Introduction To Antimicrobial Therapy PDF

Introductio n to Antimicrobi al Therapy Objectives By the end of this lecture, you should be able to: Appreciate the concept of “selective toxicity” of antimicrobial agents. Define the term empiric therapy and evaluate its application. Differentiate between bacteriostatic and bactericid...

Introductio n to Antimicrobi al Therapy Objectives By the end of this lecture, you should be able to: Appreciate the concept of “selective toxicity” of antimicrobial agents. Define the term empiric therapy and evaluate its application. Differentiate between bacteriostatic and bactericidal antibiotics. Define the term chemotherapeutic spectrum of an antibiotic. Appreciate the concept of bacterial resistance and discuss mechanisms of antibiotic resistance Discuss the genetic determinants of resistance to antibiotics. Objectives cont’d Discuss the implications associated with using antibiotic combinations and evaluate cases in which combinations are used. Evaluate the use of prophylactic antibiotics in certain clinical conditions. State some general complications associated with using antibiotics. Classify antibiotics based on their mechanism of action. Chemotherapy of Infections “Chemotherapy” The term was developed by Ehrlich at the beginning of the 20th century to describe the use of chemicals to treat diseases, particularly infectious diseases. “Antibiotics” Substances produced naturally by microorganisms or synthetically that kill or inhibit the growth of other microorganisms. Why are antimicrobial drugs effective in the treatment of infections? Selective Toxicity Chemotherapeutic drugs should be toxic to invading organisms and innocuous to the host This can be based on biochemical differences between the pathogens and the host Selective toxicity is relative not absolute; so drug concentration must be carefully monitored so it attacks the microorganism without affecting the host Activity 1 What do you think are the factors you should know before selecting Antimicrob a drug to treat a ial Drug certain Selection condition? Empiric Therapy Some critically ill patients require urgent therapy - choosing a drug in the absence of sensitivity data - which is influenced by the site of infection and patient history This is empiric therapy Therapy should be initiated after specimens for laboratory analysis are taken and before culture results are available Antimicrobial Drugs Bacteriostatic Drugs Bactericidal Drugs N.B. This classification is too simple; certain drugs may be bacteriostatic for one organism and Chemotherapeutic Spectra Extended Spectrum Narrow Spectrum Affects gram + and a Affects a single or limited significant number of gram group of mo. – bacteria E.g. Isoniazid active E.g. Ampicillin acts on against mycobacteria only gram + and some gram – bacteria Broad Spectrum Affect a wide variety of microbial species E.g. Tetracyclines and Chloramphenicol Drug Resistance It is the ability of a microorganism to withstand an antibiotic to which they where once sensitive to Resistance is a biological phenomenon that can be accelerated by a variety of factors, including human practices  Drug Resistance Video and Report https://www.reactgroup.org/antibiotic-resistance/the-threat/ Antibiotic Sensitivity Test Type of Bacteria Resistance of Bacteria How would you react to reduce drug resistance ?? Read through pages 622- 623 of your Rang and Dale textbook Mutations Gene Amplifications Plasmids Transposons Gene Casettes and Integrons Conjugations Transductions Transformation  Bacterial Resistance  Antibiotic Resistanc e Innate Acquired Activity 2: Drug Resistance Read through pages 622-623 of your textbook What are the genetic determinants of antibiotic resistance? What do each of them mean? Gene Mutations Plasmids Amplification (A) (B&C) (E) Plasmi d Activity 2: Drug Resistance Read through pages 622-623 of your textbook How can resistant genes be transferred between genetic elements in a bacterium? Gene cassettes Transposons and (F) integrons (F) Activity 2: Drug Resistance Read through pages 622-623 of your textbook How can resistant genes be transferred between bacteria? Transformati Conjugation Transduction on (C) (G) (D)  Mutation A s Plasmids B C Plasmids/Conjugation G Transduction  Transformation D E Gene Amplification F Biochemical Mechanisms of ResistanceAlteration of drug- sensitive binding site E.g. aminoglycoside binding site on 30S subunit Erythromycin binding site on 50S subunit PBP site in MRSA Production of enzymes Decreased drug that inactivate the drug accumulation in bacteria through inhibition of E.g. β-lactamase for cleavage of β- porin synthesis and lactam ring in penicillins/cephalosporins promotion of efflux Chloramphenicol acetyltransferase pumps Phosphorylation of aminoglycosides E.g.Tetracyclines Alteration of enzyme pathways E.g. trimethoprim no longer has affinity to dihydrofolate reductase enzyme Biochemical Mechanisms of Resistance  Antimicrobial Combinations / Prophylaxis It is therapeutically advisable to treat patients with one agent specific for the infecting microorganism and it is also unadvisable to use antibiotics prophylactically - WHY?? In some situations, the use of antibiotic combinations is necessary: Life threatening Mixed infections conditions When there is a risk of developing resistant microorganisms as in TB  Prophylactic Antibiotics Prevention of Pretreatment of streptococcal patients undergoing infections in patients dental extractions with rheumatic heart who have implanted disease prosthetic devices Prevention of TB or meningitis in Treatment prior to individuals in close certain surgical contact with procedures infected patients  Complications of Antibiotic Therapy Direct Toxicity Hypersensitivity E.g. Aminoglycosides E.g. Penicillins cause cause ototoxicity by hypersensitivity reactions interfering with the ranging from uticaria to membrane function in anaphylactic shock hair cells of organ of Corti Superinfection Therapy with broad spectrum antibiotics may lead to alterations in normal flora allowing overgrowth of opportunistic organisms Classification of Antimicrobial Agents Classification of Antimicrobial Agents Objectives By the end of this lecture, you should be able to: Appreciate the concept of “selective toxicity” of antimicrobial agents. Define the term empiric therapy and evaluate its application. Differentiate between bacteriostatic and bactericidal antibiotics. Define the term chemotherapeutic spectrum of an antibiotic. Appreciate the concept of bacterial resistance and discuss mechanisms of antibiotic resistance Discuss the genetic determinants of resistance to antibiotics. Objectives cont’d Discuss the implications associated with using antibiotic combinations and evaluate cases in which combinations are used. Evaluate the use of prophylactic antibiotics in certain clinical conditions. State some general complications associated with using antibiotics. Classify antibiotics based on their mechanism of action. Thank You!!