Antibacterial | Pengertian dan defenisi antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria. The term is often used synonymously with the term antibiotic(s); today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic(s) has come to denote a broader range of antimicrobial compounds, including anti-fungal and other compounds.

The term "antibiotic" was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria but are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 2000 atomic mass units.

With advances in medicinal chemistry, most of today's antibacterials chemically are semisynthetic modifications of various natural compounds. These include, for example, the beta-lactam antibacterials, which include the penicillins (produced by fungi in the genus 'Penicillium'), the cephalosporins, and the carbapenems. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis. Accordingly, many antibacterial compounds are classified on the basis of chemical/biosynthetic origin into natural, semisynthetic, and synthetic. Another classification system is based on biological activity; in this classification antibacterials are divided into two broad groups according to their biological effect on microorganisms: bactericidal agents kill bacteria, and bacteriostatic agents slow down or stall bacterial growth.

Before the early twentieth century, treatments for infections were based primarily on medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago. Many ancient cultures, including the ancient Egyptians and ancient Greeks used specially selected mold and plant materials and extracts to treat infections. More recent observations made in the laboratory of antibiosis between micro-organisms led to the discovery of natural antibacterials produced by microorganisms. Louis Pasteur observed that, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics".

Florey and Chain succeeded in purifying penicillin. 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. 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. For their discovery and development of penicillin as a therapeutic drug, Ernst Chain, Howard Florey, and Alexander Fleming shared the 1945 Nobel Prize in Medicine. Florey credited 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.

The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial. A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells. These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection. Since the activity of antibacterials depends frequently on its concentration, in vitro characterization of antibacterial activity commonly includes the determination of the minimum inhibitory concentration and minimum bactericidal concentration of an antibacterial. To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its pharmacokinetic profile, and several pharmacological parameters are used as markers of drug efficacy.

Like antibiotics, antibacterials are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most antibacterial antibiotics target bacterial functions or growth processes. Antibiotics that target the bacterial cell wall (such as penicillins and cephalosporins), or cell membrane (for example, polymixins), or interfere with essential bacterial enzymes (such as quinolones and sulfonamides) have bactericidal activities. Those that target protein synthesis, such as the aminoglycosides, macrolides, and tetracyclines, are usually bacteriostatic. Further categorization is based on their target specificity. "Narrow-spectrum" antibacterial antibiotics target specific types of bacteria, such as Gram-negative or Gram-positive bacteria, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year hiatus in discovering new classes of antibacterial compounds, three new classes of antibiotics have been brought into clinical use. These new antibacterials are cyclic lipopeptides (including daptomycin), glycylcyclines (e.g., tigecycline), and oxazolidinones (including linezolid).

Since the first pioneering efforts of Florey and 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 fermentation, usually in strongly aerobic conditions.

Antibacterials are screened for any negative effects on humans or other mammals before approval for clinical use and are usually considered safe and most are well-tolerated. However, some antibacterials have been associated with a range of adverse effects. Side-effects range from mild to very serious depending on the antibiotics used, the microbial organisms targeted, and the individual patient. Safety profiles of newer drugs are often not as well established as for those that have a long history of use. Adverse effects range from fever and nausea to major allergic reactions including photodermatitis and anaphylaxis. Common side-effects include diarrhea, resulting from disruption of the species composition in the intestinal flora, resulting, for example, in overgrowth of pathogenic bacteria, such as Clostridium difficile. Antibacterials can also affect the vaginal flora, and may lead to overgrowth of yeast species of the genus Candida in the vulvo-vaginal area. Additional side-effects can result from interaction with other drugs, such as elevated risk of tendon damage from administration of a quinolone antibiotic with a systemic corticosteroid.

The majority of studies indicate that antibiotics do not interfere with contraceptive pills, such as clinical studies that suggest that the failure rate of contraceptive pills caused by antibiotics is very low (about 1%). In cases where antibacterials have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibacterial 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. 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. Clinicians have recommended that extra contraceptive measures are applied during therapies using antibacterials that are suspected to interact with oral contraceptives.

Several molecular mechanisms of antibacterial resistance exist. Intrinsic antibacterial resistance may be part of the genetic makeup of bacterial strains. 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. Antibacterial-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibacterial-resistant strains. The spread of antibacterial resistance often occurs through vertical transmission of mutations during growth and by genetic recombination of DNA by horizontal genetic exchange. For instance, antibacterial resistance genes can be exchanged between different bacterial strains or species via plasmids that carry these resistance genes. Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials. 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.

Antibacterial-resistant strains and species, sometimes referred to as "superbugs", now contribute to the emergence of diseases which were for a while well-controlled. For example, emergent bacterial strains causing tuberculosis (TB) 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. For example, NDM-1 is a newly identified enzyme conveying bacterial resistance to a broad range of beta-lactam antibacterials. United Kingdom Health Protection Agency has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections."

Inappropriate antibacterial treatment and overuse of antibiotics have contributed to the emergence of antibacterial-resistant bacteria. Self prescription of antibacterials and their use as growth promoters in agriculture are additional examples of misuse. Many antibacterials are frequently prescribed to treat symptoms or diseases that do not respond to antibacterial therapy or are likely to resolve without treatment, or incorrect or sub-optimal antibacterials are prescribed for certain bacterial infections. The overuse of antibacterials, like penicillin and erythromycin, have been associated with emerging antibacterial resistance since the 1950s. Widespread usage of antibacterial drugs in hospitals has also been associated with increases in bacterial strains and species that no longer respond to treatment with the most common antibacterials.

Common forms of antibacterial misuse include excessive use of prophylactic antibiotics in travelers and failure of medical professionals to prescribe the correct dosage of antibacterials 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 antibacterial, incorrect dosage and administration, or failure to rest for sufficient recovery. Inappropriate antibacterial treatment, for example, is the prescription of antibacterials to treat viral infections such as the common cold. One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who appeared to expect them". Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics.

In agriculture, antibacterials are often used to promote weight gain in livestock animals. More than 70% of the antibacterials used in U.S. are given to livestock animals in the absence of infectious diseases. This practice has been associated with the emergence of antibacterial-resistant strains of bacteria including Salmonella spp., Campylobacter spp., Escherichia coli, and Enterococcus spp. The emergence of antibacterial resistance has prompted restrictions on antibacterial use in the UK in 1970 (Swann report 1969), and the EU has banned the use of antibacterials as growth-promotional agents since 2003. Moreover, 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. However, commonly there are delays in regulatory and legislative actions to limit the use of antibacterials, partly attributable to resistance against such regulation by industries using or selling antibacterials, and to the time required for research to test causal links between antibacterial use and resistance. Two federal bills (S.742 and H.R. 2562) aimed at phasing out non-therapeutic use of antibacterials in US food animals were proposed but have not passed. 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).

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