Introduction to Antimicrobials - Spring 24 PDF

DISCLAIMER This session is being recorded. Class recordings are distributed for the exclusive use of students in the LMU DeBusk College of Osteopathic Medicine. Student access to and use of class recordings are conditioned on agreement with the terms and conditions set below. Any student who does no...

DISCLAIMER This session is being recorded. Class recordings are distributed for the exclusive use of students in the LMU DeBusk College of Osteopathic Medicine. Student access to and use of class recordings are conditioned on agreement with the terms and conditions set below. Any student who does not agree to them is prohibited from accessing or making any use of such recordings. INTRODUCTION TO ANTIMICROBIALS Mohammed Sayed, Ph.D. [email protected] Any student accessing class recordings (1) acknowledges the faculty members’ intellectual property rights in recorded lectures and class materials and that distribution of the recordings violates the DCOM Copyright Policy; (2) recognizes the privacy rights of fellow students who speak in class; (3) accepts that distributing, posting, or uploading class recordings to students or any other third party not authorized to receive them or to those outside DCOM is an Honor Code violation; and (4) agrees that recordings are to be accessed and used only as directed by the faculty member(s) teaching the course. 1 LECTURE OBJECTIVES Define factors that impact appropriate antibiotic selection List side effects common to all antibiotics Explain common mechanisms that bacteria use to resist the actions of antibacterial agents and list specific actions that help reduce emergence of resistance Differentiate between prophylactic use, empirical use, and definitive use of antibiotics; -cidal versus -static; time dependent versus concentration dependent action Given a patient case, determine appropriate clinical action regarding the transition from empiric to definitive therapy 3 2 DEFINITIONS MIC: Minimum Inhibitory Concentration- lowest concentration of antibiotic that inhibits bacterial growth MBC: Minimum Bactericidal Concentration - lowest concentration of antibiotic that kills 99.9% of bacteria Bacteriostatic: arrest growth and replication of bacteria Bactericidal: kill bacteria at drug serum levels achievable in the patient Nosocomial: “nosus”- disease + “komeion” – to take care of Any disease contracted by a patient while under medical care 4 WHAT ARE “ANTIMICROBIALS”? Agents that kill microorganisms or stop their growth Antibiotics: work mainly against bacteria. Antifungals: against fungi. Antivirals: against viruses. Antiprotozoals: against protozoan parasites. Anthelmintics: against parasitic worms. In addition to disinfectants (used on inanimate surfaces) and antiseptics (used on living tissues). PENICILLIN: THE FATHER OF ANTIBIOTICS Discovered in 1928 when Sir Alexander Fleming, noticed that spores of a green mold, Penicillium rubens killed his bacterial cultures, and ruined his work. He postulated that the mold produced an unseen molecule, which he called (Penicillin), which is successful in killing bacteria. This discovery was probably the most important discovery of the 20th century, saving the lives of billions of people, animals and plants! 5 6 DEFINITIVE VS EMPIRIC VS PROPHYLAXIS Severe infections need to begin therapy immediately Broad spectrum utilized for empiric therapy with narrow spectrum for definitive Definitive  Address sensitivity of known pathogen Empiric  After specimens have been obtained but before the results are finalized  Critically ill patients, a delay until susceptibility is known could prove fatal STRATEGIES OF ANTIMICROBIAL THERAPY 7 Prophylaxis  Prevent infection during invasive procedures  Prevent transmission in persons with increased risk 8 DEFINITIVE TREATMENT EMPIRIC THERAPY In utopia, the antimicrobial agent is selected after the identification and susceptibility have been established In reality, we have to use empiric therapy. Microbiologic or serologic diagnosis with susceptibilities known or presumed Timing  Initiate therapy AFTER specimens for lab analysis have been obtained but BEFORE the results are available Want most effective, least toxic, narrowest spectrum, and most cost-effective agent  May be a combination of drugs Selecting a drug  Influenced by site of infection and patient history  Broad-spectrum may be initially indicated  Influenced by known association of a particular organism in a clinical setting. Susceptibility Testing Drug, dose, route, interval, and duration is disease state and patient specific  know the alternatives, especially for patients with allergy to drug of choice Remember: When you hear hooves, think horses, not zebras! 9 10 PROPHYLAXIS HOW DO WE SELECT A SUITABLE ANTIBIOTIC? 11 12 There are literally hundreds of them! FACTORS CONSIDERED IN SELECTION OF ANTIMICROBIAL AGENTS Organism’s identity Organism’s susceptibility SELECTION OF AGENTS: ORGANISM IDENTITY Site of infection Patient factors Safety Cost 13 IDENTIFYING THE ORGANISM 14 GRAM STAIN Gram Stain (+ve vs. –ve) Culture and sensitivity Detection of antigens Detection of RNA or DNA Detection of Host Immune Response Peptidoglycan = Murein 15 16 Gram +ve is Purple Gram -ve is Pink 17 18 ORGANISM’S SUSCEPTIBILITY SELECTION OF AGENTS: ORGANISM SUSCEPTIBILITY Susceptible - isolates are inhibited by the achievable concentrations of antimicrobial agent when the recommended dosage is used for site of infection Intermediate - clinical efficacy in body sites where the drugs are physiologically concentrated or when a higher-than-normal dosage of a drug can be used Resistant - isolates are not inhibited by the usually achievable concentrations of the agent 19 20 EXAMPLE OF C/S REPORTING Final Release D/T: >100,000 CFU/ML GRAM NEGATIVE RODS >100,000 CFU/ML ESCHERICHIA COLI AMPICILLIN 4 S AMOX/CLAV ACID