General considerations for Antimicrobials

Question 1

What are 4 basic principles that should be considered before antimicrobial therapy even begins?

Answer 1

1. An infectious agent must be involved in the
   disease process for antimicrobial therapy to
   be effective
2. Antimicrobial therapy must be necessary to rid the
   host of the disease
3. Host defense mechanisms must contribute to
   the patient’s recovery
4. 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

Question 2

When is concurrent use of more than one
antimicrobial drug appropriate?

(name 3)

Answer 2

• Life threatening conditions
• Mixed infections
• Need for synergistic activity

Question 3

What easy diagnostic test will allow you to initiate therapy before culture results?

Answer 3

GRAM STAIN!!

Question 4

If successful treatment of bacterial infection can
occur by halting multiplication of bacteria, use a …

Answer 4

… bacteriostatic drug

Question 5

If host defenses are inadequate, use a …

Answer 5

… bactericidal drug

Question 6

What drugs does pus like to bind to (and inhibit the action of)?

(2)

Answer 6

Aminoglycosides and vancomycin

Question 7

What drugs does hemoglobin like to bind to?

(2)

Answer 7

Penicillins and tetracyclines

Question 8

Is pH in abscess cavities high or low?

Answer 8

Low

Question 9

Low pH has what effects on what drugs?

(4)

Answer 9

• Reduces activity of aminoglycosides, erythromycin, clindamycin
• Increases activity of chlortetracyclines

Question 10

What should one do with abscesses and foreign bodies prior to drug treatment?

Answer 10

Drain abscesses and remove foreign bodies

Question 11

What is the difference between gram positive and negative bacteria?

Answer 11

• 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)

Question 12

Name 3 gram positive and 5 gram negative aerobic bacteria

Answer 12

• Gram positive: Enterococcus, Staphylococcus, Streptococcus
• Gram negative: E. coli, Kelbsiella, Proteus, Pseudomonas, Pasteurella, Brucella

Question 13

In what situations would you use a BACTERICIDAL drug?

Answer 13

• Neutropenic
• Immunosuppressed
• Septicemia
• Minigits
• Endocarditis
• Osteomyelitis

Question 14

What effect does concentration have on bactericidal/static drug function?

Answer 14

• Bactericidal drugs may become bacteriostatic if appropriate concentration is not reached
• Bacteriostatic drugs may become bactericidal if concentrated in some tissues

Question 15

What is Postantibiotic Effect (PAE)?

Answer 15

Persistent suppression of bacterial growth following removal of the antibiotic

Question 16

How is MIC different than MBC?

Answer 16

• 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

Question 17

What is the PDC?

Answer 17

Targeted plasma drug concentration calculated by multiplying MIC x “therapeutic factor”

Question 18

How does PAE affect treatment paradigm?

Answer 18

Dosing interval = time when PDC > MIC + PAE, so can stretch time between doses with longer PAE, good for toxic drugs

Question 19

Drugs with a short PAE are what type of drugs (time/concentration)?

Answer 19

Time dependent

Question 20

Drugs with a long PAE are what type of drugs (time/concentration)?

Answer 20

Concentration dependent

Question 21

What types of drugs are bacterioidal? Static?

Answer 21

• Bacteriocidal- Nucleic acid synthesis inhibitors, Cell wall synthesis inhibitors
• Bacteriostatic- Folic acid synthesis inhibitors (unless combined), Protein synthesis inhibitors (Except Aminoglycosides bc irreversible)

Question 22

Can you use bacteriostatic and cidal drugs in combination?

Answer 22

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.

Question 23

What is a concentration-dependent drug and what are 2 examples?

Answer 23

Drug where higher dose gives a better kill. Aminoglycosides and Fluoroquinolones.

Question 24

What is a time-dependent drug and what are 2 examples?

Answer 24

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.

Question 25

Are bacteriostatic drugs time or concentration dependent?

Answer 25

Neither, area under the curve kinetics

Question 26

What doe a plasma drug concentration vs time curve look like for time- and concentration-dependent drugs?

Answer 26

Concentration dependent: concentrations spike up high and go to zero between doses.
Time dependent: concentrations only dip to or below MIC slightly between doses.

Question 27

What are 3 general ways in which bacteria develop drug resistance?

Answer 27

• 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

Question 28

How do you know if an organism is susceptible to an agent?

Answer 28

Quantitatively by MIC test (serial dilutions in liquid media) or qualitatively by Kirby Bauer test (growth inhibition on plates)

Question 29

What is a breakpoint?

Answer 29

• 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

Question 30

What are 2 factors that in vitro MIC and Kirby Bauer tests DO NOT account for?

Answer 30

– 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