Lecture 7: Introduction to Antimicrobial Drugs PDF

Lecture 7 Introduction to Antimicrobial drugs Dr. Mahmoud H. Taleb Assistant Professor of Clinical Pharmacology &Therapeutics Department of Pharmacology and Medical Sciences, Faculty of Pharmacy- Al Azhar University Dr. Mahmoud H. Taleb 2...

Lecture 7 Introduction to Antimicrobial drugs Dr. Mahmoud H. Taleb Assistant Professor of Clinical Pharmacology &Therapeutics Department of Pharmacology and Medical Sciences, Faculty of Pharmacy- Al Azhar University Dr. Mahmoud H. Taleb 2024-2025  Antimicrobial drugs Arc those used in the treatment of infections because of their relatively selective toxicity; the ability to kill an invading microorganism without harming the cells of the host. Antimicrobial drugs include: Antibacterial: against bacteria. Antiviral; against viruses. Antifungal: against fungi Antiparastic: against parasites Dr. Mahmoud H. Taleb 2024-2025  Clinical uses of antimicrobial agents 1- Empirical therapy or initial therapy: the antimicrobial should coverall the likely pathogens because the infecting organism(s) has not yet been defined. 2- Definitive therapy or pathogen-directed therapy: once the infecting microorganism is identified, definitive antimicrobial therapy should be instituted with a narrow-spectrum, low-toxicity agent to complete the course of treatment. ~. Qr. Mahruoud H. Taleb 2024-2025,. Ml 3- Prophylactic or preventive therapy. Therapeutic uses of antimicrobial drugs Protroatment of patient* undergoing dental extraction* wHo Kavo implanted prosthetic devices, such a* artificial heart valves, to prevent seeding of the prosthesis. For treatment of infections. For prevention of infections Prevention of tuber­ culosis or meningitis among individuals \a/Ko (prophylaxis). are irs close contact with infected patients. Treatment of the mother with r/dovud/ne to protect the fetus ir» the ca*o of an Dr. Mahmoud H. Taleb 2024-2025 HIV-infected, pregnant woman. Antimicrobial prophylaxis - Antimicrobial agents are effective in preventing infections in many settings. - In general, if a single, effective, nontoxic drug is used to prevent infection by a specific microorganism or to eradicate an early infection, then chemoprophylaxis frequently is successful. On the other hand, if the aim of prophylaxis is to prevent colonization or infection by any or all microorganisms present in the environment of a patient, then prophylaxis often fails. - Since the discriminate use of antimicrobial agents can result in bacterial resistance and superinfection, prophylactic use is restricted to clinical situations in which benefits outweigh the potential risk. - Antimicrobial prophylaxis may be divided into surgical prophylaxis and nonsurgical prophylaxis. k Dr. Mahmoud H. Taleb 2024-2025 a) Surgical Prophylaxis - Surgical wound infections are a major category of nosocomial infections. - General principles of antimicrobial surgical prophylaxis include the following: The antibiotic should be active against common surgical wound pathogens; unnecessarily broad coverage should be avoided. The antibiotic should have proved efficacy in clinical trials. The antibiotic must achieve concentrations greater than the MIC of suspected pathogens, and these concentrations must be present at the time of incision. The shortest possible course—ideally a single dose—of the most effective and least toxic antibiotic should be used. The newer broad-spectrum antibiotics should be reserved for therapy of resistant infections. If all other factors are^equaP/thd-least expensive agent should b) Nonsurgical prophylaxis - Nonsurgical prophylaxis is indicated in individuals who are at high risk for temporary exposure to selected virulent pathogens and in patients who are at increased risk for developing infection because of underlying disease (e.g. immunocompromised hosts). - Prophylaxis is most effective when directed against organisms that are predictably susceptible to antimicrobial agents. o Dr. Mahmoud H. Taleb 2024-2025  Nosocomial Infection “Nosocomial Infection “ comes from two Greek words — “ nosus” meaning “ disease “ + “ kometon “ meaning “ to take care of‘ - Also called as Hospital Acquired Infections “ HAI “ - Infections are considered nosocomial if they first appear 48 hrs or more after hospital admission or within 30 days after discharge. Dr. Mahmoud H. Taleb 2024-2025  Factors Predispose HAI (Nosocomial Infection rise as a result of4 factors) Microbial agent. Patient susceptibility. Presence of Immunocompromised microorganisms in patients hospital environment Environmental factors Bacterial Resistance Transmission of pathogens between staff and patients and among patients Dr. Mahmoud H. Taleb 2024-2025 Sources of Hospital-Acquired Infections Contaminated Hospital Environment Instruments Fluid Food Air Medications Patient Flora Invasive Devices Cutaneous Urinary catheters Gastrointestinal Vascular catheters ------------------------► Genitourinary Endotracheal tubes Respiratory Wounds -------------------------- Endoscopes Medical Personnel Colonized Infected Transient Carriers Dr. Mahmoud H. Taleb 2024-2025 (c) 2004, David Syndman. MD Sources of Nosocomial Infection Endogenous - Patients own flora may invade patients tissue during some surgical operations or instrumental manipulations. - Normal commensals of the skin , respiratory , GI , UG tract Exogenous - From another patient, staff member, environment in the hospital - Environmental sources : Inanimate objects , air, water , food - Cross infection from : other patients , hospital staff ( suffering from infections or asymptomatic carriers ) Dr. Mahmoud H. Taleb 2024-2025 Problems ofnosocomial infection - Additional suffering - Prolong hospital stay - - Increase the cost of care significantly Results - May cause death * - Increase emotional stress of the patient - Increase morbidity & mortality' ratio J J - Excess costs on stay J - Can be transmitted to discharged patients or visitors - Hi$di antibiotic resistance Dr. Mahmoud H. Taleb 2024-2025 Prevention: - Not shaving the operation site with a razor - Disinfection of the skin at the incision site - Appropriate use of preopcrative antibiotics when indicated Preoperative antibiotics started immediately before surgery and continued for 24 hrs after are effective Dr. Mahmoud H. Taleb 2024-2025  Prevention: - General hygienic measures - Use of barrier isolation materials - Routine decontamination of respiratory equipments - Using gloves , gowns & masks - Annual influenza immunization of patient and hospital staff g Dr. Mahmoud H. Taleb 2024-2025 Drug resistance Bacteria are said to be resistant when they are not sensitive to the maximum level of the antibiotic to which they were normallv sensitive. Some organisms are inherently resistant to an antibiotic (example: gram negative bacteria and vancomycin) Resistance to a certain drug may develop in one species that was normallv responsive to it and then spread to others. Dr. Mahmoud H. Taleb 2024-2025 Drug resistance may be acquired by mutation and selection, with passage of the trait vertically to daughter cells, or more commonly by horizontal transfer of resistance determinants from a donor cell, often of another bacterial species, by Transduction (acquisition of bacterial DNA from a phage). Transformation (the uptake and incorporation into the host genome by homologous recombination of free DNA released into the environment by other bacterial cells). Conjugation (Conjugation is gene transfer by direct cell-to-cell contact through bridge). Dr. Mahmoud H. Taleb 2024-2025  Drug resistance- mechanisms Drug resistance Drug resistance due Drug resistance due to due to altered targets to decreased accumulation enzymatic inactivation | Permeability | Efflux Aminoglycosides Aminoglycosides Chloramphenicol OiloramphtnKol Clindamycin Fluoroquinolone* Fluoroquinolones Fluoroquinolone* Lac tarns iVLactams ILLactam* Macrolides Macrolide* Macrolide* Rifampin Sulfonamides Tetracydine Tetracycline Tetracycline Tttraqdmt Trimethoprim (VLactams enter gram­ Vancomycin negative cells through Tetracycline was porln channels. effective against gyne­ (n$e£obactfr is largely cologic infection due resistant to cephalo­ to but now |$-Lactamases (pcnicillinasesl sporins by producing destroy antibiotic with the these organisms are (Vlactamase*. However, |L lactam nucleus. Alteration in the target resistant due to the resistant organisms Neisseria qonorrhoeae enzyme, ONA gyrate, presence of plasmid- may also have altered is now largely resistant to ha* resulted in mediated protein that porin channels through penicillin because of resistance to fluoro­ penicillinase activity. which cephalosporins drug. quinolone*. do not pass. ur. Manmoua m. laieo Classification of antibiotics 1-Cell wall synthesis inhibitors Dr. Mahmoud H. Taleb 2024-2025  Cell wall synthesis inhibitors B-LACTAMASE INHIBITORS - Clavulank acid - Sulbactam _ Bacitracin - Tozobactam - Vancomycin *- Daptomycin PENICILLINS MONOBACTAMS - Amoxicillin Aztrrociam - Ampicillin - Dkloxacillin - Indanyl carbenkillin - Methkillin lit GENERATION 2nd GENERATION 3rd GENERATION 4th GENERATION Nafcdlin Oxacillin _ Cefadroxil. Cefador _ Cefdinir. Cefepime Penkillin G _ Cefazolin. CefprozJ - Cefixime Penkillin V. Cephalexin - Cefuroxime _ Cefotaxime Piperacillin. Cefoxitin. Ceftazidime Ticarcillin _ Ceftibuten _ Ceftizoxime Ceftnaxonr