Principles of Antimicrobial Chemotherapy

Question 1

What are the 5 steps in the “approach to empiric therapy”?

Answer 1

1. clinical Dx
2. obtain specimens for lab
3. microbiologic Dx
4. Is ET necessary?
5. Institutive Tx

Question 2

What is the “rule of thumb” for the duration of antimicrobial therapy in febrile patients?

Answer 2

continued therapy for 7-10 days after patient becomes afebrile

Question 3

What is selective toxicity?

Answer 3

the ability of a drug or chemical to injure a target cell or organism without injuring other cells or organisms that should not be injured

Question 4

What are 5 things to consider in selection of antibiotics to a clinically-relevant case scenario?

Answer 4

1. organism identity and sensitivity to a particular agent
2. the site of infection
3. the safety of the agent
4. patient factors
5. cost of therapy

Question 5

What is a combination broad spectrum antibiotic that can be used for empiric therapy?

Answer 5

1. clindamycin

2. gentamycin

Question 6

What are single broad-spectrum antibiotics that can be used for empiric therapy?

Answer 6

imipenem/cilastatin

Question 7

What are 3 possible ways target action is distinguished from host action (selective toxicity of antibiotic)?

Answer 7

1. unique target must be present in pathogen and absent in host
2. target must be structurally different in pathogen than in host
3. target must be more important in pathogen than in host.

Question 8

What are 5 general sites of antibiotic action?

Answer 8

1. disruption of bacterial cell wall - i.e. penicillins and cephalosporins
2. inhibition of an enzyme unique to bacteria - i.e. sulfonamides compete with PABA and inhibit dihydropteroate synthase which is needed for folic acid production in bacteria
3. disruption of bacterial protein synthesis - employs ribosomes
4. inhibition of nucleic acid - DNA gyrase inhibitors: fluroquinolones
5. inhibition of membrane function: fungal membranes

Question 9

What are 3 things that determine an anti-microbial’s effectiveness against organisms?

Answer 9

1. Failure of drug to reach its target - outer membrane of gram negative bacteria - drug must enter through porins, slow drug entry via porin (mutation can inhibit entry), target of drug is IC and rug needs active transport, efflux pump, sometimes an antibiotic is metabolized in the body and sometimes it’s not
2. drug inactivation - bacterial resistance to aminglycosides and B-lactam antibiotics usually results from production of enzymes that modify or destroy the antibiotic, i.e. prodrug can depend on bacteria interaction to become active like M. tuberculosis and isonizad
3. Target activation

Question 10

How do bacterial cell membranes exhibit resistance mechanisms via controlling active transport across the membrane?

Answer 10

If the target is IC and the drug requires active transport across the cell membrane, resistance can result from mutations that inhibit this transport mechanism.
i.e. Gentamycin targets the ribosome and is actively transported across the cell membrane using energy provided by the membrane electrochemical gradient. This electrochemical gradient is generated by specific enzymes that couple electron transfer and oxidative phosphorylation. A mutation in this pathway or anaerobic conditions would slow entry of gentamycin into the cell, therefore resulting in resistance.

Question 11

How do efflux pumps confer resistance to antibiotics and give 5 antibiotic classes that are affected by this type of resistance?

Answer 11

• bacteria have efflux pumps that can transport drugs out of cells:
  1. tetracyclines
  2. chloramphenicol
  3. fluoroquinolones
  4. macrolides
  5. B-lactam antibiotics

Question 12

What is a superinfection?

Answer 12

A superinfection is a new infection that appears during the course of Tx for a primary infection. A new infection can develop because antibiotics can eliminate the inhibitory influence of normal flora therefore allowing a second infectious agent to flourish. This reaction is more common with broad-spectrum agents.

Question 13

What are 3 principal factors to consider in choosing an appropriate antibiotic?

Answer 13

1. The identity of the infecting organism
2. Drug sensitivity of the infecting organism
3. Host factors such as site of infection and the status of host defenses.

Question 14

What are 3 conditions in which a primary drug of choice would not be used?

Answer 14

1. allergy to drug of choice
2. inability of drug of choice to penetrate site in infection
3. unusual susceptibility of pt to a toxicity of the first choice drug

Question 15

When should sulfonamides not be used?

Answer 15

In newborns. Sulfonamides in newborns can produce kernicterus which is a severe neurologic disorder caused by the displacement of bilirubin from plasma proteins

Question 16

What are 5 reasons to use antibiotic combinations?

Answer 16

1. initial therapy of severe infection
2. mixed infections
3. prevention of resistance
4. decreased toxicity
5. enhanced antibacterial action

Question 17

Describe synergistic action and provide 3 examples.

Answer 17

The effect of the combo is greater than the sum of the effects of the individual agents. One of the 2drugs must show at least 4-fold increase in activity:

1. Trimethoprim + sulfamethoxazole: blockade of sequential steps in metabolic sequence (i.e. folic acid production)
2. beta lactams + beta lactamase inhibitor (sulbactam) - inhibit enzymatic inactivation
3. penicillins + aminoglycosides enhance antibiotic uptake

Question 18

Describe antagonistic action and provide 2 examples.

Answer 18

Combo of 2 antibiotics may be less effective than one of the agents by itself (generally, static agents are antagonistic to cidal agents)

1. chloramphenicol (bacteriostatic) + penicillin (bactericidal)
2. tetracycline (bacteriostatic) + penicillin (bactericidal)

Question 19

Describe how the “disk diffusion” test evaluates resistance and sensitivity

Answer 19

The disk diffusion test is the most commonly used method to test microbial SUSCEPTIBILITY to antibiotics. This technique is done by placing disks that contain antibiotics on culture dishes and inoculate them with the microorganisms to be tested. The growth of the organism indicates resistance to the drug. Lack of growth indicates sensitivity to the drug.

Question 20

Describe the relationship between bacterial growth vs. bacteriostatic drug, bactericidal drug, and using no agent

Answer 20

No drug - bacteria keeps growing
Bacteriostatic drug - bacteria plateaus
Bacteriocidal drug - bacteria declines

Question 21

What do bactericidal drugs do and list 6 examples?

Answer 21

• bactericidal drugs kill living bacteria
  1. Bacitracin
  2. B-lactams
  3. Quinolones - interfere with synthesis of bacterial DNA or RNA
  4. Aminoglycocides
  5. Polymyxins
  6. Rifampin - interferes with synthesis of bacterial DNA or RNA

Question 22

What do bacteriostatic drugs do and list 6 of them?

Answer 22

1. Tetracyclines - inhibit protein synthesis
2. Sulfonamides - prevent bacterial production of folate
3. Trimethoprim - prevents bacterial production of folate
4. Chloramphenicol - prevents bacterial DNA synthesis
5. Macrolides - target 50S ribosomal unit of bacteria
6. Novobiocin

Question 23

What are 5 disadvantages of using antibiotic therapy?

Answer 23

1. increased risk of toxic and allergic reactions
2. possible antagonism of antimicrobial effects
3. increased risk of superinfection
4. selection of drug resistant bacteria
5. increased cost

Question 24

What are 2 situations in which antibiotics are used prophylactically?

Answer 24

1. surgery (cardiac, peripheral vascular, orthopedic, GI)

2. bacterial endocarditis (congenital valvular heart disease or prostehtic heart valves)

Question 25

What are 4 conditions where antibiotics are not appropriate?

Answer 25

1. using them for untreatable infections (i.e. viral infections)
2. infection of fever of unknown origin
3. improper dosage
4. omission of surgical drainage (when appropriate, surgical drainage and cleansing should be performed to promote antimicrobial effects)