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Antibiotics

ANTIMICROBIALS AND ANTIBIOTICS

INTRODUCTION

CATEGORIES OF ANTIMICROBIAL AGENTS Heavy Metals - arsenic, bismuth Antibiotics - Penicillins, etc. Synthetic drugs - Quinolones Azo dye derivatives - Sulfonamides Antiseptics - alcohol

BASIC PRINCIPLES

ANTIBIOTICS Characteristics Soluble Produced by microorganisms Inhibit the growth of other microbes

MECHANISMS OF ACTION OF ANTIBIOTICS Inhibit cell wall synthesis Alter cell membrane permeability Alter synthesis of cellular components Inhibit cell metabolism

TYPES OF MICROBIAL RESISTANCE Natural Acquired

"Natural resistance is present before..." Natural resistance is present before contact with the antibiotic Acquired resistance develops during exposure to the antibiotic Acquired resistance can result from acquiring a plasmid such as the R Factors mentioned previously

"Sometimes resistance to one antibiotic..." Sometimes resistance to one antibiotic confers resistance to another antibiotic This is referred to as cross-resistance

Methods of Resisting  Antibiotics Antibiotic inactivation by bacterial enzymes Development of alternate metabolic pathways Alteration in the bacteria, preventing uptake or binding with the antibiotic

Factors making antibiotics ineffective Not high enough dose to reach the site in an adequate concentration Not given for a sufficient length of time Not antagonized by other drugs

Spectrum of Activity No one antibiotic will be effective against all bacteria Specific / Narrow - Good when monoinfected Broad - Good in mixed infections

Superinfection Treatment with antibiotics can suppress healthy flora - Then - Pathogenic organisms  proliferate and cause disease This is called a superinfection

TYPES OF ANTIBIOTIC ACTION Bacteriostatic - growth and multiplication are inhibited The person’s own defense mechanisms can then deal with them Bactericidal - kill the microorganism Bacteriostatic & Bactericidal – some, depending on blood concentration

Antibiotic  Synergism When the combination of 2 bactericidal antibiotics is more lethal than the sum of the 2 antibiotics if given separately, the result is called Antibiotic Synergism

Antibiotic  Antagonism When the combination of 2 antibiotics is less lethal than the action of either one of the antibiotics if given separately, the result is called Antibiotic Antagonism

Antibiotic  Antagonism Antibiotic antagonism often occurs because the bacteriocidal antibiotic needs a reproducing cell in order for it to kill the cell The bacteriostatic drugs often inhibit cell reproduction and thus prevent the cell from being susceptible to the bacteriocidal antibiotic

Antibiotics & Pregnancy Use with caution

Antibiotics & Pregnancy Tetracycline can affect calcium formation This may cause slow bone growth & altered tooth enamel formation resulting in permanent tooth discoloration Many antibiotics also appear in breast milk but usually there are no problems

Most common side effect of antibiotic use The most common side effect of antibiotic use is gastrointestinal change This usually translates to diarrhea This is due to the antibiotic affecting the flora in the bowel and causing a massive die-off that results in diarrhea

Antibiotic susceptibility testing in dentistry In medicine - isolate the organism or organisms from a lesion, culture it, and then do antibiotic susceptibility tests

Antibiotic Sensitivities

"An isolate of bacteria may..." An isolate of bacteria may show some sensitivity to many antibiotics But showing sensitivity in a culture dish doesn’t mean it is sensitive to the concentration of the antibiotic one can achieve in tissues An antibiotic, must achieve sufficient tissue levels to be effective

Antibiotic susceptibility testing in dentistry In dentistry - this can be done More often the choice is made based on the experience of the practitioner Many dental practitioners prefer treating oral infections with tetracycline as their first choice antibiotic because it is a broad spectrum antibiotic

ANTIBIOTICS USED IN DENTISTRY

ANTIBIOTICS USED IN DENTISTRY Antibiotic Bacteriostatic Bactericidal Penicillins + Erythromycin + (+) Tetracycline + Cephalosporins + Metronidazole +

ANTIBIOTICS USED IN DENTISTRY Antibiotic Bacteriostatic Bactericidal Nystatin + Bacitracin + Lincomycin + Vancomycin + Streptomycin +

PENICILLIN

PENICILLIN The first penicillin discovered was  penicillin G It is produced by a mold called Penicillium notatum It is still effective but can be broken down by penicillinase

PENICILLIN Types All have a beta lactam ring All are inactivated by beta lactamase Beta lactamase = Penicillinase Some newer semisynthetic Penicillins are resistant to beta lactamase (Augmentin)

PENICILLIN Mechanism of Action Inhibits cell wall synthesis Only effective when the cell is growing Bactericidal

PENICILLIN Spectrum of Activity Most effective against Gram + aerobes and both Gram + and Gram – anaerobes Least effective against  Gram – aerobes or facultatives

PENICILLIN Adverse Effects One of the safest drugs But 1-5% are allergic These may be life threatening Topical and aerosol =  most dangerous Oral = safest Allergy to penicillins ~= cephalosporins

CEPHALOSPORINS

CEPHALOSPORINS Types Structurally similar to penicillin (have a beta-lactam ring)

CEPHALOSPORINS Mode of Action Act against cell wall synthesis Some bacteria produce cephalosporinases

CEPHALOSPORINS Spectrum of Activity Active against Gram + aerobes Active against Gram + and Gram - anaerobes Also effective against some Gram - aerobes

CEPHALOSPORINS Adverse Effects Allergic incidence almost = penicillin May damage blood cells and kidney cells

ERYTHROMYCIN

ERYTHROMYCIN Referred to as macrolide antibiotics because of their chemical structure Often used in place of penicillin

ERYTHROMYCIN Mechanism of Action Bacteriostatic or bactericidal depending on dose and on the microorganisms Inhibit bacterial protein synthesis

ERYTHROMYCIN Spectrum of Activity Most Gram + bacteria that are sensitive to penicillin

ERYTHROMYCIN Adverse Effects Generally very safe Sometimes gastric upset after oral use Estolate form can cause hepatitis Allergy is low but can occur

TETRACYCLINE

VARIOUS TETRACYCLINES Generic Name Trade Name Chlortetracycline Aureomycin Demeclocycline Declomycin Doxycycline Vibramycin Methacycline Rondomycin Minocycline Minocin Oxytetracycline Tetramycin Tetracycline Achromycin

TETRACYCLINE Often used in place of penicillin or erythromycin Concentrate in gingival crevicular fluid and act directly on the bacteria in the crevice

TETRACYCLINE Mechanism of Action Bacteriostatic Inhibits protein synthesis Because it is bacteriostatic it is ANTAGONISTIC TO PENICILLIN

TETRACYCLINE Spectrum of Activity Broad spectrum Many Gram + and Gram - A few viruses, mycoplasma, chlamydia and rickettsia

TETRACYCLINE Adverse Effects Broad spectrum activity means they can wipe out the normal flora This leads to superinfections by other organisms and yeast infections of the mouth and vagina Elimination of much of the normal intestinal flora often leads to diarrhea

TETRACYCLINE Adverse Effects They have an affinity for the dentin during tooth development This can take place in the womb or later before the permanent teeth erupt This results in permanent staining of teeth

METRONIDAZOLE

METRONIDAZOLE Mechanism of Action Metronidazole inhibits nucleic acid synthesis Specifically it inhibits DNA replication

METRONIDAZOLE Spectrum of Activity Originally used to treat infections with Trichomonas vaginalis (a protozoan) Gram + and Gram - anaerobes and spirochetes It is therefore very useful for oral infections Acts synergistically with penicillin It is used to treat periodontal disease

METRONIDAZOLE Adverse Effects Nausea Diarrhea Not be be used during pregnancy due to the rare possibility it could cause mutations in the fetus

LINCOMYCIN and CLINDAMYCIN

LINCOMYCIN and CLINDAMYCIN Mechanism of Action Inhibit protein synthesis Usually bacteriostatic but bactericidal in high doses

LINCOMYCIN and CLINDAMYCIN Spectrum of Activity Effective against anaerobic organisms Often effective against organisms resistant to penicillin and erythromycin

LINCOMYCIN & CLINDAMYCIN Adverse Effects Diarrhea is common Pseudomembraneous colitis (hemorrhagic colitis) - sometimes fatal Glossitis, stomatitis, nausea, vomiting, skin rashes, vaginitis, and changes in blood cells

QUINOLONES

QUINOLONES Ciprofloxin is the most common in this group Used successfully in the treatment of periodontal disease

QUINOLONES Mechanism of Action Interfere with bacterial DNA synthesis Bacteriostatic in low concentrations Bactericidal in high concentration

QUINOLONES Spectrum of Activity Gram - bacteria (used mainly for urinary tract infections) Some Gram + cocci

QUINOLONES Adverse Effects Xerostomia Increased gag reflex Nausea Vomiting

VANCOMYCIN

VANCOMYCIN Mechanism of Action Effects cell wall synthesis Bactericidal

VANCOMYCIN Spectrum of Activity Gram + bacteria

VANCOMYCIN Adverse Effects - systemic administration Deafness Phlebitis Kidney damage Anaphylaxis Skin rashes Fever

VANCOMYCIN Adverse Effects - topical administration None

NYSTATIN

NYSTATIN Common names are Mycostatin and Nilstat

NYSTATIN Mechanism of Action Inhibits cell membrane permeability Permits leakage of cell ingredients and potassium ions

NYSTATIN Spectrum of Activity Antifungal Used for the treatment of oral and vaginal yeast infections

NYSTATIN Adverse Effects Rare Nausea Vomiting Diarrhea

KETOCONAZOLE

KETOCONAZOLE Common name  = Nizoral

KETOCONAZOLE Mechanism of Action Interferes with synthesis of chemicals needed to form the plasma membrane of fungi

KETOCONAZOLE Spectrum of Activity Used for the treatment of oral fungal infections

KETOCONAZOLE Adverse Effects Nausea Pruritis (severe itching)

STREPTOMYCIN

STREPTOMYCIN Can be very toxic and therefore it has limited use

STREPTOMYCIN Mechanism of Action Inhibits protein synthesis Bactericidal

STREPTOMYCIN Spectrum of Activity Gram + Gram - and Acid-Fast* organisms But bacterial resistance develops rapidly *The Acid-Fast stain is used to stain the organisms causing tuberculosis

STREPTOMYCIN Adverse Effects Severe 8th nerve damage (balance & hearing) Blood disorders Severe kidney damage Allergic reactions can occur

BACITRACIN

BACITRACIN Used topically for dental infections Used in periodontal dressings Often combined with neomycin and polymyxin - broad  spectrum

BACITRACIN Spectrum of Activity Gram + and Fusobacterium

BACITRACIN Adverse Effects None when used topically Kidney damage if used parenterally

SULFONAMIDES

SULFONAMIDES Synthetic antibiotics containing sulfur Not usually used for oral infections Used mainly for lower urinary tract infections

SULFONAMIDES Mechanism of Action Inhibits folic acid metabolism Bacteriostatic

SULFONAMIDES Spectrum of Activity Many Gram + Some Gram - Some large viruses

SULFONAMIDES Adverse Effects Many bacteria develop a high resistance Allergy Nausea, vomiting, diarrhea, headache, dizziness, vertigo, tinnitus, and mental depression Blood dycrasias

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