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ANTIMICROBIALCHEMOTHERAPYDR. MEDHAT A. ELDAKERLecturer of Microbiology & ImmunologyFaculty of Medicine – Mansoura University

Cell Wall InhibitorsII. GlycopeptidesVancomycin- Resistant Gram-positive bacteria.- MRSA.Cycloserine- TBBacitracin- Diagnostic- TopicalIII. PolypeptidesA. CycloserineB. Bacitracin1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker10

Protein Synthesis Inhibitors30 S50 SAminoglycosideTetracyclinMacrolideChloramphenicolB-cidalB.staticB-cidalBothGm –ve & PseuSpir-Rick-ChlaGm +ve> -veEnteric feverGentamicinOxytetracyclinErythromycinChloramphenicolAmikacinDoxycyclinAzythromycinTobramyscinClindamycinNeomycinKanamycinStreptomycin1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker12

DNA Replication InhibitorsI. SulphonamidesBactiristaticUTI-Chemoprophylaxis- e.g Trimethoprim.Inhibition of precursorII. QuinolonesBactricidalBroad spectrum- Ofloxacin - Ciprofloxacin- Gatifloxacin - LevofloxacinInhibition of DNApolymerase- Nitrofurantoin (UTI)III. RifampicinBactricidalTBInhibition of RNApolymerase1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker13

Cytoplasmic membrane InhibitorsPolyenesBactiristatic- Polymyxin B topical- Amphotercin B antifungal- Mitronidazole anaerobes1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker14

• Def:Antibiotic Combination• Synergism:‣ 1+1= > 2‣ Cidal + Cidal• Antagonism:‣ 1 + 1 = 0‣ Cidal + Static1- Sequential block of a metabolic pathway2- One drug may enhance the uptake of theother.3- One drug may facilitate the entry of thesecond drug.4- Suicidal ring.• Addition:‣ 1 + 1 = 2‣ Static + Static1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker15

Antibiotic Combination• Indications:‣ Serious microbial infections.‣ Resistant pathogens.‣ Mixed infection.• Disadvantages:‣ Side effects.‣ Antagonism (drug reaction).‣ Economic impacts.1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker16

Antimicrobial chemoprophylaxisI) prophylaxis in persons of normal susceptibilityexposed to specific pathogen.- Prophylaxis from Rheumatic fever by long actingPenicillin.- Prophylaxis from meningitis by Rifampicin.II) Prophylaxis in persons of increased susceptibility:- Heart diseases.- Respiratory diseases (Chronic).- Recurrent urinary tract infections.- Immunosuppressed host.III) Surgical prophylaxis1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker17

Bacterial Resistance toAntimicrobial Drugs• Mechanism:‣ Decreased permeability.‣ Inactivation.‣ Alteration of target site.‣ Alteration of metabolic pathway.‣ Alteration of metabolic enzymes.1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker18

Bacterial Resistance toAntimicrobial DrugsOrigin of Drug ResistanceGeneticNon-geneticChromosomalExtra-chromosomalPlasmidsTransposonos1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker19

Chromosomal Resistance(Drug Resistant Mutants)• Mechanism:‣ Spontaneous mutation Altered target.‣ Rare.‣ Need the presence of antibiotic selective pressurefactor.‣ Low frequency of transmission.• Example:‣ P12 of 30 S ribosomal subunit R (Streptomycin)1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker20

• Mechanism:Plasmid Resistance(R Factor)‣Presence of R factor???‣Enzymatic:B lactamasesAcetyl transferase‣No need for selective pressure factor.‣High frequency of transmission by ???- Plasmid carry genes of resistance.- If transmissible epidimicresistance1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker21

Transposons Resistance(jumping genes)• Mechanism:‣Presence of transposons ???‣Enzymatic: B lactamases‣No need for selective pressure factor.‣High frequency of transmission by ???1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker22

Non-Genetic Resistance(Biochemical Resistance)• Mechanism:‣Decreased permeability.‣Alteration of target site.‣ Metabolic pathway.‣ Metabolic enzymes.• Characters:‣ Non transmissible.1/4/2011 10:16:17 AM Dr. Medhat A. Eldaker24

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