Pharmacology antimicrobials Flashcards
Minimum Inhibitory Concentration (MIC)
The lowest concentration of drug that inhibits visible bacterial growth
MIC90: concentration for inhibiting 90% of the bacteria
Minimum Bactericidal Concentration (MBC)
The lowest concentration of a drug that kills 99.9% of bacteria
Mutant Prevention Concentration (MPC)
The concentration to kill the least susceptible single-step mutant
In theory, kills them all so mutants (ie resistant bacteria) can’t form
bacteriostatic
Stop bacteria from multiplying; don’t kill them
* MBC much larger than the MIC (not always able to reach MBC)
Elimination of infection requires host immune response
* Requires an immunocompetent patient
Not as good for
* Sepsis
* Neonates
* Animals on glucocorticoids
* Animals on cancer chemotherapy
* (anything with not great immune system)
bactericidal
Kill bacteria if concentrations reach MBC for a certain period of time
* MBC at or near the MIC
Preferred for:
* immunosuppressed animals
* Preferred for severely ill patients
* Sepsis
* Neonates
* Animals on glucocorticoids
* Animals on cancer chemotherapy
Bactericidal antimicrobials are NOT always bactericidal
* Static at concentrations below MBC
* Dose dependent
* Bacteria dependent
* Bacteria must be multiplying for bactericidal antibiotic to work
* Combinations of –static and –cidal???
postantibiotic effect (PAE)
Persistent drug effect after plasma concentrations decline below the MIC/MBC
Mechanisms
* Decreased virulence of the bacteria
* Development of abnormal cell wall or septum
* Increased susceptibility to host defenses
* Persistence at sites of infection
Only occurs with some drugs and is bacteria-dependent
pharmokinetic- pharmodynamic interactions
Predict the success of antimicrobial therapies
* Relate concentration of drug to MIC of the pathogen
* Vary by class of drug
* Vary with each pathogen
Guidelines for successful treatment:
* Meeting them increases chance of success
* Not meeting them increases chance of failure
“Drug-Bug” Interactions
time dependent antibiotics
T>MIC: Duration plasma concentration is above the MIC over 24 hours
concentration dependent antibiotics
Cmax:MIC ratio of the maximum plasma concentration (Cmax) to the MIC
concentration/time dependent antibiotics
AUC:MIC: ratio of the AUC (area under curve 0-24h) to the MIC
3 main categories of antibiotic mechanism of action
cell wall: inhibit synthesis
protein synthesis: inhibit 50s or 30s ribsomal subunit
nucleic acids: inhibit synthesis or function
spectrum of activity
Describes the general activity of an antimicrobial
Narrow spectrum
* Implies activity against a limited subset of bacteria
Broad Spectrum
* Implies activity against a wide range of bacteria
* May include mycoplasma, rickettsia, and chlamydia
Tells you that the bacteria CAN BE affected by the antimicrobial
* Individual isolates of bacteria may be resistant to an antimicrobialeven though they are part of its spectrum!
antibacterial spectrum (4 quadrants)
Aerobic bacteria
* Gram (+)
* Gram (-)
Anaerobic bacteria
* Gram (+)
* Gram (-)
Broad Spectrum
* Gets all four quadrants
* Gets other categories
Narrow Spectrum
* 1-2/4 quadrants
antibiotic spectrum (6 quadrants)
Aerobic bacteria (includes facultatice aerobes)
Gram (+)
* Streptococci
* Staphylococci
Gram (-)
* Respiratory pathogens
* Enteric pathogens
Anaerobic bacteria
* Gram (+)
* Gram (-)
additive/indifferent antimicrobial interaction
Typically used to **extend the spectrum **
Does not enhance activity of either
Example:
Horse with pneumonia
Culture – Strep. zooepidemicus (Gm +) and E. coli (Gm -)
Treatment:
Penicillin (for strep) and enrofloxacin (for e coli)
2+2=4
synergistic antimicrobial interaction
Synergism – what we hope for
Combination enhances activity
* Trimethoprim / sulfonamide: Static alone; -cidal together
* Ampicillin / clavulanic acid: CA prevents degradation by β-lactamases
* β-lactams and aminoglycosides: β-lactam increases permeability of cell to aminoglycoside
2+2=6
antagonistic antimicrobial interaction
Antagonism – what we worry about
Activity of the combination is less than the sum
Example: Static plus Cidal
* Penicillin plus tetracycline
Probably depends on the drug/bug
Not necessarily contraindicated, but avoided when possible
2+2=2
IV route of antibiotics
- Highest concentrations
- Highest risk for adverse effects
- Severe systemic illness
- Owner comfort level/animal temperament
IM/SQ route for antibiotics
Bioavailability often complete
* Dehydration/shock may affect absorption
Risk of drug toxicity less than IV
* Injections site reactions
Owner comfort level/animal temperament
oral route for antibiotics
Ileus/colitis
Malabsorption
Drug interactions
transdermal route for antibiotics
DO NOT GIVE to treat systemic infection
topical route for antibiotics
Eyes
Skin
Wounds?
MICs may underestimateactivity of topically/locally applied antibacterial drugs! (MICs are based on plasma concentrations)
site of infections: ISF
For most pathogens, the site of infection is the ISF
* Protein binding is major determinant of drug distribution to the ISF
* Low protein bound drugs have good distribution
* Highly protein bound drugs have limited distribution (>80%)
In general, MICs adequately predict success for infections in the ISF