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Principles of Antimicrobial Chemotherapy Cheat Sheet by

science     biology     pharmacy     antimicrobial     antibiotics     pharmacology


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


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

Ability to kill or injure an invading microo­rganism without harming the cells of the host
Lethal dose at 50%; should be high
Minimal inhibitory concen­tra­tion; should be low; the lowest concen­tration of antibiotic that INHIBITS bacterial growth; lowest concen­tration that will stop the growth of bacteria
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

Cause inhibition of cell wall synthesis
Alter the function of the cytopl­asmic membrane; destroy cytopl­asmic membranes
Inhibit protein synthesis
Inhibit nucleic acid synthesis
Inhibit metabolite activity

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
DNA Synthesis &
Integrity Inhibi­tors
Tran­scr­iption &
Translation Inhibi­tors

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

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

Spiral shaped bacteria
Rod shaped bacteria
Spherical shaped bacteria

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

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

Eg: beta-l­actams and aminog­lyc­osides
Drug antagonism
Eg: combining bacter­ios­tatic drug with bacter­icidal drug
Eg: giving a patient tetrac­ycline with penicillin or cephal­osp­orins
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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