PK and PD of abx

  1. What is the definition of MIC?
    • minimum inhibitory concentration
    • lowest drug concentration without visible growth for 16-20 hours at 35 degree celsius
  2. Does MIC mean that the bacteria is all eradicated?
    • Nope
    • it is the drug concetnration that results in stasis
  3. What is MIC50?
    • 50% of inhibition of inoculum.
    • we usually use MIC90
  4. Does MIC inform the potency of antimicrobial activity?
  5. Does MIC inform the time course of antimicrobial activity?
  6. Does MIC inform growth inhibitory effects that may persist after antimicrobial exposure?
  7. If MIC is low, what does this mean?
    • the bug is sensitive
    • the higher the number, the more antibiotic you need
  8. For MIC, how much fold of antibiotic dilution do you add? how long do you incubate the tube?
    • 2 fold
    • 18-24 hours
  9. Does ceftriaxone cover pseudomonas?
  10. Which bacteria depends less on the host immune system?
    cidal vs. static
  11. PCN is bactericidal or static?
    • bactericidal
    • inhibit cell wall/memb
  12. cephalosporin is bactericidal or static?
    • cidal
    • inhibit bacteria cell wall/memb
  13. FQ is bactericidal or static?
    • cidal
    • interfere with bacterial enzymes
  14. sulfa abx is bactericidal or static?
    • static
    • inhibit protein synthesis
  15. tetracycline is bactericidal or static?
    • static
    • inhibit protein synthesis
  16. linezolid is bactericidal or static?
    • static
    • inhibit protein synthesis
  17. How does toxin production work in bactericidal activity? How should you manage?
    • sudden lysis of bacteria leads to a sudden increase in bacterial products and this stimulate cytokine production
    • this can be harmful to the host and cause inflammation
    • co-administer steroids in meningitis
    • add bacteriostatic agents because they directly inhibit the production of toxin (clindamycin)
  18. What regimen do you give for meningitis?
    must give abx adn steroid together on day 1 because of toxin production and inflammation
  19. What regimen do you give for PCP in HIV patients?
    Bactrim for 21 days + steroid taper
  20. What kind of bacteria does clindamycin cover?
    • gram positive
    • anaerobe
    • inhibit toxin production
  21. when would you choose cidal antibiotics?
    • endocarditis, meningitis, osteomyelitis
    • immunocompromised patietns
  22. Can you use moxifloxacin for UTI?
  23. Enterococcal endocarditis does not have much cidal agents for us to use. What would you do?
    • use synergy
    • aminoglycoside + b-lactams
  24. When is the combination of tetracycline and b-lactams good?
    • this is a trick question
    • they antagonize each other
    • cidal agents work only when the cells are duplicating so don't combine cidal and static
  25. what is the definition of pharmacodynamic?
    describes the relationship between measurements of drug exposure in serum, tissues and body fluids and the pharmacologic and toxic effects of the drug.
  26. What is Cmax/MIC?
    ratio of highest concentration attained in a dosing interval to the MIC
  27. what is AUC/MIC?
    ratio of measure of the total exposure of drug to the MIC
  28. what is %T>MIC?
    time that drug concentration exceeds MIC. stated as a percentage of the dosing interval.
  29. Explain how concentration dependent abx should do in terms of MIC.
    need high MIC
  30. Explain how time dependent abx should do in terms of MIC.
    need to stay above MIC for the dosing interval at least 60-80% of the time.
  31. What is post antibiotic effect?
    • persistent inhibitory effect on a bug that results from drug exposure after drug has been completely removed.
    • delay before microorganism recover and reenter a log growth period
    • this is only in concentration dependent abx.
  32. Is PAE seen in concentration dependent abx?
    • Yes
    • not time dependent
  33. Is PAE seen in time dependent abx?
    • Nope
    • just in concentration dep abx
  34. PAE depends on what factors?
    • influences
    • bacteria
    • inoculum size
    • concentration antibiotic
    • duration of exposure
  35. Image Upload 2
    • A: peak/MIC (Cmax/MIC)
    • B: AUC/MIC
    • C: Time > MIC
    • D: sub-MIC
    • E: PAE
  36. What kind of effects does concentration dependent abx have?
    moderate and prolonged persistent effects
  37. Rate and extent of bactericidal action increases with ____ (inc/dec) drug concentration for concentration dependent abx.
  38. What is the goal for concentration dependent abx? Explain in terms of pharmacodynamic terms.
    • maximize concentration
    • AUC/MIC and peak/MIC
  39. Aminoglycoside
    concentration or time dependent?
  40. FQ
    concentration or time dependent?
  41. ketolides (telithromycin)
    concentration or time dependent?
  42. metronidazole
    concentration or time dependent?
  43. amphotericin B
    concentration or time dependent?
  44. daptomycin
    concentration or time dependent?
  45. High dose extended interval for AG optimizes PD concentration dependent killing in treatment of what kind of infection?
    gram negative infections
  46. what is gentamycin dosing for extended interval dosing?
  47. what is tobramycin dosing for extended interval dosing?
  48. what is amikacin dosing for extended interval dosing?
  49. What is the goal for extended interval dosing for AG in terms of peak and trough?
    • to have high peaks
    • and UNDETECTABLE troughs
  50. Does high dose extended interval AG have PAE?
    yes post antibiotic effect
  51. What is the benefit of high dose extended interval AG compared to traditional dosing?
    • less nephrotoxic: saturable transport system regarding uptake of drug in the kidney (kidneys can only absorb max amount per time so qd is better than more often). less frequent single daily dose may minimize accumulation (drug free interval).
    • ototox is uncertain
  52. What should the trough of high dose extended interval dosing AG be?
  53. What should the trough of traditional dosing AG be?
    • <2mg/L for gent and tobra
    • <10mg/L for amikacin
  54. what is the synergy dosing for gentamycin? what should the trough be?
    • 1mg/kg q8h
    • trough: <1
  55. When a resident asks you if the trough for AG is okay, what should you question?
    • need to know what dosing interval was used
    • need to know if it was used for synergy for Gram positive
  56. When should you sample extended interval dosing AG (peak and trough) troigu? how does it accumulate?
    • no significant accumulation
    • trough: measurement can be obtained after any dose
    • peak: no need to measure peak
  57. how do you infuse traditional dosing AG? when do you draw peak and trough?
    • infuse over half hour, wait one half hour
    • then draw peak
    • trough drawn before next dose (or within half hour of dose)
  58. What are key pharmacodynamic parameters for AG?
    • peak/MIC ratio (unlike in FQ, peak is used here because AG loves water so it doesn't go into CNS and cause CNS tox)
    • AUC/MIC ratio or AUIC
    • AUC24= 70-100mghr/L
  59. What is AUC formula?
    AUC = dose / clearance
  60. What are key pharmacodynamic parameters for fluoroquinolone? (what are target numbers?)
    • AUC/MIC ratio (125-250)
    • peak/MIC ratio is NOT used because if the peak is high, CNS issue
  61. Is ciprofloxacin good for S. pneumo?
    • not really
    • levofloxacin is better
  62. For FQ, what AUC:MIC ratio is good for gram negative rods?
    > 125 for gram negative
  63. For FQ, what AUC:MIC ratio is good for gram positive cocci?
    >30 for gram positive
  64. The higher the MIC, how much drug would you need?
    MORE drug
  65. Extent of bacterial killing for time-dependent bacteria depends on the ____.
    time the active drug cnocentration remains above the MIC.
  66. What kind of effect does time dependent abx have?
    mild/moderate persistent effect
  67. Beta lactams
    concentration or time dependent?

    concentration or time dependent?

  68. macrolides (azithromycin, clarithromycin, erythromycin)
    concentration or time dependent?
  69. clindamycin
    concentration or time dependent?
  70. Oxazolidionones (linezolid)
    concentration or time dependent?
  71. flucytosine
    concentration or time dependent?
  72. Which time dependent abx has prolonged persistent effect, as opposed to minimal/moderate persistent effect?
    • Azithromycin
    • Tetracycline
    • Glycopeptide (vancomycin, televancin)
    • Q/D (quinupristin dalfopristin)
    • fluconazole
  73. Tetracycline
    concentration or time dependent?
  74. Glycopeptides (vancomyin, televancin)
    concentration or time dependent?
  75. Q/D
    concentration or time dependent?
  76. fluconazole
    concentration or time dependent?
  77. What is the goal for time dependent abx?
    optimize duration of exposure (time >MIC)
  78. What is the benefit of continuous infusion over intermittent for time dependent abx?
    • therapeutic efficacy
    • because do not need to give as much drug: cost saving - amount drug/time; reduced risk of dose related toxicity
  79. What are problems of continuous infusion for time dependent abx?
    • stability at room temperature
    • no drug free interval so adverse reaction
    • access (for other drugs etc)
  80. What is the extended infusion dosing for Zosyn?
    3.375g IVPB TRO 4 hours q8h (>40ml/min), q12h (10-39ml/min)
  81. what does APACHE stand for?
    • acute physiologya nd chronic health evaluation
    • assess risk of mortality
  82. What should fT>MIC be for time dependent abx to be good?
  83. Vancomyin failures have been observed when MIC is ____mg/L.
  84. What should we monitor in vancomycin?
    • check trough
    • peak is not necessary
  85. what does penetration into tissue for vancomycin depend on?
    • affected by inflammation and disease state
    • i.e.)
    • meningitis: higher penetration if inflamed
    • DM: lower penetration in diabetics
  86. what is the MIC for vancomyin?
  87. what should vancomycin trough be?
  88. what is the relationship between trough and MIC for vancomycin in in patients with MRSA infection?
    trough is 4x MIC in patients with MRSA
  89. When would you use high trough of vancomycin?
    • 20mg/L
    • osteomyelitis, endocarditis, bacteremia
  90. What should the target AUC/MIC for vancomycin be for MRSA?
  91. What do you use to dose vancomycin?
    • nomogram (many are outdated)
    • patient specific
    • use actual body weight
  92. What is the loading dose for vanco? why is it needed?
    • 25-30mg/kg (~2g)
    • vanco Css is reached within 24-48 h but many need LD because of clinical status.
  93. what is the infusion rate for vancomyin?
  94. How do you infuse vancomycin? (in terms of rate and dose?)
    • if >1g, divide by 15mg/min for the rate
    • if <1g, infuse 1g over an hour.
  95. What should you do for monitoring for vancomycin for critically ill patient?
    attain target trough earlier
  96. what is the dosing strategy of vanco for patients with normal renal function?
    • may load 25-30mg/kg (~2g)
    • then 15-20 mg/kg q8-12h
  97. If the patient's condition is too serious (i.e. SICU), what should you do for vancomycin treatment?
    • 1) may consider daptomycin
    • 2) increase vancomycin level but check trough q4 day and check creatinine
  98. Is ototoxicity for vancomycin common?
    • rare
    • usually seen in patients receiving other ototoxic agents (i.e. gent)
  99. how do you assess vancomyin nephrotoxicity?
    >0.5mg/dL over baseline or increase of 50% for 2 consecutive assays.
  100. what are risk factors for nephrotoxicity for vanco?
    • older age
    • larger patient (b/c vanco goes to fat)
    • longer treatment courses
    • ICU stay
    • higher trough serum vanco concentration (30-65mg/L)
    • more than 4g/day
  101. Is linezolid nephrotoxic?
    • nope
    • but vanco is
  102. when should you consider linezolid over vancomycin?
    • nephrotoxic patients
    • fat patients
    • ICU stay patients
  103. what are risk factors for ototox for vanco?
    • older impure formulation
    • lever >40mg/L (very high)
    • concomitant ototox agent (i.e. gent)
    • pediatric pneumococcal meningitis
  104. how often should you get vanco trough monitor? how about for elderly?
    • q week
    • for elderly, q 4 days
  105. If MIC is 1mg/L for vanco, what should the target trough be?
    at least 15mg/L
  106. what is the target AUC/MIC for vanco?
  107. what does pharmacokinetic tell you?
    • movement of drug
    • ADME
  108. what does pharmacodynamic tell you?
    concentration and efficacy of drug
  109. what pharmacodynamic parameters do concentration dependent abx use?
    • Cmax/MIC
    • AUC/MIC
    • PAE
  110. what pharmacodynamic parameter does time dependent abx use?
Card Set
PK and PD of abx
PK, PD, abx