Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections.[1][2] They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity.[3][4] Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza;[5] drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.
"Antibacterial" redirects here. For other uses, see Antibacterial (disambiguation).
Sometimes, the term antibiotic—literally "opposing life", from the Greek roots ἀντι anti, "against" and βίος bios, "life"—is broadly used to refer to any substance used against microbes, but in the usual medical usage, antibiotics (such as penicillin) are those produced naturally (by one microorganism fighting another), whereas non-antibiotic antibacterials (such as sulfonamides and antiseptics) are fully synthetic. However, both classes have the same effect of killing or preventing the growth of microorganisms, and both are included in antimicrobial chemotherapy. "Antibacterials" include bactericides, bacteriostatics, antibacterial soaps, and chemical disinfectants, whereas antibiotics are an important class of antibacterials used more specifically in medicine[6] and sometimes in livestock feed.
Antibiotics have been used since ancient times. Many civilizations used topical application of moldy bread, with many references to its beneficial effects arising from ancient Egypt, Nubia, China, Serbia, Greece, and Rome.[7] The first person to directly document the use of molds to treat infections was John Parkinson (1567–1650). Antibiotics revolutionized medicine in the 20th century. Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s.[8] Alexander Fleming (1881–1955) discovered modern day penicillin in 1928, the widespread use of which proved significantly beneficial during wartime. The first sulfonamide and the first 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.[9][10][11] However, the effectiveness and easy access to antibiotics have also led to their overuse[12] and some bacteria have evolved resistance to them.[1][13][14][15] The World Health Organization has classified antimicrobial resistance as a widespread "serious threat [that] is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country".[16] Global deaths attributable to antimicrobial resistance numbered 1.27 million in 2019.[17]
Etymology[edit]
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.[8][18][19] 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.[18][20] These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1947.[21]
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 antagonistic to the growth of other microorganisms in high dilution.[18][22] This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the 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.[23][24]
The term "antibiotic" derives from anti + βιωτικός (biōtikos), "fit for life, lively",[25] which comes from βίωσις (biōsis), "way of life",[26] and that from βίος (bios), "life".[27][28] The term "antibacterial" derives from Greek ἀντί (anti), "against"[29] + βακτήριον (baktērion), diminutive of βακτηρία (baktēria), "staff, cane",[30] because the first bacteria to be discovered were rod-shaped.[31]
Usage[edit]
Medical uses[edit]
Antibiotics are used to treat or prevent bacterial infections,[32] and sometimes protozoan infections. (Metronidazole is effective against a number of parasitic diseases). When an infection is suspected of being responsible for an illness but the responsible pathogen has not been identified, an empiric therapy is adopted.[33] This involves the administration of a broad-spectrum antibiotic based on the signs and symptoms presented and is initiated pending laboratory results that can take several days.[32][33]
When the responsible pathogenic microorganism is already known or has been identified, definitive therapy can be started. This will usually involve the use of a narrow-spectrum antibiotic. The choice of antibiotic given will also be based on its cost. Identification is critically important as it can reduce the cost and toxicity of the antibiotic therapy and also reduce the possibility of the emergence of antimicrobial resistance.[33] To avoid surgery, antibiotics may be given for non-complicated acute appendicitis.[34]
Antibiotics may be given as a preventive measure and this is usually limited to at-risk populations such as those with a weakened immune system (particularly in HIV cases to prevent pneumonia), those taking immunosuppressive drugs, cancer patients, and those having surgery.[32] Their use in surgical procedures is to help prevent infection of incisions. They have an important role in dental antibiotic prophylaxis where their use may prevent bacteremia and consequent infective endocarditis. Antibiotics are also used to prevent infection in cases of neutropenia particularly cancer-related.[35][36]
The use of antibiotics for secondary prevention of coronary heart disease is not supported by current scientific evidence, and may actually increase cardiovascular mortality, all-cause mortality and the occurrence of stroke.[37]
Routes of administration[edit]
There are many different routes of administration for antibiotic treatment. Antibiotics are usually taken by mouth. In more severe cases, particularly deep-seated systemic infections, antibiotics can be given intravenously or by injection.[1][33] Where the site of infection is easily accessed, antibiotics may be given topically in the form of eye drops onto the conjunctiva for conjunctivitis or ear drops for ear infections and acute cases of swimmer's ear. Topical use is also one of the treatment options for some skin conditions including acne and cellulitis.[38] Advantages of topical application include achieving high and sustained concentration of antibiotic at the site of infection; reducing the potential for systemic absorption and toxicity, and total volumes of antibiotic required are reduced, thereby also reducing the risk of antibiotic misuse.[39] Topical antibiotics applied over certain types of surgical wounds have been reported to reduce the risk of surgical site infections.[40] However, there are certain general causes for concern with topical administration of antibiotics. Some systemic absorption of the antibiotic may occur; the quantity of antibiotic applied is difficult to accurately dose, and there is also the possibility of local hypersensitivity reactions or contact dermatitis occurring.[39] It is recommended to administer antibiotics as soon as possible, especially in life-threatening infections. Many emergency departments stock antibiotics for this purpose.[41]
Global consumption[edit]
Antibiotic consumption varies widely between countries. The WHO report on surveillance of antibiotic consumption published in 2018 analysed 2015 data from 65 countries. As measured in defined daily doses per 1,000 inhabitants per day. Mongolia had the highest consumption with a rate of 64.4. Burundi had the lowest at 4.4. Amoxicillin and amoxicillin/clavulanic acid were the most frequently consumed.[42]
Interactions[edit]
Birth control pills[edit]
There are few well-controlled studies on whether antibiotic use increases the risk of oral contraceptive failure.[52] The majority of studies indicate antibiotics do not interfere with birth control pills,[53] such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%).[54] Situations that may increase the risk of oral contraceptive failure include non-compliance (missing taking the pill), vomiting, or diarrhea. Gastrointestinal disorders or interpatient variability in oral contraceptive absorption affecting ethinylestradiol serum levels in the blood.[52] Women with menstrual irregularities may be at higher risk of failure and should be advised to use 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.[52]
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.[53] Effects on the intestinal flora, which might result in reduced absorption of estrogens in the colon, have also been suggested, but such suggestions have been inconclusive and controversial.[55][56] Clinicians have recommended that extra contraceptive measures be applied during therapies using antibiotics that are suspected to interact with oral contraceptives.[53] 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.[52]
Alcohol[edit]
Interactions between alcohol and certain antibiotics may occur and may cause side effects and decreased effectiveness of antibiotic therapy.[57][58] 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.[59] Therefore, potential risks of side effects and effectiveness depend on the type of antibiotic administered.[60]
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.[59] In addition, the efficacy of doxycycline and erythromycin succinate may be reduced by alcohol consumption.[61] Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound.[27]
Molecular targets of antibiotics on the bacteria cell
Protein synthesis inhibitors (antibiotics)
Antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes.[8] Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell membrane (polymyxins), or interfere with essential bacterial enzymes (rifamycins, lipiarmycins, quinolones, and sulfonamides) have bactericidal activities, killing the bacteria. Protein synthesis inhibitors (macrolides, lincosamides, and tetracyclines) are usually bacteriostatic, inhibiting further growth (with the exception of bactericidal aminoglycosides).[73] 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 classes of antibacterial compounds, four new classes of antibiotics were introduced to clinical use in the late 2000s and early 2010s: cyclic lipopeptides (such as daptomycin), glycylcyclines (such as tigecycline), oxazolidinones (such as linezolid), and lipiarmycins (such as fidaxomicin).[74][75]