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[[ผู้ใช้:Thomson_Walt/กระบะทราย_Plan|แผน]] • [[ผู้ใช้:Thomson_Walt/ทดลองเขียน|ทดลองเขียน]] • '''กระบะทราย''' • [[ผู้ใช้:Thomson_Walt/กระบะทราย|1]] • [[ผู้ใช้:Thomson_Walt/กระบะทราย_2|2]] • [[ผู้ใช้:Thomson_Walt/กระบะทราย_3|3]] • [[ผู้ใช้:Thomson_Walt/กระบะทราย_4|4]] • [[ผู้ใช้:Thomson_Walt/กระบะทราย_5|5]] • [[ผู้ใช้:Thomson_Walt/กระบะทราย_6|6]] • [[ผู้ใช้:Thomson_Walt/กระบะทราย_7|7]]
=[[ยาปฏิชีวนะ]]=
{{about|ยาปฏิชีวนะ และการรักษาโรคที่เกิดจากการติดเชื้อแบคทีเรีย|ยาปฏิชีวนะยับยั้งเนื้องอก (Antitumor antibiotics)|เคมีบำบัด}}
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| Image = Staphylococcus aureus (AB Test).jpg
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| Caption = การทดสอบความไวของแบคทีเรีย ''[[Staphylococcus aureus]]'' ต่อยาปฏิชีวนะด้วยวิธี [[Kirby-Bauer antibiotic testing|Kirby-Bauer disk diffusion method]] โดยยาปฏิชีวนะจะกระจายเข้าไปในจานเพาะเลี้ยงที่มีเชื้อแบคทีเรียอยู่และส่งผลยับยั้งการเจริญเติบโตของ ''S. aureus'' ทำให้เกิดวงยับยั้งเชื้อ (Zone of inhibition) ขึ้น
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| Drugs.com = <!-- {{Drugs.com|drug-class|?}} -->
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'''ยาปฏิชีวนะ''' ({{lang-en|Antibiotics}} จาก[[กรีซโบราณ|ภาษากรีซโบราณ]] αντιβιοτικά, ''antiviotika'') หรือเรียกอีกชื่อหนึ่งว่า '''ยาฆ่าเชื้อแบคทีเรีย''' (Antibacterials) เป็นกลุ่มย่อยของยาอีกกลุ่มหนึ่งใน[[ยาต้านจุลชีพ|กลุ่มยาต้านจุลชีพ]] (Antimicrobial drugs)<ref>{{cite web | url=http://newsghana.com.gh/?p=853675 | title=Utilizing antibiotics agents effectively will preserve present day medication| publisher=News Ghana | date=21 November 2015 | accessdate=21 November 2015}}</ref> ซึ่งเป็น[[ยารักษาโรค|ยา]]ที่ถูกใช้ใน[[การรักษา]]และ[[การป้องกันด้วยยาปฏิชีวนะ|ป้องกัน]][[แบคทีเรียก่อโรค|การติดเชื้อแบคทีเรีย]]<ref name="NHSB">{{cite web | url=https://www.nhs.uk/conditions/Antibiotics-penicillins/Pages/Introduction.aspx | title=Antibiotics| publisher=NHS | date=5 June 2014 | accessdate=17 January 2015}}</ref><ref>{{cite web | url=http://ecdc.europa.eu/en/eaad/antibiotics/Pages/factsExperts.aspx | title=Factsheet for experts | publisher=European Centre for Disease Prevention and Control | accessdate=21 December 2014}}</ref> โดยอาจ[[สารฆ่าเชื้อแบคทีเรีย|ออกฤทธิ์ฆ่า]]หรือ[[สารต้านเชื้อแบคทีเรีย|ยับยั้งการเจริญเติบโต]]ของ[[แบคทีเรีย]]อย่างใดอย่างหนึ่ง ยาปฏิชีวนะบางชนิดอาจมีคุณสมบัติเป็นมีคุณสมบัติเป็น[[สารต้านโพรโทซัว]]ได้ เช่น [[เมโทรนิดาโซล]]<ref>{{cite web|title=Metronidazole|url=http://www.drugs.com/monograph/metronidazole.html|publisher=The American Society of Health-System Pharmacists|accessdate=31 July 2015}}</ref><ref name=Antibioticandantiprotozal>{{cite book|title=Chemical Analysis of Antibiotic Residues in Food.|date=2012|publisher=John Wiley & Sons, Inc.|isbn=9781449614591|pages=1–60|url=http://www.newbooks-services.de/MediaFiles/Texts/6/9780470490426_Excerpt_001.pdf}}</ref> ทั้งนี้ ยาปฏิชีวนะไม่มีฤทธิ์ในการต้าน[[ไวรัส]]ที่เป็นสาเหตุของโรคต่างๆ เช่น [[ไข้หวัด]] หรือ [[ไข้หวัดใหญ่]] เป็นต้น โดยยาที่มีฤทธิ์ต่อเชื้อไวรัสจะถูกจัดอยู่ใน[[ยาต้านไวรัส|กลุ่มยาต้านไวรัส]] ซึ่งเป็นกลุ่มย่อยอีกกลุ่มหนึ่งของ[[ยาต้านจุลชีพ]]
ในบางครั้ง คำว่า '''ยาปฏิชีวนะ''' (ซึ่งหมายถึง "การต่อต้านชีวิต") ถูกนำมาใช้เพื่อสื่อความถึงสารใดๆที่นำมาใช้เพื่อต้าน[[จุลินทรีย์]]<ref>{{cite web | url = https://www.ahdictionary.com/word/search.html?q=antibiotic | title = American Heritage Dictionary of the English Language |edition=5th |year=2011 |quote = A substance, such as penicillin or erythromycin, produced by or derived from certain microorganisms, including fungi and bacteria, that can destroy or inhibit the growth of other microorganisms, especially bacteria. Antibiotics are widely used in the prevention and treatment of infectious diseases. }}</ref> synonymous with antimicrobial.<ref>{{cite book | url = https://books.google.com/books?id=aW0zkZl0JgQC&lpg=PA108&ots=CDvWf9vQop&dq=antibiotic&pg=PA108#v=onepage&q=antibiotic&f=false| title=Mosby's Medical Dictionary |edition=9th | publisher=Elsevier | year=2013|quote = 1. pertaining to the ability to destroy or interfere with the development of a living organism. 2. an antimicrobial agent, derived from cultures of a microorganism or produced semi-synthetically, used to treat infections}}</ref> บางแหล่งมีการใช้คำว่า ยาปฏิชีวนะ และ ยาฆ่าเชื้อแบคทีเรีย ในความหมายที่แยกจากกันไป โดยคำว่า ''ยา (สาร) ฆ่าเชื้อแบคทีเรีย'' จะสื่อความถึง [[สบู่ต้านเชื้อแบคทีเรีย|สบู่]] และ[[น้ำยาฆ่าเชื้อ]] ขณะที่คำว่า ''ยาปฏิชีวนะ'' จะมายถึงยาที่ใช้ในทางการแพทย์เพื่อฆ่าเชื้อแบคทีเรีย<ref>{{cite web | url=http://www.tufts.edu/med/apua/about_issue/agents.shtml#1 | title=General Background: Antibiotic Agents | work=Alliance for the Prudent Use of Antibiotics | accessdate=21 December 2014}}</ref>
การพัฒนายาปฏิชีวนะเริ่มต้นในช่วงศตวรรษที่ 20<ref>{{Cite book|title = Antibiotics: Targets, Mechanisms and Resistance|url = https://books.google.com/books?id=3SZrAAAAQBAJ|publisher = John Wiley & Sons|date = 4 December 2013|isbn = 9783527333059|first = Claudio O.|last = Gualerzi|first2 = Letizia|last2 = Brandi|first3 = Attilio|last3 = Fabbretti|first4 = Cynthia L.|last4 = Pon|pages = 1}}</ref> พร้อมกับการพัฒนาเรื่อง[[การให้วัคซีน]]เพื่อป้องกันโรคจากเชื้อจุลชีพต่างๆ การเกิดขึ้นของยาปฏิชีวนะนำมาซึ่งการกำจัดโรคติดเชื้อแบคทีเรียต่างๆ ออกไปหลายชนิด เช่น กรณีของ[[วัณโรค]]ที่ระบาดใน[[ประเทศกำลังพัฒนา]] อย่างไรก็ตาม ด้วยประสิทธิภาพที่ดีและการเข้าถึงยาที่ง่ายนำไปสู่[[การใช้ยาปฏิชีวนะในทางที่ผิด]] <ref>{{cite news|url=http://www.abc.net.au/news/2016-06-10/superbug-fears-over-antibiotic-use-in-australian-nursing-homes/7497664|title=Antibiotics being incorrectly prescribed in Australian nursing homes, prompting superbug fears|work=[[ABC (Australia)|ABC Australia]]|date=10 June 2016|accessdate=12 June 2016}}</ref><ref>{{cite web|url=http://www.cctv-america.com/2016/05/19/uk-study-warns-of-threat-of-antibiotics-overuse-lack-of-new-drugs|title=UK study warns of threat of antibiotics overuse, lack of new drugs|work=CCTV America|date=19 May 2016|accessdate=12 June 2016}}</ref><ref>{{cite web|url=http://www.cbsnews.com/news/superbugs-could-kill-more-people-than-cancer-report-warns/|title=Superbugs could kill more people than cancer, report warns|publisher=CBS News|date=19 May 2016|accessdate=12 June 2016}}</ref> พร้อมๆกับการที่แบคทีเรียมีการพัฒนาจนกลายพันธุ์เป็น[[แบคทีเรียดื้อยา|เชื้อแบคทีเรียที่ดื้อต่อยาปฏิชีวนะ]]<ref name="NHSB"/><ref>{{cite web|last1=Brooks|first1=Megan|title=Public Confused About Antibiotic Resistance, WHO Says|url=http://www.medscape.com/viewarticle/854564|website=Medscape Multispeciality|accessdate=21 November 2015|date=16 November 2015}}</ref> ปัญหาดังข้างต้นได้แพร่กระจายเป็นวงกว้าง จนเป็นปัญหาสำคัญของการสาธารณสุขในทุกประเทศทั่วโลก จน[[องค์การอนามัยโลก]] (World Health Organization) ได้ประกาศให้ปัญหาการดื้อยาของเชื้อแบคทีเรียเป็น "ปัญหาสำคัญเร่งด่วนที่สุดที่เกิดขึ้นในทุกภูมิภาคทั่วโลกและทุกคนล้วนจะต้องได้รับผลกระทบจากปัญหานี้ ไม่ว่าวัยใด หรือประเทศใดก็ตาม"<ref name=WHO2014>{{cite web | url=http://apps.who.int/iris/bitstream/10665/112642/1/9789241564748_eng.pdf?ua=1 | title=Antimicrobial resistance: global report on surveillance | publisher=The World Health Organization | date= April 2014 | accessdate=13 June 2016 |isbn=978 92 4 156474 8 }}</ref>
==การใช้ประโยชน์ทางการแพทย์==
ยาปฏิชีวนะเป็น[[ยารักษาโรค|ยา]]ที่ถูกใช้ใน[[การรักษา]]และ[[การป้องกันด้วยยาปฏิชีวนะ|ป้องกัน]][[แบคทีเรียก่อโรค|การติดเชื้อแบคทีเรีย]]<ref name="NHSB"/><ref name=Antibiotic>{{cite book|title=Antibiotics Simplified.|date=2011|publisher=Jones & Bartlett Publishers|isbn=9781449614591|pages=15–17|url=https://books.google.com/books?id=vIRgA57q414C&dq=Antibiotics&source=gbs_navlinks_s}}</ref> และในบางครั้งถูกใช้เป็น[[ยาต้านโพรโทซัว]] ([[เมโทรนิดาโซล]] สำหรับรักษาโรคที่เกิดจากการติดเชื้อโพรโตซัวบางสายพันธุ์ และในบางครั้งก็อาจถูกนำมาใช้เป็น[[ยาต้านปรสิต]]ได้เช่นกัน เมื่อพบว่ามีการติดเชื้อแบคทีเรียหรือมีอาการที่อาจบ่งบอกได้ว่าเป็นการติดเชื้อแบคทีเรีย แต่ยังไม่สามารถจำแนกสายพันธุ์ของเชื้อก่อโรคได้ จะมีการให้การรักษาด้วยยาปฏิชีวนะที่เรียกว่า [[การให้ยาปฏิชีวนะแบบครอบคลุมเชื้ออย่างกว้าง]] (empiric therapy) เพื่อให้ครอบคลุมเชื้อที่อาจเป็นสาเหตุทั้งหมด<ref name=":2">{{Cite journal|last=Leekha|first=Surbhi|last2=Terrell|first2=Christine L.|last3=Edson|first3=Randall S.|date=1 February 2011|title=General principles of antimicrobial therapy|journal=Mayo Clinic Proceedings|volume=86|issue=2|pages=156–167|doi=10.4065/mcp.2010.0639|issn=1942-5546|pmc=3031442|pmid=21282489}}</ref> อย่างไรก็ตาม การให้[[ยาปฏิชีวนะชนิดออกฤทธิ์กว้าง|ยาปฏิชีวนะที่ออกฤทธิ์กว้าง]] (broad-spectrum antibiotic) จะขึ้นอยู่อาการและอาการแสดงของผู้ป่วยและผลการจรวจทางห้องปฏิบัติการในแต่ละวัน ซึ่งอาจต้องใช้เวลาหลายวันในการระบุเชื้อสาเหตุที่แน่ชัดได้<ref name="Antibiotic" /><ref name=":2" />
เมื่อทราบถึงสายพันธุ์ของเชื้อก่อโรคดังข้างต้นแล้ว แบบแผนการรักษาด้วยยาปฏิชีวนะจะถูกปรับเปลี่ยนให้จำเพาะเจาะจงกับเชื้อสาเหตุนั้นๆมากขึ้น โดยทั่วไปมักเลือกใช้ยาปฏิชีวนะที่มีขอบเขตการออกฤทธิ์ครอบคลุมเชื้อที่แคบลง (narrow-spectrum antibiotic) ทั้งนี้ การปรับเปลี่ยนแบบแผนการรักษานี้จะขึ้นอยู่กับข้อบ่งใช้ ราคา ประสิทธิภาพ ความปลอดภัย และความสะดวกในการใช้ยานั้น การระบุชนิดของเชื้อก่อโรคที่จำเพาะถือเป็นจุดสำคัญในการรักษา เนื่องจากจะช่วยลดค่าใช้จ่าย รวมไปถึงความเสี่ยงที่อาจเกิดพิษหรืออาการไม่พึงประสงค์ จากการที่ต้องได้รับการรักษายาปฏิชีวนะที่ออกฤทธิ์กว้างหรือหลายชนิดร่วมกัน อีกทั้งยังช่วยลดความเป็นไปได้ที่จะเกิดภาวะเสี่ยงจากการดื้อยาของเชื้อแบคทีเรียได้ด้วย<ref name=":2" /> ในอีกกรณีหนึ่ง การมีการใช้ยาปฏิชีวนะในผู้ป่วยที่มีภาวะ[[ไส้ติ่งอักเสบ]]เฉียบพลัน เป็นทางเลือกหนึ่งโดยไม่ต้องทำการผ่าตัด<ref>{{cite journal|last1=Rollins|first1=KE|last2=Varadhan|first2=KK|last3=Neal|first3=KR|last4=Lobo|first4=DN|title=Antibiotics Versus Appendicectomy for the Treatment of Uncomplicated Acute Appendicitis: An Updated Meta-Analysis of Randomised Controlled Trials.|journal=World journal of surgery|date=19 May 2016|pmid=27199000|doi=10.1007/s00268-016-3561-7|volume=40|pages=2305–2318}}</ref>
นอกจากนี้แล้ว ยังมีการใช้ยาปฏิชีวนะเพื่อเป็น[[การดูแลสุขภาพโดยการป้องกัน|การป้องกัน]] (prophylactic) เฉพาะในผู้ที่มีความเสี่ยงต่อการติดเชื้อแบคทีเรียสูง เช่น ผู้ที่มี[[ภูมิคุ้มกันบกพร่อง]] (โดยเฉพาะผู้ป่วย[[เอดส์]] เพื่อป้องกัน[[ปอดบวม|โรคปอดบวม]]), ผู้ที่กำลังอยู่ระหว่างการใช้[[ยากดภูมิคุ้มกัน]], ผู้ป่วย[[มะเร็ง]] และผู้ป่วยที่ต้องได้รับ[[ศัลยศาสตร์|การผ่าตัด]]<ref name=Antibiotic /> อาจการใช้ยาปฏิชีวนะก่อนและหลังการผ่าตัดเพื่อช่วยป้องกันการติดเชื้อแบคทีเรียบริเวณ[[แผลผ่าตัด|แผล]] และมีการใช้ในทางทันตกรรมเพื่อเป็น[[การใช้ยาปฏิชีวนะเพื่อการป้องกันในทางทันตกรรม|การป้องกัน]][[ภาวะเลือดมีแบคทีเรีย|การติดเชื้อแบคทีเรียในกระแสเลือด]]และการเกิด[[เยื่อบุหัวใจอักเสบติดเชื้อ|ภาวะเยื่อบุหัวใจอักเสบติดเชื้อ]] รวมไปถึงการใช้ยาปฏิชีวนะในการป้องกันการติิดเชื้อแบคทีเรียในผู้ป่วยที่มี[[นิวโตรฟิลในเลือดต่ำ]] โดยเฉพาะอย่างยิ่ง ในผู้ป่วย[[มะเร็ง]]<ref>{{Cite journal|last=Flowers|first=Christopher R.|last2=Seidenfeld|first2=Jerome|last3=Bow|first3=Eric J.|last4=Karten|first4=Clare|last5=Gleason|first5=Charise|last6=Hawley|first6=Douglas K.|last7=Kuderer|first7=Nicole M.|last8=Langston|first8=Amelia A.|last9=Marr|first9=Kieren A.|date=20 February 2013|title=Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=31|issue=6|pages=794–810|doi=10.1200/JCO.2012.45.8661|issn=1527-7755|pmid=23319691}}</ref><ref>{{Cite journal|last=Bow|first=Eric J.|date=1 July 2013|title=Infection in neutropenic patients with cancer|journal=Critical Care Clinics|volume=29|issue=3|pages=411–441|doi=10.1016/j.ccc.2013.03.002|issn=1557-8232|pmid=23830647}}</ref>
===การบริหารยา===
การบริหารยาปฏิชีวนะนั้นสามารถกระทำได้หลาย[[ช่องทางการบริหารยา|ช่องทาง]] โดยปกติแล้วมักใช้การบริหารยาโดยการรับประทาน[[การบริหารยาทางปาก|ทางปาก]] แต่ในกรณีที่ผู้ป่วยมีอาการรุนแรง โดยเฉพาะอย่ายิ่ง ในผู้ป่วยที่มี[[โรคทางระบบ|การติดเชื้อในกระแสเลือด]]อย่างรุนแรง จะบริหารยาให้แก่ผู้ป่วยด้วยวิธี[[การฉีดเข้าหลอดเลือดดำ]] หรือการฉีดอื่น<ref name="NHSB"/><ref name=":2" /> ในกรณีที่ตำแหน่งที่เกิดการติดเชื้ออยู่ในบริเวณที่ยาปฏิชีวนะสามารถแพร่กระจายเข้าไปได้โดยง่าย อาจบริหารยาปฏิชีวนะนั้นๆได้ด้วยการใช้ในรูปแบบ[[ยาใช้ภายนอก]] อาทิ การใช้[[ยาหยอดตา]]หยอดลง[[เยื่อตา|เยื่อบุตา]]ในกรณี[[เยื่อตาอักเสบ|เยื่อบุตาอักเสบ]] หรือการใช้[[ยาหยอดหู]] ในกรณีติดเชื้อแบคทีเรียในหูหรือ[[หูชั้นนอกอักเสบ]]เฉียบพลัน (acute otitis externa) ยาใช้ภายนอกในรูปแบบยาทาเป็นอีกทางเลือกหนึ่งสำหรับผู้ที่มีการติดเชื้อบริเวณผิวหนังที่ไม่รุนแรง เช่น [[สิวสามัญ|สิวอักเสบจากการติดเชื้อแบคทีเรีย]] (acne vulgaris) และ[[เซลล์เนื้อเยื่ออักเสบ]] (Cellulitis)<ref>{{Cite journal|last=Pangilinan|first=Ronald|last2=Tice|first2=Alan|last3=Tillotson|first3=Glenn|date=1 October 2009|title=Topical antibiotic treatment for uncomplicated skin and skin structure infections: review of the literature|journal=Expert Review of Anti-Infective Therapy|volume=7|issue=8|pages=957–965|doi=10.1586/eri.09.74|issn=1744-8336|pmid=19803705}}</ref> โดยประโยชน์จากการใช้ยาปฏิชีวนะในรูปแบบยาใช้ภายนอก ได้แก่ บริเวณที่เกิดการติดเชื้อจะมีความเข้มข้นของยาสูงและมีความสม่ำเสมอ, ลดความเสี่ยงที่อาจเกิดพิษหรืออาการไม่ประสงค์บางอย่างจากการใช้ยา, และปริมาณยาที่ต้องใช้ในการรักษาลดลง นอกจากนี้ยังลดปริมาณ[[การใช้ยาปฏิชีวนะในทางที่ผิด]]ได้อีกด้วย<ref name=":3">{{Cite journal|last=Lipsky|first=Benjamin A.|last2=Hoey|first2=Christopher|date=15 November 2009|title=Topical antimicrobial therapy for treating chronic wounds|journal=Clinical Infectious Diseases|volume=49|issue=10|pages=1541–1549|doi=10.1086/644732|issn=1537-6591|pmid=19842981}}</ref> นอกจากนี้ การทายาปฏิชีวนะชนิดทาในกรณีแผลผ่าตัดนั้นก็สามารถลดความเสี่ยงในการเกิดการติดเชื้อในแผลผ่าตัดได้<ref>{{Cite journal|last=Heal|first=Clare F|last2=Banks|first2=Jennifer L|last3=Lepper|first3=Phoebe D|last4=Kontopantelis|first4=Evangelos|last5=van Driel|first5=Mieke L|title=Topical antibiotics for preventing surgical site infection in wounds healing by primary intention|url=http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011426.pub2/full|journal=Cochrane Database of Systematic Reviews 2016|issue=11|doi=10.1002/14651858.CD011426.pub2}}</ref> อย่างไรก็ตาม ยังมีบางประเด็นที่กังวลเกี่ยวกับการใช้ยาปฏิชีวนะชนิดใช้ภายนอก เนื่องจากอาจมีการดูดซึมยาเข้าสู่กระแสเลือดได้ในบางกรณี, ปริมาณยาที่ใช้ในแต่ละครั้งนั้นยากที่จะกำหนดให้แม่นยำได้ และอาจทำให้เกิด[[ภาวะภูมิไวเกิน]] หรือ[[ผื่นแพ้สัมผัส]]ได้<ref name=":3" />
==อาการไม่พึงประสงค์==
[[File:Choosing Wisely antibiotics poster small English.pdf|thumb|right|ข้อความโฆษณาทางสุขภาพที่แนะนำให้ให้ผู้ป่วยซักถามแพทย์ของเขาถึงความปลอดภัยในการใช้ยาปฏิชีวนะ]]
ยาปฏิชีวนะนั้นจำเป็นต้องมีการศึกษาทดลองเพื่อค้นหา[[อาการไม่พึงประสงค์จากยา|อาการไม่พึงประสงค์]]ต่างๆของยาที่อาจเกิดขึ้นได้ก่อนจะมีการอนุมัติให้ใช้เพื่อการบำบัดรักษาโรคในมนุษย์ และยาได้รับอนุมัตินั้นต้องมีความปลอดภัยและผู้ป่วยสามารถยอมรับหรือทนต่ออาการข้างเคียงที่อาจเกิดขึ้นได้ อย่างไรก็ตาม ยาปฏิชีวนะบางชนิดนั้นมีความสัมพันธ์กับการเกิดอาการไม่พึงประสงค์หลายอย่าง ตั้งแต่รุนแรงเล้กน้อยไปขนถึงรุนแรงมาก ขึ้นอยู่กับชนิดของยาปฏิชีวนะที่ถูกใช้, จุลชีพเป้าหมาย, และปัจจัยอื่นที่เป็นปัจเจก<ref name="pmid15993671"/><ref>{{Cite web|title = Antibiotics and Selective Toxicity – Boundless Open Textbook|url = https://www.boundless.com/microbiology/textbooks/boundless-microbiology-textbook/antimicrobial-drugs-13/overview-of-antimicrobial-therapy-153/antibiotics-and-selective-toxicity-773-727/|website = Boundless|access-date = 12 February 2016}}</ref> [[อาการไม่พึงประสงค์จากยา]]นั้นอาจเป็นผลมาจากมาจากคุณสมบัติทาง[[เภสัชวิทยา]]หรือ[[พิษวิทยา]]ของยานั้นหรือเกิดจากการเหนี่ยวนำให้เกิด[[ภาวะภูมิไวเกิน]] หรือ[[ปฏิกิริยาการแพ้ยา]]<ref name=Antibioticandantiprotozal>{{cite book|title=Chemical Analysis of Antibiotic Residues in Food.|date=2012|publisher=John Wiley & Sons, Inc.|isbn=9781449614591|pages=1–60|url=http://www.newbooks-services.de/MediaFiles/Texts/6/9780470490426_Excerpt_001.pdf}}</ref> โดยอาการไม่พึงประสงค์ที่เกิดขึ้นอาจมีตั้งแต่ [[ไข้]] หนาวสั่น [[คลื่นไส้]] ไปจนถึงอาการที่รุนแรงอย่าง[[ปฏิกิริยาการแพ้ยา]]ได้ เช่น [[ผื่นแพ้แสงแดด]] (photodermatitis) และ[[ปฎิกิริยาภูมิแพ้เฉียบพลันรุนแรง]] (Anaphylaxis) <ref>{{cite web|title=Antibiotics – Side effects |website=NHS Choices |publisher=National Health Service (NHS), UK |url=http://www.nhs.uk/Conditions/Antibiotics-penicillins/Pages/Side-effects.aspx |date=6 May 2014 |accessdate=6 February 2016}}</ref> Safety profiles of newer drugs are often not as well established as for those that have a long history of use.<ref name="pmid15993671"/>
อาการไม่พึงประสงค์จากยาปฏิชีวนะที่เกิดขึ้นได้ทั่วไปในผู้ที่ได้รับการรักษาด้วยยาปฏิชีวนะอย่าง [[ท้องเสีย|อาการท้องเสีย]]นั้นเป็นผลมาจากการรบกวนสมดุล[[จุลินทรีย์ประจำถิ่นในลำไส้|เชื้อจุลินทรีย์ประจำถิ่นในลำไส้]] (intestinal flora) ทำให้เกิดการเจริญเติบโตของเชื้อแบคทีเรียก่อโรคอื่นๆ เช่น ''[[Clostridium difficile|Clostridium difficile]]''.<ref>{{cite web |title=Antibiotic-Associated Diarrhea – All you should know |accessdate=28 December 2014|url=http://www.bestnaturalremedies.net/antibiotic-associated-diarrhea}}</ref> นอกจากนี้ ยาปฏิชีวนะยังส่งผลต่อสมดุล[[จุลินทรีย์ประจำถิ่นในช่องคลอด|เชื้อจุลินทรีย์ประจำถิ่นในช่องคลอด]] (vaginal flora) ได้ด้วย ทำให้เกิดการเพิ่มจำนวนขึ้นของ[[ยีสต์]][[Candida|สกุลแคนดิดา]]ใน[[ช่องคลอด]]และ[[โยนี|บริเวณปากช่องคลอด]]ได้<ref name="Pirotta and Garland"/> ทั้งนี้ อาการไม่พึงประสงค์จากยาปฏิชีวนะอาจเกิดขึ้นได้จากการเกิด[[อันตรกิริยาระหว่างยา]] (drug interaction) ระหว่างยาปฏิชีวนะกับยาอื่นได้ เช่น ความเสี่ยงที่อาจเกิดความเสียหายต่อ[[เอ็นกล้ามเนื้อ]] (tendon) จากการใช้[[ควิโนโลน|ยาปฏิชีวนะกลุ่มควิโนโลน]] (quinolone antibiotic) ร่วมกับ[[คอร์ติโคสเตอรอยด์]]ที่ให้ผ่านทางระบบ<ref>{{cite journal|last1=Lewis|first1=Trevor|last2=Cook|first2=Jill|title=Fluoroquinolones and Tendinopathy: A Guide for Athletes and Sports Clinicians and a Systematic Review of the Literature|journal=Journal of Athletic Training|date=1 January 2014|volume=49|issue=3|pages=422–427|doi=10.4085/1062-6050-49.2.09|pmc=4080593|issn=1062-6050|pmid=24762232}}</ref>
===สหสัมพันธ์กับโรคอ้วน===
การสัมผัสกับยาปฏิชีวนะในช่วงต้นของชีวิตมีความสัมพันธ์กับการเพิ่มขึ้นของมวลกายในมนุษย์และหนูทดลอง<ref>{{Cite journal|title = Adding weight to the microbiota's role in obesity—exposure to antibiotics early in life can lead to increased adiposity|last = Ray|first = Katrina|date = September 2012|journal = Nature Reviews Endocrinology|doi = 10.1038/nrendo.2012.173|volume=8|pages=623}}</ref> ทั้งนี้ เนื่องมาจากในช่วงตอนต้นของชีวิตนั้นเป็นช่วงที่มีการสร้างสม[[จุลินทรีย์ประจำถิ่นในลำไส้]] และการพัฒนา[[เมแทบอลิซึม|ระบบเมแทบอลิซึม]]ของร่างกาย<ref name=":0">{{Cite journal|title = Microbiota, Antibiotics, and Obesity|last = Jess|first = Tine|date = December 2014|journal = The New England Journal of Medicine|doi = 10.1056/NEJMcibr1409799|volume=371|pages=2526–2528}}</ref> ในหนูทดลองที่สัมผัสกับยาปฏิชีวนะในระดับที่ต่ำกว่าที่ใช้ในการรักษาโรค (subtherapeutic antibiotic treatment; STAT) ชนิดใดชนืดหนึ่ง ได้แก่ [[เพนิซิลลิน]], [[แวนโคมัยซิน]], หรือ [[คลอร์เตตราไซคลีน]] นั้นจะเกิดการรบกวนการสร้างสม[[จุลินทรีย์ประจำถิ่นในลำไส้]] รวมไปถึงความสามารถใน[[เมแทบอลิซึม|การเผาผลาญสารอาหาร]]ของร่างกาย (metabolism)<ref>{{Cite journal |title = Antibiotics in early life alter the murine colonic microbiome and adiposity|last = Cho|first = Ilseung|date = August 2012 |journal = Nature|doi = 10.1038/nature11400|pmid =22914093 |pmc=3553221 |display-authors=etal |volume=488 |pages=621–6}}</ref> มีการศึกษาที่พบว่าหนูไมซ์ (mice) ที่ได้รับ[[เพนิซิลลิน|ยาเพนิซิลลิน]]ในขนาดต่ำ (1 ไมโครกรัม/น้ำหนักตัว 1 กรัม) ตั้งแต่แรกเกิดจนถึงช่วง[[หย่านม]] มีการเพิ่มขึ้นของมวลร่างกายและมวลไขมัน, มีการเจริญเติบโตที่เร็วมากขึ้น, และมีการเพิ่มการแสดงออกของยีนของตับที่เหนี่ยวนำให้เกิด[[กระบวนการสร้างเซลล์ไขมัน]] ในอัตราที่มากกว่าหนูตัวอื่นในกลุ่มควบคุมที่ไม่ได้รับยาปฏิชีวนะ<ref name=":1">{{Cite journal |title = Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences |last = Cox|first = Laura |date = 14 August 2014 |journal = Cell |volume=158 |issue=4|pages=705–21|doi = 10.1016/j.cell.2014.05.052 |pmid = 25126780 |pmc=4134513 |display-authors=etal}}</ref> นอกจากนี้ การได้รับเพนิซิลลินร่วมกับอาหารที่มีปริมาณไขมันสูงนั้นมีผลเพิ่มระดับอินซูลินขณะที่ท้องว่างในหนูไมซ์<ref name=":1" /> อย่างไรก็ตาม ยังไม่เป็นทราบแน่ชัดว่า โดยแท้จริงแล้วยาปฏิชีวนะเป็นสาเหตุหนึ่งที่ทำให้เกิด[[โรคอ้วน]]ในมนุษย์ได้หรือไม่ การศุกษาบางการศึกษาพบการมีสหสัมพันธ์ระหว่างการได้รับยาปฏิชีวนะตั้งแต่ในวัยทารก (อายุ <6 เดือน) กับการเพิ่มขึ้นของมวลกาย (ที่อายุ 10 และ 20 เดือน)<ref>{{Cite journal|title = Infant antibiotic exposures and early-life body mass|url = http://www.nature.com/ijo/journal/v37/n1/full/ijo2012132a.html|journal = International Journal of Obesity|date = 1 January 2013|issn = 0307-0565|pmc = 3798029|pmid = 22907693|pages = 16–23|volume = 37|issue = 1|doi = 10.1038/ijo.2012.132|language = en|first = L.|last = Trasande|first2 = J.|last2 = Blustein|first3 = M.|last3 = Liu|first4 = E.|last4 = Corwin|first5 = L. M.|last5 = Cox|first6 = M. J.|last6 = Blaser}}</ref> อีกการศึกษาหนึ่งพบว่า ชนิดของยาปฏิชีวนะที่ได้รับนั้นมีความสัมพันธ์กับการเกิดโรคอ้วน โดยผู้ที่ได้รับ[[แมโครไลด์|ยากลุ่มแมโครไลด์]] จะมีความเสี่ยงต่อการเกิดภาวะน้ำหนักเกินสูงกว่าผู้ที่ได้รับ[[เพนิซิลลิน|ยาเพนิซิลลิน]]หรือ[[เซฟาโลสปอริน]]อย่างมีนัยสำคัญ<ref>{{Cite journal|title = Napping, development and health from 0 to 5 years: a systematic review |url = http://adc.bmj.com/content/100/7/615 |journal = Archives of Disease in Childhood |date = 1 July 2015 |pmid =25691291 |pages = 615–622 |volume = 100 |issue = 7 |doi = 10.1136/archdischild-2014-307241 |language = en|first = Karen|last = Thorpe|first2 = Sally|last2 = Staton|first3 = Emily|last3 = Sawyer|first4 = Cassandra|last4 = Pattinson|first5 = Catherine|last5 = Haden|first6 = Simon|last6 = Smith}}</ref> ดังนั้น จึงอาจสรุปได้ว่าการได้รับยาปฏิชีวนะในช่วงวัยทารกนั้นมีความสัมพันธ์กับการเกิด[[โรคอ้วน]]ในมนุษย์ แต่ความสัมพันธ์เชิงเหตุผลในประเด็นดังกล่าวนั้นยังไม่เป็นที่ทราบแน่ชัด ทั้งนี้ ถึงแม้ว่าจะมีความสัมพันธ์ระหว่างการเกิดโรคอ้วนกับการได้รับยาปฏิชีวนะก็ตาม การใช้ยาปฏิชีวนะในทารกก็ควรที่จะชั่งน้ำหนักถึงความเสี่ยงที่อาจเกิดขึ้นกับประโยชน์ทางคลินิกที่จะได้รับอยู่เฉกเช่นเดิมเสมอ<ref name=":0" />
==Interactions==
===Birth control pills===
Well controlled studies on the effect of [[oral contraceptive pill|oral contraceptive]] failure and antibiotics are very limited.<ref name=":8">{{Cite journal|last=Anderson|first=Keri C.|last2=Schwartz|first2=Michael D.|last3=Lieu|first3=Siam O.|date=1 January 2013|title=Antibiotics and OC effectiveness|journal=JAAPA: official journal of the American Academy of Physician Assistants|volume=26|issue=1|pages=11|issn=1547-1896|pmid=23355994|doi=10.1097/01720610-201301000-00002}}</ref> The majority of studies indicate antibiotics do not interfere with [[combined oral contraceptive pill|birth control pill]]s,<ref name="Weaver1999"/> such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%).<ref name="pmid10384856"/> Situations that may increase the risk of oral contraceptive failure include [[Compliance (medicine)|non-compliance]] (missing taking the pill), vomiting or diarrhea. Gastrointestinal disorders or interpatient variability in oral contraceptive absorption affecting [[ethinylestradiol]] [[Serum (blood)|serum levels]] in the blood.<ref name=":8" /> Women with [[Irregular menstruation|menstrual irregularities]] may be at higher risk of failure and should be advised to use [[Contraception|backup contraception]] during antibiotic treatment and for one week after its completion. If patient-specific risk factors for reduced oral contraceptive efficacy are suspected, backup contraception is recommended.<ref name=":8" />
In cases where antibiotics have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibiotic [[rifampicin]], these cases may be due to an increase in the activities of hepatic liver enzymes' causing increased breakdown of the pill's active ingredients.<ref name="Weaver1999" /> Effects on the intestinal flora, which might result in reduced absorption of [[estrogen]]s in the colon, have also been suggested, but such suggestions have been inconclusive and controversial.<ref name="pmid3155374" /><ref name="pmid2256523" /> Clinicians have recommended that extra contraceptive measures be applied during therapies using antibiotics that are suspected to interact with oral [[contraceptives]].<ref name="Weaver1999" /> More studies on the possible interactions between antibiotics and birth control pills (oral contraceptives) are required as well as careful assessment of patient-specific risk factors for potential oral contractive pill failure prior to dismissing the need for backup contraception.<ref name=":8" />
===Alcohol===
Interactions between alcohol and certain antibiotics may occur and may cause side-effects and decreased effectiveness of antibiotic therapy.<ref name="bmj"/><ref name="antibiotics-and-alcohol"/> While moderate alcohol consumption is unlikely to interfere with many common antibiotics, there are specific types of antibiotics with which alcohol consumption may cause serious side-effects.<ref name="NHS" /> Therefore, potential risks of side-effects and effectiveness depend on the type of antibiotic administered.<ref>{{cite journal|last1=Moore|first1=Alison A.|last2=Whiteman|first2=Elizabeth J.|last3=Ward|first3=Katherine T.|title=Risks of Combined Alcohol-Medication Use in Older Adults|journal=The American journal of geriatric pharmacotherapy|date=1 March 2007|volume=5|issue=1|pages=64–74|pmc=4063202|issn=1543-5946|pmid=17608249|doi=10.1016/j.amjopharm.2007.03.006}}</ref>
Antibiotics such as [[metronidazole]], [[tinidazole]], [[cephamandole]], [[latamoxef]], [[cefoperazone]], [[cefmenoxime]], and [[furazolidone]], cause a [[disulfiram]]-like chemical reaction with alcohol by inhibiting its breakdown by [[acetaldehyde dehydrogenase]], which may result in vomiting, nausea, and shortness of breath.<ref name="NHS"/> In addition, the efficacy of doxycycline and [[erythromycin]] succinate may be reduced by alcohol consumption.<ref>{{cite book |last= Stockley |first= IH |year= 2002 |title= Stockley's Drug Interactions |edition= 6th |location= London |publisher= Pharmaceutical Press}}{{page needed|date=December 2013}}</ref> Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound.<ref name="Antibiotics FAQ"/>
==Pharmacodynamics==
{{Main article|Antimicrobial pharmacodynamics}}
The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include [[Immune system|host defense mechanisms]], the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial.<ref name="Pankey2004"/> A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells.<ref name="Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells"/> These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection.<ref name="Pankey2004"/><ref>{{cite book |authors=Pelczar MJ, Chan EC, Krieg NR |year=2010 |contribution=Host-Parasite Interaction; Nonspecific Host Resistance |title=Microbiology Concepts and Applications |edition=6th |publisher=McGraw-Hill |location=New York |pages=478–479}}</ref> Since the activity of antibacterials depends frequently on its concentration,<ref name="Rhee2004"/> ''in vitro'' characterization of antibacterial activity commonly includes the determination of the [[minimum inhibitory concentration]] and minimum bactericidal concentration of an antibacterial.<ref name="Pankey2004"/><ref name="Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC)of antimicrobial substances"/>
To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its [[Pharmacokinetics|pharmacokinetic]] profile, and several pharmacological parameters are used as markers of drug efficacy.<ref>{{cite journal |title=A long journey from minimum inhibitory concentration testing to clinically predictive breakpoints: deterministic and probabilistic approaches in deriving breakpoints |authors=Dalhoff A, Ambrose PG, Mouton JW |journal=Infection |date=August 2009 |volume=37|issue=4|pages=296–305|doi=10.1007/s15010-009-7108-9 |pmid=19629383 }}</ref>
===Combination therapy===
In important infectious diseases, including tuberculosis, [[combination therapy]] (i.e., the concurrent application of two or more antibiotics) has been used to delay or prevent the emergence of resistance. In acute bacterial infections, antibiotics as part of combination therapy are prescribed for their [[Drug synergy|synergistic]] effects to improve treatment outcome as the combined effect of both antibiotics is better than their individual effect.<ref name=":4">{{Cite journal|last=Ocampo|first=Paolo S.|last2=Lázár|first2=Viktória|last3=Papp|first3=Balázs|last4=Arnoldini|first4=Markus|last5=Abel zur Wiesch|first5=Pia|last6=Busa-Fekete|first6=Róbert|last7=Fekete|first7=Gergely|last8=Pál|first8=Csaba|last9=Ackermann|first9=Martin|date=1 August 2014|title=Antagonism between bacteriostatic and bactericidal antibiotics is prevalent|journal=Antimicrobial Agents and Chemotherapy|volume=58|issue=8|pages=4573–4582|doi=10.1128/AAC.02463-14|issn=1098-6596|pmc=4135978|pmid=24867991}}</ref><ref name=":5">{{Cite journal|last=Bollenbach|first=Tobias|date=1 October 2015|title=Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution|journal=Current Opinion in Microbiology|volume=27|pages=1–9|doi=10.1016/j.mib.2015.05.008|issn=1879-0364|pmid=26042389}}</ref> [[Methicillin-resistant Staphylococcus aureus]] infections may be treated with a combination therapy of [[fusidic acid]] and rifampicin.<ref name=":4" /> Antibiotics used in combination may also be antagonistic and the combined effects of the two antibiotics may be less than if the individual antibiotic was given as part of a [[monotherapy]].<ref name=":4" /> For example, [[chloramphenicol]] and [[tetracyclines]] are antagonists to [[penicillins]] and [[aminoglycosides]]. However, this can vary depending on the species of bacteria.<ref>{{cite web |url=http://medical-dictionary.thefreedictionary.com/antibiotic+antagonism |title=antagonism |accessdate=25 August 2014}}</ref> In general, combinations of a bacteriostatic antibiotic and bactericidal antibiotic are antagonistic.<ref name=":4" /><ref name=":5" />
==Classes==
{{Main article|List of antibiotics}}
[[File:Antibiotics action.svg|right|thumb|150px|Molecular targets of antibiotics on the bacteria cell]]
Antibiotics are commonly classified based on their [[mechanism of action]], [[chemical structure]], or spectrum of activity. Most target bacterial functions or growth processes.<ref name="CALDERIN2007"/> Those that target the bacterial cell wall ([[penicillin]]s and [[cephalosporin]]s) or the cell membrane ([[polymyxin]]s), or interfere with essential bacterial enzymes ([[rifamycin]]s, [[lipiarmycin]]s, [[Quinolone antibiotic|quinolones]], and [[Sulfonamide (medicine)|sulfonamides]]) have [[Bactericide|bactericidal]] activities. [[Protein synthesis inhibitor]]s ([[macrolide]]s, [[lincosamides]] and [[tetracycline]]s) are usually [[bacteriostatic]] (with the exception of bactericidal [[aminoglycoside]]s).<ref name="The importance of bactericidal drugs: future directions in infectious disease"/> Further categorization is based on their target specificity. "Narrow-spectrum" antibiotics target specific types of bacteria, such as [[gram-negative]] or [[gram-positive]], whereas [[broad-spectrum antibiotics]] affect a wide range of bacteria. Following a 40-year break in discovering new classes of antibacterial compounds, four new classes of antibiotics have been brought into clinical use in the late 2000s and early 2010s: cyclic [[lipopeptide]]s (such as [[daptomycin]]), [[glycylcyclines]] (such as [[tigecycline]]), [[oxazolidinone]]s (such as [[linezolid]]), and [[lipiarmycin]]s (such as [[fidaxomicin]]).<ref>Cunha BA. Antibiotic Essentials 2009. Jones & Bartlett Learning, {{ISBN|978-0-7637-7219-2}} p. 180, for example.</ref><ref>{{cite journal | authors = Srivastava A, Talaue M, Liu S, Degen D, Ebright RY, Sineva E, Chakraborty A, Druzhinin SY, Chatterjee S, Mukhopadhyay J, Ebright YW, Zozula A, Shen J, Sengupta S, Niedfeldt RR, Xin C, Kaneko T, Irschik H, Jansen R, Donadio S, Connell N, Ebright RH | title = New target for inhibition of bacterial RNA polymerase: 'switch region' | journal = Curr. Opin. Microbiol. | volume = 14 | issue = 5 | pages = 532–43 | year = 2011 | pmid = 21862392 | pmc = 3196380 | doi = 10.1016/j.mib.2011.07.030 }}</ref>
==Production==
{{Main article|Production of antibiotics}}
With advances in [[medicinal chemistry]], most modern antibacterials are [[semisynthetic]] modifications of various natural compounds.<ref name="Nussbaum2006">{{cite journal|last1=von Nussbaum|first1=Franz|last2=Brands|first2=Michael|last3=Hinzen|first3=Berthold|last4=Weigand|first4=Stefan|last5=Häbich|first5=Dieter|title=Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival?|journal=Angewandte Chemie International Edition|date=4 August 2006|volume=45|issue=31|pages=5072–5129|doi=10.1002/anie.200600350|url=http://onlinelibrary.wiley.com/doi/10.1002/anie.200600350/abstract;jsessionid=1D843B672707790C436223082CDC24FC.f04t02|accessdate=3 August 2016|language=en|issn=1521-3773|pmid=16881035}}</ref> These include, for example, the [[beta-lactam antibiotics]], which include the [[penicillin]]s (produced by fungi in the genus ''[[Penicillium]]''), the [[cephalosporin]]s, and the [[carbapenem]]s. Compounds that are still isolated from living organisms are the [[aminoglycoside]]s, whereas other antibacterials—for example, the [[Sulfonamide (medicine)|sulfonamides]], the [[Quinolone antibiotic|quinolones]], and the [[oxazolidinone]]s—are produced solely by [[chemical synthesis]].<ref name="Nussbaum2006"/> Many antibacterial compounds are relatively [[small molecule]]s with a [[molecular weight]] of less than 1000 [[dalton (unit)|dalton]]s.<ref>{{cite book|url=https://books.google.com/books?id=av5SHPiHVcsC&lpg=PA800&ots=Poh9XTWpBC&dq=oral%20drug%20molecular%20weight%20distribution%20antibiotics&pg=PA800#v=onepage&q&f=false |title=Antibiotic Discovery and Development |author1=Dougherty TJ |author2=Pucci MJ |publisher=Springer |date=18 December 2011 |page=800}}</ref>
Since the first pioneering efforts of [[Howard Florey]] and [[Ernst Boris Chain|Chain]] in 1939, the importance of antibiotics, including antibacterials, to [[medicine]] has led to intense research into producing antibacterials at large scales. Following screening of antibacterials against a wide range of bacteria, production of the active compounds is carried out using [[Industrial fermentation|fermentation]], usually in strongly aerobic conditions.{{citation needed|date=January 2017}}
==Resistance==
{{Main article|Antibiotic resistance}}
[[File:Human neutrophil ingesting MRSA.jpg|thumb|left|[[Scanning electron micrograph]] of a human [[neutrophil]] ingesting [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] (MRSA)]]
The emergence of resistance of bacteria to antibiotics is a common phenomenon. Emergence of resistance often reflects [[evolution]]ary processes that take place during antibiotic therapy. The antibiotic treatment may [[Natural selection|select]] for bacterial strains with physiologically or genetically enhanced capacity to survive high doses of antibiotics. Under certain conditions, it may result in preferential growth of resistant bacteria, while growth of susceptible bacteria is inhibited by the drug.<ref name="Balancing the drug-resistance equation"/> For example, antibacterial selection for strains having previously acquired antibacterial-resistance genes was demonstrated in 1943 by the [[Luria–Delbrück experiment]].<ref name="Mutations of Bacteria from Virus Sensitivity to Virus Resistance"/> Antibiotics such as penicillin and erythromycin, which used to have a high efficacy against many bacterial species and strains, have become less effective, due to the increased resistance of many bacterial strains.<ref name="voanews.com"/>
Resistance may take the form of biodegredation of pharmaceuticals, such as sulfamethazine-degrading soil bacteria introduced to sulfamethazine through medicated pig feces.<ref>{{cite journal | authors = Topp E, Chapman R, Devers-Lamrani M, Hartmann A, Marti R, Martin-Laurent F, Sabourin L, Scott A, Sumarah M | title = Accelerated Biodegradation of Veterinary Antibiotics in Agricultural Soil following Long-Term Exposure, and Isolation of a Sulfamethazine-degrading sp | journal = J. Environ. Qual. | volume = 42 | issue = 1 | pages = 173–8 | year = 2013 | pmid = 23673752 | doi = 10.2134/jeq2012.0162 | url = http://www.agr.gc.ca/eng/abstract/?id=27587000000610 }}</ref>
The survival of bacteria often results from an inheritable resistance,<ref name="Witte2004"/> but the growth of resistance to antibacterials also occurs through [[horizontal gene transfer]]. Horizontal transfer is more likely to happen in locations of frequent antibiotic use.<ref>{{cite book|last=Dyer|first=Betsey Dexter|title=A Field Guide To Bacteria|year=2003|publisher=Cornell University Press|isbn=978-0-8014-8854-2|chapter=Chapter 9, Pathogens|url=http://www.audible.com/pd/ref=sr_1_1?asin=B002VA8L4Y&qid=1305345229&sr=1-1}}</ref>
Antibacterial resistance may impose a biological cost, thereby reducing [[biological fitness|fitness]] of resistant strains, which can limit the spread of antibacterial-resistant bacteria, for example, in the absence of antibacterial compounds. Additional mutations, however, may compensate for this fitness cost and can aid the survival of these bacteria.<ref name="The biological cost of mutational antibiotic resistance: any practical conclusions?"/>
Paleontological data show that both antibiotics and antibiotic resistance are ancient compounds and mechanisms.<ref name="D'Costa2011"/> Useful antibiotic targets are those for which mutations negatively impact bacterial reproduction or viability.<ref name="Gladki2013"/>
Several molecular mechanisms of antibacterial resistance exist. Intrinsic antibacterial resistance may be part of the genetic makeup of bacterial strains.<ref name="Alekshun2007"/><ref>{{cite journal |journal=Nature Communications|volume=7|pages= 1–10|date=December 2016 | doi= 10.1038/ncomms13803|title=A diverse intrinsic antibiotic resistome from a cave bacterium|last1=Pawlowski |first1=Andrew C| last2=Wang|first2=Wenliang |last3=Koteva|first3=Kalinka| last4=Barton|first4=Hazel| last5=McArthur |first5=Andrew G| last6=Wright|first6=Gerard D| pmid=27929110}}</ref> For example, an antibiotic target may be absent from the bacterial [[genome]]. Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extra-chromosomal DNA.<ref name="Alekshun2007"/> Antibacterial-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibacterial-resistant strains.<ref name="Glycopeptide antibiotic resistance genes in glycopeptide-producing organisms"/><ref name="Multidrug Resistance in Bacteria"/> The spread of antibacterial resistance often occurs through vertical transmission of mutations during growth and by genetic recombination of DNA by [[Horizontal gene transfer|horizontal genetic exchange]].<ref name="Witte2004"/> For instance, antibacterial resistance genes can be exchanged between different bacterial strains or species via [[plasmids]] that carry these resistance genes.<ref name="Witte2004"/><ref name="Baker2006"/> Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials.<ref name="Baker2006"/> Cross-resistance to several antibacterials may also occur when a resistance mechanism encoded by a single gene conveys resistance to more than one antibacterial compound.<ref name="Baker2006"/>
Antibacterial-resistant strains and species, sometimes referred to as "superbugs", now contribute to the emergence of diseases that were for a while well controlled. For example, emergent bacterial strains causing tuberculosis that are resistant to previously effective antibacterial treatments pose many therapeutic challenges. Every year, nearly half a million new cases of [[multidrug-resistant tuberculosis]] (MDR-TB) are estimated to occur worldwide.<ref>"[http://www.who.int/mediacentre/news/releases/2009/tuberculosis_drug_resistant_20090402/en/index.html Health ministers to accelerate efforts against drug-resistant TB]". ''World Health Organization (WHO).''</ref> For example, [[NDM-1]] is a newly identified enzyme conveying bacterial resistance to a broad range of [[beta-lactam]] antibacterials.<ref name="Are you ready for a world without antibiotics?"/> The United Kingdom's [[Health Protection Agency]] has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections."<ref name="Health Protection Report"/> On 26 May 2016 an [[Escherichia coli|E coli bacteria]] "[[Antimicrobial resistance|superbug]]" was identified in the [[United States]] resistant to [[colistin]], [[Drug of last resort|"the last line of defence" antibiotic]].<ref>{{Cite journal|last=McGann|first=Patrick|last2=Snesrud|first2=Erik|last3=Maybank|first3=Rosslyn|last4=Corey|first4=Brendan|last5=Ong|first5=Ana C.|last6=Clifford|first6=Robert|last7=Hinkle|first7=Mary|last8=Whitman|first8=Timothy|last9=Lesho|first9=Emil|date=26 May 2016|title=Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First report of mcr-1 in the USA|url=http://aac.asm.org/content/early/2016/05/25/AAC.01103-16|journal=Antimicrobial Agents and Chemotherapy|language=en|pages=AAC.01103–16|doi=10.1128/AAC.01103-16|issn=0066-4804|pmid=27230792|volume=60|pmc=4914657}}</ref><ref>{{Cite web|url=http://www.scientificamerican.com/article/dangerous-new-antibiotic-resistant-bacteria-reach-u-s/|title=Dangerous New Antibiotic-Resistant Bacteria Reach U.S.|last=Moyer|first=Melinda Wenner|website=Scientific American|access-date=27 May 2016}}</ref>
===Misuse===
[[File:CDC Get Smart poster healthy adult.png|thumb|This poster from the US Centers for Disease Control and Prevention "Get Smart" campaign, intended for use in doctors' offices and other healthcare facilities, warns that antibiotics do not work for viral illnesses such as the common cold.]]
{{main article|Antibiotic misuse}}
Per ''The ICU Book'' "The first rule of antibiotics is try not to use them, and the second rule is try not to use too many of them."<ref name="Marino"/> Inappropriate antibiotic treatment and overuse of antibiotics have contributed to the emergence of antibiotic-resistant bacteria. [[Self-prescribing|Self prescription]] of antibiotics is an example of misuse.<ref name="Larson2007"/> Many antibiotics are frequently prescribed to treat symptoms or diseases that do not respond to antibiotics or that are likely to resolve without treatment. Also, incorrect or suboptimal antibiotics are prescribed for certain bacterial infections.<ref name="pmid15993671"/><ref name="Larson2007"/> The overuse of antibiotics, like penicillin and erythromycin, has been associated with emerging antibiotic resistance since the 1950s.<ref name="voanews.com"/><ref name="Hawkey2008"/> Widespread usage of antibiotics in hospitals has also been associated with increases in bacterial strains and species that no longer respond to treatment with the most common antibiotics.<ref name="Hawkey2008"/>
Common forms of antibiotic misuse include excessive use of [[prophylaxis|prophylactic]] antibiotics in travelers and failure of medical professionals to prescribe the correct dosage of antibiotics on the basis of the patient's weight and history of prior use. Other forms of misuse include failure to take the entire prescribed course of the antibiotic, incorrect dosage and administration, or failure to rest for sufficient recovery. Inappropriate antibiotic treatment, for example, is their prescription to treat viral infections such as the [[common cold]]. One study on [[respiratory tract infection]]s found "physicians were more likely to prescribe antibiotics to patients who appeared to expect them".<ref name="pmid17467120"/> Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics.<ref name="pmid17509729"/><ref>{{cite journal|last1=Coxeter|first1=Peter|title=Interventions to facilitate shared decision making to address antibiotic use for acute respiratory infections in primary care|journal=Cochrane Database of Systematic Reviews|date=11 November 2015|volume=11|pmid=26560888|url=http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010907.pub2/abstract|doi=10.1002/14651858.CD010907.pub2|pages=CD010907}}</ref>
Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibiotics.<ref name="Larson2007"/> The issues of misuse and overuse of antibiotics have been addressed by the formation of the US Interagency Task Force on Antimicrobial Resistance. This task force aims to actively address antimicrobial resistance, and is coordinated by the US [[Centers for Disease Control and Prevention]], the [[Food and Drug Administration]] (FDA), and the [[National Institutes of Health]] (NIH), as well as other US agencies.<ref name="pharmguide"/> An NGO campaign group is ''Keep Antibiotics Working''.<ref name="Keep Antibiotics Working"/> In France, an "Antibiotics are not automatic" government campaign started in 2002 and led to a marked reduction of unnecessary antibiotic prescriptions, especially in children.<ref>{{cite journal|authors=Sabuncu E, David J, Bernède-Bauduin C, Pépin S, Leroy M, Boëlle PY, Watier L, Guillemot D |title=Significant reduction of antibiotic use in the community after a nationwide campaign in France, 2002–2007 |journal=PLoS Med. |volume=6 |issue=6 |pages=e1000084 |year=2009 |pmid=19492093 |pmc=2683932 |doi=10.1371/journal.pmed.1000084 |url=http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000084 |editor1-last=Klugman |archiveurl=https://www.webcitation.org/5uJyYYA93?url=http://www.plosmedicine.org/article/info%3Adoi/10.1371/journal.pmed.1000084 |deadurl=no |editor1-first=Keith P. |archivedate=18 November 2010 |df=dmy }}</ref>
The emergence of antibiotic resistance has prompted restrictions on their use in the UK in 1970 (Swann report 1969), and the EU has banned the use of antibiotics as growth-promotional agents since 2003.<ref>{{cite web|url=http://www.legaltext.ee/text/en/T80294.htm |title=Regulation (EC) No 1831/2003 of the European Parliament and of the Council |deadurl=yes |archiveurl=https://web.archive.org/web/20090109031010/http://www.legaltext.ee/text/en/T80294.htm |archivedate=9 January 2009 |df= }}</ref> Moreover, several organizations (including the World Health Organization, the [[National Academy of Sciences]], and the [[U.S. Food and Drug Administration]]) have advocated restricting the amount of antibiotic use in food animal production.<ref>{{cite web|url=http://consumersunion.org/news/the-overuse-of-antibiotics-in-food-animals-threatens-public-health-2/ |accessdate=4 July 2016 |title=The Overuse of Antibiotics in Food Animals Threatens Public Health |publisher=Consumer Reports}}{{MEDRS|date=July 2016}}</ref> However, commonly there are delays in regulatory and legislative actions to limit the use of antibiotics, attributable partly to resistance against such regulation by industries using or selling antibiotics, and to the time required for research to test causal links between their use and resistance to them. Two federal bills (S.742<ref name="USbill1"/> and H.R. 2562<ref name="USbill2"/>) aimed at phasing out nontherapeutic use of antibiotics in US food animals were proposed, but have not passed.<ref name="USbill1"/><ref name="USbill2"/> These bills were endorsed by public health and medical organizations, including the American Holistic Nurses' Association, the American Medical Association, and the American Public Health Association (APHA).<ref>{{cite web |url= http://www.acpm.org/2003051H.pdf |accessdate= 12 November 2008 |title=Kee Antibiotics Working|archiveurl=https://web.archive.org/web/20090325225525/http://www.acpm.org/2003051H.pdf |archivedate=25 March 2009 |deadurl=yes}}</ref>
Despite pledges by food companies and restaurants to reduce or eliminate meat that comes from animals treated with antibiotics, the purchase of antibiotics for use on farm animals has been increasing every year.<ref>http://www.npr.org/sections/thesalt/2016/12/22/506599017/despite-pledges-to-cut-back-farms-are-still-using-antibiotics</ref>
There has been extensive use of antibiotics in animal husbandry. In the United States, the question of emergence of antibiotic-resistant bacterial strains due to [[Antibiotic use in livestock|use of antibiotics in livestock]] was raised by the US [[Food and Drug Administration]] (FDA) in 1977. In March 2012, the United States District Court for the Southern District of New York, ruling in an action brought by the [[Natural Resources Defense Council]] and others, ordered the FDA to revoke approvals for the use of antibiotics in livestock, which violated FDA regulations.<ref>{{cite news |title=FDA Told to Move on Antibiotic Use in Livestock |url=http://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/31792 |accessdate=24 March 2012 |newspaper=MedPage Today|date=23 March 2012|author=John Gever}}</ref>
== History ==
=== Biological antibiotics derived from molds ===
{{See also|Timeline of antibiotics}} {{See also|History of penicillin}}
Substances with antibiotic properties had been used for various purposes since ancient times.
[[File:Penicillin core.svg|thumb|170px|[[Penicillin]], the first natural antibiotic discovered by [[Alexander Fleming]] in 1928]]
Before the early 20th century, treatments for infections were based primarily on [[folk medicine|medicinal folklore]]. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago.<ref name="Considerations for Determining if a Natural Product Is an Effective Wound-Healing Agent"/> Many ancient cultures, including the [[Ancient Egyptian medicine|ancient Egyptians]] and [[Ancient Greek medicine|ancient Greeks]], used specially selected [[mold]] and plant materials and extracts to treat [[infection]]s.<ref name="Early history of wound treatment"/><ref name="Moulds in ancient and more recent medicine"/> More recent observations made in the laboratory of antibiosis between microorganisms led to the discovery of natural antibacterials produced by microorganisms. [[Louis Pasteur]] observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics".<ref name="Kingston2008"/>
In 1874, physician Sir [[William Roberts (physician)|William Roberts]] noted that cultures of the mold ''[[Penicillium glaucum]]'' that is used in the making of some types of [[blue cheese]] did not display bacterial contamination.<ref>{{cite journal|last1=Foster|first1=William|last2=Raoult|first2=Alain|title=History of Medicine: Early descriptions of antibiosis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2157443/pdf/jroyalcgprac00228-0073.pdf |accessdate=31 January 2017|pages=889–94|quote=the first scientific observations of the antagonistic actions of various micro-organisms were made ... by William Roberts of Manchester (1874) and John Tyndall of London (1876).|pmc=2157443|pmid=4618289|volume=24|date=December 1974|journal=J R Coll Gen Pract}}</ref> In 1876, physicist [[John Tyndall]] also contributed to this field.<ref>{{cite journal|last1=Foster|first1=William|last2=Raoult|first2=Alain|title=History of Medicine: Early descriptions of antibiosis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2157443/pdf/jroyalcgprac00228-0073.pdf |accessdate=31 January 2017|pages=889–94|quote=Both Roberts and Tyndall indicated that the Penicillium molds had some property or had an activity which inhibited bacterial growth.|pmc=2157443|pmid=4618289|volume=24|date=December 1974|journal=J R Coll Gen Pract}}</ref> Pasteur conducted research showing that ''[[Bacillus anthracis]]'' would not grow in the presence of the related mold ''[[Penicillium notatum]]''.
In 1895 [[Vincenzo Tiberio]], Itallian physician, published a paper on the antibacterial power of some extracts of mold.<ref>{{Cite journal|last=Bucci|first=Roberto|last2=Gallì|first2=Paola|date=2012-05-11|title=Public Health History Corner Vincenzo Tiberio: a misunderstood researcher|url=http://ijphjournal.it/article/view/5688|journal=Italian Journal of Public Health|language=en|volume=8|issue=4|issn=1723-7815}}</ref>
In 1897, doctoral student [[Ernest Duchesne]] submitted a dissertation, "Contribution à l'étude de la concurrence vitale chez les micro-organismes: antagonisme entre les moisissures et les microbes" (Contribution to the study of vital competition in micro-organisms: antagonism between molds and microbes),<ref>{{cite web|last1=Duchesne|first1=Ernest|last2=Witty|first2=Michael (Translator)|title=Duchesne's Antagonism between molds and bacteria, an English Colloquial Translation|url=https://www.amazon.com/dp/B00DZVXPIK|publisher=Amazon.com|accessdate=31 January 2017}}</ref> the first known scholarly work to consider the therapeutic capabilities of molds resulting from their anti-microbial activity. In his thesis, Duchesne proposed that bacteria and molds engage in a perpetual battle for survival. Duchesne observed that ''[[Escherichia coli|E. coli]]'' was eliminated by ''Penicillium glaucum'' when they were both grown in the same culture. He also observed that when he [[Inoculation|inoculated]] laboratory animals with lethal doses of [[typhoid]] bacilli together with ''Penicillium glaucum'', the animals did not contract typhoid. Unfortunately Duchesne's army service after getting his degree prevented him from doing any further research.<ref name="Academic Press">{{cite book|last1=Straand|first1=Jørund|last2=Gradmann|first2=Christoph|last3=Simonsen|first3=Gunnar Skov|last4=Lindbæk|first4=Morten|title=International Encyclopedia of Public Health: Antibiotic Development and Resistance|date=2008|publisher=Academic Press|pages=200|url=http://www.sciencedirect.com/topics/page/Arsphenamine|accessdate=31 January 2017}}</ref> Duchesne died of [[tuberculosis]], a disease now treated by antibiotics.<ref name="Academic Press"/>
[[File:Alexander Fleming.jpg|thumb|left|Alexander Fleming was awarded a Nobel prize for his role in the discovery of penicillin]]In 1928, Sir [[Alexander Fleming]] identified [[penicillin]], a molecule produced by certain molds that kills or stops the growth of certain kinds of bacteria. Fleming was working on a culture of [[pathogen|disease-causing]] bacteria when he noticed the [[spore]]s of a green mold, ''[[Penicillium chrysogenum]]'', in one of his [[agar plate|culture plates]]. He observed that the presence of the mold killed or prevented the growth of the bacteria.<ref>{{Cite journal|last=Tan|first=Siang Yong|last2=Tatsumura|first2=Yvonne|date=1 July 2015|title=Alexander Fleming (1881–1955): Discoverer of penicillin|journal=Singapore Medical Journal|volume=56|issue=7|pages=366–367|doi=10.11622/smedj.2015105|issn=0037-5675|pmc=4520913|pmid=26243971}}</ref> Fleming postulated that the mold must secrete an antibacterial substance, which he named penicillin in 1928. Fleming believed that its antibacterial properties could be exploited for chemotherapy. He initially characterized some of its biological properties, and attempted to use a crude preparation to treat some infections, but he was unable to pursue its further development without the aid of trained chemists.<ref name="Fleming1929"/><ref name="Sykes2001"/>
[[Ernst Chain]], [[Howard Florey]] and [[Edward Abraham]] succeeded in purifying the first penicillin, [[penicillin G]], in 1942, but it did not become widely available outside the Allied military before 1945. Later, [[Norman Heatley]] developed the back extraction technique for efficiently purifying penicillin in bulk. The chemical structure of penicillin was first proposed by Abraham in 1942<ref>{{Cite journal|last=Jones|first=David S.|last2=Jones|first2=John H.|date=1 December 2014|title=Sir Edward Penley Abraham CBE. 10 June 1913 – 9 May 1999|url=http://rsbm.royalsocietypublishing.org/content/60/5.1|journal=Biographical Memoirs of Fellows of the Royal Society|language=en|volume=60|pages=5–22|doi=10.1098/rsbm.2014.0002|issn=0080-4606}}</ref> and then later confirmed by [[Dorothy Crowfoot Hodgkin]] in 1945. Purified penicillin displayed potent antibacterial activity against a wide range of bacteria and had low toxicity in humans. Furthermore, its activity was not inhibited by biological constituents such as pus, unlike the synthetic [[sulfonamides]]. (see below) The discovery of such a powerful antibiotic was unprecedented, and the development of penicillin led to renewed interest in the search for antibiotic compounds with similar efficacy and safety.<ref name="Use of Micro-organisms for therapeutic purposes"/> For their successful development of penicillin, which Fleming had accidentally discovered but could not develop himself, as a therapeutic drug, Chain and Florey shared the 1945 [[Nobel Prize in Medicine]] with Fleming.
Florey credited [[Rene Dubos]] with pioneering the approach of deliberately and systematically searching for antibacterial compounds, which had led to the discovery of gramicidin and had revived Florey's research in penicillin.<ref name=Epps2006/> In 1939, coinciding with the start of [[World War II]], Dubos had reported the discovery of the first naturally derived antibiotic, [[tyrothricin]], a compound of 20% [[gramicidin]] and 80% [[tyrocidine]], from ''B. brevis.'' It was one of the first commercially manufactured antibiotics and was very effective in treating wounds and ulcers during World War II.<ref name="Epps2006"/> Gramicidin, however, could not be used systemically because of toxicity. Tyrocidine also proved too toxic for systemic usage. Research results obtained during that period were not shared between the [[Axis powers|Axis]] and the [[Allied powers of World War II|Allied powers]] during World War II and limited access during the [[Cold War]].<ref>{{Cite journal|last=Capocci|first=Mauro|date=1 January 2014|title=Cold drugs. Circulation, production and intelligence of antibiotics in post-WWII years|journal=Medicina Nei Secoli|volume=26|issue=2|pages=401–421|issn=0394-9001|pmid=26054208}}</ref>
=== Synthetic antibiotics derived from dyes ===
Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with [[Paul Ehrlich]] in the late 1880s.<ref name="CALDERIN2007"/> Ehrlich noted certain dyes would color human, animal, or bacterial cells, whereas others did not. He then proposed the idea that it might be possible to create chemicals that would act as a selective drug that would bind to and kill bacteria without harming the human host. After screening hundreds of dyes against various organisms, in 1907, he discovered a medicinally useful drug, the first synthetic antibacterial [[salvarsan]]<ref name="CALDERIN2007"/><ref name="Limbird2004"/><ref name="Bosch2008"/> now called arsphenamine.
[[File:Paul Ehrlich and Sahachiro Hata.jpg|thumb|left|[[Paul Ehrlich]] and [[Sahachiro Hata]] ]]
The era of antibacterial treatment began with the discoveries of arsenic-derived synthetic antibiotics by [[Alfred Bertheim]] and Ehrlich in 1907.<ref>{{cite journal | authorsvauthors = Williams KJ | title = The introduction of 'chemotherapy' using arsphenamine – the first magic bullet | journal = J R Soc Med | volume = 102 | issue = 8 | pages = 343–8 | year = 2009 | pmid = 19679737 | pmc = 2726818 | doi = 10.1258/jrsm.2009.09k036 }}</ref><ref name="goodman">{{cite book |last1=Goodman |first1=Louis S. |author-link1=Louis S. Goodman |last2=Gilman |first2=Alfred |author-link2=Alfred Gilman, Sr. |title=[[The Pharmacological Basis of Therapeutics]] |publisher=Macmillan |location=New York |year=1941}}</ref> Ehrlich and Bertheim experimented with various chemicals derived from dyes to treat [[trypanosomiasis]] in mice and [[spirochaeta]] infection in rabbits. While their early compounds were too toxic, Ehrlich and [[Sahachiro Hata]], a Japanese bacteriologist working with Erlich in the quest for a drug to treat [[syphilis]], achieved success with the 606th compound in their series of experiments. In 1910 Ehrlich and Hata announced their discovery, which they called drug "606", at the Congress for Internal Medicine at [[Wiesbaden]].<ref name="jmvh.org">{{cite journal|last1=Frith|first1=John|title=Arsenic – the "Poison of Kings" and the "Saviour of Syphilis"|journal=Journal of Military and Veterans' Health|volume=21|issue=4|url=http://jmvh.org/article/arsenic-the-poison-of-kings-and-the-saviour-of-syphilis/|accessdate=31 January 2017|publisher=Australasian Military Medicine Association}}</ref> The [[Hoechst AG|Hoechst]] company began to market the compound toward the end of 1910 under the name Salvarsan. This drug is now known as [[arsphenamine]].<ref name="jmvh.org"/> The drug was used to treat syphilis in the first half of the 20th century. In 1908, Ehrlich received the [[Nobel Prize in Physiology or Medicine]] for his contributions to [[immunology]].<ref name=nobel>[https://www.nobelprize.org/nobel_prizes/medicine/laureates/1908/ehrlich-bio.html The Nobel Prize in Physiology or Medicine 1908, Paul Erlich – Biography]</ref> Hata was nominated for the [[Nobel Prize in Chemistry]] in 1911 and for the Nobel Prize in Physiology or Medicine in 1912 and 1913.<ref>[https://www.nobelprize.org/nomination/archive/show_people.php?id=3941 Sachachiro Hata – Nomination Database]</ref>
The first [[Sulfonamide (medicine)|sulfonamide]] and the first [[wikt:systemic|systemically]] active antibacterial drug, [[Prontosil]], was developed by a research team led by [[Gerhard Domagk]] in 1932 or 1933 at the [[Bayer]] Laboratories of the [[IG Farben]] conglomerate in Germany,<ref name="goodman"/><ref name="ReferenceA">{{cite journal | authors = Aminov RI | title = A brief history of the antibiotic era: lessons learned and challenges for the future | journal = [[Frontiers in Microbiology]] | volume = 1 | pages = 134 | year = 2010 | pmid = 21687759 | pmc = 3109405 | doi = 10.3389/fmicb.2010.00134 }}</ref><ref name="Bosch2008"/> for which Domagk received the 1939 Nobel Prize in Physiology or Medicine.<ref>{{cite web |url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1939/press.html |title=Physiology or Medicine 1939 – Presentation Speech |publisher=Nobel Foundation |accessdate=14 January 2015}}</ref> Sulfanilamide, the active drug of Prontosil, was not patentable as it had already been in use in the dye industry for some years.<ref name="ReferenceA"/> Prontosil had a relatively broad effect against [[Gram-positive]] [[Coccus|cocci]], but not against [[Enterobacteriaceae|enterobacteria]]. Research was stimulated apace by its success. The discovery and development of this sulfonamide [[drug]] opened the era of antibacterials.<ref>{{Cite journal|last=Wright|first=Peter M.|last2=Seiple|first2=Ian B.|last3=Myers|first3=Andrew G.|date=18 August 2014|title=The evolving role of chemical synthesis in antibacterial drug discovery|journal=Angewandte Chemie (International Ed. in English)|volume=53|issue=34|pages=8840–8869|doi=10.1002/anie.201310843|issn=1521-3773|pmc=4536949|pmid=24990531}}</ref><ref>{{Cite journal|last=Aminov|first=Rustam I.|date=1 January 2010|title=A brief history of the antibiotic era: lessons learned and challenges for the future|journal=Frontiers in Microbiology|volume=1|pages=134|doi=10.3389/fmicb.2010.00134|issn=1664-302X|pmc=3109405|pmid=21687759}}</ref>
==Etymology==
The term 'antibiosis', meaning "against life", was introduced by the French bacteriologist [[Jean Paul Vuillemin]] as a descriptive name of the phenomenon exhibited by these early antibacterial drugs.<ref name="CALDERIN2007"/><ref name=Saxena/><ref>{{cite journal | authors = Foster W, Raoult A | title = Early descriptions of antibiosis | journal = J R Coll Gen Pract | volume = 24 | issue = 149 | pages = 889–94 | date = December 1974 | pmid = 4618289 | pmc = 2157443 }}</ref> Antibiosis was first described in 1877 in bacteria when Louis Pasteur and [[Robert Koch]] observed that an airborne bacillus could inhibit the growth of ''[[Bacillus anthracis]]''.<ref name=Saxena>Sanjai Saxena, Applied Microbiology</ref><ref>{{cite journal |first= H |last= Landsberg |title= Prelude to the discovery of penicillin |journal= Isis |volume= 40 |issue= 3 |pages= 225–7 |year= 1949 |doi=10.1086/349043}}</ref> These drugs were later renamed antibiotics by [[Selman Waksman]], an American microbiologist, in 1942.<ref name="CALDERIN2007"/><ref name=Saxena/><ref name="Wakeman1947"/>
The term ''antibiotic'' was first used in 1942 by [[Selman Waksman]] and his collaborators in journal articles to describe any substance produced by a microorganism that is [[wikt:antagonism|antagonistic]] to the growth of other microorganisms in high dilution.<ref name=Saxena/><ref name="Wakeman1947"/> This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as [[gastric juices]] and [[hydrogen peroxide]]). It also excluded [[chemical synthesis|synthetic]] antibacterial compounds such as the [[Sulfonamide (medicine)|sulfonamides]]. In current usage, the term "antibiotic" is applied to any medication that kills bacteria or inhibits their growth, regardless of whether that medication is produced by a microorganism or not.<ref>{{Cite book|title=The Antimicrobial Drugs|last=Scholar E. M.|first=Pratt W. B.|publisher=Oxford University Press, USA|year=2000|isbn=978-0195125290|location=|pages=3|via=}}</ref><ref>{{Cite journal|last=Davies|first=Julian|last2=Davies|first2=Dorothy|date=1 September 2010|title=Origins and evolution of antibiotic resistance|journal=Microbiology and molecular biology reviews: MMBR|volume=74|issue=3|pages=417–433|doi=10.1128/MMBR.00016-10|issn=1098-5557|pmc=2937522|pmid=20805405}}</ref>
The term "antibiotic" derives from ''anti'' + βιωτικός (''biōtikos''), "fit for life, lively",<ref>{{cite book |url= http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3Dbiwtiko%2Fs |chapter= βιωτικός |editor1-first= Henry George |editor1-last= Liddell |editor2-first= Robert |editor2-last= Scott |title= A Greek-English Lexicon |via= [[Perseus Project]]}}</ref> which comes from βίωσις (''biōsis''), "way of life",<ref>{{cite book |url= http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3Dbi%2Fwsis |chapter= βίωσις |editor1-first= Henry George |editor1-last= Liddell |editor2-first= Robert |editor2-last= Scott |title= A Greek-English Lexicon |via= [[Perseus Project]]}}</ref> and that from βίος (''bios''), "life".<ref name="Antibiotics FAQ" /><ref>{{cite book |url= http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3Dbi%2Fos1 |chapter= βίος |editor1-first= Henry George |editor1-last= Liddell |editor2-first= Robert |editor2-last= Scott |title= A Greek-English Lexicon |via= [[Perseus Project]]}}</ref> The term "antibacterial" derives from [[Greek language|Greek]] ἀντί (''anti''), "against"<ref>{{cite book |url= http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3Da%29nti%2F |chapter= ἀντί |editor1-first= Henry George |editor1-last= Liddell |editor2-first= Robert |editor2-last= Scott |title= A Greek-English Lexicon |via= [[Perseus Project]]}}</ref> + βακτήριον (''baktērion''), diminutive of βακτηρία (''baktēria''), "staff, cane",<ref>{{cite book |url= http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3Dbakthri%2Fa |chapter= βακτηρία |editor1-first= Henry George |editor1-last= Liddell |editor2-first= Robert |editor2-last= Scott |title= A Greek-English Lexicon |via= [[Perseus Project]]}}</ref> because the first ones to be discovered were rod-shaped.<ref>[http://oxforddictionaries.com/definition/bacterium?q=bacterial#bacterium__2 bacterial], on Oxford Dictionaries</ref>
==Research==
===Alternatives===
The increase in bacterial strains that are resistant to conventional antibacterial therapies together with decreasing number of new antibiotics currently being developed in the [[drug pipeline]] has prompted the development of bacterial disease treatment strategies that are alternatives to conventional antibacterials.<ref name=":9">{{Cite journal|last=Moloney|first=Mark G.|date=1 August 2016|title=Natural Products as a Source for Novel Antibiotics|journal=Trends in Pharmacological Sciences|volume=37|issue=8|pages=689–701|doi=10.1016/j.tips.2016.05.001|issn=1873-3735|pmid=27267698}}</ref><ref>{{Cite journal|last=Abedon|first=Stephen T|last2=Kuhl|first2=Sarah J|last3=Blasdel|first3=Bob G|last4=Kutter|first4=Elizabeth Martin|date=1 January 2011|title=Phage treatment of human infections|journal=Bacteriophage|volume=1|issue=2|pages=66–85|doi=10.4161/bact.1.2.15845|issn=2159-7073|pmc=3278644|pmid=22334863}}</ref> Non-compound approaches (that is, products other than classical antibacterial agents) that target bacteria or approaches that target the host including [[phage therapy]] and [[vaccine]]s are also being investigated to combat the problem.<ref>{{Cite journal|last=Czaplewski|first=Lloyd|last2=Bax|first2=Richard|last3=Clokie|first3=Martha|last4=Dawson|first4=Mike|last5=Fairhead|first5=Heather|last6=Fischetti|first6=Vincent A.|last7=Foster|first7=Simon|last8=Gilmore|first8=Brendan F.|last9=Hancock|first9=Robert E. W.|date=1 February 2016|title=Alternatives to antibiotics-a pipeline portfolio review|journal=The Lancet. Infectious Diseases|volume=16|issue=2|pages=239–251|doi=10.1016/S1473-3099(15)00466-1|issn=1474-4457|pmid=26795692}}</ref>
===Resistance-modifying agents===
One strategy to address bacterial drug resistance is the discovery and application of compounds that modify resistance to common antibacterials. Resistance modifying agents are capable of partly or completely suppressing bacterial resistance mechanisms.<ref name=":6">{{Cite journal|last=Abreu|first=Ana Cristina|last2=McBain|first2=Andrew J.|last3=Simões|first3=Manuel|date=7 August 2012|title=Plants as sources of new antimicrobials and resistance-modifying agents|url=http://xlink.rsc.org/?DOI=c2np20035j|journal=Natural Product Reports|language=en|volume=29|issue=9|doi=10.1039/c2np20035j|issn=1460-4752|pages=1007–21|pmid=22786554}}</ref> For example, some resistance-modifying agents may inhibit multidrug resistance mechanisms, such as [[drug efflux]] from the cell, thus increasing the susceptibility of bacteria to an antibacterial.<ref name=":6" /><ref name=":7" /> Targets include:
* The [[Efflux (microbiology)|efflux inhibitor]] Phe-Arg-β-naphthylamide.<ref name=":7">{{cite journal | authors = Marquez B | title = Bacterial efflux systems and efflux pumps inhibitors | journal = Biochimie | volume = 87 | issue = 12 | pages = 1137–47 | year = 2005 | pmid = 15951096 | doi = 10.1016/j.biochi.2005.04.012 }}</ref>
* [[Beta-lactamase inhibitor]]s, such as [[clavulanic acid]] and [[sulbactam]]<ref>{{Cite journal|last=Drawz|first=Sarah M.|last2=Bonomo|first2=Robert A.|date=1 January 2010|title=Three Decades of β-Lactamase Inhibitors|journal=Clinical Microbiology Reviews|volume=23|issue=1|pages=160–201|doi=10.1128/CMR.00037-09|issn=0893-8512|pmc=2806661|pmid=20065329}}</ref>
Metabolic stimuli such as sugar can help eradicate a certain type of antibiotic-tolerant bacteria by keeping their metabolism active.<ref>{{cite journal | authors = Allison KR, Brynildsen MP, Collins JJ | title = Metabolite-enabled eradication of bacterial persisters by aminoglycosides | journal = Nature | volume = 473 | issue = 7346 | pages = 216–20 | year = 2011 | pmid = 21562562 | pmc = 3145328 | doi = 10.1038/nature10069 }}</ref>
===Vaccines===
[[Vaccine]]s rely on [[immune]] modulation or augmentation. Vaccination either excites or reinforces the immune competence of a host to ward off infection, leading to the activation of [[macrophages]], the production of [[antibody|antibodies]], [[inflammation]], and other classic immune reactions. Antibacterial vaccines have been responsible for a drastic reduction in global bacterial diseases.<ref>{{cite book | title= Emerging Trends in Antibacterial Discovery: Answering the Call to Arms | publisher = Horizon Scientific Press | year = 2011 |author1=Alita A. Miller |author2=Paul F. Miller | chapter = Current Strategies for Antibacterial Vaccine development | page = 283}}</ref> Vaccines made from attenuated whole cells or lysates have been replaced largely by less reactogenic, cell-free vaccines consisting of purified components, including capsular polysaccharides and their conjugates, to protein carriers, as well as inactivated toxins (toxoids) and proteins.<ref>{{cite book | author= Miller, AA |editor=Miller, PF | year=2011 | title=Emerging Trends in Antibacterial Discovery: Answering the Call to Arms | publisher=[[Caister Academic Press]] | isbn= 978-1-904455-89-9}}{{page needed|date=December 2013}}</ref>
===Phage therapy===
{{Main article|Phage therapy}}
[[File:Phage injecting its genome into bacteria.svg|thumb|100 px|Phage injecting its genome into bacterial cell]]
[[Phage therapy]] is another method for treating antibiotic-resistant strains of bacteria. Phage therapy infects pathogenic bacteria with their own viruses, [[bacteriophage]]s and their host ranges are extremely specific for certain bacteria, thus they do not disturb the host organism and intestinal microflora unlike antibiotics.<ref name=":11" /> Bacteriophages, also known simply as phages, infect and can kill bacteria and affect bacterial growth primarily during lytic cycles.<ref name=":11" /><ref name=Sulakvelidze>{{Cite journal | author = Sulakvelidze, A. |author2=Alavidze, Z. |author3=Morris, Jr J. G. |year = 2001 | title = Bacteriophage Therapy | journal = Antimicrob Agents Chemother | volume = 45 | issue = 3 | pages = 649–659 | doi=10.1128/aac.45.3.649-659.2001 | pmid=11181338 | pmc=90351}}</ref> Phages insert their DNA into the bacterium, where it is transcribed and used to make new phages, after which the cell will lyse, releasing new phage able to infect and destroy further bacteria of the same strain.<ref name=Sulakvelidze/> The high specificity of phage protects "good" bacteria from destruction. However, some disadvantages to use of bacteriophages also exist. Bacteriophages may harbour virulence factors or toxic genes in their genomes and identification of genes with similarity to known virulence factors or toxins by genomic sequencing may be prudent prior to use. In addition, the oral and IV administration of phages for the eradication of bacterial infections poses a much higher safety risk than topical application, and there is the additional concern of uncertain immune responses to these large antigenic cocktails. There are considerable regulatory hurdles that must be cleared for such therapies.<ref name=":11">{{Cite journal|last=Gill|first=Erin E.|last2=Franco|first2=Octavio L.|last3=Hancock|first3=Robert E. W.|date=1 January 2015|title=Antibiotic adjuvants: diverse strategies for controlling drug-resistant pathogens|journal=Chemical Biology & Drug Design|volume=85|issue=1|pages=56–78|doi=10.1111/cbdd.12478|issn=1747-0285|pmc=4279029|pmid=25393203}}</ref> The use of bacteriophages as a replacement for antimicrobial agents against MDR pathogens no longer respond to conventional antibiotics remains an attractive option despite numerous challenges.<ref name=":11" /><ref>{{Cite journal|last=Opal|first=Steven M.|date=16 December 2016|title=Non-antibiotic treatments for bacterial diseases in an era of progressive antibiotic resistance|journal=Critical Care (London, England)|volume=20|issue=1|pages=397|doi=10.1186/s13054-016-1549-1|issn=1466-609X|pmid=27978847|pmc=5159963}}</ref>
===Phytochemicals===
Plants are an important source of antimicrobial compounds and traditional healers have long used plants to prevent or cure infectious diseases.<ref name="cowen">{{Cite journal|last=Cowan|first=M. M.|date=1 October 1999|title=Plant products as antimicrobial agents|journal=Clinical Microbiology Reviews|volume=12|issue=4|pages=564–582|issn=0893-8512|pmc=88925|pmid=10515903}}</ref><ref>{{Cite journal|last=Abreu|first=Ana Cristina|last2=McBain|first2=Andrew J.|last3=Simões|first3=Manuel|date=1 September 2012|title=Plants as sources of new antimicrobials and resistance-modifying agents|journal=Natural Product Reports|volume=29|issue=9|pages=1007–1021|doi=10.1039/c2np20035j|issn=1460-4752|pmid=22786554}}</ref> There is a recent renewed interest into the use of natural products for the identification of new members of the 'antibiotic-ome' (defined as natural products with antibiotic activity), and their application in antibacterial drug discovery in [[Genomics|the genomics era]].<ref name=":9" /><ref name=":10" /> Phytochemicals are the active biological component of plants and some phytochemicals including [[tannin]]s, [[alkaloid]]s, [[terpenoid]]s and [[flavonoid]]s possess antimicrobial activity.<ref name="cowen"/><ref name="Monte">{{Cite journal|last=Monte|first=Joana|last2=Abreu|first2=Ana C.|last3=Borges|first3=Anabela|last4=Simões|first4=Lúcia Chaves|last5=Simões|first5=Manuel|date=18 June 2014|title=Antimicrobial Activity of Selected Phytochemicals against Escherichia coli and Staphylococcus aureus and Their Biofilms|journal=Pathogens (Basel, Switzerland)|volume=3|issue=2|pages=473–498|doi=10.3390/pathogens3020473|pmc=4243457|pmid=25437810}}</ref><ref>{{Cite journal|last=Cushnie|first=T. P. Tim|last2=Cushnie|first2=Benjamart|last3=Lamb|first3=Andrew J.|date=1 November 2014|title=Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities|journal=International Journal of Antimicrobial Agents|volume=44|issue=5|pages=377–386|doi=10.1016/j.ijantimicag.2014.06.001|issn=1872-7913|pmid=25130096}}</ref> Some [[antioxidant]] [[dietary supplement]]s also contain phytochemicals ([[polyphenol]]s), such as [[grape seed extract]], and demonstrate ''[[in vitro]]'' anti-bacterial properties.<ref>{{cite journal|author=Al-Habib A |author2=Al-Saleh, E|title=Bactericidal effect of grape seed extract on methicillin-resistant Staphylococcus aureus (MRSA)|journal=Journal of Toxicology Science|year=2010|volume=35|issue=3|pages=357–64|pmid=20519844|doi=10.2131/jts.35.357}}</ref><ref>{{cite journal |doi=10.1159/000104791 |title=The Antibacterial Activity of Plant Extracts Containing Polyphenols against ''Streptococcus mutans'' |year=2007 |last1=Smullen |first1=J. |last2=Koutsou |first2=G.A. |last3=Foster |first3=H.A. |last4=Zumbé |first4=A. |last5=Storey |first5=D.M. |journal=Caries Research |volume=41 |issue=5 |pages=342–9 |pmid=17713333}}</ref><ref>{{cite journal|title=Recent advances in understanding the antibacterial properties of flavonoids. |journal=Int J Antimicrob Agents |date= Aug 2011 |volume=38 |issue=2|pages=99–107. |doi=10.1016/j.ijantimicag.2011.02.014 |pmid=21514796 |authors=Cushnie TP, Lamb AJ }}</ref> Phytochemicals are able to inhibit peptidoglycan synthesis, damage microbial membrane structures, modify bacterial membrane surface hydrophobicity and also modulate quorum-sensing.<ref name="Monte"/> With increasing antibiotic resistance in recent years, the potential of new plant-derived antibiotics is under investigation.<ref name=":10">{{cite journal | author1=Kenny, CR |author2=Furey, A | title=A post-antibiotic era looms: can plant natural product research fill the void? | journal=British Journal of Biomedical Science | year=2015 | volume=72 | issue=4 | pages=191–200 | pmid=26738402 | doi=10.1080/09674845.2015.11665752}}</ref>
===Development of new antibiotics===
In April 2013, the [[Infectious Disease Society of America]] (IDSA) reported that the weak antibiotic pipeline does not match bacteria's increasing ability to develop resistance. Since 2009, only 2 new antibiotics were approved in the United States. The number of new antibiotics approved for marketing per year declines continuously. The report identified seven antibiotics against the [[Gram-negative bacilli]] (GNB) currently in [[Phases of clinical research#Phase II|phase 2]] or [[Phases of clinical research#Phase III|phase 3]] clinical trials. However, these drugs do not address the entire spectrum of resistance of GNB.<ref>{{cite news |title=Drug pipeline for worst superbugs 'on life support': report |author=Steenhuysen, Julie |url=http://in.reuters.com/article/2013/04/18/us-antibiotics-superbugs-idINBRE93H05520130418|agency=Reuters |date=18 April 2013 |accessdate=23 June 2013}}</ref><ref name=IDSA2013>{{cite journal | authors = Boucher HW, Talbot GH, Benjamin DK, Bradley J, Guidos RJ, Jones RN, Murray BE, Bonomo RA, Gilbert D | title = 10 x '20 Progress—development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America | journal = Clin. Infect. Dis. | volume = 56 | issue = 12 | pages = 1685–94 | year = 2013 | pmid = 23599308 | pmc = 3707426 | doi = 10.1093/cid/cit152 |others= Infectious Diseases Society of America }}</ref>
Some of these antibiotics are combination of existent treatments:{{citation needed|date=October 2016}}
[[File:Tazobactam structure.svg|thumb|150 px|Tazobactam]]
{{columns-list|2|
*[[Ceftolozane]]/[[tazobactam]] (CXA-201; CXA-101/tazobactam): [[Antipseudomonal]] [[cephalosporin]]/[[β-lactamase]] inhibitor combination (cell wall synthesis inhibitor). FDA approved on 19 December 2014.
*[[Ceftazidime]]/[[avibactam]] (ceftazidime/NXL104): Antipseudomonal cephalosporin/β-lactamase inhibitor combination (cell wall synthesis inhibitor). In phase 3.
*[[Ceftaroline]]/avibactam (CPT-avibactam; ceftaroline/NXL104): Anti-[[MRSA]] cephalosporin/ β-lactamase inhibitor combination (cell wall synthesis inhibitor)
*[[Imipenem]]/MK-7655: [[Carbapenem]]/ β-lactamase inhibitor combination (cell wall synthesis inhibitor). In phase 2.
*[[Plazomicin]] (ACHN-490): [[Aminoglycoside]] ([[protein synthesis inhibitor]]). In phase 2.
*[[Eravacycline]] (TP-434): Synthetic [[tetracycline]] derivative / protein synthesis inhibitor targeting the ribosome. Development by Tetraphase, Phase 2 trials complete.<ref>Stynes, T. [https://www.wsj.com/article/BT-CO-20130715-705197.html Tetraphase Pharma's Eravacycline Gets Qualified-Infectious-Disease-Product Status.] Wall Street J. Monday, 15 July 2013.</ref>
*[[Brilacidin]] (PMX-30063): Peptide defense protein mimetic (cell membrane disruption). In phase 2.
}}
''Streptomyces'' research is expected to provide new antibiotics, including treatment against [[MRSA]] and infections resistant to commonly used medication. Efforts of [[John Innes Centre]] and universities in the UK, supported by BBSRC, resulted in the creation of spin-out companies, for example Novacta Biosystems, which has designed the type-b [[lantibiotic]]-based compound NVB302 (in phase 1) to treat ''Clostridium difficile'' infections.<ref>{{cite journal |last=Osbourn |first=Anne |last2=Goss |first2=Rebecca J. |last3=Carter |first3=Guy T. |date=28 March 2014 |title=Discovery and Development of NVB302, a Semisynthetic Antibiotic for Treatment of ''Clostridium difficile'' Infection |url=http://onlinelibrary.wiley.com/doi/10.1002/9781118794623.ch24/summary |journal=Natural Products: Discourse, Diversity, and Design |publisher=John Wiley & Sons, Inc. |doi=10.1002/9781118794623.ch24 |accessdate=19 January 2015 |pages=455–468}}</ref><ref>[http://www.bbsrc.ac.uk/research/impact/streptomyces-antibiotics.aspx Investing in world-class bioscience research and training on behalf of the UK public]</ref>
Possible improvements include clarification of clinical trial regulations by FDA. Furthermore, appropriate economic incentives could persuade pharmaceutical companies to invest in this endeavor.<ref name=IDSA2013/> In the US, the [[Antibiotic Development to Advance Patient Treatment]] (ADAPT) Act was introduced with the aim of fast tracking the drug development of antibiotics to combat the growing threat of 'superbugs'. Under this Act, FDA can approve antibiotics and antifungals treating life-threatening infections based on smaller clinical trials. The [[Centers for Disease Control and Prevention|CDC]] will monitor the use of antibiotics and the emerging resistance, and publish the data. The FDA antibiotics labeling process, 'Susceptibility Test Interpretive Criteria for Microbial Organisms' or 'breakpoints', will provide accurate data to healthcare professionals.<ref>{{cite web|url=http://green.house.gov/press-release/green-gingrey-introduce-adapt-act-safeguard-public-health|title=Green, Gingrey Introduce ADAPT Act to Safeguard Public Health|author=Press Release|publisher=US Congress|date=12 December 2013}}</ref><ref>{{cite web|url=http://assets.fiercemarkets.net/public/lifesciences/HR3742.pdf|title=Antibiotic Development to Advance Patient Treatment Act of 2013|publisher=US Congress|date=12 December 2013}}</ref> According to Allan Coukell, senior director for health programs at The Pew Charitable Trusts, "By allowing drug developers to rely on smaller datasets, and clarifying FDA's authority to tolerate a higher level of uncertainty for these drugs when making a risk/benefit calculation, ADAPT would make the clinical trials more feasible."<ref>{{cite web|last1=Clarke|first1=Toni|title=U.S. Congress urged to pass bill to speed development of antibiotics|url=https://www.reuters.com/article/2014/09/19/us-usa-congress-antibiotics-idUSKBN0HE25W20140919|agency=Reuters|accessdate=19 September 2014}}</ref>
==See also==
{{columns-list|2|
*[[Antiviral drug|Antiviral]]
*[[Antifungal medication|Antifungal]]
*[[Antiprotozoal]]
*[[Antimalarial]]
*[[Magic bullet (medicine)|Magic bullet]]
*[[Probiotic]]
}}
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==แหล่งข้อมูลเพิ่มเติม==
{{columns-list|2|
*{{cite journal|last1=Davies|first1=Julian|last2=Davies|first2=Dorothy|title=Origins and Evolution of Antibiotic Resistance|journal=Microbiology and Molecular Biology Reviews : MMBR|date=1 September 2010|volume=74|issue=3|pages=417–433|doi=10.1128/MMBR.00016-10|issn=1092-2172|pmc=2937522|pmid=20805405}}
*{{cite web|title=Antibiotics: MedlinePlus|url=https://medlineplus.gov/antibiotics.html?PHPSESSID=1550cb08d53a1c0c39064bf62aee6247|publisher=NIH.gov|accessdate=19 July 2016}}
*{{cite web|title=WHO's first global report on antibiotic resistance reveals serious, worldwide threat to public health|url=http://www.who.int/mediacentre/news/releases/2014/amr-report/en/|website=WHO}}
*{{Cite journal|title=Short-course versus long-course antibiotic treatment for hospital-acquired pneumonia in adult intensive care patients {{!}} Cochrane|url=http://www.cochrane.org/CD007577/ARI_short-course-versus-long-course-antibiotic-treatment-hospital-acquired-pneumonia-adult-intensive|doi=10.1002/14651858.CD007577.pub3 | journal=Reviews}}
*{{cite journal|last1=Giedraitienė|first1=Agnė|last2=Vitkauskienė|first2=Astra|last3=Naginienė|first3=Rima|last4=Pavilonis|first4=Alvydas|title=Antibiotic resistance mechanisms of clinically important bacteria|journal=Medicina (Kaunas, Lithuania)|date=1 January 2011|volume=47|issue=3|pages=137–146|issn=1648-9144|pmid=21822035}}
}}
==แหล่งข้อมูลอื่น==
{{Commons category|Antibiotics}}
* {{Dmoz|Health/Pharmacy/Drugs_and_Medications/Antibiotics/}}
{{ยาปฏิชีวนะ − ประเด็นด้านสังคมและวัฒนธรรม}}
{{ยาปฏิชีวนะ}}
{{กลุ่มยาหลัก}}
{{โครงเภสัชกรรม}}
The first [[Sulfonamide (medicine)|sulfonamide]] and the first [[wikt:systemic|systemically]] active antibacterial drug, [[Prontosil]], was developed by a research team led by [[Gerhard Domagk]] in 1932 or 1933 at the [[Bayer]] Laboratories of the [[IG Farben]] conglomerate in Germany,<ref name="goodman"/><ref name="ReferenceA">{{cite journal | vauthors = Aminov RI | title = A brief history of the antibiotic era: lessons learned and challenges for the future | journal = [[Frontiers in Microbiology]] | volume = 1 | pages = 134 | year = 2010 | pmid = 21687759 | pmc = 3109405 | doi = 10.3389/fmicb.2010.00134 }}</ref><ref name="Bosch2008"/> for which Domagk received the 1939 Nobel Prize in Physiology or Medicine.<ref>{{cite web |url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1939/press.html |title=Physiology or Medicine 1939 – Presentation Speech |publisher=Nobel Foundation |accessdate=14 January 2015}}</ref> Sulfanilamide, the active drug of Prontosil, was not patentable as it had already been in use in the dye industry for some years.<ref name="ReferenceA"/> Prontosil had a relatively broad effect against [[Gram-positive]] [[Coccus|cocci]], but not against [[Enterobacteriaceae|enterobacteria]]. Research was stimulated apace by its success. The discovery and development of this sulfonamide [[drug]] opened the era of antibacterials.<ref>{{Cite journal|last=Wright|first=Peter M.|last2=Seiple|first2=Ian B.|last3=Myers|first3=Andrew G.|date=18 August 2014|title=The evolving role of chemical synthesis in antibacterial drug discovery|journal=Angewandte Chemie (International Ed. in English)|volume=53|issue=34|pages=8840–8869|doi=10.1002/anie.201310843|issn=1521-3773|pmc=4536949|pmid=24990531}}</ref><ref>{{Cite journal|last=Aminov|first=Rustam I.|date=1 January 2010|title=A brief history of the antibiotic era: lessons learned and challenges for the future|journal=Frontiers in Microbiology|volume=1|pages=134|doi=10.3389/fmicb.2010.00134|issn=1664-302X|pmc=3109405|pmid=21687759}}</ref>
[[หมวดหมู่:อะมิโนไกลโคไซด์]]
[[หมวดหมู่:กวานิดีน]]
[[หมวดหมู่:ยาหลักขององค์การอนามัยโลก]]
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