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An „
„ is a substance that kills or inhibits the growth of

microorganisms[1] such as bacteria, fungi, or protozoans. Antimicrobial drugs
either kill microbes (microbicidal) or prevent the growth of microbes
(microbistatic). Disinfectants are antimicrobial substances used on non-living
objects.

The history of antimicrobials begins with the observations of Pasteur and Joubert,
who discovered that one type of bacteria could prevent the growth of another. They
did not know at that time that the reason one bacterium failed to grow was that the
other bacterium was producing an antibiotic. Technically, antibiotics are only those
substances that are produced by one microorganism that kill, or prevent the
growth, of another microorganism. Of course, in today's common usage, the term
antibiotic is used to refer to almost any drug that attempts to rid your body of a
bacterial infection. Antimicrobials include not just antibiotics, but synthetically
formed compounds as well.

The discovery of antimicrobials like penicillin and tetracycline paved the way for
better health for millions around the world. Before penicillin became a viable
medical treatment in the early 1940's, no true cure for gonorrhea, strep throat, or
pneumonia existed. Patients with infected wounds often had to have a wounded
limb removed, or face death from infection. Now, most of these infections can be
cured easily with a short course of antimicrobials.

However, the future effectiveness of antimicrobial therapy is somewhat in doubt.

Microorganisms, especially bacteria, are becoming resistant to more and more
antimicrobial agents. Bacteria found in hospitals appear to be especially resilient,
and are causing increasing difficulty for the sickest patients±those in the hospital.
Currently, bacterial resistance is combated by the discovery of new drugs.
However, microorganisms are becoming resistant more quickly than new drugs are
being made available; thus, future research in antimicrobial therapy may focus on
finding how to overcome resistance to antimicrobials, or how to treat infections
with alternative means, such as species-specific phage
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Vc Chemical structure
Vc Mechanism of action
Vc Type of organisms against which primarily active.
Vc èpectrum of activity
Vc Type of action
Vc Antibiotics are obtained from.

Chemical structure
Vc èulfonamides and related drugs: èulfadiazine and other, èulfones ±
Dapsone(DDè), Paraaminaosalicyclic (PAè)
Vc Diaminopyrimidines: Trimethoprim, Pyrimethamine.
Vc ‰uinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin etc.
Vc   -lactam antibiotics: Penicillins, Cephalosporins, Monobactams,
Carbapenems.
Vc Tetracyclines: Oxytetracycline, Doxycycline etc.
Vc Nitrobenzene derivative: Chloramphenicol
Vc Aminoglycosides: ètreptomycin, Gentamicin, Neomycin etc.
Vc Macrolide antibiotics: Erythromycin, Roxithromycin, Azithromycin etc.
Vc Polypepetide antibiotics: Polymyxin-B, Colistin, Bacitracin, Tyrothricin.
Vc Nitrofuran derivatives: Nitrofurantoin, Furazolidone.
Vc Nitroimidazoles: Metronidazole, Tinidazole.
Vc Nicotinic acid derivatives: Isoniazid, Pyrazinamide, Ethionamide.
Vc Polyene antibiotics: Nystatin, Amphotericin-B, Hamycin.
Vc Imidazole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole.
Vc Others: Rifampin, Lincomycin, Clindamycin, èpectinomycin, Vancomycin,
èod. Fusidate, Cycloserine, Viomycin, Ethambutol, Thiacetazone,
Clofazimine, Griseofulvin.

MECHANIèM OF ACTION
Vc Inhibit cell wall synthesis: Penicillins, Cephalosporins, Cycloserine,
Vancomycin, Bacitracin.
Vc Cause leakage from cell membranes:
*c Polypeptides : Polymyxins, Colistin, Bacitracin
*c Polyenes ± Amphotericin B, Nystatin, Hamycin.
Vc Inhibit protein synthesis: Tetracyclines, Chloramphenicol, Erythromycin,
Clindamycin.
Vc Cause misreading of m-RNA code and affect permeability: Aminoglycosides ±
ètreptomycin, Gentamicin etc.
Vc Inhibit DNA gyrase: Fluoroquinolones ± Ciprofloxacin.
Vc Interfere with DNA function: Rifampin, Metronidazole.
Vc Interfere with DNA synthesis: Idoxuridine, Acyclovir, Zidovudine.
Vc Interfere with intermediary metabolism: èulfonamides, èulfones, PAè,
Trimethoprim, Pyrimethamine, Ethambutol.

TYPE OF ORGANIèMè AGAINèT WHICH PRIMARILY ACTIVE

Vc Antibacterial: Penicillins, Aminoglycosides, Eruthromycin etc.
Vc Antifungal: Griseofulvin, AmphotericinB, Ketoconazole etc.
Vc Antiviral: Idoxuridine, Acyclovir, Amantadine, Zidovudine etc.
Vc Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, Diloxanide etc.
Vc Anthelmintic: Mebendazole, Pyrantel, Niclosamide, Diethyl carbamazine etc.
 èPECTRUM OF ACTIVITY
Vc NARROW èPECTRUM: Penicillin G, ètreptomycin Erthromycin
Vc BROAD èPECTRUM: Tetracyclines, Chloramphenicol.

TYPE OF ACTION
Vc PRIMARILY BACTERIOèTATIC:
Vc èulfonamides, Tetracyclines, Chloramphenicol, Erythromycin, Ethambutol
Vc PRIMARILY BACTERICIDAL: Penicillins, Aminoglycosides, Polypeptides,
Rifampin, Cotrimoxazole, Cephalosporins, Vancomycin, Nalidixic acid,
Ciprofloxacin, Isoniazid.

ANTIBIOTICè ARE OBTAINED FROM

Vc FUNGI: Penicillin, Cepholosporin,Griseofulvin.
Vc BACTERIA: Polymyxin B, Colistin, Bacitracin, Tyrothricin, Aztreonam.
Vc ACTINOMYCETEè: Aminoglycosides, Tetracyclines, Chloramphenicol,
Macrolides, Polyenes.
PROBLEMè THAT ARIèE WITH THE UèE OF AMAs.
Vc TOXICITY:
Vc HYPERèENèITIVITY REACTIONè:
Vc DRUG REèIèTANCE
*c Mutation
*c Gene Transfer
*c Cross resistance
*c Prevention of drug resistance.
Vc èUPERINFECTION (èUPRAINFECTION)
 TOXICITY:
Vc A) LOCAL IRRITANCY: Erythromycin, Tetracyclines, certain
cephalosporins and chloramphenicol.
Vc B) èYèTEMIC TOXICITY: Dose related and predictable organ toxicities
Vc - High therapeutic index ± Penicillins, some cephalosporins and erythromycin.
Vc - Lower Therapeutic index ± individualized and toxicity watched
Vc Aminoglycosides: 8 th cranial nerve and kidney toxicity.
Vc Tetracyclines : Liver and kidney damage, antianabolic effect.
Vc Chloramphenicol: Bone marrow depression.
Vc - Very low Therapeutic index - Use is highly restricted
Vc Polymyxin B : neurological and renal toxicty.
Vc Vancomycin : hearing loss, kidney damage.
Vc Amphotericin B : kidney, bone marrow and neurological toxicity.

HYPERèENèITIVITY REACTIONè:
Vc Practically All AMAs.
Vc Unpredictable and unrelated to dose.
Vc Reactions from rashes to anaphylactic shock.
Vc Penicillins, cephalosporins, sulfonamides.

DRUG REèIèTANCE:
Vc Natural resistance: always resistance.
Vc Pencillin G ± Gram ±ve bacilli.
Vc Tetracyclines ± M.tuberculosis
Vc Acquired resistance: develop resistance
Vc rapid acquisition ± staphylococci, coliforms, tubercle bacilli.
Vc ètrep.pyogenes & spirochetes ± penicillin when >40 years.
Vc Gonococci ± quick to sulfonamides but low to penicillin.
Vc Resistance may be developed by mutation or gene transfer

Vc MUTATION:
Vc 1. èingle ètep: high degree of resistance, emerges rapidly ± e.g. Enterococci to
streptomycin
Vc E.Coli and ètaphylococci to Rigampin
Vc ù. Multistep: Resistance to erythromycin, tetracyclines and chloramphenicol
Vc Low grade penicillin resistant gonococci have decreased virulence.
ètaphylococci to rifampin.

Vc Gene transfer (infectious resistance) from one organism to another can occur
by:
*c Conjugation: R ± factor (Resistance transfer factor (RTF)).
Chloramphenicol resistance of typhoid bacilli, streptomycin resistance of
E.coli, Penicillin resistance of Haemophilus and gonococci.
*c Transduction: Penicillin, erythromycin and Chloramphenicol ± phage
mediated.
*c Tranformation: Pneumococcal resistance to penicillin G due to altered
penicillin binding protein.

Vc Resistant Organisms can be:

Vc Drug tolerant: loss of affinity of the target biomolecule of the microorganism
for a particular AMA. E.g., resistant ètaph.aureus and E.coli developa RNA
polymerase that does not bind rifampin.
Vc Drug destroying:   - lactamase by ètaphylococci, Haemophilus, Gonococci
etc., which inactivate penicillin G. Chloramphenicol acetyl transferase is
acquired by resistant E.coli, H.influenzae and è.typhi.
Vc Aminoglycoside resistant coliforms ± produce enzymes which
adenulate/acetylate/phosphorylate specific aminoglycoside antibitotics.
Vc c) Drug impermeable: Many hydrophilic antibiotics access though porins, or
need specific transport mechanisms. Glycosides and tetracyclines in the
resistant gram negative bacterial strains.

Vc Cross resistance: Acquisition of resistance to one AMA conferring resistance

to another AMA, to which the organism has not been exposed, is called cross
resistance.
Vc èulfonamide ± to all others.
Vc Tetracycline ± insensitivity to all others.
Vc Aminoglycoside ± not extend to another
*c Gentamicin - amikacin also
*c Cross resistance e.g., between tetracyclines and chloramphenicol, between
erythromycin and lincomycin.
*c Newmycin resistance by enterobacteriaceae ± insensitive to streptomycin.

Vc 4. èuperinfection ( èuprainfection)
Vc Appearance of a new infection as a result of antimicrobial therapy.
Vc The normal flora contributes to host defence by elaborating substances called
bacteriocins which inhibit pathogenic organisms.
Vc èuperinfections are more common when host defence is compromised, as in:
Vc Corticosteriod therapy
Vc Leukemias and other malignancies (WBC count)
Vc Acquired immunodeficiency syndrome (AIDè)
Vc Agranulocysis
Vc Diabetes, disseminated Lupus Erythematosus.
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