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The following objectives are intended to be used as a general guide for focusing your studying for the midquarter examination. This is not all-inclusive but can be used as a general reference. Supplemental study guide materials may be distributed later in the course to augment this guide.

Please remember that you are responsible for mechanisms of action and resistance covered in-depth in Dr. Remmel's class.

This study guide is NOT intended to replace your notes, readings, lecture handouts. The purpose of this study guide is to assist you in focusing your studying efforts only.

PHARMACODYNAMICS

Understand:

Pharmacokinetics vs. Pharmacodynamics
Concentration-dependent killing vs. concentration-independent killing
Know which drugs are concentration-dependent killers and concentration-independent killers
MICs, MBCs, SITs, SBTs
Bacteriostatic
Bactericidal
Tolerance
Synergy
Antagonism
Importance of pharmacodynamic outcome predictors (best predictors for each antibiotic class)

AMINOGLYCOSIDES

Gentamicin, Tobramycin, Amikacin, Streptomycin

Concentration-dependent killing
Conventional dosing
Single daily dosing (rationale, Hartford Nomogram)
Know average half-life (approx. 2 hours), volume of distribution (0.25-0.35 L/kg)
Understand peak and trough levels (what levels are you trying to achieve)
Post-antibiotic effect
Toxicity: ototoxicity, nephrotoxicity
Complete computer tutorial modules 1 and 2
Dosing:
  Conventional dosing
  Single daily dosing
Pharmacokinetics:
  Know how to calculate:
  LBW, dosing weight
  Creatinine clearance
  Know how to determine:
  Predicted half-life based on population based data
  Determine appropriate starting dose, regimen for a patient
  Aminoglycoside levels:
  Understand significance of 1st dose levels, 2nd dose levels, and steady-state levels
  Using logarithmic graph paper, determine patient-specific half-life
  Determine other patient-specific parameters: volume of distribution
  Recommend new dose, regimen based on desired peak/trough levels and patient data
  Complete modules (AGI, AGII, AG kinetics tutorial, AG study guide, AG study guide 2

MICROBIOLOGY

Understand chemical tests used to identify organisms:

Catalase
Coagulase
Indole
Glucose fermentation
Bile-Esculin test
6.5% sodium chloride
Oxidase test

Understand:

  E test
  MIC/MBC testing
  Exponential growth (bacterial curve growth)
  Stationary growth

Gram Positive:

  Understand/Memorize flow chart
  Aerobic/anaerobic/facultative
  Cocci: Staphylococcus, Streptococcus, Enterococcus
  Bacilli: Listeria, Clostridium
  Differentiate types of hemolysis

Gram Negative:

  Understand/memorize flow chart
  Aerobic/anaerobic/facultative
  Cocci: Neisseria, Moraxella
  Bacilli: Enterobacteriaceae group, Pseudomonas, Helicobacter pylori, Stenotrophomonas
  Complete microbiology module

VANCOMYCIN

Understand:

  Spectrum:
  Gram positive
  Pharmacokinetics:
  No oral absorption
  Expected half-life
  Volume of distribution
  Elimination: renal
  Concentration independent killer
  Biexponential decay
  One compartment vs. multicompartment modeling
  Pharmacodynamics:
  Bactericidal/bacteriostatic
  Synergy with aminoglycosides/rifampin
  Appropriate use: (CDC recommendations)
  MRSA/MRSE (present or suspected)
  PCN allergy
  PCN-resistant Strep. pneumoniae
  Adverse Effects:
  Nephrotoxicity
  Ototoxicity
  Phlebitis
  Red Man Syndrome
  Dosing/Monitoring:
  10 mg/kg/dose (interval based on renal function)
  Peak/trough levels:
  Usually only monitor trough levels (5 to 10 mcg/mL)
  Dosing in renal dysfunction/failure (increased half-life)
  CDP controversy
  Resistance:
  Vancomycin resistance enterococcus (VRE)
  Plasmid mediated
  Transfer to Staphylococcus (VISA/GISA)
  (See BACTERIAL RESISTANCE Lecture)
  Complete vancomycin module

BACTERIAL RESISTANCE

Understand:

  Different mechanisms of resistance
  Influx alterations: porin channel modification
  Environmental changes
  Transport changes
  Enzyme production: beta-lactamases
  Chromosomal vs. plasmid mediated
  Target alteration: penicillin binding alteration
  Beta-Lactamases:
  Mechanism of resistance
  Chromosomally mediated, plasmid mediated
  Induction: What organisms can be induced to produce beta-lactamases
  Classification schemes: Richmond Sykes (esp. Type I/Type IIIs)
  H. influenzae: beta-lactamase producers (> 90%)
  Moraxella catarrhalis: beta-lactamase producers (> 90%)
  Specific Antibiotic Destruction:
  Aminoglycosides
  Adenylation/Acetylation/Phosphorylation
  Macrolides
  50s ribosome alteration
  Resistance to one, means resistance to all
  Cephalosporins
  Beta-lactamases
  Penicillins
  Penicillinases
  Fluoroquinolones
  DNA gyrase alteration
  TMP/SMX
  Metabolic bypass (folic acid)
  Vancomycin
  Metabolic bypass
  Penicillin binding alteration:
  PCN resistance Strep. pneumoniae
  Sensitive MIC less than or equal to 0.6 mg/L/ Nonsusceptible MIC 0.12 to 1.0 mg/L/Resistant greater than or equal to 2mg/L
  Prevalence
  Drugs of choice based on sensitivities
  MRSA/MRSE
  PBP-2
  Enterococcus:
  Mechanisms of resistance:
  PBP (approx. 98%)
  Tolerance
  Beta-lactamase production: PCN resistance (approx. 2%)
  High level gentamicin, streptomycin resistance
  Vancomycin resistance (alteration of amino acid)
  E. faecium > (vanco/ampicillin) resistance than E. faecalis
  Van A, Van B, Van C
  Van A: high level resistance vanco/teicoplanin; transferable/inducible/transposon
  Van B: Moderate vanco resistance/susceptible teicoplanin; Chromosomal/transferable
  Van C: Low level resistance vanco/susceptible teicoplanin
  Therapeutic options based on mode of resistance
  H. fluenzae
  Mechanisms of resistance
  Prevalence
  M. catarrhalis
  Mechanisms of resistance
  Prevalence

MACROLIDES (not lectured on, but may be included in the midquarter) (Erythromycin, Azithromycin, Clarithromycin, Dirithromycin, Roxithromycin)

Understand:

  Spectrum: Strep/H. flu/M. catarrhalis/H. pylori/Gr. A. Strep/Chlamydia/Legionella/Mycoplasma/ Mycobacterium
  Mechanism of action: binds 50s ribosome
  Bacteriostatic antibiotics