Lecturer name: Dr. Fawzia Alotaibi & Dr. Ali Somily Department of Pathology, Microbiology Unit
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Transcript of Lecturer name: Dr. Fawzia Alotaibi & Dr. Ali Somily Department of Pathology, Microbiology Unit
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Lecturer name: Lecturer name: Dr. Fawzia Dr. Fawzia Alotaibi Alotaibi & Dr. Ali Somily
Department of Pathology, Microbiology Unit
Lecture Title:Lecture Title:ANTIBIOTICS
(Foundation Block, Microbiology) (Foundation Block, Microbiology)
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Lecture Objectives..Lecture Objectives..
• By the end of this lecture the student should be able to:
• Define antibiotic ,chemotherapy and selective toxicity
• Describe the difference between bactericidal and bacteriostatic antibiotics
• Recognize the narrow and broad spectrum antibiotics
• Define the therapeutic index
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Lecture Objectives..Lecture Objectives..
• Know the mechanism of action of antimicrobial agents.
• Recognize the various classes of antimicrobial agents(action, spectrum and side effects)
• Explain the criteria for an ideal antimicrobial
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ANTIMICROBIAL AGENTS
ANTIBIOTICS: Natural compounds produced by
microorganism which inhibit the growth of other microorganism .
CHEMOTHERAPY:Synthetic compounds .
Antimicrobial agents.
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SELECTIVE TOXICITY:
The ability to kill or inhibit the growth of a microorganism without harming the host cells.
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ActivityBACTERICIDAL: kills bacteriaBACTERIOSTATIC: prevents multiplication.
Spectrum of activity Broad spectrum : Gram positive & Gram negative
bacteria Narrow spectrum : selected organism.
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THERAPEUTIC INDEX:
The RATIO of the dose toxic to the host to the effective therapeutic dose.
Examples: Penicillin: High Aminoglycosides : low Polymyxin B : the lowest
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MECHANISMS OF ACTION OF ANTIMICROBIALS
1) Inhibition of cell wall synthesis.
2) alteration of cell membrane
3) Inhibition of protein synthesis
4) Inhibition of nucleic acid synthesis
5) Anti-metabolite OR competitive antagonism.
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ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESIS
1- Beta –Lactam antimicrobial agents
Penicillins Cephalosporins Cephamycin Carbapenems ( imipenem &
meropenem) Monobactam (aztreonam) Beta-lactamase inhibitors 2- Vancomycin ( Teicoplanin )
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- LACTAM ANTIBIOTICS:
Contain : Beta- Lactam ring & organic acid. Natural & Semi-synthetic Bactericidal Bind to PBP, interfere with trans-peptidation
reactionToxicity: mainly;
hypersensitivity Anaphylaxis , Diarrhea, ..etc
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Penicillins:
Benzyl penicillin – - Penicillin V
Procaine penicillin Benzathine penicillin
Isoxazolyl penicillins : cloxacillin – Staph.Amino-penicillins -ampicillin –Enterobacteria.Acylaminopenicillins: piperacillin,mezlocillin- Psudomonas.
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CEPHALOSPORINS:
First Generation:Cephradine Ceohalexine
Second generation:Cefuroxime Cephamycin
(Cefoxitin)
Third generation: expanded
spectrum
eg. Ceftriaxone Ceftazidime
Fourth generation:
Cefepim
Fourth generation:
Ceftobiprole
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β-Lactamase inhibitors
• β-Lactams with no antibacterial activity
• Irreversibly bind to β-lactamase enzyme
• Clavulanic acid, Sulbactam, Tazobactam
• Effective on staph. Penicillinases and broad spectrum β-lactamases.
• eg. amoxicillin/clavulanic acid, ticarcillin /clavulanic acid and piperacillin /tazobactam.
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VANCOMYCIN
Glycopeptides
Bactericidal .Acts on Gram positive bacteria only.
Inhibit cell wall synthesis
Given by injection only.
Used for MRSA ,S.epidermidis, pseudomembranous colitis.
Red man syndrome ,phlebitis, nephrotoxic & ototoxic.
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ANTIBIOTICS THAT ALTER CELL MEMBRANES
Polymyxin B and Colistin
Polymyxin B :a Peptide active against Gram negative bacteria only.
Bactericidal. Only used LOCALLY due to serious
nephrotoxicity Colistin used for the treatment of multi-
resistant organisms (MRO) such as :Pseudomonas and Acinetobacter infections.
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ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESIS
AMINOGLYCOSIDES S30S ribosomal subunit
TETRACYCLINE S30S ribosomal subunit
CHLORAMPHENICOL 50 Sub Unit of 23 r RNA
MACROLIDES 50 Sub Unit of 23 r RNA
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AMINOGLYCOSIDES:
BactericidalActs only on Gram negative bacteriaStreptococci & anaerobes are
naturally resistantExamples: Gentamicin ,Amikacin ,
Neomycin , Given by injection .Nephrotoxic & Ototoxic - dose
related.
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TETRACYCLINES
Broad spectrum , bacteriostaticOral absorption Intracellular organisms eg. Mycoplasma,
Chlamydia ,Brucella also for V. cholera & Nocardia
Classes:Short acting: Tetracycline Long acting: Minocycline , Doxycycline
( CSF penetration).New tetracycline : Tigycycline
( MRSA,MSSA, some Gram negative bacteria and anaerobes.
Side effects :Teeth discoloration , GIT disturbance
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CHLORAMPHENICOL
Broad spectrum ,bactericidalAffects bone marrow cells and
cause a plastic anemia
Used for severe infections not responding to treatment , also for Rickettsial diseases.
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MACROLIDES: Erythromycin & Clindamycin
Bacteriostatic
Legionella, Camylobacter, Gram negative and positive infections for patients allergic to Penicillins and Cephalosporins.
Clindamycin acts on anaerobes as well
Cause GIT disturbance, Pseudomembraneous colitis.
New Macrolides : Azithromycin & Clarithromycin .
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ANTIMICROBIALS THAT ACT ON NUCLEIC ACID
Rifampicin
Quinolones
Metronidazole
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RIFAMPICIN:
Semi-synthetic, bactericidal , acts on Gram positive bacteria and selected Gram negative bacteria.
Reserved for Tuberculosis
Resistance develops quickly Used in combination
Causes discoloration of body fluids & hepatotoxicity
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QUINOLONES:
Synthetic, bactericidal, inhibit DNA Gyrase and /or topoisomerase.
Generations: first generation: nalidexic acid –locally
actingSecond generation: fluoroquinolones eg.
ciprofloxacin, norfloxacin, ofloxacin,levofloxacin
Third generation: sparfloxacin, gatifloxacin
Fourth generation: moxifloxacin, trovafloxacin
• Side effects: on cartilage & heart
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Metronidazole
• Nitroimidazole active on anaerobic bacteria, and parasite
• Caused DNA breakage• Used for B.fragilis , Trichomonas
vaginalis , amoebiasis and giardiasis.
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ANTIMETABOLITES ( folate inhibitor s):
Trimethoprim-Sulfamethoxazole ( TMP-SMX)
Combination of TMP-SMX called : Bactrim / Septrin
Block sequential steps in folic acid synthesis
Used to treat :Nocardia, Chlamydia, Protozoa & P.cranii
UTI, LRTI, OM., Sinusitis, infectious diarrhea.
Side effects: GIT, hepatitis , bone marrow depression, hypersensitivity
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ANTITUBERCULOUS AGENTS
First line: - INHRIFAMPICINETHAMBUTOLPYRAZINAMID
E
Second line:STREPTOMYCIN PASA CYCLOSERINE,CAPREOMYCIN
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ISONIAZIDE (INH)
BactericidalAffects mycobacteria at different
sites of lung tissuesUsed for the treatment &
prophylaxis of tuberculosis
Cause peripheral neuritis( pyridoxine (vitamin B6)
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Ethambutol BACTERICIDAL CONCENTRATED IN
PHAGOLYSOSOME OF ALVEOLI
OPTIC NEURITIS
Pyrazinamide ACID
ENVIRONMENT OF MACROPHAGES
HEPATITIS & ARTHRALGIA
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ANTIBIOTIC RESISTANCE IN BACTERIA
INDISCRIMINATE USE OF ANTIMICROBIALSSELECTIVE ADVANTAGE OF ANTIBIOTICS
TYPES OF RESISTANCE:PRIMARY: Innate eg. Streptococcus & anaerobes are
resistant to gentamicin.
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ANTIBIOTIC RESISTANCE IN BACTERIA (Continue)
Acquired resistance : 1- MUTATION: MTB RESISTANT TO SRTEPTOMYCIN
2- GENE TRANSFER: plasmid mediated or through transposons
Cross resistance : Resistance to one group confer resistance to
other drug of the same group . eg. Resistance to erythromycin and clindamycinDissociate resistance: resistance to gentamicin does not confer
resistance to tobramicin .
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MECHANISMS OR RESISTANCE
1- Permeability changed
2- modification of site of action, eg. MUTATION
3- inactivation by enzymes . eg. Beta- Lactamase & aminoglycoside inactivating enzymes
4- passing blocked metabolic reaction eg. PABA ---------folic acid , plasmid mediated.
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PRINCIPLES OF ANTIMICROBIAL THERAPY:
INDICATION CHOICE OF DRUG ROUTE DOSAGE DURATION DISTRIBUTION EXCRETION TOXICITY COMBINATION PROPHYLAXIS:
SHORT TERM:
MENINGITIS
LONG TERM:
TB, UTI , RHEUMATIC FEVER
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CRITERIA FOR IDEAL ANTIMICROBIAL:
SELECTIVE TOXICITY
NO HYPERSENSITIVITY
PENETERATE TISSUES QUICKLY
RESISTANCE NOT DEVELOP QUICKLY
NO EFFECT ON NORMAL FLORA
BROAD SPECTRUM
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Reference book and Reference book and the relevant page the relevant page numbers..numbers..
• Sherries Medical Microbiology, an introduction to Infectious Diseases. Latest edition, Kenneth Ryan and George Ray. Publisher: Mc Graw Hill.
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(Foundation Block, Microbiology) (Foundation Block, Microbiology)
TThank You hank You