Antimicrobial Chemotherapy Lecture Notes PDF

ANTIMICROBIAL CHEMOTHERAPY  Lecture Title ANTIMICROBIAL CHEMOTHERAPY  Instructor information Contact: Professor Doctor Mohammed Mahmoud El-Naggar Department. Medical Microbiology and Immunology Official email: [email protected] Mobile (optional): 01...

ANTIMICROBIAL CHEMOTHERAPY  Lecture Title ANTIMICROBIAL CHEMOTHERAPY  Instructor information Contact: Professor Doctor Mohammed Mahmoud El-Naggar Department. Medical Microbiology and Immunology Official email: [email protected] Mobile (optional): 01126625177 Academic hours:  Sunday: 10:00-12:00 AM  Learning outcomes By the end of this lecture the students will be able to: Describe the mechanism of action of different classes of antimicrobials. Identify causes and mechanisms of bacterial resistance. Identify different methods of antibiotic sensitivity  Contents Classification, Mechanism of action of antimicrobials on bacteria Bacterial resistance to antimicrobials  Antimicrobial agents Is a chemical substance derived from a biological source or produced by chemical synthesis that kills or inhibits the growth of microorganisms. Antibiotic: Is a naturally occurring and synthetically derived organic compound that inhibit or destroy selective bacteria.  Antimicrobial drugs Antibacterial drugs (antibiotics) Antiviral drugs Antifungal drugs  Antibacterial Agents Mechanism of action: – Cell wall synthesis. – Cell membrane function. – Protein synthesis. – DNA replication. – Other. 4/13/2009 12:06:46 AM Dr. Medhat A. Eldaker 8  Desired properties of antibiotics (ideal antibiotic) 1. Selective toxicity. 2. Bacteriocidal rather than bacteriostatic. 3. Broad spectrum. 4. Water soluble and stable. 5. Long plasma half-life. 6. Good tissue distribution. 7. Non-allergic. 8. Do not develop antibacterial resistance.  I. Cell wall inhibitors 1. Beta lactams a. Penicillins b. Cephalosporins c. Monobactams d. Carbapenems  a. Penicillins: Gram positive organisms Natural Penicillin G not produce beta- penicillins lactamases Penicillinase- penicillinase-producing resistant Methicillin Staphylococci penicillins Extended- many strains of Gram spectrum Amoxycillin negative bacteria penicillins  b. Cephalosporins 1st 2nd 3rd 4th Next generation generation generation generation generation Gram Gram positive Gram positive negative activity activity activity > Broadest activity >Gram =Gram Gram positive spectrum of against negative negative action (MRSA) + activity activity Pseudomonas Cephalothin Cefuroxime Cefotaxime Cefepime Ceftobiprole  2. Glycopeptides Inhibit cell wall synthesis at a site different than the β-lactams. Vancomycin Used mainly in treatment of MRSA. 3. Lipoglycopeptide 4. Polypeptides  II. Inhibitors of Protein Synthesis: Large 50S subunit 30S Small subunit  Inhibitors of Protein Synthesis 30S inhibitors 50S inhibitors Aminoglycoside Tetracyclin Macrolides Chloramphenicol Gentamicin Oxytetracyclin Erythromycin Chloramphenicol Amikacin III. Inhibitors of Cell membrane  Polymyxins Cyclic Lipopeptides Polymyxin B  topical. Daptomycin Amphotercin B  antifungal. Active against Gram positive. IV. Inhibitors of Nucleic Acid Synthesis:  1. Sulphonamides: – Act through inhibition of precursor for DNA synthesis. Trimethoprim, used in Chemoprophylaxis against meningococcal meningitis.  2. Quinolones: – Target Topoisomerases, (e.g. DNA gyrase). e.g Ciprofloxacin, levofloxacin  3. Furanes: – Act through damaging bacterial DNA. – e.g. Nitrofurantoin, has a broad spectrum activity and used mainly in treatment in urinary tract infections. 4. Rifampicin:  Acts through inhibition of RNA polymerase.  Reserved as antituberculous.  Mechanisms of resistance 1. Reduction of intracellular antibiotic accumulation by decreasing permeability and/or increasing active efflux of the antibiotic (efflux pump). 2. Enzymatic inactivation: β-lactamases, that inactivate β-lactams. 3. Alteration of target site: Occurs due to mutations that alter the site targeted by the antibiotic. P12 of 30S ribosomal subunit  R (Streptomycin). 4. Alteration of metabolic pathway:  Origin of Drug Resistance 1. Non-genetic. 2. Genetic: a) Chromosomal. b) Extra chromosomal. - The following antimicrobial agents act through inhibition of cell wall synthesis. a. Sulphanamides b. Rifampicin c. Cephalosporins d. Aminoglycosides e. Tetracyclin  References or further readings Brooks, G. F., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2013). Jawetz, Melnick, & Adelberg's medical microbiology. New York: McGraw Hill Medical. Topley and Wilson’s Microbiology and Microbial Infections: 10th edition.