Lecture 12 - Drugs, Microbes and Hosts Flashcards
Three factors must be known before starting antimicrobial therapy:
- The identity of the microorganism causing the infection
- the degree of the microorganisms susceptibility to various drugs
- the overall medical condition the patient
Small discs containing premeasured amounts of antibiotics are dispensed onto the bacterial lawn
A zone of inhibition formed during incubation is measured and compared with a standard for each drug
kirby-bauer technique
profile of antimicrobial sensitivity
antibiogram
- the smallest concentration (highest dilution) of drug that visibly inhibits growth
- Useful in determining the smallest effective dosage of a drug
- Provides a comparative index against other antimicrobials
- performed by automated machinery
tube dilution tests - minimum inhibitory concentration
reasons why treatment can fail
- inability of the drug to diffuse into that body comportment
- resistant microbes the infection that didn’t make it into the sample collected for testing
- an infection caused by more than one pathogen
- The ratio of the dose of the drug that is toxic to humans to its minimum effective dose
- The closer these two figures are to each other (the smaller the ratio), the greater potential for toxic drug reactions
therapeutic index
- Central concept in antibiotic treatment
- Antimicrobial drugs should kill or inhibit microbial cells without simultaneously damaging host tissues
- The best drugs in current use block the actions or synthesis of molecules in microorganisms but not vertebrate cells
selective toxicity
- Effective against more than one group of bacteria Example: tetracyclines
Broad spectrum drugs:
- Only target a specific group
- Examples: polymyxin and penicillins
narrow spectrum drugs
Can be obtained naturally or synthesized in the laboratory
Consist of three parts: Thiazolidine ring
Beta lactam ring
Variable side chain
penicillin
Isolated in the 1940s from Cephalosporium
acremonium
Have a beta-lactam ring that can be chemically altered
Similar mode of action to penicillins
cephalosporins
Derived from Bacillus polymyxa Toxic to the kidney
polymyxins
High potency Broad spectrum Readily absorbed from the intestine Side effects: Seizures and other brain disturbances
fluoroquinolones
Composed of one or more amino sugars and an aminocyclitol ring
Products of actinomyces Streptomyces
Micromonospora
Broad antimicrobial spectrum
amino glycoside drugs
Natural parent compound and synthetic derivatives
Broad spectrum effects
Side effects:
Gastrointestinaldisruption Deposition in hard tissues
tetracyclines
Newer derivatives of tetracyclines
Block 30s ribosomal subunit
Effective against bacteria that have become resistant to tetracyclines
glycylcyclines
Macrolide ring
Broad spectrum, low toxicity
erythromycin
adverse reactions theGI tract limits its use
clindamycin
respiratory tract infections suspected to be caused by resistant microbes
telithromycin
Synthetic: do not originate from bacteria or fungi
sulfonamides
Interrupting quorum sensing pathways
Adding DNase to antibiotics Pretreatment
treatment of biofilms
Quinine: principal treatment for hundreds of years Replaced by chloroquine and primaquine: less toxicity
antimalarial drugs
chemotherapy for other protozoa infections
metronidazole: amoebicide
anthelminthic drug therapy:
Mebendazole and albendazole
Pyrantel
Praziquantel
Three major modes of action in antiviral chemotherapeutic agents:
Barring penetration of the virus into the host cell
Blocking the transcription and translation of viral molecules
Preventing maturation of viral particles
how does drug resistance develop
resistance through
- spontaneous mutation
- horizontal transfer
- sharing of resistance genes
Plasmids that are transferred through conjugation, transformation,
or transduction
resistance factors
duplicated and inserted from one plasmid to another or from the plasmid to the chromosome
transposable drug resistance sequences
new enzymes are synthesized
- inactivate the drugs
- only occurs when new genes are acquired
permeability or uptake of the drug into a bacterium is decrease
- occurs via mutation
- drug is immediately eliminated
- acquisition of new genes
- binding sites for drugs are decreased in number or affinity
can occur via mutation or acquisition of new genes
an affected metabolic pathway is shut down or alternative pathway is used
- occurs due to mutation of original enzyme or enzymes
long term strategies to control drug resistance
- restriction of the use of first line antibiotics
- enhanced surveillance mechanisms
- PulseNet, WHONET
- Track foodLborne pathogens and pathogenic microbial populations
- Provides up to date views of the changes in resistance genes
surveillance mechanisms
Finding new targets in the bacterial cell
Customizing drugs that aim for these new targets
past approach
Disabling host molecules that the invaders use to enhance their position
novel approach
Using bacteriophages in Eastern European countries
Incorporating phage into wound dressings
Phage are extremely specific and only infect one species of bacteria, leaving normal microbiota alone
low tech solutions
Preparations of live microorganisms fed to animals and humans to improve intestinal biota
Replace microbes lost during antimicrobial therapy
Augment the biota already there
probiotics
Nutrients that encourage the growth of beneficial
microbes in the intestine
prebiotics
Bind to the enamel of teeth, causing a permanent gray to brown discoloration
Cause liver damage in pregnant women
Cross the placenta and are deposited in fetal bones and teeth
tetracycline
Most common complaint associated with oral antimicrobial therapy
Can progress to severe intestinal irritation or colitis
Some drugs directly irritate the intestinal lining
Also caused by disruption of the intestinal microbiota
diarrhea
Drug acts as an antigen that stimulates the allergic
response
Can be provoked by the intact drug molecule or alteration of the drug
allergy
Treats infection
Destroys normal biota, even those far removed from the original infection
broad spectrum antimicrobial
Beneficial resident species are destroyed through
antibiotic therapy
Microbes once small in number begin to overgrow and cause disease
superinfection
