Principles of Antimicrobial Therapy Flashcards
Why is selective toxicity relative?
Concentration of drug must be carefully controlled to avoid damage to the host.
Antimicrobial agents must be chosen based on
Identity of the organism Organisms susceptibility to agent Site of infection Patient factors (kidney and liver function) Safety of the agent Cost of therapy
Empiric Therapy
It is often not clinically possible to determine the organism prior to treatment.
Take sample
Initiate therapy
Get results
Make changes if needed
Drug choice is determined by
Site of infection
Patient medical history
Broad spectrum antibiotic is usually choice. Attacks many organisms.
Bacteriostatic vs bactericidal
Bacteriostatic drugs arrest the growth and replication of bacteria. Then body’s immune system clears. Requires good immune system of pt. (may become bacteriocidal at high concentrations)
Bactericidal drugs kill bacteria. More aggressive, used for seriously ill patients.
How does a Bacteriostatic vs bactericidal drug look on a graph
Number of viable bacteria will decline quickly with a bactericidal drug.
Number of viable bacteria will remain the same with bacteriostatic drug.
Minimum Inhibitory Concentration (MIC)
Lowest concentration of antibiotic that inhibits bacterial growth.
Clinically obtainable antibiotic concentration must be greater than the MIC.
Minimum Bactericidal Concentration
Lowest concentration of antibiotic that kills the bacteria.
Entry to CNS is influenced by
- Lipid solubility. Molecules that are ionized cannot enter. CNS inflammation (meningitis) can decrease function of BBB.
- Molecular weight. Smaller is better. Larger compounds still have a hard time getting thru BBB, even if there is inflammation.
- Protein binding. Will restrict entry.
Why antibiotic selection should be influenced by the condition of the patient. and what are examples of things that can affect the immune system?
Immune system of the patient should be considered. Host defense system must ultimately eliminate the invading organisms.
Things that affect the immune system: Alcoholism Diabetes HIV Malnutrition Autoimmune disease Pregnancy Age Immunosuppressive drugs.
Why it’s important to ask pt about kidney and liver function when prescribing meds
Poor kidney function can cause accumulation of antibiotics (if pt can’t eliminate)
Poor liver function will reduce metabolism. Some antibiotics should not be used.
Rational dosing is based on
Pharmacodynamics. Relationship of concentration to effect. and Pharmacokinetics. ADME.
Three properties have significant influence:
- Concentration dependent killing
- Time dependent killing
- Post antibiotic effect.
Concentration dependent killing
The more you increase the concentration of the drug, the better it will be at killing bacteria. Rate of killing increases.
These type of agents favor once-a-day bolus infusion.
If you ever notice a dose increase and rate of taking drug decrease, what is it due to?
Concentration dependent killing.
Certain agents show significant increase in the rate of bacterial killing as the concentration of the antibiotic increases. Favor 1x per day bolus infusion.
Ex: aminoglycosides.
Time dependent killing
Increasing concentration does not significantly increase the rate of kill.
Concentration Independent
Time dependent killing is best predicted by
Effect is best predicted by the percentage of time that blood concentrations remain about MIC.
Time dependent killing favor what kind of administration?
Extended or continuous infusion instead of intermittent dosing.
Concentration dependent killing favors what kind of administration?
favor once-a-day bolus infusion.
Examples of time dependent killing drugs
Beta lactase, glycopeptides, macrolides, clindamycin, and linezolid.
Concentration dependent vs time dependent killing on a graph
Concentration dependent: as you increase the MIC of the drug, the rate of bacterial killing increases.
Time dependent killing: Even if you increase the MIC, the rate of bacterial killing does not significantly increase. Time is the important factor.
Post antibiotic effect (PAE)
Persistent suppression of microbial growth that occurs after antibiotic levels have fallen bellow MIC
Long PAE may affect dosing schedules how?
Long PAE may only require one dose a day.
Z pack is a combo of
Concentration dependent killing and PAE.
Narrow spectrum antibiotic
Act on single or limited group of micro organisms. Ex: only act on Gram + bacteria.
Extended spectrum antibiotcs
Effective against gram positive organisms and also against a significant number of gram negative
Broad spectrum antibiotics
Affects a wide variety of microbial species. Gram positive, gram negative, aerobic, anaerobic.
Can alter normal flora and cause super infection.
Where are gram positive bacteria likely found
Staph epidermis and aureus are present on the skin. Likely to infect wounds and surgical sites.
Step pneumonia is often cause of community acquired pneumonia.
85% on eye are gram positive infections.
Differences in cell wall of gram positive and gram negative
Gram positive: Surrounded by peptidoglycan cell wall.
Gram negative: Surrounded by outer membrane. Have pores which prohibit entry of many antibiotics. Must be hydrophilic to pass through pores.
Four groups of gram negative organisms
Enterics: found in GI and urinary tract.
Haemophilus influenza: Kids and elderly in nursing home
Neisseria: Gohnerrhea
Pseudomonas: Cornea infections from CL wear.
Which type of bacteria cause anaerobic infections?
Usually a mix of gram positive and gram negative.
Where can anaerobic infections occur
Colonize the mouth, GI tract, and skin. Infection occurs when bacteria invade poorly oxygenated tissues. Causes bad smells.
Bacteria are said to be resistant if
The max level of antibiotic that can be tolerated by the host does not halt their growth.
Can be natural or developed
How can resistance be developed?
- genetic alterations
- Spontaneous mutations
- DNA transfer of resistance - altered expressions or proteins (Aka develop a new protein)
- Modification of target sites
- Decreased accumulation
- Enzymatic inactivation
How can spontaneous mutation cause a genetic altercation that leads to resistance?
Insertion, deletion, or substitution in DNA.
If not lethal, mutation will be passed to progeny.
How can DNA transfer of resistance cause a genetic altercation that leads to resistance?
One bacterium may transfer resistance to another. Resistance properties are usually found in plasmids and can be transferred.
How can modification of target sites lead to altered expression of proteins, eventually leading to resistance?
Change in structure of binding site may produce resistance. Often mutation.
How can decreased accumulation lead to altered expression of proteins, eventually leading to resistance?
Decreased update of drug or increased efflux may limit drug from gaining access to site of action.
How can enzymatic activity lead to altered expression of proteins, eventually leading to resistance?
Some bacteria can destroy or inactivate the antimicrobial agent.
Prophylactic antibiotics
Use of antibiotics for prevention rather than treatment
When to use prophylactic antibiotics and why you shouldn’t do it often
Restricted to situations where the benefits outweigh the potential risks.
Use in cases of surgery,
May cause resistance.
Direct toxicity
High concentrations of antibiotics can directly affect host cellular processes
Ex: Aminoglycosides and ototoxicity
Superinfections
Alterations in the normal microbial flora. Permits overgrowth (yeast) and infections are often difficult to treat.
Most antibiotics have one of the following mechanisms of action
Inhibit bacterial cell wall synthesis
inhibit bacterial protein synthesis
inhibit bacterial DNA replication/synthesis.
-Inhibits synthesis of folic acid or inhibits important replication enzymes.
