Antibiotic
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2008-07-17T04:59:23Z
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The term '''antibiotic''' (from [[Greek language|Greek]] ''αντί'' - ''anti'', "against" + ''βιοτικός'' - ''biotikos'', "fit for life"<ref %3A1999.04.0057%3Aentry%3D%239779 Anti, Henry George Liddell, Robert Scott, "A Greek-English Lexicon", at Perseus]</ref><ref>[http://www.perseus.tufts.edu/cgi-bin/ptext?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3D%2320016 Biotikos, Henry George Liddell, Robert Scott, "A Greek-English Lexicon", at Perseus]</ref>) was coined by [[Selman Waksman]] in 1942, to refer to any substance produced by a micro-organism that is antagonistic to the growth of others in high dilution (which therefore excludes other naturally occuring substances such as gastric juice and hydrogen peroxide). The strict definition therefore excludes synthetic compounds such as the [[sulphonamide]]s (which are antimicrobial agents). In modern usage, the term "antibiotic" is now also more loosely used to refer to any [[chemotherapeutic agent]] or antimicrobial agent with activity against micro-organisms ([[bacteria]],[[fungus|fungi]], [[protozoa]]).<ref>{{cite book|author=Davey PG|chapter=Antimicrobial chemotherapy|editor=Ledingham JGG, Warrell DA|title=Concise Oxford Textbook of Medicine|publisher=Oxford University Press|location=Oxford|pages=1475|year=2000|isbn=0192628704}}</ref>
Many antibiotic compounds used in modern medicine are produced and isolated from living organisms, such as the [[penicillin|penicillin class]] produced by fungi in the genus ''[[Penicillium]]'', or [[streptomycin]] from bacteria of the genus ''[[Streptomyces]]''. With advances in [[medicinal chemistry]] many antibiotics are now modified chemically from their original form found in nature. In addition, some modern antibiotics have been created through purely synthetic means. Many antibiotics are relatively [[small molecule]]s with a [[molecular weight]] less than 2000 [[Atomic mass unit|Da]].
== Overview ==
{{SectOR|date=March 2008}}
Unlike previous treatments for infections, which often consisted of administering chemical compounds such as [[strychnine]] and [[arsenic]], with high [[toxicity]] also against [[mammals]], antibiotics from microbes had no or few side effects and high effective target activity. Most anti-bacterial antibiotics do not have activity against viruses, fungi, or other [[microbes]]. Anti-bacterial antibiotics can be categorized based on their target specificity: "narrow-spectrum" antibiotics target particular types of bacteria, such as [[Gram-negative]] or [[Gram-positive]] bacteria, while [[broad-spectrum antibiotic]]s affect a wide range of bacteria.
The environment of individual antibiotics varies with the location of the infection, the ability of the antibiotic to reach the site of infection, and the ability of the microbe to inactivate or excrete the antibiotic. Some anti-bacterial antibiotics destroy bacteria (bactericidal), whereas others prevent bacteria from multiplying (bacteriostatic).
Oral antibiotics are simply ingested, while [[intravenous]] antibiotics are used in more serious cases, such as deep-seated [[systemic infection]]s. Antibiotics may also sometimes be administered [[topical]]ly, as with [[eye drop]]s or [[ointment]]s.
In the last few years three new classes of antibiotics have been brought into clinical use. This follows a 40-year hiatus in discovering new classes of antibiotic compounds. These new antibiotics are of the following three classes: cyclic lipopeptides (daptomycin), glycylcyclines (tigecycline), and oxazolidinones (linezolid). Tigecycline is a broad-spectrum antibiotic, while the two others are used for gram-positive infections. These developments show promise as a means to counteract the growing bacterial resistance to existing antibiotics.
== History ==
{{see also|Timeline of antibiotics}}
[[Image:Penicillin-core.png|thumb|170px|Penicillin]]
Although potent antibiotic compounds for treatment of human diseases caused by bacteria (such as [[tuberculosis]], [[bubonic plague]], or [[leprosy]]) were not isolated and identified until the twentieth century, the first known use of antibiotics was by the [[Traditional Chinese medicine|ancient Chinese]] over 2,500 years ago.<ref>[http://science.enotes.com/how-products-encyclopedia/antibiotic How Products Are Made: Antibiotics]</ref> Many other ancient cultures, including the [[Ancient Egyptian medicine|ancient Egyptians]], [[Ancient Greek medicine|ancient Greeks]] and [[Islamic medicine|medieval Arabs]] already used [[mold]]s and plants to treat [[infection]]s, owing to the production of antibiotic substances by these organisms, a phenomenon known as [[antibiosis]]<ref>http://en.wiktionary.org/wiki/antibiosis</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>{{cite journal |author=H. Landsberg |title=Prelude to the discovery of penicillin |journal=Isis |volume=40 |issue=3 |pages=225–227. |year=1949|doi=10.1086/349043}}</ref> The antibiotic properties of ''Penicillium sp.'' were first described in [[France]] by [[Ernest Duchesne]] in 1897. However, his work went by without much notice from the scientific community until [[Alexander Fleming]]'s discovery of [[Penicillin]] (see below).
Modern research on antibiotic therapy began in [[Germany]] with the development of the narrow-spectrum antibiotic [[Salvarsan]] by [[Paul Ehrlich]] in 1909, for the first time allowing an efficient treatment of the then-widespread problem of [[Syphilis]]. The drug, which was also effective against other [[spirochaete|spirochaetal]] infections, is no longer in use in modern medicine.
Antibiotics were further developed in Britain following the discovery of [[Penicillin]] in 1928 by [[Alexander Fleming]]. More than ten years later, [[Ernst Chain]] and [[Howard Florey, Baron Florey|Howard Florey]] became interested in his work, and came up with the purified form of penicillin. The three shared the 1945 Nobel Prize in Medicine. In 1939, [[Rene Dubos]] isolated [[gramicidin]], one of first antibiotics to be manufactured commercially used during World War II proving highly effective in the treatment of wounds and ulcers.<ref name=Epps2006>{{cite journal |author=Van Epps HL |title=René Dubos: unearthing antibiotics |journal=J. Exp. Med. |volume=203 |issue=2 |pages=259 |year=2006 |pmid=16528813 |doi=}}</ref>. Florey credited Dubos for reviving his research on penicillin<ref name=Epps2006/>
"Antibiotic" was originally used to refer only to substances extracted from a [[fungus]] or other [[microorganism]], but has come to also include the many synthetic and semi-synthetic drugs that have antibacterial effects. Antibiotics can help succeed in curing many illnesses.
== Classes of antibiotics ==
At the highest level, antibiotics can be classified as either [[bactericidal]] or [[bacteriostatic]]. Bactericidals kill bacteria directly where bacteriostatics prevent them from dividing. However, these classifications are based on laboratory behavior; in practice, both of these are capable of ending a bacterial infection.<ref>Pelczar, M.J., Chan, E.C.S. and Krieg, N.R. (1999) “Host-Parasite Interaction; Nonspecific Host Resistance”, In: Microbiology Conceptsand Applications, 6th ed., McGraw-Hill Inc., New York, U.S.A. pp. 478-479.</ref>
{| class="wikitable"
|+ '''Antibiotics<ref>For common Uses and possible side effects reference is: Robert Berkow (ed.) ''[[Merck Manual|The Merck Manual of Medical Information - Home Edition]]''. Pocket (September 1999), ISBN 0-671-02727-1.</ref>'''
|-
! Generic Name !! Brand Names !! Common Uses !! Possible Side Effects !! Mechanism of action
|-
! colspan="5" | [[Aminoglycoside]]s
|-
| [[Amikacin]] || [[Amikin]] || rowspan="8" | Infections caused by [[Gram-negative bacteria]], such as ''[[Escherichia coli]]'' and ''[[Klebsiella]]'' particularly ''[[Pseudomonas aeruginosa]]''. Effective against Aerobic bacteria (not obligate/facultative anaerobes).
| rowspan="8" |
*[[Ototoxicity|Hearing loss]]
*[[Vertigo (medical)|Vertigo]]
*[[Nephrotoxicity|Kidney damage]]
| rowspan="8" | Binding to the bacterial [[30S]] [[ribosome|ribosomal]] subunit (some work by binding to the [[50S]] subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth.
|-
|[[Gentamicin]] || [[Garamycin]]
|-
|[[Kanamycin]] || [[Kantrex]]
|-
|[[Neomycin]] ||
|-
|[[Netilmicin]] || [[Netromycin]]
|-
|[[Streptomycin]] ||
|-
|[[Tobramycin]] || [[Nebcin]]
|-
|[[Paromomycin]] || [[Humatin]]
|-
! colspan="5" | [[Ansamycin]]s
|-
|[[Geldanamycin]] || || rowspan="2" | Experimental, as [[antineoplastic|antitumor antibiotics]]
| rowspan="2" |
| rowspan="2" |
|-
|[[Herbimycin]] ||
|-
!colspan="5" | [[Carbacephem]]
|-
|[[Loracarbef]] || [[Lorabid]] || || || prevents bacterial cell division by inhibiting cell wall synthesis.
|-
!colspan="5" | [[Carbapenem]]s
|-
|[[Ertapenem]] || [[Invanz]] || rowspan="4" | Bactericidal for both Gram-positive and Gram-negative organisms and therefore useful for empiric broad-spectrum antibacterial coverage. (Note MRSA resistance to this class.)
| rowspan="4" |
*Gastrointestinal upset and diarrhea
*Nausea
*Seizures
*Headache
*Rash and Allergic reactions
| rowspan="4" | Inhibition of cell wall synthesis
|-
|[[Doripenem]] || [[Finibax]]
|-
|[[Imipenem]]/[[Cilastatin]] || [[Primaxin]]
|-
|[[Meropenem]] || [[Merrem]]
|-
!colspan="5" | [[Cephalosporin]]s ([[Cephalosporins#First Generation Cephalosporins|First generation]])
|-
|[[Cefadroxil]] || [[Duricef]] || rowspan="4" |
| rowspan="4" |
*Gastrointestinal upset and diarrhea
*Nausea (if alcohol taken concurrently)
*Allergic reactions
| rowspan="4" | Same mode of action as other [[beta-lactam antibiotic]]s: disrupt the synthesis of the [[peptidoglycan]] layer of bacterial [[cell wall]]s.
|-
|[[Cefazolin]] || [[Ancef]]
|-
|[[Cefalotin]] or [[Cefalothin]] || [[Keflin]]
|-
|[[Cefalexin]] || [[Keflex]]
|-
!colspan="5" | [[Cephalosporin]]s ([[Cephalosporins#Second Generation Cephems|Second generation]])
|-
|[[Cefaclor]] || [[Ceclor]] || rowspan="5" | || rowspan="5" |
* Gastrointestinal upset and diarrhea
* Nausea (if alcohol taken concurrently)
* Allergic reactions
| rowspan="5" | Same mode of action as other [[beta-lactam antibiotic]]s: disrupt the synthesis of the [[peptidoglycan]] layer of bacterial [[cell wall]]s.
|-
|[[Cefamandole]] || [[Mandole]]
|-
|[[Cefoxitin]] || [[Mefoxin]]
|-
|[[Cefprozil]] || [[Cefzil]]
|-
|[[Cefuroxime]] || [[Ceftin, Zinnat]]
|-
!colspan="5" | [[Cephalosporin]]s ([[Cephalosporins#Third Generation Cephalosporins|Third generation]])
|-
|[[Cefixime]] || [[Suprax]] || rowspan="10" | || rowspan="10" |
* Gastrointestinal upset and diarrhea
* Nausea (if alcohol taken concurrently)
* Allergic reactions
| rowspan="10" | Same mode of action as other [[beta-lactam antibiotic]]s: disrupt the synthesis of the [[peptidoglycan]] layer of bacterial [[cell wall]]s.
|-
|[[Cefdinir]] || [[Omnicef]]
|-
|[[Cefditoren]] || [[Spectracef]]
|-
|[[Cefoperazone]] || [[Cefobid]]
|-
|[[Cefotaxime]] || [[Claforan]]
|-
|[[Cefpodoxime]] ||
|-
|[[Ceftazidime]] || [[Fortaz]]
|-
|[[Ceftibuten]] || [[Cedax]]
|-
|[[Ceftizoxime]] ||
|-
|[[Ceftriaxone]] || [[Rocephin]]
|-
!colspan="5" | [[Cephalosporin]]s ([[Cephalosporins#Fourth Generation Cephalosporins|Fourth generation]])
|-
|[[Cefepime]] || [[Maxipime]] || ||
* Gastrointestinal upset and diarrhea
* Nausea (if alcohol taken concurrently)
* Allergic reactions
| Same mode of action as other [[beta-lactam antibiotic]]s: disrupt the synthesis of the [[peptidoglycan]] layer of bacterial [[cell wall]]s.
|-
!colspan="5" | [[Cephalosporin]]s ([[Cephalosporins#Fifth Generation Cephalosporins|Fifth generation]])
|-
|[[Ceftobiprole]] || || ||
|-
* Gastrointestinal upset and diarrhea
* Nausea (if alcohol taken concurrently)
* Allergic reactions
|-
!colspan="5" | [[Glycopeptide antibiotic|Glycopeptides]]
|-
|[[Teicoplanin]] || || rowspan="2" | || rowspan="2" | || rowspan="2" | inhibiting [[peptidoglycan]] synthesis
|-
|[[Vancomycin]] || [[Vancocin]]
|-
!colspan="5" | [[Macrolide]]s
|-
|[[Azithromycin]] || [[Zithromax]], [[Sumamed]], Zitrocin || rowspan="6" | [[Streptococcal infection]]s, [[syphilis]], [[respiratory infection]]s, [[mycoplasmal infection]]s, [[Lyme disease]] || rowspan="6" |
* Nausea, vomiting, and diarrhea (especially at higher doses)
* [[Jaundice]]
| rowspan="8" |[[enzyme inhibitor|inhibition]] of bacterial [[protein biosynthesis]] by binding irreversibly to the subunit [[50S]] of the bacterial [[ribosome]], thereby inhibiting translocation of peptidyl [[Transfer RNA|tRNA]].
|-
|[[Clarithromycin]] || [[Biaxin]]
|-
|[[Dirithromycin]] ||
|-
|[[Erythromycin]] || [[Erythocin]], [[Erythroped]]
|-
|[[Roxithromycin]] ||
|-
|[[Troleandomycin]] ||
|-
|[[Telithromycin]] || [[Ketek]] || [[Pneumonia]] || Visual Disturbance, LIVER TOXICITY.<ref>
{{cite journal
|last= Splete
|first= Heidi
|coauthors= Kerri Wachter
|year= 2006
|month= March
|title= Liver toxicity reported with Ketek
|journal= Internal Medicine News}}
</ref>
|-
|[[Spectinomycin]] || || [[Antimetabolite]], [[Anticancer]] ||
|-
!colspan="5" | [[Monobactams]]
|-
|[[Aztreonam]] || || || || Same mode of action as other [[beta-lactam antibiotic]]s: disrupt the synthesis of the [[peptidoglycan]] layer of bacterial [[cell wall]]s.
|-
!colspan="5" | [[Penicillin]]s
|-
|[[Amoxicillin]] || [[Novamox]], [[Amoxil]] || rowspan="14" | Wide range of infections; penicillin used for [[streptococcal infection]]s, [[syphilis]], and [[Lyme disease]] || rowspan="14" |
* Gastrointestinal upset and diarrhea
* Allergy with serious [[anaphylactic reaction]]s
* Brain and kidney damage (rare)
| rowspan="14" | Same mode of action as other [[beta-lactam antibiotic]]s: disrupt the synthesis of the [[peptidoglycan]] layer of bacterial [[cell wall]]s.
|-
|[[Ampicillin]] ||
|-
|[[Azlocillin]] ||
|-
|[[Carbenicillin]] ||
|-
|[[Cloxacillin]] ||
|-
|[[Dicloxacillin]] ||
|-
|[[Flucloxacillin]] || [[Floxapen]]
|-
|[[Mezlocillin]] ||
|-
|[[Meticillin]] ||
|-
|[[Nafcillin]] ||
|-
|[[Oxacillin]] ||
|-
|[[Penicillin]] ||
|-
|[[Piperacillin]] ||
|-
|[[Ticarcillin]] ||
|-
!colspan="5" | [[Polypeptide antibiotics|Polypeptides]]
|-
|[[Bacitracin]] || || rowspan="3" | Eye, ear or bladder infections; usually applied directly to the eye or inhaled into the lungs; rarely given by injection || rowspan="3" | Kidney and nerve damage (when given by injection)
| Inhibits [[isoprenyl pyrophosphate]], a molecule which carries the building blocks of the [[peptidoglycan]] bacterial [[cell wall]] outside of the inner membrane <ref>[http://www.pnas.org/cgi/content/abstract/68/12/3223 Mechanism of Action of Bacitracin: Complexation with Metal Ion and C55-Isoprenyl Pyrophosphate] K. John Stone and Jack L. Strominger</ref>
|-
|[[Colistin]] || ||rowspan=2| Interact with the bacterial [[cytoplasmic membrane]], changing its permeability.
|-
|[[Polymyxin B]] ||
|-
!colspan="5" | [[Quinolone]]s
|-
|[[Ciprofloxacin]] || [[Cipro]], [[Ciproxin]], Ciprobay || rowspan="9" | Urinary tract infections, [[bacterial prostatitis]], community-acquired [[pneumonia]], [[bacterial diarrhea]], [[mycoplasmal infections]], [[gonorrhea]] || rowspan="9" | Nausea (rare), tendinosis (rare)
| rowspan="9" |inhibit the bacterial [[DNA gyrase]] or the [[topoisomerase]] IV enzyme, thereby inhibiting [[DNA]] replication and transcription.
|-
|[[Enoxacin]] ||
|-LEVOFLOXACIN (TAVANIC)
|[[Gatifloxacin]] || [[Tequin]]
|-
|[[Levofloxacin]] || [[Levaquin]]
|-
|[[Lomefloxacin]] ||
|-
|[[Moxifloxacin]] || [[Avelox]]
|-
|[[Norfloxacin]] || Noroxin
|-
|[[Ofloxacin]] || [[Ocuflox]]
|-
|[[Trovafloxacin]] || [[Trovan]]
|-
!colspan="5" | [[Sulfonamide (medicine)|Sulfonamides]]
|-
|[[Mafenide]] || || rowspan="9" | [[Urinary tract infection]]s (except sulfacetamide and mafenide); mafenide is used topically for burns || rowspan="9" |
* Nausea, vomiting, and diarrhea
* [[Allergy]] (including skin rashes)
* Crystals in urine
* [[Renal failure|Kidney failure]]
* Decrease in [[white blood cell]] count
* Sensitivity to sunlight
| rowspan="9" | [[Folate synthesis]] inhibition. They are [[competitive inhibitor]]s of the enzyme [[dihydropteroate synthetase]], DHPS. DHPS catalyses the conversion of PABA ([[para-Aminobenzoic acid|''para''-aminobenzoate]]) to [[dihydropteroic acid|dihydropteroate]], a key step in [[folate]] synthesis. Folate is necessary for the cell to synthesize [[nucleic acid]]s (nucleic acids are essential building blocks of [[DNA]] and [[RNA]]), and in its absence cells will be unable to divide.
|-
|[[Prontosil]] (archaic) ||
|-
|[[Sulfacetamide]] ||
|-
|[[Sulfamethizole]] ||
|-
|[[Sulfanilimide]] (archaic) ||
|-
|[[Sulfasalazine]] ||
|-
|[[Sulfisoxazole]] ||
|-
|[[Trimethoprim]] ||
|-
|[[Trimethoprim]]-[[Sulfamethoxazole]] ([[Co-trimoxazole]]) ([[TMP-SMX]]) || [[Bactrim]]
|-
!colspan="5" | [[Tetracycline antibiotics|Tetracycline]]s
|-
|[[Demeclocycline]] || || rowspan="5" | [[Syphilis]], [[Chlamydia infection|chlamydial]] infections, [[Lyme disease]], [[mycoplasmal infection]]s, acne [[rickettsia]]l infections || rowspan="5" |
* Gastrointestinal upset
* Sensitivity to sunlight
* Staining of teeth (especially in children)
* Potential toxicity to mother and fetus during pregnancy
| rowspan="5" |inhibiting the binding of [[aminoacyl-tRNA]] to the [[mRNA-ribosome]] complex. They do so mainly by binding to the [[30S ribosomal subunit]] in the [[mRNA translation]] complex.<ref>[http://www.life-extension-drugs.com/doxycycline.html Life-Extension-Drugs.com - Doxycycline]</ref>
|-
|[[Doxycycline]] || [[Vibramycin]]
|-
|[[Minocycline]] || [[Minocin]]
|-
|[[Oxytetracycline]] || [[Terracin]]
|-
|[[Tetracycline]] || [[Sumycin]]
|-
!colspan="5" | Others
|-
|[[Arsphenamine]] || [[Salvarsan]] ||[[Spirochaete|Spirochaetal]] infections (obsolete) || ||
|-
|[[Chloramphenicol]] || [[Chloromycetin]] || || || Inhibits bacterial protein synthesis by binding to the 50S subunit of the ribosome|
|-
|[[Clindamycin]] || [[Cleocin]] || [[acne]] infections, prophylaxis before surgery || ||
|-
|[[Lincomycin]] || || [[acne]] infections, prophylaxis before surgery || ||
|-
|[[Ethambutol]] || || [[Antituberculosis]] || ||
|-
|[[Fosfomycin]] || || || ||
|-
|[[Fusidic acid]] || [[Fucidin]] || || ||
|-
|[[Furazolidone]] || || || ||
|-
|[[Isoniazid]] || || [[Antituberculosis]] || ||
|-
|[[Linezolid]] || [[Zyvox]] || || ||
|-
|[[Metronidazole]] || [[Flagyl]] ||[[Giardia]] || ||
|-
|[[Mupirocin]] || [[Bactroban]] || || ||
|-
|[[Nitrofurantoin]] || [[Macrodantin]], [[Macrobid]] || || ||
|-
|[[Platensimycin]] || || ||
|-
|[[Pyrazinamide]] || || [[Antituberculosis]] || ||
|-
|[[Quinupristin/Dalfopristin]] || [[Syncercid]] || || ||
|-
|[[Rifampin]] or [[Rifampicin]] || || mostly [[Gram-positive]] and [[mycobacteria]] ||Reddish-orange sweat, tears, and urine || Binds to the β subunit of [[RNA polymerase]] to inhibit transcription
|-
|[[Tinidazole]] || || || ||
|-
! Generic Name !! Brand Names !! Common Uses !! Possible Side Effects !! Mechanism of action
|}
== Production ==
{{main|Production of antibiotics}}
Since the first pioneering efforts of [[Howard Florey, Baron Florey|Florey]] and [[Ernst Boris Chain|Chain]] in 1939, the importance of antibiotics to [[medicine]] has led to much research into discovering and producing them. The process of production usually involves screening of wide ranges of microorganisms, testing and modification. Production is carried out using [[Industrial fermentation|fermentation]], usually in strongly aerobic fermentation.
== Usage ==
Antibiotics are only intended to be used by a doctor's prescription. Doctors always specify dosage and duration of antibiotic treatment. It is very important to follow the prescription and complete the entire course (see [[#Antibiotic_misuse|Antibiotic misuse]]).
In general, alcohol should be avoided when taking antibiotics as it causes a variety of things to happen in the body, and some of them can impair the effectiveness of antibiotics<ref> {{cite web|url=http://answers.yahoo.com/question/index?qid=20070429025701AA5khrm |title=Exploding the urban myth: alcohol and antibiotics |accessdate=2008-02-17 |publisher=Yahoo answers }}</ref>; It also competes with liver enzymes, which break down the antibiotics.<ref> {{cite web|url=http://www.mcgill.ca/studenthealth/information/generalhealth/antibiotics/ |title=Antibiotics FAQ |accessdate=2008-02-17 |publisher=McGill University, Canada }}</ref> Additionally, certain antibiotics chemically react with alcohol, leading to serious body reactions (severe vomiting, nausea, etc.). These include (but not limited to): Metronidazole, Tinidazole, co-trimoxazole, cephamandole, ketoconazole. '''Such antibiotics are explicitly prohibited to be used with alcohol'''.<ref> {{cite web|url=http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=871 |title=Can I drink alcohol while taking antibiotics? |accessdate=2008-02-17 |publisher=NHS Direct (UK electronic health service) }}</ref>
== Side effects ==
Possible side effects are varied, depending on the antibiotics used and the microbial organisms targeted. Adverse effects can range from fever and nausea to major allergic reactions including [[photodermatitis]].{{Fact|date=April 2007}} One of the more common side effects is [[diarrhea]], sometimes caused by the anaerobic bacterium ''[[Clostridium difficile]]'', which results from the antibiotic disrupting the normal balance of the [[intestinal flora]],<ref>University of Michigan Health System: [http://www.med.umich.edu/1libr/aha/aha_aadiarrh_crs.htm Antibiotic-Associated Diarrhea], November 26, 2006</ref> Such overgrowth of pathogenic bacteria may be alleviated by ingesting [[probiotics]] during a course of antibiotics. {{Fact|date=April 2007}}. An antibiotic-induced disruption of the population of the bacteria normally present as constituents of the normal vaginal flora may also occur, and may lead to overgrowth of yeast species of the genus ''[[Candida (genus)|Candida]]'' in the vulvo-vaginal area. <ref name="Pirotta and Garland">{{cite journal|author=Pirotta MV, Garland SM|year= 2006|title=Genital Candida species detected in samples from women in Melbourne, Australia, before and after treatment with antibiotics|journal=J Clin Microbiol.|volume=44|pages=3213–3217|pmid=16954250|doi=10.1128/JCM.00218-06}}</ref> Other side effects can result from interaction with other drugs, such as elevated risk of [[tendon]] damage from administration of a [[Quinolones|quinolone]] antibiotic with a systemic [[corticosteroid]].
Hypothetically, some antibiotics might interfere with the efficiency of birth control pills. However there have been no conclusive studies that proved that; on the contrary, the majority of the studies indicate that antibiotics do not interfere with contraception<ref> {{cite web|url=http://www.wdxcyber.com/ncontr10.htm |title=Drugs Affecting Birth Control Pills |accessdate=2008-02-17 }}</ref>, even though there is a possibility that a small percentage of women may experience decreased effectiveness of birth control pills while taking an antibiotic.<ref> {{cite web|url=http://answers.yahoo.com/question/index;_ylt=AmTUUjVc3edfYh8cZaxmJ00jzKIX;_ylv=3?qid=20070524151339AAw8vfi |title=Antibiotic and birth control |accessdate=2008-02-17 |publisher=Yahoo answers }}</ref>
== Antibiotic misuse ==
Common forms of antibiotic misuse include failure to take the entire prescribed course of the antibiotic, or failure to rest for sufficient recovery to allow clearance of the infecting organism. These practices may facilitate the development of bacterial populations with [[#Antibiotic_resistance|antibiotic resistance]]. Inappropriate antibiotic treatment is another common form of antibiotic misuse. A common example is the prescription and use of antibiotics to treat viral infections such as the [[common cold]] that have no effect.
===Animals===
It is estimated that greater than 70% of the antibiotics used in U.S. are given to feed animals (e.g. chickens, pigs and cattle) in the absence of disease.<ref>Mellon, M ''et al''. (2001) ''Hogging It!: Estimates of Antimicrobial Abuse in Livestock'', 1st ed. Cambridge, MA: [[Union of Concerned Scientists]].</ref> Antibiotic use in food animal production has been associated with the emergence of antibiotic-resistant strains of bacteria including ''Salmonella'' spp., ''Campylobacter'' spp., ''Escherichia coli'', and ''Enterococcus'' spp. Evidence from some US and European studies suggest that these resistant bacteria cause infections in humans that do not respond to commonly prescribed antibiotics. In response to these practices and attendant problems, several organizations (e.g. The American Society for Microbiology (ASM), American Public Health Association (APHA) and the American Medical Association (AMA)) have called for restrictions on antibiotic use in food animal production and an end to all non-therapeutic uses. {{Fact|date=May 2007}} However, delays in regulatory and legislative actions to limit the use of antibiotics are common, and may include resistance to these changes by industries using or selling antibiotics, as well as time spent on research to establish causal links between antibiotic use and emergence of untreatable bacterial diseases. Today, there are two federal bills (S.742 and H.R. 2562) aimed at phasing out non-therapeutic antibiotics in US food animal production. These bills are endorsed by public health and medical organizations including the American Nurses Association (ANA), the American Academy of Pediatrics (AAP), and the American Public Health Association (APHA). {{Fact|date=May 2007}}
===Humans===
One study on [[respiratory tract infection]]s found "physicians were more likely to prescribe antibiotics to patients who they believed expected them, although they correctly identified only about 1 in 4 of those patients".<ref name="pmid17467120">{{cite journal |author=Ong S, Nakase J, Moran GJ, Karras DJ, Kuehnert MJ, Talan DA |title=Antibiotic use for emergency department patients with upper respiratory infections: prescribing practices, patient expectations, and patient satisfaction |journal=Annals of emergency medicine |volume=50 |issue=3 |pages=213–20 |year=2007 |pmid=17467120 |doi=10.1016/j.annemergmed.2007.03.026}}</ref> Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescribing of antibiotics. <ref name="pmid17509729">{{cite journal |author=Metlay JP, Camargo CA, MacKenzie T, ''et al'' |title=Cluster-randomized trial to improve antibiotic use for adults with acute respiratory infections treated in emergency departments |journal=Annals of emergency medicine |volume=50 |issue=3 |pages=221–30 |year=2007 |pmid=17509729 |doi=10.1016/j.annemergmed.2007.03.022}}</ref> Delaying antibiotics for 48 hours while observing for spontaneous resolution of respiratory tract infections may reduce antibiotic usage; however, this strategy may reduce patient satisfaction.<ref name="pmid17636757">{{cite journal |author=Spurling G, Del Mar C, Dooley L, Foxlee R |title=Delayed antibiotics for respiratory infections |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD004417 |year=2007 |pmid=17636757 |doi=10.1002/14651858.CD004417.pub3}}</ref>
Excessive use of [[prophylaxis|prophylactic]] antibiotics in travelers may also be classified as misuse.
== Antibiotic resistance ==
{{main|Antibiotic resistance}}
[[Image:MRSA7820.jpg|right|thumb|200px|[[Scanning electron micrograph|SEM]] depicting [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] bacteria.]]
Use or misuse of antibiotics may result in the development of ''antibiotic resistance'' by the infecting organisms, similar to the development of [[pesticide resistance]] in insects. [[Evolutionary theory]] of [[selection|genetic selection]] requires that as close as possible to 100% of the infecting organisms be killed off to avoid selection of resistance; if a small subset of the population survives the treatment and is allowed to multiply, the average susceptibility of this new population to the compound will be much less than that of the original population, since they have descended from those few organisms that survived the original treatment. This survival often results from an inheritable resistance to the compound that was infrequent in the original population, but became more frequent in the descendants.
Antibiotic resistance has become a serious problem in both developed and underdeveloped nations. By 1984 half of those with active [[tuberculosis]] in the [[United States]] had a strain that resisted at least one antibiotic. {{Fact|date=January 2008}} In certain settings, such as hospitals and some childcare locations, the rate of antibiotic resistance is so high that the usual, low-cost antibiotics are virtually useless for treatment of frequently seen infections. This leads to more frequent use of newer and more expensive compounds, which in turn leads to the rise of resistance to those drugs. A struggle to develop new antibiotics ensues to prevent losing future battles against infection. To date, tuberculosis and pneumococcus are prominent examples of once easily treated infections where drug-resistance has become a problem.
[[Image:Antibiotics action.png|left|thumb|150px|Points of attack on bacteria by antibiotics]]
Another example of selection is ''[[Staphylococcus aureus]]'' ('golden staph'), which could be treated successfully with [[penicillin]] in the 1940s and 1950s. At present, nearly all strains are resistant to penicillin, and many are resistant to [[nafcillin]], leaving only a narrow selection of drugs such as [[vancomycin]] useful for treatment. The situation is complicated by the fact that genes coding for antibiotic resistance can be transferred between bacteria via [[plasmids]], making it possible for bacteria never exposed to an antibiotic to acquire resistance from those which have. The problem of antibiotic resistance is made more widespread when antibiotics are used to treat disorders in which they have no efficacy, such as the common cold or other viral complaints, and when they are used broadly as prophylaxis rather than treatment (as in, for example, animal feeds), because this exposes more bacteria to selection for resistance.
===Resistance modifying agents===
One solution to combat resistance currently being researched is the development of pharmaceutical compounds that would revert multiple antibiotic resistance. These so called resistance modifying agents may target and inhibit MDR mechanisms, rendering the bacteria susceptible to antibiotics to which they were previously resistant. These compounds targets include among others
*[[Efflux (microbiology)|Efflux inhibition]](Phe-Arg-β-naphthylamide)<ref>B. Marquez. (2005). Bacterial efflux systems and efflux pumps inhibitors. ''Biochimie''87 1137–1147</ref>
*Beta Lactamase inhibitors - Including [[Clavulanic acid]] and [[Sulbactam]]
== Beyond antibiotics ==
The comparative ease of identifying compounds which safely cured bacterial infections was more difficult to duplicate in treatments of fungal and viral infections. Antibiotic research led to great strides in the knowledge of [[biochemistry]], establishing large differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. This explained the observation that many compounds that are toxic to bacteria are non-toxic to human cells. In contrast, the basic biochemistries of the fungal cell and the [[mammal]]ian cell are much more similar. This restricts the development and use of therapeutic compounds that attack a fungal cell, while not harming mammalian cells. Similar problems exist in antibiotic treatments of [[virus|viral]] diseases. Human viral metabolic biochemistry is very closely similar to human biochemistry, and the possible targets of antiviral compounds are restricted to very few components unique to a mammalian virus.
Research into [[bacteriophage]]s for use as antibiotics is presently ongoing. Several types of bacteriophage appear to exist that are specific for each bacterial taxonomic group or species.{{Fact|date=May 2007}} Research into bacteriophages for medicinal use is just beginning, but has led to advances in microscopic imaging.<ref>Purdue University "Biologists build better software, beat path to viral knowledge", see Imaging of Epsilon 15, a virus that infects the bacterium Salmonella [http://news.uns.purdue.edu/UNS/html4ever/2006/060201.Jiang.salmonella.html News report]</ref> While bacteriophages provide a possible solution to the problem of antibiotic resistance, there is no clinical evidence yet that they can be deployed as therapeutic agents to cure disease.{{Fact|date=March 2008}}
[[Phage therapy]] has been used in the past on humans in the US and Europe during the 1920s and 1930s, but these treatments had mixed results. With the discovery of penicillin in the 1940s, Europe and the US changed therapeutic strategies to using antibiotics. However, in the former Soviet Union phage therapies continued to be studied. In the Republic of Georgia, the Eliava Institute of Bacteriophage, Microbiology & Virology continues to research the use of phage therapy. Various companies and foundations in North America and Europe are currently researching phage therapies. {{Fact|date=May 2007}} However, phage are living and reproducing; concerns about genetic engineering in freely released viruses currently limit certain aspects of phage therapy.
[[Bacteriocin]]s are also a growing alternative to the classic small-molecule antibiotics <ref>{{cite journal |author=Gillor O, Kirkup BC, Riley MA |title=Colicins and microcins: the next generation antimicrobials |journal=Adv. Appl. Microbiol. |volume=54 |issue= |pages=129–46 |year=2004 |pmid=15251279 |doi=10.1016/S0065-2164(04)54005-4}}</ref>. Different classes of bacteriocins have different potential as therapeutic agents. Small molecule bacteriocins ([[microcin]]s, for example, and [[lantibiotic]]s) may be similar to the classic antibiotics; [[colicin]]-like bacteriocins are more likely to be narrow-spectrum, demanding new molecular diagnostics prior to therapy but also not raising the spectre of resistance to the same degree. One drawback to the large molecule antibiotics is that they will have relative difficulty crossing membranes and travelling systemically throughout the body. For this reason, they are most often proposed for application topically or gastrointestinally<ref name="pmid17168847">{{cite journal |author=Kirkup BC |title=Bacteriocins as oral and gastrointestinal antibiotics: theoretical considerations, applied research, and practical applications |journal=[[Curr. Med. Chem.]] |volume=13 |issue=27 |pages=3335–50 |year=2006 |pmid=17168847 |doi=}}</ref>. Because bacteriocins are peptides, they are more readily engineered than small molecules<ref name="pmid15777256">{{cite journal |author=Gillor O, Nigro LM, Riley MA |title=Genetically engineered bacteriocins and their potential as the next generation of antimicrobials |journal=[[Curr. Pharm. Des.]] |volume=11 |issue=8 |pages=1067–75 |year=2005 |pmid=15777256 |doi=}}</ref>. This may permit the generation of cocktails and dynamically improved antibiotics that are modified to overcome resistance.
[[Probiotic]]s are another alternative that goes beyond traditional antibiotics by employing a live culture which may establish itself as a symbiont, competing, inhibiting, or simply interfering with colonization by pathogens. It may produce antibiotics or bacteriocins, essentially providing the drug ''in vivo'' and ''in situ'', potentially avoiding the side effects of systemic administration.
==References==
{{Reflist|2}}
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==External links==
{{commonscat|Antibiotics}}
* [http://www.genomenewsnetwork.org/categories/index/drugs/resist.php Antibiotic News from Genome News Network (GNN)]
* [http://www.jaapa.com/issues/j20040601/articles/antibiotics0604.html JAAPA: New antibiotics useful in primary care]
* [http://www.isracast.com/tech_news/090605_tech.htm A new method for controlling bacterial activity without antibiotics] - Research conducted at the Hebrew University
* [http://www.eu-burden.info/ BURDEN of Resistance and Disease in European Nations ]
* [http://www.tgw1916.net/movies.html Antibiogram technique] video
* [http://www.esac.ua.ac.be/ European Surveillance of Antimicrobial Consumption (ESAC)]
=== Resources ===
* [http://www.bacteriatd.com Bacteria Tower Defense - Antibiotic Coverage Resource and Game]
* [http://www.apua.org Alliance for the Prudent Use of Antibiotics]
{{antibiotics}}
{{Major Drug Groups}}
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