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AntibioticsSubances produced by a microorganism that (at low concentration) inhibit or kill other microorganisms | Talking about chemical produce by living organisms that can kill or inhibit | BASICALLY: life destroys life |
ChemotherapyThe use of drugs to treat a disease |
Antimicrobial DrugsAny substance of natural, synthetic or semi-synthetic origin that kills or inhibits the growth of a microorganism | Causes little or no host damage |
Selection of Antimicrobial Agents Requires knowing the following: | - The organism's identity | - The organism's susceptibility to a particular agent | - The site of infection | - Patient's factors | - The safety of the agent | - The cost of therapy |
Selective ToxicityDefinition: | Ability to kill or injure an invading microorganism without harming the cells of the host | LD50 | Lethal dose at 50%; should be high | MIC | Minimal inhibitory concentration; should be low; the lowest concentration of antibiotic that INHIBITS bacterial growth; lowest concentration that will stop the growth of bacteria | MBC | Minimal bactericidal concentration; should be; minimum concentration of antibiotic that KILLS the bacteria |
Mechanism of Selective TargetingSelective Toxicity: goal of antimicrobial drug therapy | Example: inhibit pathways or targets critical for pathogen survival at drug concentrations lower than those required to affect host pathways |
Types of PathwaysUnique Pathways | Also known as Cell Wall Synthesis Inhibitors; drug that inhibits the cell wall synthesis in microbes; the walls will lyse and the bacteria will die | Selective Pathways | Also known as protein synthesis inhibitors | Common Pathways | Also known as metabolites |
Types of Antibiotic Agents Type | Example | Cause inhibition of cell wall synthesis | Beta-Lactamas | Alter the function of the cytoplasmic membrane; destroy cytoplasmic membranes | Isoniazid | Inhibit protein synthesis | Macrolides | Inhibit nucleic acid synthesis | Quinolones | Inhibit metabolite activity | Sulfonamides |
Chemotherapeutic Spectra of Antibacterial AgentsNarrow Spectrum | Preferentially active
against single or limited group of microorganisms
Tx eg: isoniazid | Extended Spectrum | Effective against gram-positive and SOME gram negative bacteria
Tx eg: ampicillin | Broad Spectrum | Active against BOTH gram positive and gram negative bacteria
Tx eg: tetracycline
Tx eg: chloramphenicol |
Site of Action of Antibacterial Drug ClassesCell Wall Inhibitors | Fosfomycine
Cylcoserine
Vancomycin
Penicillin
Cephalosporins
Monobactams
Carbapenems
Ehambutol
Pyrrazinamide
Isoniazid | DNA Synthesis &
Integrity Inhibitors | Sulfonamides
Trimethoprim
Quinolones | Transcription &
Translation Inhibitors | Rifampin
Axminoglycosdes
Spectinomycin
Tetracyclines
Macrolides
Chloramphenicol
Streptogramins
Oxazolidinones |
| | Site of Action of Antibacterial Drug Classes
Types of Bacterial Infections
Bacteriostatic DrugsINHIBIT the growth of pathogens without causing cell death | Eg: sulfonamides (DNA synthesis & intercity inhibitor) | Eg: chloramphenicol (transcription & translation inhibitor) | Bacteriostatic effectiveness relies on an intact host immune system to CLEAR THE NONGROWING (but viable) bacteria |
Bactericidal DrugsKILL BACTERIA | Eg: penicillin (cell wall inhibitor) | Eg: streptomycin (transcription and translation inhibitor) | Eg: give this to patients with AIDS because they don't have immunity |
Bacteria MorphologySpirilla | Spiral shaped bacteria | Bacilla | Rod shaped bacteria | Cocci | Spherical shaped bacteria | Diplo- | Pair | Staphylo- | Culsters | Strepto- | Chain |
Gram POSITIVE BacteriaLooks violet or dark blue in gram staining | Retains the crystal violet stain | Single layered membrane -- it lacks the second outer phospholipid bilayer | Thick layer of peptidoglycan -- only this forms the cell wall | Easier to treat with antibiotics because it only has one phospholipid bilayer |
Gram NEGATIVE BacteriaDon't retain crystal violet dye from gram staining | They are pink or red colored | Thin peptidoglycan wall | Two phospholipid bilayers (two membranes) | Consist of outer membrane and thin peptidoglycan wall as cell wall | The cell wall is thinner than gram positive | This is harder to treat with antibiotics because it has two phospholipid bilayers |
Acid-Fast BacteriaDefinition: bacteria which resist decolorization with an acid-alcohol mixture during the acid-fast stain procedure | It retains the initial dye (carbofuchsin) | Acid-fast bacteria (mycobacteria and some of the related actinomycetes) appear red |
Medically Important Microorganisms Gram Positive Cocci | Gram Positive Bacilli | Gram Positive Cocci | Gram Negative Bacilli | Anaerobe Organisms | Spirochetes | Mycoplasma | Chlamydia | Other |
| | Purpose of Using Single Drug to Treat a PatientReasons to Use Single Treatment Instead of Combinations of Antimicrobial Drugs | 1. Reduces the possibility of superinfection | 2. Reduces the emergence of resistant organisms | 3. Minimizes toxicity |
Combinations of Antimicrobial DrugsAdvantage: | Synergism
Eg: beta-lactams and aminoglycosides | Disadvantage: | Drug antagonism
Eg: combining bacteriostatic drug with bactericidal drug
Eg: giving a patient tetracycline with penicillin or cephalosporins | BASICALLY: | Don't combine bacteriostatic drugs with bactericidal drugs |
Prophylactic Antibiotics- Use of antibiotics for prevention instead of treatment of infection | - May cause resistance and superinfection | - Use is limited |
Complications of Antibiotic Therapy1. Hypersensitivity | 2. Direct toxicity | 3. Superinfection |
Antimicrobial ResistanceDefinition: relative or complete lack of effect of antimicrobial against a previously susceptible microbe | Increase in MIC (remember MIC is lowest concentration needed to inhibit bacterial growth) | May be innate (an escape from antibiotic effect) | OR it may be acquired |
Result of Acquired Antibiotic Resistance1. Spontaneous, random chromosomal mutations. The mutations are due to change in either a structural protein receptor for an antibiotic or a protein involved in drug transport | 2. Extrachromosomal transfer of drug-resistant genes | 2a. Transformation: transfer of naked DNA between cells of same species | 2b. Transduction through R plasmids: R plasmids are a sexual transfer of plasmid DNA in a bacteria virus between bacteria of the same species | 2c. Conjugation: the passage of gene from bacteria to bacteria via direct contact through a sex plus or bridge. Conjugation occurs primarily in GRAM NEGATIVE BACILLI. It is the principal mechanism of acquired resistant among enterobacteria | 2d. Transposition: occurs as a result of movement or "jumping or transposons" (stretches of DNA containing insertion sequences at each end) from plasmid to plasmid or from plasmid to chromosome and back |
Mechanisms of Antimicrobial Resistance1. Reduced entry of antibiotic into pathogen | 2. Enhanced export of antibiotic by pathogen efflux pumps | 3. release of microbial enzymes that destroy the antibiotic | 4. Alterations of microbial enzymes that are required to transform products to the effective moieties | 4. Alterations of target proteins | 5. Development of alternative biochemical pathways to those inhibited by the antibiotic |
Factors that Promote Antimicrobial Resistance1. Exposure to sub-optimal levels of antimicrobial | 2. Exposure to microbes carrying resistance genes |
Inappropriate Antimicrobial Use- Prescriptions not taken correctly | - Antibiotics for viral infections (you don't give antibiotics for viral infections) | - Antibiotics sold without medical supervision | - Spread of resistant microbes in hospitals due to lack of hygiene | - Lack of quality control in manufacture of outdated antimicrobial | - Inadequate surveillance of defective susceptibility assays | - Poverty or way | - Use of antibiotics in foods |
Antibiotics in FoodsAntibiotics are used in animal feeds and sprayed on plants to prevent infection and promote growth | Multi-drug resistant Salmonella typhi has been found in some people who eat beef fed antibiotics |
MRSA "mer-sah"Methicillin-Resistant Staphylococcus Aureus | Most frequent nosocomial (hospital-acquired) pathogen | Usually resistant to several other antibiotics |
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