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Principles of Antimicrobial Chemotherapy Cheat Sheet by

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
 

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
 

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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