Linezolid: Perbedaan antara revisi

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'''Linezolid''' merupakan [[antibiotik]] yang digunakan untuk pengobatan [[infeksi]] yang disebabkan oleh [[bakteri Gram-positif]] yang [[resistensi antibiotik|resisten]] terhadap antibiotik lainnya.<ref name=Roger2018>{{cite journal | vauthors = Roger C, Roberts JA, Muller L | title = Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones | journal = Clinical Pharmacokinetics | volume = 57 | issue = 5 | pages = 559–575 | date = Mei 2018 | pmid = 29063519 | doi = 10.1007/s40262-017-0601-x }}</ref><ref name=AHFS2016/> Linezolid aktif melawan sebagian besar bakteri Gram-positif yang menyebabkan penyakit seperti [[Streptokokus]], [[Enterokokus resisten vankomisin]] (''Vancomycin-resistant enterococcus'', VRE), dan [[Staphylococcus aureus resisten metisilin|''Staphylococcus aureus'' resisten metisilin]] (''Methicillin-resistant'' Staphylococcus aureus, MRSA).<ref name=Roger2018 /><ref name="Zyvox FDA label">{{cite web | title=Zyvox- linezolid injection, solution Zyvox- linezolid tablet, film coated Zyvox- linezolid suspension | website=DailyMed | date=21 Februari 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6e70e63b-bfd5-478d-a8ee-8ba22c9efabd | access-date=17 Maret 2020}}</ref> Indikasi utama dari obat ini adalah untuk infeksi pada [[kulit]] dan [[pneumonia]], walau obat ini juga dapat digunakan untuk mengobati infeksi lainnya seperti [[tuberkulosis resisten multi-obat]] (''Multi-drug-resistant tuberculosis'', MDR-TB) .<ref name=AHFS2016/><ref name=WHO2015Use>{{cite book | vauthors = ((World Health Organization)) | year = 2015 | title = The selection and use of essential medicines. Twentieth report of the WHO Expert Committee 2015 (including 19th WHO Model List of Essential Medicines and 5th WHO Model List of Essential Medicines for Children) | url = https://archive.org/details/selectionuseofes0000whoe | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/189763 | id = WHO technical report series;994 | hdl-access=free | isbn = 9789241209946 | issn = 0512-3054 | pages=[https://archive.org/details/selectionuseofes0000whoe/page/n26 26]–33 }}</ref> Obat ini diberikan melalui [[infus]] (suntikan) atau berupa [[tablet]].<ref name=AHFS2016/>
 
Ketika diberikan dalam jangka pendek, linezolid merupakan antibiotik yang relatif aman.<ref name=Marino2007>{{cite book |vauthors=Marino PL, Sutin KM |chapter=Antimicrobial therapy |title=The ICU book |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2007 |page=817 |isbn=978-0-7817-4802-5}}</ref> Obat ini dapat digunakan oleh pasien segala umur dan pasien dengan [[penyakit hati]] atau [[gagal ginjal]].<ref name=AHFS2016/> Efek samping yang umum terjadi pada penggunaan jangka pendek antara lain [[sakit kepala]], [[diare]], ruam, dan [[mual]].<ref name=AHFS2016/> Efek samping berat yang mungkin terjadi antara lain [[Sindrom Serotonin|sindrom serotonin]], [[mielosupresi]], dan [[Laktikasidemia|peningkatan kadar laktat dalam darah]]. Efek samping berat tersebut terjadi terutama setelah penggunaan lebih dari dua pekan.<ref name=AHFS2016/><ref name=SFX2016/> Jika diberikan lebih lama, maka dapat menyebabkan [[Neuropati perifer dirangsang kemoterapi|kerusakan saraf]] seperti [[Neuropati optik|kerusakan saraf optik]] permanen.<ref name=SFX2016>{{cite web|title=Linezolid Side Effects in Detail|url=https://www.drugs.com/sfx/linezolid-side-effects.html|website=drugs.com|accessdate=11 Desember 2016|url-status=live|archiveurl=https://web.archive.org/web/20161220233415/https://www.drugs.com/sfx/linezolid-side-effects.html|archivedate=20 Desember 2016}}</ref>
 
Sebagai [[inhibitor sintesis protein]], linezolid bekerja dengan menghambat [[Translasi (genetik)|proses translasi pada bakteri]].<ref name=Swaney1998/> Hal tersebut menjadikan obat ini dapat [[bakteriostatik|menghentikan pertumbuhan]] atau [[bakterisida|membunuh bakteri]].<ref name=AHFS2016/> Walau banyak antibiotik lain yang bekerja dengan cara serupa, [[mekanisme aksi]] pasti dari linezolid tampak berbeda karena dia menghambat proses inisiasi sintesis protein daripada menghambat di tahapan-tahapan berikutnya.<ref name=Swaney1998>{{cite journal | vauthors = Swaney SM, Aoki H, Ganoza MC, Shinabarger DL | title = The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria | journal = Antimicrobial Agents and Chemotherapy | volume = 42 | issue = 12 | pages = 3251–5 | date = Desember 1998 | pmid = 9835522 | pmc = 106030 | url = http://aac.asm.org/cgi/reprint/42/12/3251.pdf | doi = 10.1128/AAC.42.12.3251 }}</ref> Hingga 2014, [[resistensi antibiotik|resistensi]] terhadap linezolid masih rendah.<ref>{{cite journal | vauthors = Mendes RE, Deshpande LM, Jones RN | title = Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms | journal = Drug Resistance Updates | volume = 17 | issue = 1–2 | pages = 1–12 | date = April 2014 | pmid = 24880801 | doi = 10.1016/j.drup.2014.04.002 | quote = Emergence of resistance has been limited&nbsp;... It is still uncertain whether the occurrences of such isolates are becoming more prevalent. }}</ref> Linezolid termasuk dalam antibiotik kelas [[2-Oksazolidon|oksazolidinon]].<ref name=AHFS2016/>
 
Linezolid ditemukan pada pertengahan 1990-an. Obat ini mendapat persetujuan untuk dipasarkan pada tahun 2000.<ref>{{cite book| vauthors = Li JJ, Corey EJ |title=Drug Discovery: Practices, Processes, and Perspectives|date=2013|publisher=John Wiley & Sons|isbn=978-1-118-35446-9|page=6|url=https://books.google.com/books?id=mIyxO5cLEAcC&pg=PA6|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910172617/https://books.google.com/books?id=mIyxO5cLEAcC&pg=PA6|archive-date=10 September 2017}}</ref><ref>{{cite book|last1=Torok|first1=Estee|last2=Moran|first2=Ed|last3=Cooke|first3=Fiona | name-list-format = vanc |title=Oxford Handbook of Infectious Diseases and Microbiology|date=2009|publisher=OUP Oxford|isbn=978-0-19-103962-1|chapter-url=https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56|language=en|chapter=Chapter 2 Antimicrobials|url-status=live|archive-url=https://web.archive.org/web/20170908143257/https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56|archive-date=8 September 2017}}</ref> Obat ini masuk dalam [[Daftar Obat Esensial Organisasi Kesehatan Dunia]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Organisasi Kesehatan Dunia mengklasifikasikan linezolid sebagai obat yang sangat penting.<ref>{{cite book | vauthors=((World Health Organization)) | year=2019 | title=Critically important antimicrobials for human medicine | edition=6th revision | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | hdl=10665/312266 | isbn=9789241515528 | hdl-access=free }}</ref> Linezolid tersedia dalam bentuk [[obat generik]] di beberapa negara.<ref name=AHFS2016>{{cite web|title=Linezolid|url=https://www.drugs.com/monograph/linezolid.html|publisher=The American Society of Health-System Pharmacists|access-date=8 Desember 2016|url-status=live|archive-url=https://web.archive.org/web/20161220231329/https://www.drugs.com/monograph/linezolid.html|archive-date=20 Desember 2016}}</ref>
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Pada umumnya, infeksi pada organ dalam seperti osteomielitis atau [[endokarditis infektif]] sebaiknya diobati dengan antibiotik bakterisida, bukan antibiotik bakteriostatik. Walau demikian, tetap dilakukan studi praklinis untuk menilai efikasi linezolid untuk infeksi tersebut dan telah digunakan untuk mengobati jenis infeksi tersebut dalam praktik klinis.<ref name="Barbachyn" /> Linezolid menjadi pilihan terapi untuk endokarditis infektif yang disebabkan bakteri Gram-positif multi-resisten walau tidak terdapat bukti yang kuat untuk mendukung penggunaannya.<ref>{{cite journal |vauthors=Pankey GA, Sabath LD |title=Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections |journal=[[Clinical Infectious Diseases]] |volume=38 |issue=6 |pages=864–70 |date=Maret 2004 |pmid=14999632 |doi=10.1086/381972 |issn=1058-4838|doi-access=free }}</ref><ref name=Falagas>{{cite journal |vauthors=Falagas ME, Manta KG, Ntziora F, Vardakas KZ |title=Linezolid for the treatment of patients with endocarditis: a systematic review of the published evidence |journal=Journal of Antimicrobial Chemotherapy |volume=58 |issue=2 |pages=273–80 |date=Agustus 2006 |pmid=16735427 |doi=10.1093/jac/dkl219 |doi-access=free }}</ref> Hasil penggunaan linezolid dalam terapi endokarditis yang disebabkan enterokokus bervariasi, dengan sebagian kasus berhasil terobati dan sebagian lainnya gagal.<ref>{{cite journal |vauthors=Babcock HM, Ritchie DJ, Christiansen E, Starlin R, Little R, Stanley S |title=Successful treatment of vancomycin-resistant ''Enterococcus'' endocarditis with oral linezolid |journal=Clinical Infectious Diseases |volume=32 |issue=9 |pages=1373–5 |date=Mei 2001 |pmid=11303275 |doi=10.1086/319986 |issn=1058-4838|doi-access=free }}</ref><ref>{{cite journal |vauthors=Ang JY, Lua JL, Turner DR, Asmar BI |title=Vancomycin-resistant ''Enterococcus faecium'' endocarditis in a premature infant successfully treated with linezolid |url=https://archive.org/details/sim_pediatric-infectious-disease-journal_2003-12_22_12/page/1101 |journal=The Pediatric Infectious Disease Journal |volume=22 |issue=12 |pages=1101–3 |date=Desember 2003 |pmid=14688576 |doi=10.1097/01.inf.0000101784.83146.0c |issn=0891-3668}}</ref><ref>{{cite journal |vauthors=Archuleta S, Murphy B, Keller MJ |title=Successful treatment of vancomycin-resistant ''Enterococcus faecium'' endocarditis with linezolid in a renal transplant recipient with human immunodeficiency virus infection |journal=Transplant Infectious Disease |volume=6 |issue=3 |pages=117–9 |date=September 2004 |pmid=15569227 |doi=10.1111/j.1399-3062.2004.00059.x |issn=1398-2273}}</ref><ref>{{cite journal |vauthors=Zimmer SM, Caliendo AM, Thigpen MC, Somani J |title=Failure of linezolid treatment for enterococcal endocarditis |journal=Clinical Infectious Diseases |volume=37 |issue=3 |pages=e29–30 |date=Agustus 2003 |pmid=12884185 |doi=10.1086/375877 |issn=1058-4838}}</ref><ref>{{cite journal |vauthors=Tsigrelis C, Singh KV, Coutinho TD, Murray BE, Baddour LM |title=Vancomycin-Resistant Enterococcus faecalis Endocarditis: Linezolid Failure and Strain Characterization of Virulence Factors |journal=[[Journal of Clinical Microbiology]] |volume=45 |issue=2 |pages=631–5 |date=Februari 2007 |pmid=17182759 |pmc=1829077 |doi=10.1128/JCM.02188-06 }}</ref><ref>{{cite journal |vauthors=Berdal JE, Eskesen A |title=Short-term success, but long-term treatment failure with linezolid for enterococcal endocarditis |journal=Scandinavian Journal of Infectious Diseases |volume=40 |issue=9 |pages=765–6 |year=2008 |pmid=18609208 |doi=10.1080/00365540802087209 |issn=0036-5548}}</ref> [[Pengobatan bertumpu bukti|Dari bukti lemah hingga sedang]] juga mendukung penggunaan linezolid pada infeksi tulang dan sendi seperti osteomielitis kronis. Hanya saja, efek samping dari linezolid perlu diperhatikan untuk penggunaan jangka panjang.<ref>{{cite journal |vauthors=Falagas ME, Siempos II, Papagelopoulos PJ, Vardakas KZ |title=Linezolid for the treatment of adults with bone and joint infections |journal=International Journal of Antimicrobial Agents |volume=29 |issue=3 |pages=233–9 |date=Maret 2007 |pmid=17204407 |doi=10.1016/j.ijantimicag.2006.08.030 |issn=0924-8579}} Review.</ref><ref>{{cite journal |vauthors=Bassetti M, Vitale F, Melica G, etal |title=Linezolid in the treatment of Gram-positive prosthetic joint infections |journal=Journal of Antimicrobial Chemotherapy |volume=55 |issue=3 |pages=387–90 |date=Maret 2005 |pmid=15705640 |doi=10.1093/jac/dki016 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Aneziokoro CO, Cannon JP, Pachucki CT, Lentino JR |title=The effectiveness and safety of oral linezolid for the primary and secondary treatment of osteomyelitis |journal=Journal of Chemotherapy |volume=17 |issue=6 |pages=643–50 |date=Desember 2005 |pmid=16433195 |issn=1120-009X |doi=10.1179/joc.2005.17.6.643}}</ref><ref>{{cite journal |vauthors=Senneville E, Legout L, Valette M, etal |title=Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study |journal=Clinical Therapeutics |volume=28 |issue=8 |pages=1155–63 |date=Agustus 2006 |pmid=16982292 |doi=10.1016/j.clinthera.2006.08.001 |issn=0149-2918}}</ref><ref>{{cite journal |vauthors=Rao N, Hamilton CW |title=Efficacy and safety of linezolid for Gram-positive orthopedic infections: a prospective case series |journal=Diagnostic Microbiology and Infectious Disease |volume=59 |issue=2 |pages=173–9 |date=Oktober 2007 |pmid=17574788 |doi=10.1016/j.diagmicrobio.2007.04.006 |issn=0732-8893}}</ref><ref>{{cite journal |vauthors=Papadopoulos A, Plachouras D, Giannitsioti E, Poulakou G, Giamarellou H, Kanellakopoulou K |title=Efficacy and tolerability of linezolid in chronic osteomyelitis and prosthetic joint infections: a case-control study |journal=Journal of Chemotherapy |volume=21 |issue=2 |pages=165–9 |date=April 2009 |pmid=19423469 |issn=1120-009X |doi=10.1179/joc.2009.21.2.165}}</ref>
 
==Interaksi obat==
Linezolid merupakan [[inhibitor monoamin oksidase]] (MAOI) yang lemah, non-selektif, dan reversibel. Pasien yang menggunaka linezolid sebaiknya tidak digunakan bersamaan dengan obat MAOI lainnya, menghindari makanan yang kaya akan [[tiramin]] (seperti babi, keju, minuman beralkohol, acar, atau makanan yang diasapi), dan menghindari penggunaan obat [[serotonergik]]. Dari hasil [[pengawasan pascapemasaran|laporan pengawasan obat]], terdapat kejadian [[sindrom serotonin]] pada pasien yang diberikan linezolid bersamaan atau segera setelah diberikan obat serotonergik, terutama obat golongan [[inhibitor ambilan kembali serotonin selektif]] (''Selective serotonin reuptake inhibitor'', SSRI) seperti [[paroksetin]] dan [[sertralin]].<ref name=French/><ref>{{cite journal | vauthors = Lawrence KR, Adra M, Gillman PK | title = Serotonin toxicity associated with the use of linezolid: a review of postmarketing data | journal = Clinical Infectious Diseases | volume = 42 | issue = 11 | pages = 1578–83 | date = Juni 2006 | pmid = 16652315 | doi = 10.1086/503839 | doi-access = free }}</ref><ref name=Huang>{{cite journal | vauthors = Huang V, Gortney JS | title = Risk of serotonin syndrome with concomitant administration of linezolid and serotonin agonists | url = https://archive.org/details/sim_pharmacotherapy_2006-12_26_12/page/1784 | journal = Pharmacotherapy | volume = 26 | issue = 12 | pages = 1784–93 | date = Desember 2006 | pmid = 17125439 | doi = 10.1592/phco.26.12.1784 }}</ref><ref>{{cite web |url=http://www.medscape.com/viewarticle/580101 |title=FDA Safety Changes: Mirena, Zyvox, Orencia | last = Waknine | first = Yael | name-list-format = vanc |date=5 September 2008 |publisher=[[Medscape]] |access-date=6 September 2008 |url-status=live |archive-url=https://web.archive.org/web/20081202190427/http://www.medscape.com/viewarticle/580101 |archive-date=2 Desember 2008 }} Dapat diakses bebas dengan registrasi.</ref> Linezolid juga dapat merangsang efek peningkatan tekanan darah dari [[obat simpatomimetik]] seperti [[pseudoefedrin]] atau [[fenilpropanolamin]].<ref name=Moellering/><ref name=Stalker>{{cite journal | vauthors = Stalker DJ, Jungbluth GL | title = Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial | journal = Clinical Pharmacokinetics | volume = 42 | issue = 13 | pages = 1129–40 | year = 2003 | pmid = 14531724 | doi = 10.2165/00003088-200342130-00004 }}</ref> Linezolid sebaiknya tidak diberikan bersamaan dengan [[petidin]] ([[meperidin]]) dalam kondisi apapun karena risiko terjadinya [[sindrom serotonin]].