What Are Antibiotics? How Do Antibiotics Work?

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The word antibiotic comes from the Greekanti meaning 'against' and bios meaning 'life' (a bacterium is a life form).' Antibiotics are also known as antibacterials, and they are drugs used to treat infections caused by bacteria. Bacteria are tiny organisms that can sometimes cause illness to humans and animals. The singular word for bacteria is bacterium. Such illnesses as tuberculosis, salmonella,syphilis and some forms of meningitis are caused by bacteria. Some bacteria are not harmful, while others are good for us. Before bacteria can multiply and cause symptoms our immune system can usually destroy them. We have special white blood cells that attack harmful bacteria. Even if symptoms do occur, our immune system can usually cope and fight off the infection. There are occasions, however, when it is all too much and our bodies need some help - from antibiotics. The first antibiotic was penicillin. Such penicillin-related antibiotics as ampicillin, amoxicillin and benzylpenicilllin are widely used today to treat a variety of infections - these antibiotics have been around for a long time. There are several different types of modern antibiotics and they are only available with a doctor's prescription in industrialized countries.

How do antibiotics work?

Although there are a number of different types of antibiotic they all work in one of two ways:

A bactericidal antibiotic kills the bacteria. Penicillin is a bactericidal. A bactericidal usually either interferes with the formation of the bacterium's cell wall or its cell contents.

A bacteriostatic stops bacteria from multiplying.

What are antibiotics for?

An antibiotic is given for the treatment of an infection caused by bacteria. Antibiotics target microorganisms such as bacteria, fungi and parasites. However, they are not effective against viruses. If you have an infection it is important to know whether it is caused by bacteria or a virus. Most upper respiratory tract infections, such as the common cold and sore throats are generally caused by viruses - antibiotics do not work against these viruses. If antibiotics are overused or used incorrectly there is a chance that the bacteria will become resistant - the antibiotic becomes less effective against that type of bacterium. A broad-spectrum antibiotic can be used to treat a wide range of infections. A narrow-spectrum antibiotic is only effective against a few types of bacteria. There are antibiotics that attack aerobic bacteria, while others work against anaerobic bacteria. Aerobic bacteria need oxygen, while anaerobic bacteria don't.
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LC/MS/MS solutions - www.painmanagement-lcmsms.com Antibiotics may be given beforehand, to prevent infection, as might be the case before surgery. This is called 'prophylactic' use of antibiotics. They are commonly used before bowel and orthopedic surgery.

What are the side-effects of antibiotics?

Below is a list of the most common side-effects of antibiotics:

Diarrhea Feeling and being sick Fungal infections of the mouth, digestive tract and vagina Below is a list of rare side-effects of antibiotics:

Formation of kidney stones (when taking sulphonamides) Abnormal blood clotting (when taking some cephalosporins)

Sensitivity to sun (when taking tetracyclines) Blood disorders (when taking trimethoprim) Deafness (when taking erythromycin and the aminoglycosides) Some patients, especially elderly ones, may experience inflamed bowels (a type of colitis) which can lead to severe diarrhea. Clindamycin, an antibiotic used for the most serious infections, commonly has this side effect. However, although much less common, penicillins, cephalosporins and erythromycin might do too.
Visit our specialized news sections MRSA News Biology / Biochemistry News Infectious Diseases / Bacteria / Viruses News Tropical Diseases News Bioterrorism News

Allergic reactions to antibiotics Some patients may develop an allergic reaction to antibiotics - especially penicillins. Side effects might include a rash, swelling of the tongue and face, and difficulty breathing. If you have ever had an allergic reaction to an antibiotic you must tell your doctor and/or pharmacist. Reactions to antibiotics can be very serious, and sometimes fatal - they are called anaphylactic reactions. Use antibiotics with extreme caution and ensure you inform your doctor/pharmacist if:

You have reduced liver or kidney function. You are pregnant You are breastfeeding

Antibiotics may clash (interact) with other medicines

If you are taking an antibiotic do not take other medicines or herbal remedies without telling your doctor first. OTC (over the counter, non-prescription) medicines might also clash with your antibiotic. Penicillins, cephalosporins, and some other antibiotics may undermine the effectiveness of oral contraceptives. If the antibiotic has caused diarrhea/vomiting the absorption of contraceptives may also be disrupted. If you are taking any of these drugs you should consider taking additional contraceptive precautions.

How to use antibiotics

Antibiotics are usually taken by mouth (orally); however, they can also be administered by injection, or applied directly to the affected part of the body. Most antibiotics start having an effect on an infection within a few hours. It is important to remember to complete the whole course of the medication to prevent the infection from coming back. If you do

not complete the course, there is a higher chance the bacteria may become resistant to future treatments - because the ones that survive when you did not complete the course have had some exposure to the antibiotic and may consequently have built up a resistance to it. Even if you are feeling better, you still need to complete the course. Some antibiotics should not be consumed with certain foods and drinks. Others should not be taken with food in your stomach - these would normally be taken about an hour before meals, or two hours after. It is crucial that you follow the instructions correctly if you want the medication to be effective. If you are taking metronidazole do not consume alcohol. Dairy products should not be consumed if you are taking tetracyclines, as they might affect the absorption of the medication.

News that may also interest you

For the latest news and research please visit the following sections: Infectious Diseases / Bacteria / Viruses MRSA / Drug Resistance Written by Christian Nordqvist Original article date: 04 July 2004 Article updated: 20 April 2009 View drug information on Clindamycin phosphate topical gel. Copyright: Medical News Today Not to be reproduced without permission of Medical News Today

Additional References Citations

Visit our infectious diseases / bacteria / viruses section for the latest news on this subject.

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Visitor Opinions In Chronological Order (36)

Unbiased
posted by Raymond Dear on 30 May 2007 at 3:47 am It is good to be able to get unbiased information without having to take up doctors time whilst at the surgery & in a basic language one the general public can understand. | post followup | alert a moderator |

antibiotics, which one?

posted by saurabh kumar on 2 Oct 2010 at 2:52 am as per medicines available in the market which antibiotic should be taken in the primary illness,while which should be given in severe cases. | post followup | alert a moderator |

aaantibiotics
posted by MANOJ SINGH on 11 Oct 2010 at 11:32 pm Antibiotics means the substances are used to kill the bacteria or inhibits the growth of microorganisms like bacteria i.e.called antibiotics

| post followup | alert a moderator |

antibiotics
posted by gangaram on 25 Oct 2010 at 1:05 am antibiotics are medicins using for treatment or controling the growth of micro organisums.these are inibiting the bacterial multification .theseare taken orally | post followup | alert a moderator |

ANTIBIOTICS
posted by sanjeev kumar katihar on 25 Oct 2010 at 2:56 am Antibiotecs is the chemical subtances which secreted the micro-organism and inhibits the growth and development of other micro-organism.known as antibiotics. | post followup | alert a moderator |

The classification of antibiotic

posted by oladoye elijah on 10 Nov 2010 at 10:50 am Please I just want to know about the classification of antibiotic | post followup | alert a moderator |

confused?
posted by m. douglas on 19 Nov 2010 at 5:13 pm funny this, but good article. a cold being a virus will not become resitant if antibiotics are taken,why then did my nurse give me it for my sore throat? internet greateset source of power,eh? | post followup | alert a moderator |

Quick Note
posted by A Smith on 4 Jan 2011 at 11:54 am I would just like to point out that your article states that antibiotics only attack "only bacteria - they do not attack other organisms, such as fungi or viruses" This is an error. As a biochemistry student I would like to make readers aware of the fact that antibiotics target bacteria AND FUNGI (although not viruses). Thankyou. | post followup | alert a moderator |

List of antibiotics
From Wikipedia, the free encyclopedia

Following is the list of antibiotics, sorted by class. The highest division is between bactericidal antibiotics and bacteriostatic antibiotics. 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.[1] See also pathogenic bacteria for a list of antibiotics sorted by target bacteria.

Antibiotics by class

Generic name

Brand names

Common uses[2]

Possible side effects[2]

Mechanism of action

Aminoglycosides Binding to the bacterial 30S ribosomal subunit (some work by binding to the50S 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.

Amikacin Gentamicin Kanamycin Neomycin Netilmicin Tobramycin

Amikin Garamycin Kantrex Mycifradin Netromycin Nebcin Infections caused by Gramnegative bacteria, such asEscherichia coli andKlebsiella particularly Pseudomonas aeruginosa. Effective against Aerobic bacteria (not obligate/facultative anaerobes) and tularemia.

Hearing loss Vertigo Kidney damage

Paromomycin

Humatin

Ansamycins Geldanamycin Herbimycin Experimental, as antitumor antibiotics Carbacephem Loracarbef Lorabid Discontinued Carbapenems Ertapenem Doripenem Imipenem/Cilastatin Invanz Doribax Primaxin Bactericidal for both Grampositive and Gram-negative organisms and therefore Gastrointestin Inhibition of cell wall synthesis al upset and prevents bacterial cell division by inhibiting cell wall synthesis.

useful for empiric broadspectrum antibacterial coverage. (Note MRSA resistance to this class.) Meropenem Merrem

diarrhea Nausea Seizures Headache Rash and allergic reactions

Cephalosporins (First generation) Cefadroxil Cefazolin Cefalotin or Cefalothin Duricef Ancef (discontinued) Keflin (discontinued) Good coverage against Gram positive infections. Gastrointestin al upset and Same mode of action as other beta-lactam Nausea (if antibiotics: disrupt the synthesis of alcohol taken the peptidoglycan layer concurrently) of bacterial cell walls. diarrhea Allergic reactions Cephalosporins (Second generation) Cefaclor Cefamandole Cefoxitin Cefprozil Raniclor Mandol (discontinued) Mefoxin (discontinued) Cefzil Ceftin, Zinnat (UK) Less gram positive cover, improved gram negative cover. Gastrointestin al upset and Same mode of action as other beta-lactam Nausea (if antibiotics: disrupt the synthesis of alcohol taken the peptidoglycan layer concurrently) of bacterial cell walls. diarrhea Allergic reactions Cephalosporins (Third generation) Cefixime Cefdinir Cefditoren Cefoperazone Cefotaxime Cefpodoxime Ceftazidime Suprax Omnicef, Cefdiel Spectracef Cefobid (discontinued) Claforan Vantin Fortaz Gastrointestin al upset and Improved coverage of Gram negative organisms, exceptPseudomonas. Reduced Gram positive cover. diarrhea Same mode of action as other beta-lactam antibiotics: disrupt the Nausea (if synthesis of alcohol taken the peptidoglycan layer of bacterial cell walls. concurrently) Allergic

Cefalexin

Keflex

Cefuroxime

Ceftibuten Ceftizoxime Ceftriaxone

Cedax Cefizox (discontinued) Rocephin Cephalosporins (Fourth generation)

reactions

Gastrointestin al upset and Same mode of action as other beta-lactam Nausea (if antibiotics: disrupt the synthesis of alcohol taken the peptidoglycan layer concurrently) of bacterial cell walls. diarrhea Allergic reactions

Cefepime

Maxipime

Covers pseudomonal infections.

Cephalosporins (Fifth generation) Gastrointestin al upset and Ceftaroline fosamil Teflaro Used to treat MRSA diarrhea Allergic reaction Gastrointestin al upset and Same mode of action as other beta-lactam Nausea (if antibiotics: disrupt the synthesis of alcohol taken the peptidoglycan layer concurrently) of bacterial cell walls. diarrhea Ceftobiprole Zeftera Used to treat MRSA Allergic reactions Glycopeptides Teicoplanin Vancomycin Telavancin Targocid (UK) Vancocin Vibativ Lincosamides Clindamycin Lincomycin Cleocin Lincocin Serious staph-, pneumo-, and streptococcal infections in penicillin-allergic patients, also anaerobic infections; Possible C. difficilerelatedpseudome mbranous Bind to 50S subunit of bacterial ribosomal RNA thereb y inhibiting protein inhibiting peptidoglyca n synthesis Same mode of action as other beta-lactam antibiotics: disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.

clindamycin topically foracne enterocolitis Lipopeptide

synthesis

Daptomycin

Cubicin

Gram-positive organisms

Bind to the membrane and cause rapid depolarization, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis

Macrolides Azithromycin Clarithromycin Dirithromycin Erythromycin Roxithromycin Zithromax,Sum amed, Zitrocin Biaxin Dynabac (discontinued) Erythocin,Eryt hroped Streptococcal infections,syphilis, upper respiratory tract infections, lower respiratory tract infections,mycoplasmal infections,Lyme disease Nausea, vomiting, and diarrhea (especially at higher doses) inhibition of bacterial protein Prolonged biosynthesis by binding QT interval reversibly to the subunit 50S of the (especially bacterialribosome, thereby inhibiting erythromycin translocation of ) peptidyl tRNA. Jaundice

Troleandomycin

Tao (discontinued)

Telithromycin Spectinomycin

Ketek Trobicin

Pneumonia Gonorrhea Monobactams

Visual Disturbance, Liver Toxicity.[3]

Aztreonam

Azactam

Same mode of action as other beta-lactam antibiotics: disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. Nitrofurans

Furazolidone

Furoxone

Bacterial or protozoaldiarrhea or enterit is

Nitrofurantoin

Macrodantin,M Urinary tract infections acrobid Penicillins

Amoxicillin

Novamox,Amo Wide range of infections; xil penicillin used

Same mode of action Gastrointestin as other beta-lactam

Ampicillin Azlocillin Carbenicillin Cloxacillin Dicloxacillin

Principen (discontinued)

forstreptococcal infections,syphilis, and Lyme disease

al upset and diarrhea Allergy with seriousanaph ylactic reactions Brain and kidney damage (rare)

antibiotics: disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.

Geocillin (discontinued) Tegopen (discontinued) Dynapen (discontinued) Floxapen(Sold to European generics Actavis Group) Mezlin (discontinued) Staphcillin (discontinued) Unipen (discontinued) Prostaphlin (discontinued) Pentids (discontinued) Veetids (PenVee-K) (discontinued) Pipracil (discontinued) Pfizerpen Negaban (UK) (discontinued) Ticar (discontinued) Penicillin combinations

Flucloxacillin

Mezlocillin Methicillin Nafcillin Oxacillin Penicillin G

Penicillin V

Piperacillin Penicillin G Temocillin Ticarcillin

Amoxicillin/clavulanat Augmentin e Ampicillin/sulbactam Piperacillin/tazobacta m Unasyn Zosyn

The second component prevents bacterial resistance to the first component

Ticarcillin/clavulanate Timentin Polypeptides 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) Inhibits isoprenyl pyrophosphate, a molecule that carries the building blocks of

Bacitracin

Colistin

Coly-Mycin-S

although the use of intravenous colistin is experiencing a resurgence due to the emergence ofmulti drug resistantorganisms.

the peptidoglycan bacte rialcell wall outside of the inner membrane[4] Interact with the gram negativebacterial outer membrane andcytoplas mic membrane. It displaces bacterial counter ions, which destabilizes the outer membrane. They act like a detergent against the cytoplasmic membrane, which alters its permeability. Polymyxin B and E are bactericidal even in an isosmotic solution.

Polymyxin B

Quinolones Ciprofloxacin Enoxacin Gatifloxacin Levofloxacin Lomefloxacin Moxifloxacin Nalidixic acid Norfloxacin Ofloxacin Trovafloxacin Grepafloxacin Sparfloxacin Temafloxacin Cipro,Ciproxin, Ciprobay Penetrex Tequin Levaquin Maxaquin Avelox NegGram Noroxin Floxin, Ocuflox Trovan Raxar Zagam Omniflox Urinary tract infections,bacterial prostatitis, communityNausea (rare), acquiredpneumonia, bacterial irreversible diarrhea, mycoplasmal damage to central infections, gonorrhea nervous system(uncommo n), tendinosis (rare) Withdrawn Withdrawn Withdrawn Withdrawn Sulfonamides Mafenide Sulfamylon Urinary tract infections(except sulfacetamide, used for eye infections, and mafenide and silver sulfadiazine, used topically for burns) Folate synthesis inhibition. vomiting, and They arecompetitive inhibitors of the diarrhea enzymedihydropteroate synthetase, DHPS. Allergy(inclu DHPS catalyses the conversion of PABA ding skin (para-aminobenzoate) rashes) todihydropteroate, a key step Crystals in in folatesynthesis. urine Folate is necessary for Nausea,

inhibit the bacterial DNA gyrase or thetopoisomerase IV enzyme, thereby inhibiting DNA replica tion and transcription.

Sulfonamidochrysoidi Prontosil ne(archaic) Sulfacetamide Sulfadiazine Silver sulfadiazine Sulfamethizole Sulfamethoxazole Sulfanilimide (archaic) Sulamyd, Bleph-10 Micro-Sulfon Silvadene Thiosulfil Forte Gantanol

Sulfasalazine Sulfisoxazole

Azulfidine Gantrisin

Trimethoprim Proloprim, Trimpex

the cell to synthesize nucleic acids(nucleic acids are failure essential building Decrease blocks inwhite blood of DNA and RNA), and in its absence cells cellcount will be unable to divide. Sensitivity to Kidney sunlight

TrimethoprimSulfamethoxazole(CoBactrim, Septra trimoxazole) (TMPSMX) Tetracyclines Demeclocycline Doxycycline Minocycline Oxytetracycline Declomycin Vibramycin Minocin Terramycin Gastrointestin al upset Sensitivity to sunlight Potential toxicity to Syphilis, chlamydialinfections , Lyme disease,mycoplasmal infections, acne rickettsial infections, *malaria *Note: Malaria is Sumycin,Achro caused by a protist and not a mycin bacterium. V, Steclin mother and fetus during pregnancy Enamel hypoplasia (staining of teeth; potentially permanent) transient depression of bone growth Drugs against mycobacteria Clofazimine Dapsone Capreomycin Cycloserine Lamprene Avlosulfon Capastat Seromycin Antileprotic Antileprotic Antituberculosis Antituberculosis, urinary tract infections inhibiting the binding of aminoacyl-tRNA to the mRNAribosome complex. They do so mainly by binding to the30S ribosomal subunit in the mRNA translation complex.

Tetracycline

Ethambutol Ethionamide Isoniazid Pyrazinamide

Myambutol Trecator I.N.H. Aldinamide

Antituberculosis Antituberculosis Antituberculosis Antituberculosis mostly Grampositive andmycobacteria Mycobacterium avium complex Antituberculosis Antituberculosis Others Neurotoxicity,otot As oxicity other aminoglycosides Reddish-orange sweat, tears, and urine rash, discolored urine, GI symptoms Binds to the subunit of RNA polymerase to inhibit transcription Inhibits peptide synthesis

Rifampicin (Rifampin Rifadin, in US) Rimactane

Rifabutin Rifapentine Streptomycin

Mycobutin Priftin

Arsphenamine

Salvarsan

Spirochaetal infections (obsolete) Inhibits bacterial protein synthesis by binding to the 50S subunit of the ribosome Inactivates enolpyruvyl transferase, thereby blocking cell wall synthesis

Chloramphenicol

meningitis, MRSA, topical use, or for low cost internal treatment. Rarely: aplastic Chloromycetin Historic: typhus,cholera. gram anemia. negative, gram positive, anaerobes

Fosfomycin

Monurol

Acute cystitis in women

Fusidic acid Linezolid

Fucidin Zyvox VRSA Thrombocytopeni a

Metronidazole

Flagyl

Produces toxic free radicals which disrupt Discolored DNA and proteins. Infections caused byanaerobic urine,headache, m This non-specific bacteria; etallic mechanism is alsoamoebiasis, trichomoniasi taste, nausea ;alco responsible for its s,Giardiasis hol is activity against a contraindicated variety of bacteria, amoebae, and protozoa. Ointment for impetigo, cream for infected cuts

Mupirocin Platensimycin

Bactroban

Quinupristin/Dalfopris Synercid tin Rifaximin Xifaxan Traveler's diarrhea caused byE. coli

Thiamphenicol

Gram-negative, Grampositive, anaerobes. widely used in veterinary medicine.

Lacks known anemic sideeffects.

A chloramphenicol analog. May inhibit bacterial protein synthesis by binding to the 50S subunit of the ribosome

Tigecycline Tinidazole

Tigacyl Tindamax Fasigyn Brand Names protozoan infections Common Uses[2] upset stomach, bitter taste, and itchiness Possible Side Effects[2] Mechanism of action

Generic Name [edit]References

1.

^ 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.

2.

a b c d

For common Uses and possible side effects reference is: Robert Berkow (ed.) The Merck Manual of

Medical Information - Home Edition. Pocket (September 1999), ISBN 0-671-02727-1. 3. 4. ^ Splete, Heidi; Kerri Wachter (March 2006). "Liver toxicity reported with Ketek". Internal Medicine News. ^ Mechanism of Action of Bacitracin: Complexation with Metal Ion and C55-Isoprenyl Pyrophosphate K. John Stone and Jack L. Strominger

Antibiotics List Classification

In the following list are grouped characteristics of each family of antibiotics, indications, major adverse events, cons-indications. Aminoglycosides. Including inter alia streptomycin (used against tuberculosis) and gentamicin, are effective antibiotics against urinary tract infections and severe intestinal. Their toxicity is primarily auditory and renal (kidney and ear). Their main indications are cons-anesthesia, renal failure, pregnancy.

The TB with ethambutol have liver toxicity, neurological and ocular (liver, nervous system and eyes). They are cons-indicated during pregnancy and in patients with impaired liver or kidney. Rifampicin and streptomycin are among TB. They are related drugs in the treatment of tuberculosis, but having a toxicity level of the ear, liver, kidneys, digestive system, and are also likely to cause allergic reactions. They are cons-indicated in cases of anesthesia, renal failure in infants, during pregnancy and in cases of allergy to these drugs. Betalactamines 1 containing penicillin G (penicillin V, penicillin F, a penicillin, ampicillin) are drugs used relatively common whose own indications are relatively large: Infections heart, skin, broncho-pulmonary, genital, ear, nose and throat, meningitis , digestive, bone, joint, urinary, Listeriosis, syphilis, etc. ... Their main side effects are possible allergic reactions, toxicity associated with neurological, renal and gastrointestinal. Their main indication is cons-allergy. In this class of antibiotics called carbapenems (imipenem) are reserved to the hospital for severe illnesses that are resistant to other antibiotics. The beta-lactam 2 include first generation cephalosporins with cefaclor, cfapirine, cefazolin. They have indicated anti-infectious very broad similar to penicillins. The second and third generations are reserved for hospital care and severe infections. The main side effects are allergic reactions associated with hemorrhage.

The lincosanides. Including clindamycin part, are reserved for certain serious conditions, but have a digestive and liver toxicity. The main cons-lincosanides is an indication of liver failure. Macrolides. With erythromycin and josamycin are the common drugs indicated mainly in case of genital infection, ear, nose and throat, lung and for infringement by toxoplasmosis. The main side effects are allergic reactions and liver toxicity and gastrointestinal. The main cons-indication Nitroimidazoles. Including gastrointestinal fragility. is metronidazole, The main are shown liver in is secondary failure. infections with

anaerobic bacteria, that is to say, can live without oxygen. The main side effect is indication cons-allergy medication.

The phnocols. Including the tiamphnicol, have indications in severe disease and failure of other antibiotics. However, their major side effects were gastrointestinal toxicity and blood. They are cons-indicated in pregnancy, infants and liver disease.

The polypeptides. Which colistin belongs, have entries in the urinary infections. Their main side effects are toxic to the nervous system and kidneys. The main indications are cons-

anesthesia

and

renal

failure.

Quinolones. With acid and nalidixic acid pipemidic are listed in the urinary and genital infections. Beware of allergic reactions. On the other hand, they have some toxicity hearing (inner ear). They are mainly cons-indicated in cases of epilepsy in some psychiatric illnesses during pregnancy and infant.

The rifamycins. With rifamycin used mainly topical, may cause allergic reactions. Rifampicin is also part of this class of antibiotics, it is used against tuberculosis, but it has a toxic digestive and liver. On the other hand, it is cons-indicated in infants.

Sulfonamides. Which may or not be associated with trimethoprim, which is part sulfadiazine and sulfamethoxazole, used in some congenital urinary tract infections but also in case of failure of other antibiotics. The main side effects and adverse reactions are allergies and toxicity in the blood and kidneys. Their main indications are cons-renal failure, pregnancy, infant.

The synergistins. Including pristinamycin and virginiamycin are part, are shown in skin infections, lung and bone. Their toxicity is mainly gastrointestinal and liver. The main consindication is liver failure.

Tetracyclines. With doxycycline, minocycline and tetracycline are common drugs primarily indicated in genital infections, cholera, typhus, lung ailments. The main side effects are allergic reactions, as well as neurological toxicity, renal and gastrointestinal. The main consindications are the children for eight years, severe liver or kidney.

Various antibiotics. Including fusidic acid, vancomycin, fosfomycin and teicoplanin, are reserved to the hospital for staph infections and other severe infections. Their toxicity is in the inner ear and kidney. The main indications are cons-allergy and liver failure.

Antibiotics: Antibacteria l Agents

Humans, and our domestic animals, can serve as hosts to a wide variety of diseasecausing organisms (pathogens):

bacteria viruses fungi protozoans helminths (worm s).

This page will examine only those chemical agents that are used to combat bacterial pathogens.

Sulfa Drugs and Folic Acid Analogs o Sulfa Drugs o Folic Acid Analogs The Beta-Lactams Aminoglycosides Tetracyclines Macrolides, Lincosamides, Streptogramins Fluoroquinolones Polypeptides Rifampin Mupirocin Cycloserine Aminocyclitol Glycopeptides Oxazolidinones Lipopeptides Resistance to Antibiotics o Intrinsic resistance o Acquired resistance Measuring Antibiotic Resistance What can you do to delay the spread of antibiotic resistance? Future Prospects

The Problem
There are many chemicals that are lethal to bacteria cyanide does a good job but they cannot be used to cure infections because they are lethal to the host as well. The problem, then, is to find substances that attack a metabolic pathway found in the bacterium but not in the host. This is not an insurmountable problem for bacterial pathogens because they differ in many respects from eukaryotes.

The Solution

Natural products. A number of natural products, penicillin for example, have been discovered that are antibiotics suitable for therapy. They were originally discovered as secretions of fungi or soil bacteria. Soils are complex

ecosystems, and it is not surprising that its inhabitants have evolved chemical defenses against each other.

The photo (courtesy of Merck & Co., Inc.) shows how the growth of bacteria on the agar in a culture dish has been inhibited by the three circular colonies of the fungus Penicillium notatum. The antibiotic penicillin, diffusing outward from the colonies, is responsible for this effect. Today, penicillin is made from cultures ofPenicillium chrysogenum that has been specially adapted for high yields.

Semi-synthetic products. These are natural products that have been chemically modified in the laboratory (and pharmaceutical facility) to o improve the efficacy of the natural product o reduce its side effects o circumvent developing resistance by the targeted bacteria o expand the range of bacteria that can be treated with it Completely synthetic products. The sulfa drugs are examples.

Sulfa Drugs and Folic Acid Analogs

Sulfa Drugs
Sulfanilamide was the first antibacterial agent. Many other sulfa drugs (such as sulfamethoxazole) have since come into use. The Chink in the Armor Both bacteria and their human hosts require folic acid for

nucleic acid synthesis (it is converted into purines and thymidine) as well as

protein synthesis (precursor of the amino acids methionine and glycine)

However,

bacteria synthesize their folic acid starting with para-aminobenzoic acid (PABA), while we must ingest our folic acid already formed; that is, for us it is a vitamin.

Sulfanilamide, and the other sulfa drugs, are analogs of PABA; they compete with PABA and, when chosen, block the synthesis of folic acid. Mammals ignore PABA and its analogs and thus can tolerate sulfa drugs.

Folic Acid Analogs

These synthetic molecules block the final step in the conversion of PABA to folic acid so they, too, block nucleotide and protein synthesis in bacteria but not in mammals. Trimethoprim is one of several in current use. These folic acid analogs are often used in combination with a sulfa drug.

The BetaLactams
The beta-lactams get their name from the characteristic ring structure shown here in blue that they all share. (The green arrow shows the bond that is broken by the beta-lactamases that are synthesized by many penicillinresistant bacteria.) They include the

penicillins such as o penicillin G (a natural product) produced by the fungus Penicillium chrysogenum o ampicillin (a semi-synthetic) o amoxicillin (semi-synthetic)

cephalosporins There are over two dozen of them in current use. Most are semi-synthetics derived from the secretion of the mold Cephalosporium. Some examples: o cephalexin (e.g., Keflex) o cefaclor (e.g., Ceclor) o cefixime (e.g., Suprax) carbapenems such as o meropenem (Merrem) o ertapenem (Invanz)

The Chink in the Armor = the bacterial cell wall The beta-lactams all work by interfering with the synthesis of the bacterial cell wall a structure that is not found in eukaryotes. The walls of bacteria are made of a complex polymeric material called peptidoglycan. It contains both amino acids and amino sugars. The amino sugars are of two kinds

N-acetylglucosamine (NAG) and its close relative N-acetylmuramic acid (NAM).

These two form a linear polymer of NAG alternating with NAM. They are linked by aglycosidic bond between the #1 and #4 carbons (this is the linkage attacked bylysozyme) and are oriented in the same way they are in cellulose. Side chains containing 4 or 5 amino acids are attached to each NAM. These form covalent bonds with amino acids in adjacent chains. The bonds may

be direct to the next chain or

include additional peptide cross bridges (e.g., 5 glycine residues) which extend to chains in the same plane (shown here) as well as to chains above and below.

This elaborate, covalently cross-linked structure provides the great strength of the cell wall. It also leads to the remarkable conclusion that the bacterial cell wall meets the definition of a single molecule! The beta-lactam antibiotics bind to and inhibit enzymes needed for the synthesis of the peptidoglycan wall. While they have little effect on resting bacteria, they are lethal to dividing bacteria as defective walls cannot protect the organism form bursting in hypotonic surroundings.

Aminoglycosides
These are products of actinomycetes (soil bacteria) or semi-synthetic derivatives of the natural products. Examples are:

streptomycin kanamycin neomycin gentamycin

The Chink in the Armor = the bacterial ribosome The 70S bacterial ribosome differs in several ways from the 80S eukaryotic ribosome. [Link] The aminoglycosides bind to the 30S subunit of the bacterial ribosome and

interfere with the formation of the initiation complex cause misreading of the mRNA.

Link to discussion of translation.

Although the eukaryotic ribosome in the cytosol is relatively unaffected by these drugs, ribosomes in the mitochondria are 70S and sensitive to their effects.

Link to a discussion of the prokaryotic nature of gene expression in mitochondria.

Tetracyclines
These are natural products derived from soil actinomycetes or their semi-synthetic derivatives. Examples:

chlortetracycline (trade name = "aureomycin") oxytetracycline (trade name = "terramycin") doxycycline

The Chink in the Armor = the bacterial ribosome Tetracyclines bind to the 30S subunit of the bacterial ribosome. They prevent the transfer of activated amino acids to the ribosome [Link] so protein synthesis is halted.

Macrolides, Lincosamides, Streptogramins

The Chink in the Armor = the bacterial ribosome All these antibiotics bind to the 23S rRNA molecule in the large (50S) subunit of the bacterial ribosome where they block the elongation of the growing peptide chain. Because of their similar action, the development of antibiotic resistance to one usually extends to all the others.

Macrolides
Macrolides are also products of actinomycetes (soil bacteria) or semi-synthetic derivatives of them. Erythromycin, azithromycin (Zithromax), and clarithromycin (Biaxin) are a commonly-prescribed macrolides.

Lincosamides

The first member of this group was also isolated from a soil actinomycete (found near Lincoln, Nebraska). A semi-synthetic derivative, called clindamycin(Cleocin), is now widely used against Gram-positive bacteria.

Streptogramins
Quinupristin and dalfopristin are examples. As of 1 October 1999, they will be sold as a mixture under the trade name Synercid. Combined, they show great promise in treating certain infections resistant to vancomycin currently the antibiotic of last resort for some hospital-acquired infections.

Fluoroquinolones
Ciprofloxacin (Cipro), levofloxacin and norfloxacin are examples. Cipro is the preferred antibiotic for people who have been intentionally exposed to anthrax, although some other antibiotics appear to be equally effective. The Chink in the Armor = DNA topoisomerases The fluoroquinolones block the action of two bacterial topoisomerases enzymes that relieve the coils that form in DNA when the helix is being opened in preparation for

replication or transcription or repair

The topoisomerases in eukaryotes are not affected.

Polypeptides
The most common of these are the polymixins. They behave as detergents, increasing the permeability of the membranes that encase bacteria and causing the contents of the bacterial cell to leak out.

Rifampin

This semi-synthetic antibiotic binds to the bacterial RNA polymerase and prevents it from carrying out its role in transcription. Its affinity for the equivalent eukaryotic enzyme is much lower. Rifampin is also known as rifampicin.

Mupirocin
This antibiotic blocks the action of the bacterial isoleucine tRNA synthetase, the enzyme responsible for attaching the amino acid isoleucine (Ile) to its tRNA in preparation for protein synthesis, so protein synthesis is inhibited. It spares the equivalent eukaryotic enzyme.

Cycloserine
Cycloserine inhibits synthesis of the bacterial cell wall but by a different mechanism than the beta-lactam antibiotics discussed above. Cycloserine is an analog of Dalanine and blocks the incorporation of D-alanine into the peptide bridges in the bacterial cell wall (look back). It is derived from an actinomycete.

Aminocyclitols
These products of another actinomycete achieve their effect by interfering with the 30S subunit of the bacterial ribosome. Spectinomycin (trade name = Trobicin) is an example. It is particularly effective against the gonococcus, the bacterium that causes the sexually-transmitted disease (STD) gonorrhea.

Glycopeptides
Glycopeptides also interfere with the synthesis of the bacterial cell wall but by a different mechanism than the beta-lactams. Vancomycin is a widely-used glycopeptide in the U.S. It binds to the D-alanines on the precursors of the peptidoglycan cross bridges preventing their cross-linking (look back). It has become the antibiotic of last resort as resistance to the other antibiotics has become more and more common.

Oxazolidinones

The first of these new antibiotics, linezolid (Zyvox), was approved by the U.S. Food and Drug Administration on 19 April 2000. It is effective against manyGram-positive bacteria that have developed resistance to the older antibiotics. Linezolid attacks a previously-unexploited chink in the bacterium's armor: the proper assembly of the two ribosomal subunits (30S and 50S). It does not affect eukaryotic ribosomes and thus translation of mRNAs in the cytosol. However, it does affect the bacterial-like mitochondrial ribosomes and can interfere with the synthesis of those mitochondrial proteins synthesized by them.

Lipopeptides
These are natural compounds derived from a species of Streptomyces. The one now in clinical use is daptomycin (Cubicin). It is effective against Gram-positive bacteria. It attacks another previously-unexploited chink in the bacterial armor the integrity of its cell membranes. So far there is no evidence of bacteria developing resistance against it.

Resistance to Antibiotics
None of the antibiotics discussed above is effective against all bacterial pathogens.

Intrinsic resistance
Some bacteria are intrinsically resistant to certain of the antibiotics. Example: Grampositive bacteria are much less susceptible to polymixins than Gram-negative bacteria. [The "Gram" designations refer to the behavior of the bacteria when stained with the Gram stain; this behavior is a reflection of the very different organization of their cell walls.]

Acquired resistance
Many bacteria acquire resistance to one or more of the antibiotics to which they were formerly susceptible. Example: In the U.S. in the decade from 19851995, resistance of Shigella (which causes gastrointestinal illness) to ampicillin grew from 32% to 67%. And, while only 7% of these isolates were resistant to the combination of sulfamethoxazole and

trimethoprim at the start of the decade, that figure had grown to 35% by the end of the decade. Bacteria develop resistance by acquiring genes encoding proteins that protect them from the effects of the antibiotic. In some cases the genes arise by mutation; in others, they are acquired from other bacteria that are already resistant to the antibiotic. The genes are often found on plasmids which spread easily from one bacterium to another even from one species of bacterium to another. Examples:

Synthesis of the enzyme penicillinase or other beta-lactamases provides protection from the beta-lactam antibiotics. These enzymes break the betalactam ring at the position shown with the green arrow in the diagram of penicillin G. Likewise synthesis of cephalosporinases defeats the cephalosporins. Defeating quinolones: o Some bacteria do this by modifying their DNA gyrase. o Others, e.g., Mycobacterium tuberculosis, develop quinolone resistance by synthesizing a protein that resembles a short length of DNA. This protein binds the gyrase so it cannot form the DNA/gyrase complex that is the target of quinolone action. Some bacteria synthesize "pumps" in their plasma membrane through which they remove antibiotics like tetracyclines from the interior of the cell. Bacteria may methylate their ribosomes obscuring the target of antibiotics (e.g., erythromycin) that ordinarily bind to and inactivate the ribosome or conversely they may enzymatically modify the antibiotic (e.g., kanamycin) so it can no longer "see" its ribosomal target. Bacteria may modify the structure of their peptidoglycan wall and thus avoid the inhibitory effects of antibiotics like cycloserine.

An alarming number of human pathogens have acquired genes to combat all the presently-used antibiotics except vancomycin and recently vancomycin-resistant bacteria have appeared. These multidrug-resistant strains are particularly common in hospitals where antibiotic use is heavy, and the patients often have weakened immune systems.

How transposons contribute to multidrug resistance.

Measuring Antibiotic Resistance

The figure illustrates the simplest method of the several available for measuring antibiotic resistance.

A suspension of the bacteria to be tested (e.g. cultured from the infected patient) is spread over the surface of a petri dish containing a solid culture medium. Disks of several different antibiotics are pressed on the surface of the agar. The concentration of antibiotic in each type of disk is standardized. Incubate overnight. The bacteria will grown into a "lawn" except where an antibiotic to which they are sensitive has diffused out from its disk. Measure the diameter of any zones of inhibition that are formed.

What can you do to delay the spread of antibiotic resistance?

Don't ask your doctor for an antibiotic to treat a viral disease (e.g., a cold) for which antibiotics are useless. (However, your doctor may prescribe an antibiotic if you are infected by an influenza virus not to fight the virus but to protect you against a secondary bacterial infection of your damaged lungs.) Stay the course. Use all doses prescribed even though you are feeling better. This will minimize the opportunity to select for resistance among the bacteria that remain late in the infection. Don't save unused antibiotics for later self-medication.

Farmers can help as well by avoiding the use of antibiotics in their livestock that are similar to those used in humans. Antibiotics are widely used in healthy livestock to improve their growth rate (by an unknown mechanism).
An article in the 20 May 1999 issue of The New England Journal of Medicine documents the recent development of quinolone resistance in Campylobacter jejuni, the most frequent

bacterial cause of gastroenteritis in humans. The rise coincides with the approval in 1995 of the use of quinolones by U. S. poultry farmers (chickens also become infected by C. jejuni). Similar recent increases in fluoroquinolone-resistant C. jejuni have been reported in the Netherlands and also in Spain (where as many as 50% of human infections are now caused by bacteria resistant to the antibiotic). In each country, the appearance of resistant strains followed the widespread introduction of quinolone treatment for animals.

Future Prospects
Drug companies after many years of complacency are now responding to the threat of antibiotic-resistant bacteria. Over a dozen new antibiotics are being developed and some have already reached clinical trials. Many of these are semi-synthetic modifications of already-existing antibiotics, including new

beta-lactams macrolides glycopeptides quinolones modifications of vancomycin

Others are entirely new, attacking previously-unexploited chinks in the bacterial armor.

Urea hydroxamates, that block the enzyme (peptide deformylase) that removes fMet from the finished protein so it can begin its work. (Eukaryotes do not begin translation with fMET.) Heteroaromatic polycycles (HARP) that bind to bacterial promoters preventing gene transcription.

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22 December 2010