Antibiotics

Question 1

Main principle of antibiotic chemotherapy

Answer 1

Steady state concentration must be achieved at the side of infection for long enough or high enough concentrations to clear the infection without adversely affecting the patient or contributing unnecessarily to the development of antibiotic resistance

Question 2

Chemotherapy

Answer 2

Use of drugs to kill or suppress growth of invasive microbial cells

Question 3

Antibiotic

Answer 3

Natural substance produced by microbes that has the ability to harm or inhibit growth of other microbes

Question 4

Selective toxicity

Answer 4

Ability of a drug to injure target cells without injury to the host

Question 5

Minimum inhibitory concentration

Answer 5

Lowest concentration of an agent that prevents visible bacterial growth

Question 6

Minimum bacteriocidal concentration

Answer 6

Lowest concentration that reduces the number of vaiable bacteria

Question 7

How do we achieve selective toxicity

Answer 7

Exploit differences between pathogen and host cells
Target unique cellular processes to the pathogen
Target similar processes using differences in drug affinity


Question 8

Bacteriostatic

Answer 8

Suppressing cell proliferation but not causing cell death
ultimately depends on the host immune system to clear the infection

Question 9

Bacteriocidal

Answer 9

Property of causing cell death
Dependent on active bacterial proliferation

Question 10

Time dependent antibiotics (T>MIC)

Answer 10

Benefits from continuous drug exposure rather than high concentrations
Ex. Cell wall inhibitors 

Question 11

Peak concentration dependent antibiotics (Peak>MIC)

Answer 11

Permits less frequent dosing schedules
Ex. Aminoglycosides, flouraquinolones

Question 12

AUC dependent antibiotics (correlates with time c concentration)

Answer 12

Total cumulative dose overtime is the factor determining infection clearance
Ex. Glycopeptides 

Question 13

Innate antibiotic resistance

Answer 13

Antibiotic was never active
Ex. Anaerobes are resistant to oxygen dependent processes
Arrows are resistant to drugs are requiring enzymatic reduction and low oxygen environments
Gram-negative bacteria are resistant to lipophilic and high molecular weight hydrophilic drugs due to the lack of penetration through the outer membrane poring
A typical bacteria lack cell walls and are therefore resistant to cell wall synthesis inhibitors

Question 14

Aquired resistance

Answer 14

Loss of formerly active antibiotic by vertical or horizontal transfer 
Ex. Inactivation by bacterial drug metabolizing enzymes
Decreased uptake and or increased efflux transporters
Reduced binding affinity due to mutations in amino acid sequence of target site proteins
Bypass blockade of target metabolic processes or pathway

Question 15

Consequences of resistance

Answer 15

Failure to clear primary infections
Increased risk of secondary infections due to antibiotic activity against her mental flora

Question 16

Antibiotics are_ and thus have poor _

Answer 16

Hydrophilic, oral bioavailability

Question 17

You should consider direct administration when treating infection in

Answer 17

Bone, eye, pulmonary epithelium, abscesses tissue, or biofilms due to their difficult to penetrate nature

Question 18

What route of antibiotic administration is preferred for critically ill patients or those with meningitis or endocarditis?

Answer 18

IV

Question 19

Duration of antibiotic use

Answer 19

Minimum duration required for maximum efficacy
Biomarkers of infection such as procalcitonin are used to optimize treatment duration

Question 20

Antibiotic distribution needs to exceed _ at site of infection

Answer 20

MIC breakpoint

Question 21

CNS infection; hydrophilic agents cross intact blood brain barrier _

Answer 21

Poorly

Question 22

Obese patients should be dosed based on _ rather than _

Answer 22

Ideal
Actual

Question 23

Antibiotic doses must be adjusted based on

Answer 23

Liver and kidney (check CrCL) function

Question 24

Combination therapy indications

Answer 24

Mixed infections
Empiric therapy
Drug synergy
Prevention of resistance

Question 25

Disadvantages of combination therapy

Answer 25

Drug antagonism
Toxicity
Superinfections

Question 26

Prophylactic therapy and its indications

Answer 26

Treat an infection before it’s an issue
Before surgery
Bacterial endocarditis
Opportunistic infections in immunocompromised patients
After exposure to sexually transmitted infections

Question 27

Aminoglycoside toxicity

Answer 27

Ototoxicity and nephrotoxicity

Question 28

Tetracycline toxicity

Answer 28

Bone growth suppression
 tooth staining

Question 29

Sulfonamide toxicity

Answer 29

Kernicterus in nursing infants

Question 30

Folate Antagonist toxicity

Answer 30

Maternal folic acid deficiency causing neural tube defects

Question 31

Fluoroquinolones

Answer 31

Toxic to developing Cartlidge

Question 32

Targets in Gram + bacteria

Answer 32

Thick peptidoglycan cell wall- antibiotics readily diffuse
Plasma membrane- hydrophilic antibiotics cross poorly 

Question 33

Targets in Gram - bacteria

Answer 33

Thin cell wall (lipid membrane) hinders transport of many antibiotics
Small hydrophilic drugs across the outer membrane via passive transport through Porins
Periplasmic space concentrates inactive enzymes 

Question 34

Atypical bacteria (chlamydia, mycoplasma, rickettsia, legionella)

Answer 34

Lack peptidoglycan layer
Resistant to cell wall inhibitors
Reside within host cells so drugs must be lipophilic to cross host cell membrane