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Antibiotics
Subances 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 |
Chemotherapy
The use of drugs to treat a disease |
Antimicrobial Drugs
Any 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 Toxicity
Definition: |
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 Targeting
Selective 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 Pathways
Unique 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 Agents
Narrow 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 Classes
Cell 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 |
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Site of Action of Antibacterial Drug Classes
Types of Bacterial Infections
Bacteriostatic Drugs
INHIBIT 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 Drugs
KILL 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 Morphology
Spirilla |
Spiral shaped bacteria |
Bacilla |
Rod shaped bacteria |
Cocci |
Spherical shaped bacteria |
Diplo- |
Pair |
Staphylo- |
Culsters |
Strepto- |
Chain |
Gram POSITIVE Bacteria
Looks 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 Bacteria
Don'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 Bacteria
Definition: 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 |
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Purpose of Using Single Drug to Treat a Patient
Reasons 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 Drugs
Advantage: |
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 Therapy
1. Hypersensitivity |
2. Direct toxicity |
3. Superinfection |
Antimicrobial Resistance
Definition: 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 Resistance
1. 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 Resistance
1. 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 Resistance
1. 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 Foods
Antibiotics 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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