u00f6lgelerin varl\u0131\u011f\u0131n\u0131n homojen bir diren\u00e7 olu\u015fturabilmek i\u00e7in yeterli olmad\u0131\u011f\u0131n\u0131 g\u00f6stermi\u015ftir. D\u00fc\u015f\u00fck diren\u00e7ten y\u00fcksek dirence ge\u00e7erken ba\u015fka genetik d\u00fczenlemeler ve mutasyonlar da gerekli olabilir (8). Cambridge \u00dcniversitesinde MRSA\u2019n\u0131n nadir olsa da k\u0131talar aras\u0131ndaki hareketlerini ve zamanla geli\u015ftirdi\u011fi diren\u00e7leri g\u00f6zlemleyen ve baz\u0131lar\u0131n\u0131n genom dizilimlerini olu\u015fturan ara\u015ft\u0131rmac\u0131lar, bu bulguya katk\u0131da bulunmu\u015ftur. Bakterinin ge\u00e7irdi\u011fi mutasyonlar\u0131n \u00f6nemli bir k\u0131sm\u0131n\u0131n, \u015fu anda kullan\u0131mda olan antibiyotiklerden kurtulmada etkili oldu\u011funu dile getirmi\u015flerdir (9). B\u00f6ylece klinik senaryolar\u0131n bakteri direncinde \u00f6nemli bir rol oynad\u0131\u011f\u0131n\u0131 g\u00f6stermi\u015flerdir. Tabii ki bakterilerin diren\u00e7 kazanma yollar\u0131 sadece mutasyonlardan da ibaret de\u011fildir: Konjugasyon ve ba\u015fka bakterilerin DNA\u2019lar\u0131 ile rekombinasyon yapabilmeleri sayesinde de bu canl\u0131lar \u00e7e\u015fitli avantajlar elde edebilirler (1).<\/p>\n\n\n\n

Bu yaz\u0131n\u0131n ilham kayna\u011f\u0131 olan \u00e7al\u0131\u015fman\u0131n ba\u015f\u0131ndaki ara\u015ft\u0131rmac\u0131 Dr. Viralkumar Panchal, MRSA\u2019nin geli\u015ftirdi\u011fi direncin evrimini, genomundaki ve h\u00fccre biyolojisindeki de\u011fi\u015fiklikleri ayd\u0131nlatmay\u0131 ama\u00e7lad\u0131klar\u0131n\u0131, bu bulgularla da MRSA\u2019ya kar\u015f\u0131 kullan\u0131labilecek yeni tedaviler geli\u015ftirmeyi hedeflediklerini dile getirmi\u015ftir (10). D\u00fcnya genelinde artmaya devam eden antibiyotik direnci, bakterilere kar\u015f\u0131 farkl\u0131 tedavilerin geli\u015ftirilmesini zorunlu k\u0131lm\u0131\u015ft\u0131r. Bu \u015fekilde de bir\u00e7ok ara\u015ft\u0131rman\u0131n odak noktas\u0131 olmu\u015ftur. Ancak MRSA, bakterilerin her ge\u00e7en g\u00fcn geli\u015ftirdi\u011fi direncin ve olu\u015fan tehlikenin sadece \u00e7ok k\u00fc\u00e7\u00fck bir k\u0131sm\u0131n\u0131 temsil etmektedir. Bakterilerin yeni stratejiler geli\u015ftirmesi, mutasyon ge\u00e7irmesi ve b\u00f6ylece gitgide daha fazla antibiyoti\u011fin kullan\u0131lamaz hale gelmesi, 1940\u2019larda bitti\u011fi d\u00fc\u015f\u00fcn\u00fclen verem hastal\u0131\u011f\u0131n\u0131n bir\u00e7ok \u00fclkede artan s\u0131kl\u0131klarla g\u00f6r\u00fclmesinin en \u00f6nemli nedenlerinden biridir (1).\u00a0<\/p>\n\n\n\n

Kaynak\u00e7a<\/h2>\n\n\n\n
  1. Pray, L. (2008) Antibiotic resistance, mutation rates and MRSA.\u00a0Nature Education<\/em>, 1(1): 30.<\/li>
  2. WebMD, \u2018Understanding MRSA Infection\u2019. (2020).\u00a0https:\/\/www.webmd.com\/skin-problems-and-treatments\/understanding-mrsa#1<\/a>. Eri\u015fim tarihi: 4 A\u011fustos 2020.<\/li>
  3. United Kingdom National Health Service, \u2018MRSA\u2019. (2008).\u00a0https:\/\/www.nhs.uk\/translationturkish\/Documents\/MRSA_Turkish_FINAL.pdf<\/a>. Eri\u015fim tarihi: 4 A\u011fustos 2020.<\/li>
  4. United Kingdom National Health Service, \u2018Hastane d\u0131\u015f\u0131nda MRSA\u2019dan etkilenenlere tavsiyeler\u2019. (2008).\u00a0https:\/\/www.thh.nhs.uk\/documents\/_Patients\/PatientLeaflets\/infectioncontrol\/MRSA\/MRSA_Advice_Turkish.pdf<\/a>. Eri\u015fim tarihi: 4 A\u011fustos 2020.<\/li>
  5. Street, C. (2010). \u2018MRSA Colonization vs. Infection\u2019.\u00a0https:\/\/mrsatopic.com\/2010\/09\/mrsa-colonization-vs-infection\/<\/a>. Eri\u015fim tarihi: 5 A\u011fustos 2020.<\/li>
  6. Stapleton, P. Ve Taylor, P. (2002). Methicillin resistance in Staphlycoccus aureus.\u00a0Sci Prog<\/em>, 85(1): 57-72.<\/li>
  7. Wu, S.W., Lencastre, H., Tomasz, A. (2001). Recruitment of the mecA gene homologue of Staphylococcus sciuri into a resistance determinant and expression of the resistant phenotype in Staphylococcus aureus.\u00a0J. Bacteriol<\/em>; 183:2417\u20132424.\u00a0<\/li>
  8. Panchal VV, Griffiths C, Mosaei H, Bilyk B, Sutton JAF, Carnell OT, et al. (2020) Evolving MRSA: High-level \u03b2-lactam resistance in Staphylococcus aureus is associated with RNA Polymerase alterations and fine tuning of gene expression.\u00a0PLoS Pathog<\/em>\u00a016(7): e1008672.\u00a0https:\/\/ doi.org\/10.1371\/journal.ppat.1008672<\/li>
  9. Harmon, K. (2020).\u00a0Sequencing Staph: New Genetic Analysis Tracks MRSA Mutations – Scientific American.\u00a0https:\/\/www.scientificamerican.com\/article\/mrsa-genome-sequencing<\/a>. Eri\u015fim tarihi: 4 A\u011fustos 2020.<\/li>
  10. University of Sheffield. (2020, July 24). Genetic mutations help MRSA to become highly resistant to antibiotics.\u00a0ScienceDaily<\/em>. Retrieved August 4, 2020 from\u00a0www.sciencedaily.com\/releases\/2020\/07\/200724143013.htm<\/a>\u00a0\u00a0<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    MRSA Nedir? Stafilokok aureus bakterileri, insanlarda g\u00f6r\u00fclen cilt enfeksiyonlar\u0131n\u0131n en yayg\u0131n nedenidir (1). MRSA ise, v\u00fccudun farkl\u0131 k\u0131s\u0131mlar\u0131nda enfeksiyona neden<\/p>\n","protected":false},"author":273,"featured_media":6907,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[452,95,187,893,132,115,810,955,956],"acf":[],"views":1536,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/6905"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/273"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=6905"}],"version-history":[{"count":1,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/6905\/revisions"}],"predecessor-version":[{"id":6909,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/6905\/revisions\/6909"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/6907"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=6905"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=6905"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=6905"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}