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NUNA 679 - ANP Pharm > Principles of Antimicrobial Therapy > Flashcards

Principles of Antimicrobial Therapy Flashcards

1
Q

What are the 4 antibiotic mechanisms of action?

A
  • Inhibition of cell wall synthesis
  • Disruption of cell membrane
  • Inhibition of protein synthesis
  • Inhibition of nucleic acid synthesis
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2
Q

What target qualities on the bacteria help to reduce antibiotic toxicity?

A
  • Target differences between bacteria & patient

- Target critical to survival and replication of bacteria

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3
Q

What antibiotic target is MOST unique?

A

Cell wall synthesis and integrity

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4
Q

How is toxicity related to therapeutic index?

A

Inversely

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5
Q

What are 4 consequences of antibiotic use?

A
  • Allergy/hypersensitivity
  • Adverse reactions/toxicity
  • Alterations in normal microbial populations (risk of superinfections)
  • Resistance
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6
Q

What are 3 approaches to antimicrobial therapy?

A
  • Empiric
  • Definitive
  • Prophylaxis
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7
Q

What is empiric antimicrobial therapy and what is an example?

A

Treatment of an infection based on presumed diagnosis (ex., macrolide or fluoroquinolone for presumed CAP)

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8
Q

What is definitive antimicrobial therapy and what is an example?

A

Treating an infection based on positive cultures (ex., switch from vanc/Zosyn to oxacillin for positive MSSA cultures)

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9
Q

What is prophylactic antimicrobial therapy and what is an example?

A

Using an antibiotic to prevent infection (ex., bactrim to prevent Pneumocystis pneumonia in an HIV patient with low CD4 counts)

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10
Q

What are some considerations when choosing a prophylactic antibiotic for surgery? (10)

A

Risk-benefit, type of surgery, renal function, liver function, allergies, immunosuppression, comorbidities, pediatrics, pregnancy (stage), cost

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11
Q

What is the time table for perioperative prophylactic antibiotics?

A

Given 1-2 hours before incision; additional dose(s) if surgery is longer than 3-4 hours or has major blood loss; discontinued within 24 hours

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12
Q

The Usual Suspects for UTI (7)

A

E. coli, Klebsiella, Pseudomonas, Proteus, Other GNB, Staph, Enterococci

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13
Q

The Usual Suspects for SSI post appendectomy (2)

A

Bacteroides (especially B. fragilis) and E. coli

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14
Q

The Usual Suspects for SSI post c-section (5)

A

Staphylococcus aureus, GNB, Staphylococcus epidermidis, Enterococci, E. coli

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15
Q

What is the minimum inhibitory concentration (MIC)?

A

The lowest concentration required to inhibit microbial growth ; drug and microbe specific; determined in vitro; compared to the breakpoint set by the CLSI.

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16
Q

What is the Minimum Bactericidal Concentration (MBC)?

A

Lowest concentration required to kill the bacterial isolate; more difficult and time consuming to determine than the MIC; generally NOT important for routine clinical care.

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17
Q

Efficacy at the site of infection depends on ________ _______ and _________ at the infection site

A

antibiotic activity; penetration

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18
Q

True/false: Adequate blood levels do not necessarily equal adequate concentrations at sites.

A

True

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19
Q

Daptomycin is inactivated by __________ __________.

A

pulmonary surfactant

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20
Q

Aminoglycosides and polymyxins are inactivated by ___ __.

A

Low pH (like in an abscess)

21
Q

What is Disk Diffusion (Kirby-Bauer Method)?

A

A method of susceptibility testing in which antibiotics are added to the plate after an organism is streaked onto the agar. After a period of incubation, a zone of inhibition can be seen that is used to determine susceptibility.

22
Q

What is Serial Dilution?

A

A susceptibility test to determine the minimum antibiotic concentration at which bacterial growth will be inhibited. The lowest concentration with no growth is used.

23
Q

What is an antibiogram?

A

Used to show trends in antibacterial resistance for an institution; aids in selecting empiric treatment; monitors resistance trends over time (over 90% susceptibility is considered good)

24
Q

What is a potential downside to broad spectrum antibiotic use on an unknown bacteria?

A

Development of resistance and side effects

25
Q

Describe the characteristics of a bactericidal antibiotic.

A

Disrupt the bacterial cell and cause death; generally primarily act on the cell wall, cell membrane, or DNA synthesis.

26
Q

Describe the characteristics of bacteriostatic antibiotics.

A

Inhibit bacterial replication without killing; generally act through inhibition of protein synthesis; works WITH host defenses to clear infectious organism; not good for immunocompromised patients.

27
Q

Which type of agent is more likely to cause antibiotic resistance? Bacteriostatic or bactericidal?

A

Bacteriostatic because bactericidal agents outright kill the bugs without allowing them a chance to develop resistance.

28
Q

Name bacteriostatic agents (5).

A

Tetracyclines, macrolides, clindamycin, linezolid, and trimethoprim/sulfamethoxazole

29
Q

How do concentrations needed to inhibit growth compare to concentrations needed to kill bacteria in a BACTEROSTATIC agent.

A

They are considerably less

30
Q

What types of infections are hard to treat with bacteriostatic agents? (5)

A

Systemic infections in a neutropenic patient
Osteomyelitis
CV infections
CNS infections
Infections associated with a foreign body (like a foley; bacteria forms a film)

31
Q

List some bactericidal agents (7).

A

Aminoglycosides, beta-lactams, vancomycin, fluoroquinolones, metronidazole, most antimycobacterial agents, streptogramins

32
Q

How does the concentration that inhibits bacterial growth compare to the concentration that kills bacteria with a BACTERICIDAL agent?

A

There is little difference

33
Q

What is the parameter of interest for a concentration-dependent antibiotic?

A

Cmax/MIC ratio (higher doses with extended intervals)

34
Q

What is the parameter of interest for a time-dependent antibiotic?

A

Time above MIC (achieved by continuous/frequent dosing; increased concentration does not increase killing)

35
Q

A 70 year-old women with creatinine clearance estimated to be
30mL/min being treated with ciprofloxacin for a urinary infection
caused by E. coli. Based on renal function, treatment guidelines
indicate to dose either (a) 250 mg orally every 12 hours or (b)
500 mg every 24 hrs.
Ciprofloxacin exhibits concentration-dependent killing
Which dosing regimen is more appropriate?
(a) 250 mg orally every 12 hours or (b) 500 mg every 24 hrs.

A

B

36
Q

If the same patient were being treated with intravenous
ampicillin which exhibits time-dependent killing, which dosing
regimen below is more appropriate:
(a) 1 g every 4 hours
(b) 2 g every 8 hours?

A

A

37
Q

What is post antibiotic effect (PAE)?

A

Continued antimicrobial effects AFTER drug levels in the body have fallen below MIC

38
Q

What theories potentially explain PAE?

A

May relate to:

  • Time it takes infectious organism to make new cellular components
  • Persistence of drug at target
  • Infectious organism becomes more susceptible to patient’s immune system
39
Q

Name the successful antimicrobial therapy drug factors in pharmacodynamics/MOA (4).

A
  • Can’t work if there’s no target
  • Static vs. cidal
  • Time or concentration-dependent activity?
  • Post-antibiotic effect (PAE)?
40
Q

Name the successful antimicrobial therapy drug factors in pharmacokinetics (6).

A
  • Can it access the infection site?
  • Does it reach effective levels (greater than MIC)?
  • Administration route?
  • Metabolism?
  • Dosage adjustment requirements?
  • Adverse effect profile
41
Q

List successful antimicrobial therapy PATIENT factors (7).

A
  • Extremes of age
  • Pregnancy
  • Allergy/hypersensitivity
  • Previous use of antimicrobials
  • Concomitant disease states
  • Genetics
  • Cost!
42
Q

List the drugs associated with pediatric-specific adverse effects (4).

A

Chloramphenicol
Sulfonamides
Tetracyclines
Fluoroquinolones

43
Q

Name the drugs associated with allergy/hypersensitivity (3).

A

Penicillin
Cephalosporins
Sulfonamides

44
Q

Name factors impacting successful antimicrobial therapy with extremes of age (2).

A

Renal/hepatic function

Pediatric-specific adverse effects

45
Q

Name patient factors impacting successful antimicrobial therapy regarding concomitant disease states (3).

A

What other meds is the patient taking?
Alterations in drug distribution, elimination (CV)
Immune system status (cidal vs. static)

46
Q

Name the patient factors associated with successful antimicrobial therapy regarding genetics (2).

A

HLA-B*5701 (Anti-HIV drug reaction)

Glucose-6-phosphate dehydrogenase deficiency (RBCs need glutathione synthesis to prevent lysis)

47
Q

What characteristics of the infectious organism impact successful antimicrobial therapy? (5)

A
  • Gram stain (positive, negative, none)
  • Serology, cultures
  • Biochemical tests
  • Bacteriologic statistics (“the usual suspects”)
  • What is the organism sensitive to? MIC: susceptible vs. resistant, local resistance patterns
48
Q

Name the two types of resistance.

A

Natural (ex., anaerobic vs. aminoglycoside)

Acquired (ex., growing in the presence of the drug)

49
Q

Name 4 mechanisms of drug resistance.

A 
Decreased penetration (ex., Vancomycin and gram negative bacteria with thickening wall)
Enzymatic inactivation or modification (ex., bacteria makes enzyme to inactivate the drug)
Target site changes (ex., PBP change so drug can't bind)
Active efflux (out of bacterial cell)

NUNA 679 - ANP Pharm (9 decks)

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