General considerations for Antimicrobials Flashcards
What are 4 basic principles that should be considered before antimicrobial therapy even begins?
- An infectious agent must be involved in the
disease process for antimicrobial therapy to
be effective - Antimicrobial therapy must be necessary to rid the
host of the disease - Host defense mechanisms must contribute to
the patient’s recovery - Therapeutic concentrations of the drug should be
achieved at the site of infection and the
microenvironment at this site should support
activity of the drug
When is concurrent use of more than one
antimicrobial drug appropriate?
(name 3)
- Life threatening conditions
- Mixed infections
- Need for synergistic activity
What easy diagnostic test will allow you to initiate therapy before culture results?
GRAM STAIN!!
If successful treatment of bacterial infection can
occur by halting multiplication of bacteria, use a …
… bacteriostatic drug
If host defenses are inadequate, use a …
… bactericidal drug
What drugs does pus like to bind to (and inhibit the action of)?
(2)
Aminoglycosides and vancomycin
What drugs does hemoglobin like to bind to?
(2)
Penicillins and tetracyclines
Is pH in abscess cavities high or low?
Low
Low pH has what effects on what drugs?
(4)
- Reduces activity of aminoglycosides, erythromycin, clindamycin
- Increases activity of chlortetracyclines
What should one do with abscesses and foreign bodies prior to drug treatment?
Drain abscesses and remove foreign bodies
What is the difference between gram positive and negative bacteria?
- Gram positives have a single cell membrane surrounded by a thick cell wall
- Gram negatives have an inner membrane and an outer membrane separated by a thin cell wall that contains lipopolysaccharide (LPS)
Name 3 gram positive and 5 gram negative aerobic bacteria
- Gram positive: Enterococcus, Staphylococcus, Streptococcus
- Gram negative: E. coli, Kelbsiella, Proteus, Pseudomonas, Pasteurella, Brucella
In what situations would you use a BACTERICIDAL drug?
- Neutropenic
- Immunosuppressed
- Septicemia
- Minigits
- Endocarditis
- Osteomyelitis
What effect does concentration have on bactericidal/static drug function?
- Bactericidal drugs may become bacteriostatic if appropriate concentration is not reached
- Bacteriostatic drugs may become bactericidal if concentrated in some tissues
What is Postantibiotic Effect (PAE)?
Persistent suppression of bacterial growth following removal of the antibiotic
How is MIC different than MBC?
- MIC is a test of serial dilutions in broth, no growth = MIC
- MBC is concentration that when put into new broth get no new growth
- MIC is close to MBC
What is the PDC?
Targeted plasma drug concentration calculated by multiplying MIC x “therapeutic factor”
How does PAE affect treatment paradigm?
Dosing interval = time when PDC > MIC + PAE, so can stretch time between doses with longer PAE, good for toxic drugs
Drugs with a short PAE are what type of drugs (time/concentration)?
Time dependent
Drugs with a long PAE are what type of drugs (time/concentration)?
Concentration dependent
What types of drugs are bacterioidal? Static?
- Bacteriocidal- Nucleic acid synthesis inhibitors, Cell wall synthesis inhibitors
- Bacteriostatic- Folic acid synthesis inhibitors (unless combined), Protein synthesis inhibitors (Except Aminoglycosides bc irreversible)
Can you use bacteriostatic and cidal drugs in combination?
No! Static drugs impair growth and division mechanisms that cidal drugs rely on for killing organisms. It is possible to use 2 static drugs together or 2 cidal drugs together for synergistic effect.
What is a concentration-dependent drug and what are 2 examples?
Drug where higher dose gives a better kill. Aminoglycosides and Fluoroquinolones.
What is a time-dependent drug and what are 2 examples?
Drug where greater dose does not lead to better kill, but time above MIC is proportional to kill. Have to dose more frequently. Beta-lactams and Cephalosporins.
Are bacteriostatic drugs time or concentration dependent?
Neither, area under the curve kinetics
What doe a plasma drug concentration vs time curve look like for time- and concentration-dependent drugs?
Concentration dependent: concentrations spike up high and go to zero between doses.
Time dependent: concentrations only dip to or below MIC slightly between doses.
What are 3 general ways in which bacteria develop drug resistance?
- Drug fails to reach its target (impermeable cell membranes, deficient in porins that allow drug thru outer membrane, pumps to pump drug out)
- Bacteria produce enzymes that inactivate the drug
- The target is altered
How do you know if an organism is susceptible to an agent?
Quantitatively by MIC test (serial dilutions in liquid media) or qualitatively by Kirby Bauer test (growth inhibition on plates)
What is a breakpoint?
- Breakpoints are operational definitions set by clinical laboratory standards institute- categorize isolates as susceptible, intermediate, or resistant
- It is an MIC selected to predict the clinical outcome
– For a specific pathogen
– For a specific disease
– In a specific species
What are 2 factors that in vitro MIC and Kirby Bauer tests DO NOT account for?
– DO NOT reflect concentrations that can be attained at sites of infection
– DO NOT take into account local factors that may affect the drug’s activity
