Antimicrobial Agents PDF
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Summary
This document introduces various aspects of antimicrobial agents, including their mechanisms of action, different types, and the concept of resistance mechanisms.
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6 ANTIMICROBIAL AGENTS Drugs- chemicals that affect physiology Chemotherapeutic Agents- drugs that treat disease Antimicrobial Agents (Antimicrobials)- drugs that treat infections Synthetics- antimicrobials—fully synthesized in a lab Antibiotics- produced naturally by organism (most used) Semisyn...
6 ANTIMICROBIAL AGENTS Drugs- chemicals that affect physiology Chemotherapeutic Agents- drugs that treat disease Antimicrobial Agents (Antimicrobials)- drugs that treat infections Synthetics- antimicrobials—fully synthesized in a lab Antibiotics- produced naturally by organism (most used) Semisynthetics- chemically altered antibiotics (more effective, easier to administer) SPECTRUM OF ACTION Broad: -effective against many organisms -specific agent unknown -reduces risk of superinfections Narrow: -limited range of effectiveness -agent is known THERAPEUTIC INDEX ***Compares blood concentration @which drug becomes toxic, and @which drug is effective*** -larger is safer 6 MECHANISMS OF ACTION OF MICROBIAL AGENTS 1. Inhibition of Cell Wall Syntheses: a) beta-lactams -cross-linkage of NAM prevented -weakened cell wall= lyse (break down) Penicillin G -natural antibiotic Ampicillin -semisynthetic Amoxicillin -semisynthetic b) semisynthetic derivatives of beta-lactams -stable in acidic environments -more readily absorbed -more active against more types of bacteria Methicillin (semisynthetic) -penicillinase resistant c) non-beta lactams Bacitracin (antibiotic) - blocks transport of NAG and NAM from cytoplasm -prevents cell wall formation Isoniazid (antibiotic) -disrupts mycolic acid 2. Inhibition of Protein Synthesis: a) prokaryotic ribosome interference b) RNA interference Tetracyclines-block tRNA docking site *Antisense Nucleic Acids-bind to RNA, blocking ribosomal subunits Mupirocin -selectively binds to isoleucyl-tRNA synthetase 3. Disruption of CM: -membrane does not remain intact w/out ergosterol Polyenes: Amphotericin B -attach to ergosterol (fungal membrane) -toxic to human kidneys Azole -inhibit ergosterol synthesis 4. Inhibition of Metabolic Pathways: Trimethoprim-interferes w/ nucleotide synthesis ***PABA + sulfonamides *** 5. Inhibition of Nucleic Acid Synthesis: -blockage of DNA replication +RNA transcription Analogs-interfere w/ Nucleic acid function -distort shape -often used against virus 6. Inhibition of Viral Infection: -prevention of virus attachment, entry, uncoating Attatchment antagonists-block viral attachment/ receptor proteins RESISTANCE Bacterial Resistance: (gained 2 ways) 1. Gene mutations 2. Acquisition of R plasmids (transformation, transduction, conjugation) 7 Mechanisms of Resistance: 1. Produce enzyme—destroy/deactivates drug 2. Slow/prevent entry of drug into cell 3. Alter target of drug 4. Alter own metabolic chemistry 5. Pump antimicrobial drug out of cell 6. bacteria in biofilms can resist 7. Mycobacterium tuberculosis produces MfpA protein (binds to DNA gyrase, prevent binding of fluoroquinolone drugs) Multiple-drug-resistant pathogens: at least 3 antimicrobial drugs Cross resistance: pathogens confer resistance to other drugs bc drugs are similar in structure Synergism: one drug enhances effect of 2nd drug (Antagonism: one drug interferes w/ another) MICROBIOME OF HUMANS a.k.a normal microbiota-organisms that colonize body w/out normally causing disease 1. Resident -part of normal microbiota; commensal 2. Transient -in body for sort period of time -Can NOT persist for 3 reasons: -MO competition -defence cell elimination -chemical/physical changes in body Opportunistic Pathogens: normal microbiota that cause disease under certain circumstances -immune suppression, stressful conditions… CHAIN OF INFECTION: Agent — Host — Environment 3 RESERVOIRS OF INFECTION: 1. Animal Reservoirs: (zoonoses) 2. Human Carriers: -Incubatory: transmit before showing symptoms -Convalescent: transmit just after recovering -Chronic: transmit for months/years -Asymptomatic reservoirs (passive/healthy carriers): contain source of infection, not sick themselves 3. Non-living Reservoirs: -soil, water, food Contamination: mere presence of microbes in body Infection: establishment in body PORTALS OF ENTRY: 1. Skin 2. Mucous Membranes (respiratory tract =most common entry) 3. Placenta Parenteral route: NOT true portal of entry (circumvents usual portals; deposited directly into tissues) ADHESION: MO attachment to cells 2 Adhesion Factors 1. Specialized structures 2. Attatchment molecules -ligands: *adhesion in bacteria *attachment proteins on viruses ***Inability to make attachment proteins/adhesions = MO avirulent*** TERMS: Infection: invasion of host by a pathogen Disease: (morbidity) if invading pathogen alters body functions Signs: objective characteristics observable by others Symptoms: subjective characteristics felt by patient Syndrome: signs and symptoms characteristic of a disease 3 VIRULENCE FACTORS: Pathogenicity: ability of MO to cause disease** Virulence: degree of pathogenicity ** 1. Extracellular Enzymes (4) -Hyaluoronase -Collagenase (destroys collagen to burrow deeper) -Coagulase (clots to protect bacteria) -Kinase (dissolves clot to release bacteria) 2. Toxins (2) -Exotoxins -Endotoxins (produced by Gram (-) bacteria: lipid A) Toxemia: presence of toxins in bloodstream 3. Antiphagocytic Factors (2) -Bacterial Capsule composed of chemicals not recognized as foreign, slippery (difficult for phagocytes to engulf) -Antiphagocytic Chemicals prevent fusion of lysosome + phagocytic vesicles, some destroy phagocytic WBC’s 5 STAGES OF INFECTIOUS DISEASE: 1. Incubation period 2. Prodromal period (vague symptoms) 3. Illness (most sever symptoms) 4. Decline ( immune system in high gear; if no decline, becomes fatal) 5. Convalescence (return to normal) MODES OF DISEASE TRANSMISSION (3): 1. Contact -Direct: -Indirect: fomites (inanimate objects) -Droplet: droplets of mucous (1m) -Waterborne -Foodborne -Bodily fluids 3. Vector -Biological: transmit pathogens and act as host ex. Fleas, ticks, lice, mosquitoes -Mechanical: passively transmit pathogens present on their body to new host ex. Houseflies, cockroaches EPIDEMIOLOGY: -study of where + when diseases occur and how they are transmitted in populations Endemic- occurs in a given area Sporadic-few scattered cases in given area Epidemic- disease occurs @greater than normal frequency Pandemic- epidemic occurs in multiple continents Outbreak- 3 cases constitutes FREQUENCY OF DISEASE: Incidence: #of new cases of a disease Prevalence: #of total cases of a disease HOSPITAL EPIDEMIOLOGY: 1. Exogenous: pathogen acquired from healthcare environment 2. Endogenous: pathogen from normal microbiota of patient 3. Iatragenic: results from modern medical procedures 4. Superinfections: use of antimicrobial drugs inhibits resident microbiota, allowing other MO’s to thrive ROLE OF PUBLIC HEALTH: Limit disease transmission -immunizations -locate ppl exposed to contagion -establish quarantine -enforce water/food cleanliness MICROBIAL CONTROL: (x7) Terms Sterilization-destruction of ALL viruses + MO’s in/on an object ex. prep of an microbiological culture Disinfection- removal of most MO’s + viruses on non-living tissue ex. alcohol, soap on surfaces Aseptic- environment/procedure free of pathogenic contaminants ex. hand-washing, sterilization of lab equipment Antisepsis- reduction in # of MO’s + viruses + pathogens on living tissue ex. iodine/alcohol to prepare skin for injection Sanitization- removal of pathogens from objects MO’s to meet public health standards ex. washing tableware in restaurants Degerming- removal of MO’s by mechanical means ex. hand-washing, alcohol swabbing @injection site Pasteurization- use of heat to destroy pathogens + reduce #of spoilage in food/beverages ACTION OF ANTIMICROBIAL AGENTS: (x4) X ↑ 1. Alteration of cell walls + cell membrane cell wall damage= bursts due to osmotic effects CM damage = contacts leak out 2. Damage to Proteins denatured by extreme heat + chemicals ↑ 3. Damage to Nucleic Acids -chemicals, radiation, heat destroy nucleic acids + DNA + RNA -halts protein synthesis 4 BIOSAFETY LEVELS: GERMICIDE Level 1: pathogens that do NOT cause disease in CLASSIFICATION: 3 Levels healthy humans 1. High level Level 2: moderately hazardous agents -ALL pathogens Level 3: microbes in safety cabinets w/ HEPA -Endospores filters 2. Intermediate-level Level 4: microbes that cause sever/fatal disease -fungal spores -protozoan cysts PHYSICAL METHODS OF MICROBIAL -viruses CONTROL (x5): -pathogenic bacteria 1. Heat-Related (moist/dry) + Refrigeration/ 3. Low level Freezing -vegetative bacteria Thermal death point: lowest temperature that kills -fungi ALL cells in 10 minutes -protozoa Thermal death time: time to sterilize volume of liquid -some viruses @set temperature Moist Heat (sterilize, disinfect, sanitize, pasteurize) Low Temperatures: ***more effective than dry heat -decrease MO metabolism, -boiling growth, reproduction -autoclaving (121 C, 15 psi, 15 min) (chemical rxns slower @low -pasteurization (flash: 72 C, 15 sec) temp -ultra-high-temperature sterilization -refrigeration halts growth of Dry Heat most pathogens -for powders + oils -higher temperatures -incineration = ultimate means of sterilization 2. Desiccation + Lypophilization Desiccation (drying)- removes water; inhibiting growth Lyophilization (freeze-drying)- long-term preservation of microbial cultures 3. Filtration (physical separation) -traps MO’s larger than the membrane pore size -sterilization 4.Osmotic Pressure -high concentrations of salt/sugar in foods to inhibit growth by osmotic pressure -cells in hypertonic solution lose water (fungi survive hypertonic environments) 5. Radiation (destroy / disable) Ionizing: (1nm) -UV light causes pyrimidine dimers in DNA (disable) disinfecting air, transparent fluids, surfaces of objects CHEMICAL METHODS OF MICROBIAL CONTROL (x10):