Lec2 Antibiotics1 PDF - Introduction to Antibiotics

Introduction to Antibiotics lecture 2 Qamraa Al-Qahtani, Ph.D. Assistant Professor at the Department of Pharmacology and Toxicology, Pharmacy College, King Saud University [email protected] (Sli...

Introduction to Antibiotics lecture 2 Qamraa Al-Qahtani, Ph.D. Assistant Professor at the Department of Pharmacology and Toxicology, Pharmacy College, King Saud University [email protected] (Slides are adopted and modified from Dr. Shakir Asharari) Objectives of the lecture: Understand the difference between Bacteriostatic and Bactericidal activity Describe the basic classification of antibiotics according to mechanism of action Explain the classification of antibiotics according to their spectrum of activity Definition of Antibiotics Chemical substances produced by various microorganisms (bacteria, fungi, actinomycetes) that have the capacity to inhibit or destroy other microorganisms. Nowadays they are chemically synthesized. c peni JI They either kill bacteria (bactericidal) or inhibit bacteria from growing (bacteriostatic). Antibiotics will not cure infections caused by viruses. Antibiotics arenot Antiviral  Bacteriostatic Versus Bactericidal Antibacterial drugs can be either bacteriostatic or bactericidal in their interactions with target bacteria. Bacteriostatic drugs cause a reversible inhibition of growth, with bacterial growth restarting after elimination of the drug. Abxi.ws in 1548 did By contrast, bactericidal drugs kill their target bacteria. Bacteriostatic Versus Bactericidal The decision of whether to use a bacteriostatic or bactericidal drugs depends on the type of infection the immune status of the patient. Bacteriostatic Versus Bactericidal In a patient with strong immune defenses, bacteriostatic and bactericidal drugs can be effective in achieving clinical cure. However, when a patient is immunocompromised, a bactericidal drug is essential for the successful treatment of infections. Regardless of the immune status of the patient, life- threatening infections such as acute endocarditis require the use of a bactericidal drug. Examples of Bacteriostatic and Bactericidal Antibiotics  Classification of Antibiotics A. According To Mechanism of Action INHIBITION OF CELL WALL SYNTHESIS e.g. Penicillins, Cephalosporin Vanomycin INHIBITION OF PROTEIN SYNTHESIS e.g. Macrolides, Tetracyclines INHIBITION OF DNA SYNTHESIS e.g. Quinolones. INHIBITION OF FOLATE METABOLISM e.g. Sulphonamides, Trimethoprim INHIBITION OF RNA synthesis by binding to RNA polymerase e.g. Rifampicin. Indicates for UTI 1413171 41 1. Antibiotics that Target Cell Wall: Cell Wall Structure https://www.onlinebiologynotes.com/bacterial-cell-wall-structure-composition-types/  1. Antibiotics that Target Cell Wall Cycloserine (structural analogue of D- alanine) competitive inhibition of alanine racemase that convert L-alanine to D- alanine residues which is important in peptidoglycan synthesis (used in the treatment of tuberculosis ) Vancomycin binds to the D-alanyl-D- alanine end of newly synthesized peptidoglycan subunits, preventing them from being incorporated into the cell wall by penicillin-binding proteins Peptidoglycan Structure. (transpeptidase) https://open.oregonstate.education/generalmicrobiology/chapter/bacteria-cell-walls/ 1. Antibiotics that Target Cell Wall Bacitracindephosphorylation of alipidcarrier Bacitracin interferes with the regeneration of the lipid carrier (lipid compound that carries peptidoglycans to the growing microbial cell wall ) by blocking its dephosphorylation. Penicillins, cephalosporins and other β-lactams inhibit the final transpeptidation by forming covalent bonds with penicillin-binding proteins (transpeptidase) thus preventing formation of the crosslinks vanco in 2. Antibiotics that Target Cell Membrane They disrupt inner cell membranes of bacteria leading to leakage of intracellular content and death Examples: Polymyxins B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections in topical preparations (eye and skin) because they are nephrotoxic and neurotoxicity, limiting their usability in systemic use. Mainly skininfection Daptomycin used for gram-positive bacteria In complicated skin and skin structure infections (cSSSI) and bacteremia 3. Antibiotics that Inhibit Protein Synthesis 50S 30S MIYS5075 ATT 305 4. Antibiotics that Inhibit RNA Synthesis; Inhibitors of RNA Polymerase 5. Antibiotics that Inhibit DNA Synthesis Quinolones are a key group of antibiotics that interfere with DNA synthesis by inhibiting topoisomerase, most frequently topoisomerase II (DNA gyrase), an enzyme involved in DNA replication. The fluoroquinolones, second-generation quinolones that include levofloxacin, norfloxacin, and ciprofloxacin, are active against both Gram-negative and Gram-positive bacteria. 6. Antibiotics that Inhibit bacterial folate synthesis Sulfonamides and trimethoprim inhibit synthesis of folate at two different sites. The sulfonamides are structurally similar to PABA and block the conversion of PABA into dihydropteroic acid. Trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate by inhibiting the enzyme dihydrofolate reductase. it is Folate, or folic acid, also known as vitamin B9, is necessary for the synthesis of nucleic acids, which are the building blocks of DNA and RNA. Examples: Sulfonamides and trimethoprim 2Bacteriostatic Bacterioloidal B. Classification of antibiotics According to spectrum  The spectrum of activity of an antibacterial drug relates to diversity of targeted bacteria. Narrow spectrum , e.g.: penicillin G, aminoglycosides Pathogens Is V6 if Broad spectrum , e.g.: ampicillin, amoxicillin mW Resistent n sons Spectrum of Activity 1. A narrow-spectrum antimicrobial targets only specific subsets of bacterial pathogens. For example, some narrow-spectrum drugs only target gram- positive bacteria, whereas others target only gram-negative bacteria. If the pathogen causing an infection has been identified, it is best to use a narrow-spectrum antimicrobial and minimize collateral damage to the normal microbiota. Normalflora Spectrum of Activity 2. A broad-spectrum antimicrobial targets a wide variety of bacterial pathogens, including both gram- positive and gram-negative species, and is frequently used when the pathogen is not identified to cover a wide range of potential pathogens while waiting on the laboratory identification of the infecting pathogen. also used for infections caused by multiple bacterial species, Used also for prevention of infections with surgery/invasive procedures. broad-spectrum antimicrobials may be selected to treat an infection when a narrow-spectrum drug fails because of development of drug resistance by the target pathogen. Spectrum of Activity The risk associated with using long-term broad-spectrum antimicrobials is that they will also target a broad spectrum of the normal microbiota (normal flora), This will increase the risk of a superinfection, a secondary infection in a patient with a preexisting infection. 41 5 dsÑl did W.tw mi Spectrum of Activity A superinfection develops when the antibacterial agent intended for the preexisting infection kills the protective microbiota, allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection. Common examples of superinfections that develop as a result of antimicrobial usage include: Yeast infections (candidiasis) and Pseudomembranous colitis caused by Clostridium difficile, which can be fatal.  Indications for Antibiotics: 1. Definitive therapy This is for proven bacterial infections Attempts should be made to confirm the bacterial infection by means of staining of secretions/fluids/exudates, culture & sensitivity, serological tests & other tests Based on the reports, a narrow spectrum, least toxic, easy to administer & cheap drug should be prescribed. Antibiotic sensitivity test 2. Empirical therapy Empirical antibacterial therapy should be restricted to critical cases, when time is inadequate for identification & isolation of the bacteria & reasonably strong doubt of bacterial infection exists: - septicemic shock/sepsis syndrome - immunocompromised patients with severe systemic infection - hectic temperature/fever - neutropenic patient (reduction in neutrophils) In such situations, drugs that cover the most probable infective agent/s should be used. Empiric antibiotic is antibiotic therapy that is begun before a specific pathogen is identified 3. Prophylactic therapy Certain clinical situations require the use of antibiotics for the prevention rather than the treatment of infections. In all these situations, only narrow spectrum & specific drugs are used The duration of prophylaxis is dictated by the duration of the risk of infection. e.g. Treatment prior to certain surgical procedures to prevent infections Indications for antibiotics prophylaxis Surgical prophylaxis bowel surgery, joint replacement, and some gynecological interventions to prevent postoperative infections. Immunosuppressed Patients Very old, very young Diabetics, Anaemics, AIDS pts ,Cancer pts. Dental extractions Pts with total joint replacements Pts with cardiac abnormalities