Antibiotic
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An antibiotic is a drug that kills or prevents the growth of bacteria. They have no effect against viruses or fungal infections. Antibiotics are one class of antimicrobials, a larger group which also includes anti-viral, anti-fungal, and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. The term, coined by Selman Waksman, originally described only those formulations derived from living organisms, in contrast to "chemotherapeutic agents", which are purely synthetic. Nowadays the term "antibiotic" is also applied to synthetic antimicrobials, such as the sulfa drugs. Antibiotics are generally small molecules with a molecular weight less than 2000 Da. They are not enzymes. Some antibiotics have been derived from mold, for example the penicillin class.
Unlike previous treatments for infections, which included poisons such as strychnine and arsenic, antibiotics were labeled "magic bullets": drugs which targeted disease without harming the host. Conventional antibiotics are not effective in viral, fungal and other nonbacterial infections, and individual antibiotics vary widely in their effectiveness on various types of bacteria. 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 antibiotics affect a larger range of bacteria.
The effectiveness 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 bacteria to resist or inactivate the antibiotic. Some antibiotics actually kill the bacteria (bactericidal), whereas others merely prevent the bacteria from multiplying (bacteriostatic) so that the host's immune system can overcome them.
Oral antibiotics are the simplest approach when effective, with intravenous antibiotics reserved for more serious cases. Antibiotics may sometimes be administered topically, as with eye drops or ointments.
Antibiotics can also be classified by the organisms against which they are effective, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue.
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[edit] History
- See also: Timeline of antibiotics
Although the principles of antibiotic action were not discovered until the twentieth century, the first known use of antibiotics was by the ancient Chinese over 2,500 years ago.[1] Many other ancient cultures, including the ancient Egyptians and ancient Greeks already used molds and plants to treat infections. This worked because some molds produce antibiotic substances. However, they couldn't distinguish or distill the active component in the molds.
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 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 became interested in his work, and came up with the purified form of penicillin. The three shared the 1945 Nobel Prize in Medicine. "Antibiotic" was originally used to refer only to substances extracted from a fungus or other microorganism, but has come to include also the many synthetic and semi-synthetic drugs that have antibacterial effects.
[edit] 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 will end a bacterial infection.
| Generic Name | Brand Names | Common Uses | Side Effects | |
|---|---|---|---|---|
| Aminoglycosides | ||||
| Amikacin | Amikin | Infections caused by Gram-negative bacteria, such as Escherichia coli and Klebsiella particularly Pseudomonas aeruginosa | ||
| Gentamicin | Garamycin | |||
| Kanamycin | ||||
| Neomycin | ||||
| Netilmicin | ||||
| Streptomycin | ||||
| Tobramycin | Nebcin | |||
| Carbacephem | ||||
| Loracarbef | Lorabid | |||
| Carbapenems | ||||
| Ertapenem | ||||
| Imipenem/Cilastatin | Primaxin | |||
| Meropenem | ||||
| Cephalosporins (First generation) | ||||
| Cefadroxil | Duricef |
|
||
| Cefazolin | Ancef | |||
| Cephalexin | Keflex | |||
| Cephalosporins (Second generation) | ||||
| Cefaclor | Ceclor |
|
||
| Cefamandole | Mandole | |||
| Cefoxitin | Mefoxin | |||
| Cefprozil | Cefzil | |||
| Cefuroxime | Ceftin | |||
| Cephalosporins (Third generation) | ||||
| Cefixime |
|
|||
| Cefdinir | Omnicef | |||
| Cefditoren | ||||
| Cefoperazone | Cefobid | |||
| Cefotaxime | Claforan | |||
| Cefpodoxime | ||||
| Ceftazidime | Fortum | |||
| Ceftibuten | ||||
| Ceftizoxime | ||||
| Ceftriaxone | Rocephin | |||
| Cephalosporins (Fourth generation) | ||||
| Cefepime | Maxipime |
|
||
| Glycopeptides | ||||
| Teicoplanin | ||||
| Vancomycin | Vancocin | |||
| Macrolides | ||||
| Azithromycin | Zithromax, Sumamed, Zitrocin | Streptococcal infections, syphilis, respiratory infections, mycoplasmal infections, Lyme disease |
|
|
| Clarithromycin | Biaxin | |||
| Dirithromycin | ||||
| Erythromycin | ||||
| Roxithromycin | ||||
| Troleandomycin | ||||
| Monobactam | ||||
| Aztreonam | ||||
| Penicillins | ||||
| Amoxicillin | Novamox | Wide range of infections; penicillin used for streptococcal infections, syphilis, and Lyme disease |
|
|
| Ampicillin | ||||
| Azlocillin | ||||
| Carbenicillin | ||||
| Cloxacillin | ||||
| Dicloxacillin | ||||
| Flucloxacillin | ||||
| Mezlocillin | ||||
| Nafcillin | ||||
| Penicillin | ||||
| Piperacillin | ||||
| Ticarcillin | ||||
| Polypeptides | ||||
| Bacitracin | Eye, ear or bladder infections; usually applied directly to the eye or inhaled into the lungs; rarely given by injection | Kidney and nerve damage (when given by injection) | ||
| Colistin | ||||
| Polymyxin B | ||||
| Quinolones | ||||
| Ciprofloxacin | Ciproxin, Ciplox | Urinary tract infections, bacterial prostatitis, bacterial diarrhea, gonorrhea | Nausea (rare), tendinosis (rare) | |
| Enoxacin | ||||
| Gatifloxacin | Tequin | |||
| Levofloxacin | Levaquin | |||
| Lomefloxacin | ||||
| Moxifloxacin | Avelox | |||
| Norfloxacin | ||||
| Ofloxacin | Ocuflox | |||
| Trovafloxacin | Trovan | |||
| Sulfonamides | ||||
| Mafenide | Urinary tract infections (except sulfacetamide and mafenide); mafenide is used topically for burns |
|
||
| Prontosil (archaic) | ||||
| Sulfacetamide | ||||
| Sulfamethizole | ||||
| Sulfanilimide (archaic) | ||||
| Sulfasalazine | ||||
| Sulfisoxazole | ||||
| Trimethoprim | ||||
| Trimethoprim-Sulfamethoxazole (Co-trimoxazole) (TMP-SMX) | Bactrim | |||
| Tetracyclines | ||||
| Demeclocycline | Syphilis, chlamydial infections, Lyme disease, mycoplasmal infections, acne rickettsial infections |
|
||
| Doxycycline | Vibramycin | |||
| Minocycline | Minocin | |||
| Oxytetracycline | ||||
| Tetracycline | Sumycin | |||
| Others | ||||
| Arsphenamine | Salvarsan | Spirochaetal infections (obsolete) | ||
| Chloramphenicol | Chloromycetin | |||
| Clindamycin | Cleocin | |||
| Ethambutol | ||||
| Fosfomycin | ||||
| Furazolidone | ||||
| Isoniazid | ||||
| Linezolid | Zyvox | |||
| Metronidazole | Flagyl | |||
| Mupirocin | ||||
| Nitrofurantoin | Macrodantin, Macrobid | |||
| Platensimycin | ||||
| Pyrazinamide | ||||
| Quinupristin/Dalfopristin | Syncercid | |||
| Rifampin | ||||
| Spectinomycin | ||||
| Telithromycin | Ketek | Pneumonia | Visual Disturbance | |
| Generic Name | Brand Names | Common Uses | Side Effects | |
[edit] Production
Since the first pioneering efforts of Florey and 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 fermentation; a process that is important in anaerobic conditions when there is no oxidative phosphorylation to maintain the production of adenosine triphosphate (ATP) by glycolysis.
[edit] Side effects
Possible side effects are varied, and range from fever and nausea to major allergic reactions. 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 intestinal flora,[3] (which some people believe may be re-balanced by taking probiotics). Other 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.
It is a common assertion that some antibiotics can interfere with the efficiency of birth control pills. Although there remain few known cases of complication, the majority of antibiotics do not interfere with contraception, despite widespread misinformation to the contrary.[4]
[edit] Antibiotic misuse
Common forms of antibiotic misuse include failure to take the entire prescribed course of the antibiotic, or failure to rest usually because the patient feels better, but before the infecting organism is completely eradicated. In addition to treatment failure, these practices can result in antibiotic resistance in which the bacteria survive the abbreviated treatment. Taking antibiotics in inappropriate situations is another common form of antibiotic misuse. Common examples of this would be the use of antibacterials for viral infections such as the common cold.
Currently, it is estimated that greater than 50% of the antibiotics used in the U.S. are given to feed animals (e.g. chickens, pigs and cattle) in the absence of disease.[5] Antibiotic use in food animal production has been associated with the emergence of antibiotic resistant strains of bacteria including Salmonella, Campylobacter, Escherichia coli and Enterococcus among others. There is substantial evidence from the US and the EU that these resistant bacteria cause antibiotic resistant infections in humans. The American Society for Microbiology (ASM), the American Public Health Association (APHA) and the American Medical Association (AMA) have called for substantial restrictions on antibiotic use in food animal production including an end to all non-therapeutic uses. The food animal and pharmaceutical industries have fought hard to prevent new regulations that would limit the use of antibiotics in food animal production. For example, in 2000 the US Food and Drug Administration (FDA) announced their intention to rescind approval for fluoroquinolone use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone resistant Campylobacter infections in humans. The final decision to ban fluoroquinolones from use in poultry production was not made until 5 years later because of challenges from the food animal and pharmaceutical industries. 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 many public health and medical organizations including the American Nurses Association (ANA), the American Academy of Pediatrics (AAP), and the American Public Health Association (APHA).
Excessive use of prophylactic antibiotics in travelers may also be classified as misuse.
[edit] Antibiotic resistance
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 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 which survived the original treatment. This survival often results from an inheritable resistance to the compound which was infrequent in the original population but is now much more frequent in the descendants thus selected entirely from those originally infrequent resistant organisms.
Antibiotic resistance has become a serious problem in both the developed and underdeveloped nations. By 1984 half of the people with active tuberculosis in the United States had a strain that resisted at least one antibiotic. In certain settings, such as hospitals and some child-care locations, the rate of antibiotic resistance is so high that the normal, 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 inexorably to the rise of resistance to those drugs, and a race to discover new and different antibiotics ensues, just to keep us from losing ground in the battle against infection. The fear is that we will eventually fail to keep up in this race, and the time when people did not fear life-threatening bacterial infections will be just a memory of a golden era.
Another example of selection is Staphylococcus aureus, 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 worsened 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 worsened 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 widely as prophylaxis rather than treatment (as in, for example, animal feeds), because this exposes more bacteria to selection for resistance.
[edit] Beyond antibiotics
Unfortunately, the comparative ease of finding compounds which safely cured bacterial infections proved much harder to duplicate with respect to fungal and viral infections. Antibiotic research led to great strides in our knowledge of basic biochemistry and to the current biological revolution; but in the process it was discovered that the susceptibility of bacteria to many compounds which are safe to humans is based upon significant differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. In contrast, despite the seemingly huge differences between fungi and humans, the basic biochemistries of the fungal cell and the mammalian cell are much more similar; so much so that there are few therapeutic opportunities for compounds to attack a fungal cell which will not harm a human cell. Similarly, we know now that viruses represent an incredibly minimal intracellular parasite, being stripped down to a few genes' worth of DNA or RNA and the minimal molecular equipment needed to enter a cell and actually take over the machinery of the cell to produce new viruses. Thus, the great bulk of viral metabolic biochemistry is not merely similar to human biochemistry, it actually is human biochemistry, and the possible targets of antiviral compounds are restricted to the relatively very few components of the actual virus itself.
Research into bacteriophages is ongoing at the moment. Bacteriophages are a specific type of virus that only targets bacteria. Research suggests that nature has evolved several types of bacteriophage for each type of bacteria. While research into bacteriophages is only in its infancy the results are promising and have already lead to major advances in microscopic imaging.[6] While bacteriophages provide a possible solution to the problem of antibacterial resistance there is as of yet no proof that we will actually be able to deploy these microscopic killers in humans.
Phage therapy has been used in the past on humans in the US and Europe during the 1920s and 1930s, however due to not fully understanding the mechanism by which phage therapy worked, these treatments had mixed results. With the discovery of penicillin in the 1940s, Europe and the US changed 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.
[edit] References
- ^ How Products Are Made: Antibiotics
- ^ Robert Berkow (ed.) The Merck Manual of Medical Information - Home Edition. Pocket (September 1999), ISBN 0-671-02727-1.
- ^ University of Michigan Health System: Antibiotic-Associated Diarrhea, November 26, 2006
- ^ Planned Parenthood: Does taking antibiotics make the pill less effective?, July 15, 2004
- ^ Mellon, M et al. (2001) Hogging It!: Estimates of Antimicrobial Abuse in Livestock, 1st ed. Cambridge, MA: Union of Concerned Scientists.
- ^ Purdue University "Biologists build better software, beat path to viral knowledge", see Imaging of Epsilon 15, a virus that infects the bacterium Salmonella News report
[edit] See also
[edit] External links
- Antibiotic News from Genome News Network (GNN)
- Are Antibiotics Killing Us? -Discover Magazine
- JAAPA: New antibiotics useful in primary care
- A new method for controlling bacterial activity without antibiotics - Research conducted at the Hebrew University
