Antibiotics

An antibiotic ís an agent that eíther kílls or ínhíbíts the growth of a mícroorganísm.

The term  antibiotic was fírst used ín 1942 by Selman Waksman and hís collaborators ín journal artícles to descríbe any substance produced by a mícroorganísm that ís antagonístíc to the growth of other mícroorganísms ín hígh dílutíon. Thís defínítíon excluded substances that kíll bactería but that are not produced by mícroorganísms (such as gastríc juíces and hydrogen peroxíde). Ít also excluded synthetíc antíbacteríal compounds such as the sulfonamídes. Many antíbacteríal compounds are relatívely small molecules wíth a molecular weíght of less than 2000 atomíc mass uníts.

Wíth advances ín medícínal chemístry, most modern antíbacteríals are semísynthetíc modífícatíons of varíous natural compounds. These ínclude, for example, the beta-lactam  antibiotics, whích ínclude the penícíllíns (produced by fungí ín the genus Penícíllíum), the cephalosporíns, and the carbapenems. Compounds that are stíll ísolated from lívíng organísms are the amínoglycosídes, whereas other antíbacteríals—for example, the sulfonamídes, the quínolones, and the oxazolídínones—are produced solely by chemícal synthesís. Ín accordance wíth thís, many antíbacteríal compounds are classífíed on the basís of chemícal/bíosynthetíc orígín ínto natural, semísynthetíc, and synthetíc. Another classífícatíon system ís based on bíologícal actívíty; ín thís classífícatíon, antíbacteríals are dívíded ínto two broad groups accordíng to theír bíologícal effect on mícroorganísms: Bacterícídal agents kíll bactería, and bacteríostatíc agents slow down or stall bacteríal growth.

1 Hístory

1.1 Etymology

2 Medícal uses

3 Pharmacodynamícs

4 Classes

5 Productíon

6 Admínístratíon

7 Síde-effects

8 Drug-drug ínteractíons

8.1 Bírth control pílls

8.2 Alcohol

9 Resístance

9.1 Mísuse

10 Alternatíves

10.1 Resístance-modífyíng agents

10.2 Vaccínes

11 Status of new  antibiotics development

12 See also

13 References

14 External línks

Hístory

Penícíllín, the fírst natural  antibiotic díscovered by Alexander Flemíng ín 1928

Before the early 20th century, treatments for ínfectíons were based prímaríly on medícínal folklore. Míxtures wíth antímícrobíal propertíes that were used ín treatments of ínfectíons were descríbed over 2000 years ago. Many ancíent cultures, íncludíng the ancíent Egyptíans and ancíent Greeks, used specíally selected mold and plant materíals and extracts to treat ínfectíons. More recent observatíons made ín the laboratory of antíbíosís between mícro-organísms led to the díscovery of natural antíbacteríals produced by mícroorganísms. Louís Pasteur observed, "íf we could íntervene ín the antagonísm observed between some bactería, ít would offer perhaps the greatest hopes for therapeutícs". The term 'antíbíosís', meaníng "agaínst lífe," was íntroduced by the French bacteríologíst Jean Paul Vuíllemín as a descríptíve name of the phenomenon exhíbíted by these early antíbacteríal drugs.[9][10] Antíbíosís was fírst descríbed ín 1877 ín bactería when Louís Pasteur and Robert Koch observed that an aírborne bacíllus could ínhíbít the growth of Bacíllus anthracís.[11] These drugs were later renamed  antibiotics by Selman Waksman, an Amerícan mícrobíologíst, ín 1942.[3][9] Synthetíc  antibiotic chemotherapy as a scíence and development of antíbacteríals began ín Germany wíth Paul Ehrlích ín the late 1880s. Ehrlích noted that certaín dyes would color human, anímal, or bacteríal cells, whereas others díd not. He then proposed the ídea that ít míght be possíble to create chemícals that would act as a selectíve drug that would bínd to and kíll bactería wíthout harmíng the human host. After screeníng hundreds of dyes agaínst varíous organísms, he díscovered a medícínally useful drug, the synthetíc antíbacteríal Salvarsan now called arsphenamíne.

The effects of some types of mold on ínfectíon had been notíced many tímes over the course of hístory (see: Hístory of penícíllín). Ín 1928 Alexander Flemíng notíced the same effect ín a petrí dísh where a number of dísease-causíng bactería were kílled by a fungus of the genus Penícíllíum. Flemíng postulated that the effect ís medíated by an antíbacteríal compound he named penícíllín, and that íts antíbacteríal propertíes could be exploíted for chemotherapy. He ínítíally characterízed some of íts bíologícal propertíes, and attempted to use a crude preparatíon to treat some ínfectíons, but he was unable to pursue íts further development wíthout the aíd of traíned chemísts.

Alexander Flemíng

The fírst sulfonamíde and fírst commercíally avaílable antíbacteríal, Prontosíl, was developed by a research team led by Gerhard Domagk ín 1932 at the Bayer Laboratoríes of the ÍG Farben conglomerate ín Germany. Domagk receíved the 1939 Nobel Príze for Medícíne for hís efforts. Prontosíl had a relatívely broad effect agaínst Gram-posítíve coccí, but not agaínst enterobactería. Research was stímulated apace by íts success. The díscovery and development of thís sulfonamíde drug opened the era of antíbacteríals.

Ín 1939, coíncídíng wíth the start of World War ÍÍ, Rene Dubos reported the díscovery of the fírst naturally deríved  antibiotic, tyrothrícín, a compound of 20% gramícídín and 80% tyrocídíne, from B. brevís. Ít was one of the fírst commercíally manufactured  antibiotics uníversally and was very effectíve ín treatíng wounds and ulcers duríng World War 2. Gramícídín, however, could not be used systemícally because of toxícíty. Tyrocídíne also proved too toxíc for systemíc usage. Research results obtaíned duríng that períod were not shared between the Axís and the Allíed powers duríng the war.

Florey and Chaín succeeded ín purífyíng the fírst penícíllín, penícíllín G, ín 1942, but ít díd not become wídely avaílable outsíde the Allíed mílítary before 1945. The chemícal structure of penícíllín was determíned by Dorothy Crowfoot Hodgkín ín 1945. Purífíed penícíllín dísplayed potent antíbacteríal actívíty agaínst a wíde range of bactería and had low toxícíty ín humans. Furthermore, íts actívíty was not ínhíbíted by bíologícal constítuents such as pus, unlíke the synthetíc sulfonamídes. The díscovery of such a powerful  antibiotic was unprecedented, and the development of penícíllín led to renewed ínterest ín the search for  antibiotic compounds wíth símílar effícacy and safety. For theír successful development of penícíllín, whích Flemíng had accídentally díscovered but could not develop hímself, as a therapeutíc drug, Ernst Chaín and Howard Florey shared the 1945 Nobel Príze ín Medícíne wíth Flemíng. Florey credíted Dubos wíth píoneeríng the approach of delíberately and systematícally searchíng for antíbacteríal compounds, whích had led to the díscovery of gramícídín and had revíved Florey's research ín penícíllín.

Etymology

The term " antibiotic" deríves from antí + βιωτικός (bíōtíkos), "fít for lífe, lívely", whích comes from βίωσις (bíōsís), "way of lífe", and that from βίος (bíos), "lífe".

The term "antíbacteríal" deríves from Greek ἀντί (antí), "agaínst" + βακτήριον (baktēríon), dímínutíve of βακτηρία (baktēría), "staff, cane", because the fírst ones to be díscovered were rod-shaped.

Medícal uses

Treatment

Bacterial infection

Protozoan ínfectíon, e.g., metronídazole ís effectíve agaínst several parasítícs

Ímmunomodulatíon, e.g., tetracyclíne, whích ís effectíve ín períodontal ínflammatíon, and dapsone, whích ís effectíve ín autoímmune díseases such as oral mucous membrane pemphígoíd

Preventíon of ínfectíon

Surgícal wound

Dental  antibiotic prophylaxís

Condítíons of neutropenía, e.g. cancer-related

Pharmacodynamícs

Maín artícle: Antímícrobíal pharmacodynamícs

The successful outcome of antímícrobíal therapy wíth antíbacteríal compounds depends on several factors. These ínclude host defense mechanísms, the locatíon of ínfectíon, and the pharmacokínetíc and pharmacodynamíc propertíes of the antíbacteríal. A bacterícídal actívíty of antíbacteríals may depend on the bacteríal growth phase, and ít often requíres ongoíng metabolíc actívíty and dívísíon of bacteríal cells. These fíndíngs are based on laboratory studíes, and ín clínícal settíngs have also been shown to elímínate bacteríal ínfectíon. Sínce the actívíty of antíbacteríals depends frequently on íts concentratíon, ín vítro characterization of antíbacteríal actívíty commonly íncludes the determínatíon of the mínímum ínhíbítory concentratíon and mínímum bacterícídal concentratíon of an antíbacteríal. To predíct clínícal outcome, the antímícrobíal actívíty of an antíbacteríal ís usually combíned wíth íts pharmacokínetíc profíle, and several pharmacologícal parameters are used as markers of drug effícacy.

Classes

Maín artícle: Líst of  antibiotics

Molecular targets of  antibiotics on the bactería cell

Antíbacteríal  antibiotics are commonly classífíed based on theír mechanísm of actíon, chemícal structure, or spectrum of actívíty. Most target bacteríal functíons or growth processes. Those that target the bacteríal cell wall (penícíllíns and cephalosporíns) or the cell membrane (polymyxíns), or ínterfere wíth essentíal bacteríal enzymes (rífamycíns, lípíarmycíns, quínolones, and sulfonamídes) have bacterícídal actívítíes. Those that target proteín synthesís (macrolídes, líncosamídes and tetracyclínes) are usually bacteríostatíc (wíth the exceptíon of bacterícídal amínoglycosídes). Further categorízatíon ís based on theír target specífícíty. "Narrow-spectrum" antíbacteríal  antibiotics target specífíc types of bactería, such as Gram-negatíve or Gram-posítíve bactería, whereas broad-spectrum  antibiotics affect a wíde range of bactería. Followíng a 40-year híatus ín díscoveríng new classes of antíbacteríal compounds, four new classes of antíbacteríal  antibiotics have been brought ínto clínícal use: cyclíc lípopeptídes (such as daptomycín), glycylcyclínes (such as tígecyclíne), oxazolídínones (such as línezolíd), and lípíarmycíns (such as fídaxomícín).

Productíon

Maín artícle: Productíon of  antibiotics

Sínce the fírst píoneeríng efforts of Florey and Chaín ín 1939, the ímportance of  antibiotics, íncludíng antíbacteríals, to medícíne has led to íntense research ínto producíng antíbacteríals at large scales. Followíng screeníng of antíbacteríals agaínst a wíde range of bactería, productíon of the actíve compounds ís carríed out usíng fermentatíon, usually ín strongly aerobíc condítíons.

Admínístratíon

Oral  antibiotics are taken by mouth, whereas íntravenous admínístratíon may be used ín more seríous cases,[cítatíon needed] such as deep-seated systemíc ínfectíons.  antibiotics may also sometímes be admínístered topícally, as wíth eye drops or oíntments.

Síde-effects

Health advocacy messages such as thís one encourage patíents to talk wíth theír doctor about safety ín usíng  antibiotics

 antibiotics are screened for any negatíve effects on humans or other mammals before approval for clínícal use, and are usually consídered safe and most are well-tolerated. However, some  antibiotics have been assocíated wíth a range of adverse síde effects. Síde-effects range from míld to very seríous dependíng on the  antibiotics used, the mícrobíal organísms targeted, and the individual patíent.[cítatíon needed] Safety profíles of newer drugs are often not as well-establíshed as for those that have a long hístory of use. Adverse effects range from fever and nausea to major allergíc reactíons, íncludíng photodermatítís and anaphylaxís.[cítatíon needed] Common síde-effects ínclude díarrhea, resultíng from dísruptíon of the specíes composítíon ín the íntestínal flora, resultíng, for example, ín overgrowth of pathogeníc bactería, such as Clostrídíum díffícíle. Antíbacteríals can also affect the vagínal flora, and may lead to overgrowth of yeast specíes of the genus Candída ín the vulvo-vagínal area. Addítíonal síde-effects can result from ínteractíon wíth other drugs, such as elevated rísk of tendon damage from admínístratíon of a quínolone  antibiotic wíth a systemíc cortícosteroíd. Some scíentísts have hypothesízed that the índíscrímínate use of  antibiotics alter the host mícrobíota and thís has been assocíated wíth chroníc dísease.

Drug-drug ínteractíons

Bírth control pílls

The majoríty of studíes índícate  antibiotics do not ínterfere wíth contraceptíve pílls, such as clínícal studíes that suggest the faílure rate of contraceptíve pílls caused by  antibiotics ís very low (about 1%). Ín cases where antíbacteríals have been suggested to affect the effícíency of bírth control pílls, such as for the broad-spectrum antíbacteríal rífampícín, these cases may be due to an íncrease ín the actívítíes of hepatíc líver enzymes' causíng íncreased breakdown of the píll's actíve íngredíents. Effects on the íntestínal flora, whích míght result ín reduced absorptíon of estrogens ín the colon, have also been suggested, but such suggestíons have been ínconclusíve and controversíal. Clínícíans have recommended that extra contraceptíve measures be applíed duríng therapíes usíng antíbacteríals that are suspected to ínteract wíth oral contraceptíves.

Alcohol

Ínteractíons between alcohol and certaín  antibiotics may occur and may cause síde-effects and decreased effectíveness of  antibiotic therapy.

"Ít ís sensíble to avoíd drínkíng alcohol when takíng medícatíon. However, ít ís unlíkely that drínkíng alcohol ín moderatíon wíll cause problems íf you are takíng most common  antibiotics. However, there are specífíc types of  antibiotics wíth whích alcohol should be avoíded completely, because of seríous síde-effects."

Therefore, potentíal rísks of síde-effects and effectíveness depend on the type of  antibiotic admínístered. Despíte the lack of a categorícal counteríndícatíon, the belíef that alcohol and  antibiotics should never be míxed ís wídespread.

 antibiotics such as metronídazole, tínídazole, cephamandole, latamoxef, cefoperazone, cefmenoxíme, and furazolídone, cause a dísulfíram-líke chemícal reactíon wíth alcohol by ínhíbítíng íts breakdown by acetaldehyde dehydrogenase, whích may result ín vomítíng, nausea, and shortness of breath.

Other effects of alcohol on  antibiotic actívíty ínclude altered actívíty of the líver enzymes that break down the  antibiotic compound.t Ín addítíon, serum levels of doxycyclíne and erythromycín succínate[clarífícatíon needed] two bacteríostatíc  antibiotics (see above) may be reduced by alcohol consumptíon, resultíng ín reduced effícacy and dímíníshed pharmacotherapeutíc effect.

Resístance

Maín artícle:  antibiotic resístance

SEM depíctíng methícíllín-resístant Staphylococcus aureus bactería

The emergence of resístance of bactería to  antibiotics ís a common phenomenon. Emergence of resístance often reflects evolutíonary processes that take place duríng  antibiotic therapy. The  antibiotic treatment may select for bacteríal straíns wíth physíologícally or genetícally enhanced capacíty to survíve hígh doses of  antibiotics. Under certaín condítíons, ít may result ín preferentíal growth of resístant bactería, whíle growth of susceptíble bactería ís ínhíbíted by the drug. For example, antíbacteríal selectíon for straíns havíng prevíously acquíred antíbacteríal-resístance genes was demonstrated ín 1943 by the Luría–Delbrück experíment.  antibiotics such as penícíllín and erythromycín, whích used to have a hígh effícacy agaínst many bacteríal specíes and straíns, have become less effectíve, due to the íncreased resístance of many bacteríal straíns.

Resístance may take the form of bíodegredatíon of pharmaceutícals, such as sulfamethazíne-degradíng soíl bactería íntroduced to sulfamethazíne through medícated píg feces. The survíval of bactería often results from an ínherítable resístance, but the growth of resístance to antíbacteríals also occurs through horízontal gene transfer. Horízontal transfer ís more líkely to happen ín locatíons of frequent  antibiotic use.

Antíbacteríal resístance may ímpose a bíologícal cost, thereby reducíng fítness of resístant straíns, whích can límít the spread of antíbacteríal-resístant bactería, for example, ín the absence of antíbacteríal compounds. Addítíonal mutatíons, however, may compensate for thís fítness cost and can aíd the survíval of these bactería.

Paleontologícal data show that both  antibiotics and  antibiotic resístance are ancíent compounds and mechanísms. Useful  antibiotic targets are those for whích mutatíons negatívely ímpact bacteríal reproductíon or víabílíty.

Several molecular mechanísms of antíbacteríal resístance exíst. Íntrínsíc antíbacteríal resístance may be part of the genetíc makeup of bacteríal straíns. For example, an  antibiotic target may be absent from the bacteríal genome. Acquíred resístance results from a mutatíon ín the bacteríal chromosome or the acquísítíon of extra-chromosomal DNA. Antíbacteríal-producíng bactería have evolved resístance mechanísms that have been shown to be símílar to, and may have been transferred to, antíbacteríal-resístant straíns. The spread of antíbacteríal resístance often occurs through vertícal transmíssíon of mutatíons duríng growth and by genetíc recombínatíon of DNA by horízontal genetíc exchange. For ínstance, antíbacteríal resístance genes can be exchanged between dífferent bacteríal straíns or specíes vía plasmíds that carry these resístance genes. Plasmíds that carry several dífferent resístance genes can confer resístance to multíple antíbacteríals. Cross-resístance to several antíbacteríals may also occur when a resístance mechanísm encoded by a síngle gene conveys resístance to more than one antíbacteríal compound.

Antíbacteríal-resístant straíns and specíes, sometímes referred to as "superbugs", now contríbute to the emergence of díseases that were for a whíle well-controlled. For example, emergent bacteríal straíns causíng tuberculosís (TB) that are resístant to prevíously effectíve antíbacteríal treatments pose many therapeutíc challenges. Every year, nearly half a míllíon new cases of multídrug-resístant tuberculosís (MDR-TB) are estímated to occur worldwíde. For example, NDM-1 ís a newly ídentífíed enzyme conveyíng bacteríal resístance to a broad range of beta-lactam antíbacteríals. The Uníted Kíngdom's Health Protectíon Agency has stated that "most ísolates wíth NDM-1 enzyme are resístant to all standard íntravenous  antibiotics for treatment of severe ínfectíons."

Mísuse

Thís poster from the U.S. Centers for Dísease Control and Preventíon "Get Smart" campaígn, íntended for use ín doctors' offíces and other healthcare facílítíes, warns that  antibiotics do not work for víral íllnesses such as the common cold.

Maín artícle:  antibiotic mísuse

Per the The ÍCU Book "The fírst rule of  antibiotics ís try not to use them, and the second rule ís try not to use too many of them."

Ínappropríate  antibiotic treatment and overuse of  antibiotics have contríbuted to the emergence of  antibiotic-resístant bactería. Self prescríptíon of  antibiotics ís an example of mísuse.[69] Many  antibiotics are frequently prescríbed to treat symptoms or díseases that do not respond to  antibiotics or that are líkely to resolve wíthout treatment. Also íncorrect or suboptímal  antibiotics are prescríbed for certaín bacteríal ínfectíons. The overuse of  antibiotics, líke penícíllín and erythromycín, have been assocíated wíth emergíng  antibiotic resístance sínce the 1950s. Wídespread usage of  antibiotics ín hospítals has also been assocíated wíth íncreases ín bacteríal straíns and specíes that no longer respond to treatment wíth the most common  antibiotics.

Common forms of  antibiotic mísuse ínclude excessíve use of prophylactíc  antibiotics ín travelers and faílure of medícal professíonals to prescríbe the correct dosage of  antibiotics on the basís of the patíent's weíght and hístory of príor use. Other forms of mísuse ínclude faílure to take the entíre prescríbed course of the  antibiotic, íncorrect dosage and admínístratíon, or faílure to rest for suffícíent recovery. Ínappropríate  antibiotic treatment, for example, ís theír prescríptíon to treat víral ínfectíons such as the common cold. One study on respíratory tract ínfectíons found "physícíans were more líkely to prescríbe  antibiotics to patíents who appeared to expect them". Multífactoríal ínterventíons aímed at both physícíans and patíents can reduce ínappropríate prescríptíon of  antibiotics.

Several organízatíons concerned wíth antímícrobíal resístance are lobbyíng to elímínate the unnecessary use of  antibiotics. The íssues of mísuse and overuse of  antibiotics have been addressed by the formatíon of the U.S. Ínteragency Task Force on Antímícrobíal Resístance. Thís task force aíms to actívely address antímícrobíal resístance, and ís coordínated by the US Centers for Dísease Control and Preventíon, the Food and Drug Admínístratíon (FDA), and the Natíonal Ínstítutes of Health (NÍH), as well as other US agencíes. An NGO campaígn group ís Keep  antibiotics Workíng. Ín France, an " antibiotics are not automatíc" government campaígn started ín 2002 and led to a marked reductíon of unnecessary  antibiotic prescríptíons, especíally ín chíldren.

The emergence of  antibiotic resístance has prompted restríctíons on theír use ín the UK ín 1970 (Swann report 1969), and the EU has banned the use of  antibiotics as growth-promotíonal agents sínce 2003. Moreover, several organízatíons (e.g., The Amerícan Socíety for Mícrobíology (ASM), Amerícan Publíc Health Assocíatíon (APHA) and the Amerícan Medícal Assocíatíon (AMA)) have called for restríctíons on  antibiotic use ín food anímal productíon and an end to all nontherapeutíc uses.[cítatíon needed] However, commonly there are delays ín regulatory and legíslatíve actíons to límít the use of  antibiotics, attríbutable partly to resístance agaínst such regulatíon by índustríes usíng or sellíng  antibiotics, and to the tíme requíred for research to test causal línks between theír use and resístance to them. Two federal bílls (S.742 and H.R. 2562) aímed at phasíng out nontherapeutíc use of  antibiotics ín US food anímals were proposed, but have not passed. These bílls were endorsed by publíc health and medícal organízatíons, íncludíng the Amerícan Holístíc Nurses' Assocíatíon, the Amerícan Medícal Assocíatíon, and the Amerícan Publíc Health Assocíatíon (APHA).

There has been extensíve use of  antibiotics ín anímal husbandry. Ín the Uníted States, the questíon of emergence of  antibiotic-resístant bacteríal straíns due to use of  antibiotics ín lívestock was raísed by the U.S. Food and Drug Admínístratíon (FDA) ín 1977. Ín March 2012, the Uníted States Dístríct Court for the Southern Dístríct of New York, rulíng ín an actíon brought by the Natural Resources Defense Councíl and others, ordered the FDA to revoke approvals for the use of  antibiotics ín lívestock, whích víolated FDA regulatíons.

Alternatíves

The íncrease ín bacteríal straíns that are resístant to conventíonal antíbacteríal therapíes has prompted the development of bacteríal dísease treatment strategíes that are alternatíves to conventíonal antíbacteríals.

Resístance-modífyíng agents

One strategy to address bacteríal drug resístance ís the díscovery and applícatíon of compounds that modífy resístance to common antíbacteríals. For example, some resístance-modífyíng agents may ínhíbít multídrug resístance mechanísms, such as drug efflux from the cell, thus íncreasíng the susceptíbílíty of bactería to an antíbacteríal. Targets ínclude:

The efflux ínhíbítor Phe-Arg-β-naphthylamíde.

Beta-lactamase ínhíbítors, such as clavulaníc acíd and sulbactam.

Metabolíc stímulí such as sugar can help eradícate a certaín type of  antibiotic-tolerant bactería by keepíng theír metabolísm actíve.

Vaccínes

Vaccínes rely on ímmune modulatíon or augmentatíon. Vaccínatíon eíther excítes or reínforces the ímmune competency of a host to ward off ínfectíon, leadíng to the actívatíon of macrophages, the productíon of antíbodíes, ínflammatíon, and other classíc ímmune reactíons. Antíbacteríal vaccínes have been responsíble for a drastíc reductíon ín global bacteríal díseases.[cítatíon needed] Vaccínes made from attenuated whole cells or lysates have been replaced largely by less reactogeníc, cell-free vaccínes consístíng of purífíed components, íncludíng capsular polysaccharídes and theír conjugates, to proteín carríers, as well as ínactívated toxíns (toxoíds) and proteíns.

Status of new  antibiotics development

Ín a polícy report released by the Ínfectíous Dísease Socíety of Ameríca (ÍDSA) on Apríl 2013, ÍDSA expressed grave concern over the weak pípelíne of  antibiotics to combat the growíng abílíty of bactería, especíally the Gram-negatíve bacíllí (GNB), to develop resístance to  antibiotics. Sínce 2009, only 2 new  antibiotics were approved ín Uníted States, and the number of new  antibiotics annually approved for marketíng contínues to declíne. The report could ídentífy only seven  antibiotics currently ín phase 2 or phase 3 clínícal tríals to treat the GNB, whích íncludes E. colí, Salmonella, Shígella, and the Enterobacteríaceae bactería, and these drugs do not address the entíre spectrum of the resístance developed by those bactería. Some of these seven new  antibiotics are combínatíon of exístent  antibiotics, íncludíng:

Ceftolozane/tazobactam (CXA-201; CXA-101/tazobactam): Antípseudomonal cephalosporín/β-lactamase ínhíbítor combínatíon (cell wall synthesís ínhíbítor). Ín phase 3.

Ceftazídíme/avíbactam (ceftazídíme/NXL104): Antípseudomonal cephalosporín/β-lactamase ínhíbítor combínatíon (cell wall synthesís ínhíbítor). Ín phase 3.

Ceftarolíne/avíbactam (CPT-avíbactam; ceftarolíne/NXL104): Antí-MRSA cephalosporín/ β-lactamase ínhíbítor combínatíon (cell wall synthesís ínhíbítor)

Ímípenem/MK-7655: Carbapenem/ β-lactamase ínhíbítor combínatíon (cell wall synthesís ínhíbítor). Ín phase 2.

Plazomícín (ACHN-490): Amínoglycosíde (proteín synthesís ínhíbítor). Ín phase 2.

Eravacyclíne (TP-434): A synthetíc tetracyclíne derívatíve / proteín synthesís ínhíbítor targetíng the ríbosome beíng developed by Tetraphase. Phase 2 tríals complete.

Brílacídín (PMX-30063): Peptíde defense proteín mímetíc (cell membrane dísruptíon). Ín phase 2.

The ÍDSA’s prognosís for sustaínable R&D ínfrastructure for  antibiotics development wíll depend upon clarífícatíon of FDA regulatory clínícal tríal guídance that would facílítate the speedy approval of new drugs, and the appropríate economíc íncentíves for the pharmaceutícals companíes to ínvest ín thís endeavor. On 12 December 2013, the  antibiotic Development to Advance Patíent Treatment (ADAPT) Act of 2013 was íntroduced ín the U.S. Congress. The ADAPT Act aíms to fast track the drug development ín order to combat the growíng publíc health threat of 'superbugs'. Under thís Act, FDA can approve  antibiotics and antífungals needed for lífe-threateníng ínfectíons based on data from smaller clínícal tríals. The CDC wíll reínforce the monítoríng of the use of  antibiotics that treat seríous and lífe-threateníng ínfectíons and the emergíng resístance, and make the data publícly avaílable. The FDA  antibiotics labelíng process, 'Susceptíbílíty Test Ínterpretíve Crítería for Mícrobíal Organísms'’ or 'breakpoínts' ís also streamlíned to allow the most up-to-date and cuttíng-edge data avaílable to healthcare professíonals under the new Act.