Pharmacology 3: Antibacterial agents for systemic therapy Flashcards
Minimum inhibitory concentration (MIC)
lowest concentration of drug that INHIBITS visible bacterial growth
ex. MIC90 = concen for INHIBITING 90% of the bacteria
Minimum Bactericidal Concentration (MBC)
KILLS
lowest concentration of a drug that KILLS 99.9% of bacteria
LARGER
Mutant Prevention Concentration (MPC)
LEAST susceptible single-step mutant
-theory, kills them all so mutants (resistant bacteria) can NOT form
What requires host immune response?
hint* something to do with infection
Elimination of infection
Bacteriostatic bacteria
STOP bacteria from multiplying; don’t kill them
MBC much LARGER that the MIC
Bacteriostatic NEED what to eliminate infection?
Requires host immune response
Bactericidal is preferred for what kin of patients?
Immunosuppressed
Severely ill patients
-sepsis
-neonates
-on glucocorticoids
-on cancer chemotherapy
Bactericidal
kill bacteria if concentration reach MBC for a certain period of time
- MBC at or near the MIC
A drug can be both Bacteriostatic and Bactericidal?
True
Bactericidal antimicrobials are or are NOT always bactericidal?
NOT
static at concentration below MBC
- dose dependent
- bacteria dependent
Bacteria must be dividing or multiplying for bactericidal to work
bacteria must be MULTIPLYING
Postantibiotic effect (PAE)
Persistent drug effect
- After plasma concentration decline below the MIC/MBC
What are mechanisms for Postantibiotic effect
decreased virulence of the bacteria
development of abnormal cell wall or septum
increased susceptibility to host defenses
Persistence at sites of infection
When does PAE occur?
Only with SOME drugs and is BACTERIA-dependent
What do we use pharmacokinetic and pharmacodynamic interactions for?
How we determine dosing
Drug bug interactions
PREDICT SUCCESS OF ANTIMICROBIAL THERAPIES
- Relate concentrations of drug to MIC of the pathogen
- vary by class of drug
- vary with each pathogen
PK refresher
Cmax: maximum plasma
AUC: area under the plasma concentration time curve
Pharmacodynamic targets
Time dependent antibiotics
- T>MIC: duration plasma concentration is above the MIC over 24h
Concentration-dependent antibiotics
- Cmax: MIC ratio of the maximum plasma concentration (C max) to the MIC
Concentration/Time dependent antibiotics
- AUC:MIC: ratio of the AUC0-24 to the MIC
Antibiotic mechanism of action
Cell wall: inhibit synthesis and function
NA: inhibit synthesis and function
Protein synthesis: inhibits 50s ribsomal, subunits
inhibt 30s ribosomal, subunits
Spectrum activity
describing general activity of antimicrobial
- narrow=limited subsets of bacteria
- broad=treats a lot (not always well)
–> may include mycoplasma, rickettsia, and chlamydia
Individual isolates of bacteria may be resistant to an antibacterial even though they are part of the SPECTRUM?
true
Antibacteral spectrum 4 quadrants
Aerobic
+ and -
Anaerobic
+ and -
Broad spectrum
- all four quadrants
- other categories
Intermediate spectrum (NOT *)
- 2-3/4 quadrants
Narrow spectrum
- 1-2/4 quadrants
Davis 6 quadrants antibacterial spectrum
Aerobic bacteria
- gram +
(step and staph) ococci
- gram -
respiratory pathogens
enteric pathogens
Anaerobic bacteria
- gram +
- gram -
PENICILLINS
- activate against streptococci, NOT most staphylococci
- NOT active against gram -
- active against most gram + and gram - anaerobes
AMINOGLYCOSIDES
- active against staphylococci, NOT most streptococci
- active against respiratory and enteric gram -
- NO activity against anaerobes
MACROLIDES
- active against gram - aerobes
- active against respiratory gram - but NOT enteric
- active against most gram + anaerobes
Facts about Facultative anaerobes
are AEROBES
-CAN grow in anaerobic conditions
-culture as aerobes
-test susceptibility in aerobic conditions
-In vitro susceptibility may NOT equal in vivo susceptibility
- when anaerobic conditions are present in the patient
antimicrobial drug interactions
additive/indifferent
- used to extend the spectrum
- does NOT enhance activity of either
Synergism
is what we HOPE for
-combo enhances in activity
-trimethoprim/sulfnamide
- static alone;-cidal together
-ampicillin/clavulanic acid
- CA prevents degradation by beta-lactamases
-Beta-lactams and aminoglycosides
- beta-lactams increases permeability of cell to aminoglycoside
Antagonism
is what we WORRY about
activity of the combo is less than the sum
ex. static plus cidal
drug and bug dependent
Judicious use of Antibacterials refers to?
IS AN ANTIBACTERIAL NECESSARY in this case.
What is most appropriate route: IV, IM/SQ, PO
–> transdermal NOT recommended
Yes = bacterial infection-systemic
No=viral, fungal, and parasitic
Maybe=protozoal, bacterial, and local
MICs may __________ activity of topically/locally applied antibacterial drugs!
UNDERESTIMATE
In general, MICs ___________ predict ___________ for infections in the ISF
Adequately
SUCCESS
MIC testing will _________ activity of antibiotics!
Overestimate
What are the exceptions rule when it comes to site of infection (judicious use)?
CNS
Eye
Prostate
Bronchus
Testes
-protective barriers that consist of tights junctions between the endothelial cells
-Limited drug movement into these areas
-Lipid solubility
Significance during inflammation
What drugs have BETTER penetration into cells when theres INTRACELLULAR infections?
Lipophilic or Hydrophilic
Lipophilic drugs
When it comes to abscesses and granulomas what factors are important to keep in mind?
Drug diffusion slow
- lower Cmax
- slower equilibrium
Lower blood supply to the area
Treatment unsuccessful without DRAINAGE
If you can DRAIN and LAVAGE the abscesses, antibacterials may NOT be necessary
**If you do NOT drain
–> choose more LIPOPHILIC drugs
–>treat for LONG periods
Local tissue factors are?
Affect the efficacy of some drugs
purulent debris
acidic environment
hemoglobin/ hemorrhage
Anaerobic conditions/necrotic tissue
- decreased blood supply
MICs do NOT take into account ______ ______ ______ !
LOCAL TISSUE FACTORS
Judicious use summarized in three statements?
Cut it out
Drain it
Fix underlying disease
Choosing an antibiotic with the Empiric treatment
Know which bacteria commonly involved in which infections
Choose drug that is likely to treat that bacteria
NARROW SPECTRUM BASED ON RESULTS OF CULTURE AND SENSITIVITY WHEN POSSIBLE
When choosing an antibiotic what 5 things are important to keep in mind?
Availability
- formulations
Ease of use
- client compliance
- patient compliance
Adverse effects
Cost
Species
