Lecture 8: Introduction to Antibiotics and Antibiotic Resistance (Almaarefa University)

# Lecture 8: Introduction to Antibiotics and Antibiotics resistance ## Almaarefa University, College of Medicine, Microbiology & Immunology Unit **Lecturer:** Dr. Rasha Mokhtar Elnagar **Credentials:** - M.B.B.C - MSc - PhD, MD Medical Microbiology and Immunology - Associate Professor of Medical...

# Lecture 8: Introduction to Antibiotics and Antibiotics resistance ## Almaarefa University, College of Medicine, Microbiology & Immunology Unit **Lecturer:** Dr. Rasha Mokhtar Elnagar **Credentials:** - M.B.B.C - MSc - PhD, MD Medical Microbiology and Immunology - Associate Professor of Medical Microbiology & Immunology - Consultant Microbiology & Immunology ## Antimicrobial agents - Are chemical substances that kill or inhibit the growth of microorganisms. - **Include:** - Antibiotics - Antivirals - Antifungals - Antiparasitic drugs - Are toxic to microbes **not** to human cells. ## Antibiotics ### Classifications of Antibiotics - **Spectrum of activity** - Broad spectrum - Narrow spectrum - **Mode of action** - Bacteriostatic - Bactericidal - **Site of action** ### 1. Spectrum of activity #### Narrow spectrum - Effective only against a single or a limited group of bacteria. - Example: Isoniazid is active only against mycobacteria #### Broad spectrum - Effective against a wide variety of bacterial species. #### Examples: - **Broad Spectrum** - Carbepenams - Chloramphenicol - 2nd, 3rd, 4th Gen Cephalosporiins - 3rd Gen Fluoroquinolones - Broad spectrum penicillins - Tetracydines - **Narrow spectrum** - Penicillin V and G - Lincosamides (Clindamycin) - Glycopeptides (Vanco and Teicoplanin) - Isoniazid ### 2. Mode of action #### Bacteriostatic - Inhibit the growth and replication of bacteria. #### Bactericidal - Kill the bacteria. #### Bacteriostatic vs Bactericidal - **EXAMPLES:** - **Bacteriostatic** - Chloramphenicol - Erythromycin - Clindamycin - Sulfonamides - Trimethoprim - Tetracyclines - **Bactericidal** - Aminoglycosides - Beta-lactams - Vancomycin - Quinolones - Rifampin - Metronidazole ### 3. Site of action - **1. Inhibition of cell wall:** - Glycopeptides - Beta Lactams - **2. Disturbance of cell membrane:** - Polymyxins - Daptomycin - **3. Inhibition of protein synthesis:** - Aminoglycosides - Spectinomycins - **4. Inhibition of nucleic acid:** - DNA gyrase - Quinolones - RNA Elongation - Actinomycin - DNA-directed RNA polymerase - Rifampin - 50s inhibitors of protein synthesis - Streptogramin - Amphenicol - Macrolids - Lincosamides - Oxazolidinones - 30S inhibitors of protein synthesis - Aminocyclitols - Tetracyclines ## Target Sites for Antibiotics in The Bacteria Cell ### 1. Cell wall synthesis inhibitors #### A. Beta - lactams - Bind to the penicillin binding proteins (transpeptidase) and inhibit peptidoglycan cross linking. #### B. Glycopeptides - Example: Vancomycin - Narrow spectrum: Gram-positive ### 2. Cell membrane inhibitors - Polymyxins - Narrow spectrum: Gram-negative - Nephrotoxicity and neurotoxicity ### 3. Protein synthesis inhibitors - Bind to the 30s or 50s ribosome and inhibit protein synthesis - **Examples:** - **Macrolides** - erythromycin - azithromycin - **Aminoglycosides** - gentamycin - **Tetracyclines** - tetracycline - Doxycycline ### 4. Nucleic acid inhibitors - **Examples:** - **Sulfonamides and trimethoprim** (as co-trimoxazole) - Inhibit folic acid pathway for purines synthesis - **Quinolones** - ciprofloxacin - Inhibit DNA gyrase or topoisomerase - **Rifampicin** - Inhibit RNA polymerase (RNA transcription) ## Causes of failure of antibiotics therapy - **Antibiotic** - Inadequate dose - Inadequate duration - Wrong route of administration - Wrong choice of antibiotics - Use of antagonistic antibiotic combination - **Bacteria** - Viral infection - Mixed bacterial infection - Antimicrobial resistance ## Drug resistance - Means unresponsiveness of bacteria to antibiotics - **Mechanism of resistance:** ### 1. Natural (Intrinsic) Resistance - Bacteria naturally resist the antibiotic without previous exposure. - They lack the target site of the antibiotic agent. #### Examples - **Mycoplasma** and **Chlamydia** naturally resist **Beta-lactam** antibiotics due to lacking cell wall peptidoglycan (target site of action for beta-lactam antibiotics). - **Gram-negative** bacteria are naturally resistant to **Vancomycin**. ### 2. Acquired resistance - Resistance mechanisms are developed after exposure to antibiotics (They were sensitive before). - **Mutation** of existing genes or **Acquisition** of new resistance genes. - The resistance genes can be transferred among bacteria by **gene transfer mechanisms:** - Conjugation (Sex pili; resistant plasmid "R plasmid") - Transduction (Bacteriophage) - Transformation ### 2. Modification of target sites of antibiotics - **Salmonella typhi:** Modified DNA gyrase→ Quinolones resistance - **Methicillin-resistant Staphylococcus aureus (MRSA)** - **Definition:** Infection by a type of Staphylococcus aureus bacteria that are resistant to many antibiotics used to treat Staphylococcus aureus infections. - **Mechanism of resistance:** Modified penicillin-binding protein (PBP) that inhibits binding of beta-lactam antibiotics - Encoded by the mecA gene - **Mode of Transmission:** - Contact with an infected person; Crowded places - Sharing personal tools (shaving razors, pillowcases, or towels) - Touching contaminated surfaces (doorknobs) ### 3. Increased Drug efflux - Pumping antibiotics outside the bacterial cell making the drug is unable to reach to the site of its action #### Examples - Gram-negative bacteria (such as E. coli and Pseudomonas aeruginosa) efflux beta-lactam antibiotics and tetracyclines ### 4. Drug inactivation - Some bacteria produce enzymes that inactivate the antibiotics. - **Examples:** - b-lactamases (penicillinases and cephalosporinases) - Adenyl transferases: inactivate aminoglycosides ## Mechanism of antibiotics Resistance - **Natural Resistance:** Lack the target site - Mycoplasma resist b-lactams - Gram negative resist vancomycin - **Mutation of existing genes or Acquisition of new resistance genes** - Resistant genes transferred by: - Conjugation (sex pili, resistant plasmids "R plasmids") - Transduction (Phage mediated) - Transformation - **Modification of target site** - MRSA resist b-lactams - Salmonella typhi resist fluoroquinolones - **Drug Inactivation** - b-lactamases - Adenyl transferase inactivate aminoglycosides - **Increased Drug Efflux** - E. coli, Pseudomonas aeruginosa resist Beta-lactam antibiotics & tetracyclines ## Mechanisms of action antibiotics & antibiotics resistance - **Antibiotic Action** - **Cell wall synthesis** - Vancomycin - Cephlospoprins - b-lactams - Bacitracin - **Protein synthesis** - Aminoglycosides - Chloramphenicol - Tetracycline - Linezolid - **Nucleic acid synthesis** - Rifampin - Metronidazole - Quinolones - Fluoroquinolones - Trimethoprim - Dapsone - Sulfonamide - **Cell membrane** - Polymyxin - Daptomycin - **Antibiotic Resistance** - **Natural Resistance** - **Efflux pumps** - Tetracycline - Aminoglycosides - b-lactams - Fluoroquinolones - **Inactivation of antibiotic substance** - Macrolides - b-lactams - Aminoglycosides - **Target by-pass** - Vancomycin - Trimethoprim - Tetracycline - Sulfonamide - **Target modification** - Vancomycin - Aminoglycosides - Fluoroquinolones - Penicillin - **Resistance genes** ## Cross-resistance - Bacteria resistant to a certain antibiotic may also be resistant to other antibiotics that have the same mechanism of action or chemical structure - **Examples:** - **Macrolides (Azithromycin)** - **Lincosamides (as Clindamycin)** ## How to Decrease Antibiotic Resistance - Avoid unnecessary antibiotic prescriptions. - Proper antibiotic selection. - Give empirical antibiotic first then modify according to culture and sensitivity results - Use antibiotics in the proper route, dose, and duration - Antibiotic recycling (stopping certain antibiotics for a period then re-evaluating their potency) - **Establishment of antibiotic stewardship program.** ## Antibiotic Stewardship program - Antibiotic stewardship is the program designed to improve how antibiotics are prescribed by clinicians and used by patients. - The Ministry of Health prepares and publishes guidelines for the treatment and prophylaxis of infections. It also determines the list of restricted antimicrobials. ### Aims of antibiotics stewardship - Treat infections: type, dose, duration, route. - Protect patients from harm caused by unnecessary antibiotic use - Decrease antibiotic resistance ## Antibiotic Combination - **Indication:** - Mixed infection - Severe life-threatening infections (such as meningitis ) - Resistant bacteria - **Aim:** - Synergism: 2 antibiotics produce a combined effect greater than the sum of their separate effects. - **Disadvantage:** - High cost - More adverse effect - **Antagonism:** 2 antibiotics oppose to each other, reduces their overall affect. ## Multiple Choice Questions - **Q1:** Which one of the following groups of antibiotic agents acts on bacteria by inhibiting protein synthesis? - A. Fluoroquinolones - **B. Aminoglycosides** - C. Penicillins - D. Vancomycin - **Q2:** The drug of first choice for the treatment of a typical pneumonia caused by Mycoplasma pneumoniae is: - A. Penicillin G - B. Vancomycin - C. Cephalosporins - **D. Macrolides** ## Reference - Lippincott Illustrated Microbiology 4th edition, Chapter 5. ## Thank You! The image is a thank you card with balloons and the text "thank you".