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What is the volume of distribution of AGs?
0.27 L/kg x DW (kg)
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What is the bioavailability of AGs?
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What is the primary site of distribution for AGs?
- extracellular fluid:
- ascitic
- pericardial
- peritoneal
- pleural
- synovial
- abscesses
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How well do AGs penetrate the CNS?
poorly and unpredictably
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What is the extent of AG protein binding?
minimal
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How are AGs metabolized?
they're not
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How are AGs eliminated?
- unchanged in the urine
- primarily by glomerular filtration
- 40-97% of a dose is excreted in 24h
- readily removed by dialysis
- ClAG (L/hr) = CrCl x 0.06
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What type of killing do AGs have?
concentration-dependent killing
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What correlates best with clinical outcomes in AGs?
peak concentrations
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What is the best correlation to toxicity in AGs?
prolonged course (> 10d)
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What trough concentrations are correlated to AG toxicity?
- > 2 mg/L gentamicin, tobramycin
- > 10 mg/L amikacin
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What factors contribute to AG toxicity?
- hypotension/shock/hypovolemia
- advanced age
- liver disease (leads to alteration in renal perfusion)
- concurrent nephrotoxic agents
- overdiuresis with diuretics
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What are the major toxicities associated with AGs?
- ototoxicity
- nephrotoxicity
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What weight is used to dose AGs?
- dosing weight
- DW = IBW + 0.4(TBW-IBW)
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When should a dosing weight be calculated for AGs?
if TBW is > 30% over IBW
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What is the goal serum levels for AGs?
- 4-10 mcg/ml tobramycin, gentamicin
- 15-30 mcg/ml amikacin
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How should AGs be monitored?
- peak and trough concentrations at steady state (on or after 3rd dose) if regimen is > 3-5d
- trough within 30 minutes of the next dose
- peak 30-60 minutes after end of infusion
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What are the goals of high-dose, extended-interval AG therapy?
- optimize bactericidal activity
- minimize toxicity
- suppress expression of adaptive resistance
- decrease costs
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How does high-dose, extended-interval dosing minimize toxicity?
"drug-free" period at end of dosing interval allows AGs to diffuse out of the ears and liver back into the blood where levels are lower.
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Who should not receive high-dose, extended-interval AG dosing?
- pregnant women
- peds/neonates
- burn patients (> 20% BSA)
- severe liver disease
- severe renal disease (CrCl < 30 ml/min)
- bacterial endocarditis, osteomyelitis, or meningitis
- neutropenic patients
- cystic fibroseis patients
- for synergy in staph or strep infections
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What is the initial dose of AGs in high-dose, extended-interval?
- Hartford: 7 mg/kg
- modified Hartford: 5 mg/kg
- modified Hartford (Amikacin): 15 mg/kg
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How is the dosing interval determined for high-dose, extended-interval AG dosing?
based on CrCl
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How should high-dose, extended-interval AG therapy be monitored and adjusted?
a single serum concentration should be pulled 6-14h after start of therapy (7mg/kg nomogram) or end of the infusion (5 mg/kg nomogram)
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How should doses be rounded for gentamicin and tobramycin?
to the nearest 20 mg
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How should doses be rounded off for amikacin?
to the nearest 50mg
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What are the absorption characteristics of vancomycin?
- oral: poor
- IM: DO NOT administer IM
-
How does vancomycin penetrate the CNS?
poorly, but may be improved slightly with inflammation of the meninges
-
How is vancomycin metabolized?
it's not
-
How is vancomycin eliminated?
- unchanged in the urine
- primarily by glomerular filtration
- > 80% of dose is eliminated within 24h
- not readily removed by dialysis (use high-flux membranes)
-
What is the half-life of vancomycin in adults?
5-11h
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What type of killing does vancomycin have?
concentration-independent (maintain at 2-4x MIC)
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What is the goal peak concentration for vancomycin?
20-60 mg/L (not generally monitored)
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What is the goal trough concentration for vancomycin?
- 5-20 mg/ml (generally 10-15)
- 15-20 mg/ml for pneumonia, osteomyelitis, septic arthritis, and meningitis
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What are the major toxicities for vancomycin?
- ototoxicity
- nephrotoxicity
- red man's syndrome
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What peak concentrations are associated with ototoxicity?
> 80 mg/ml
-
What trough concentrations are associated with nephrotoxicity?
> 15 mg/ml
-
What are the risk factors associated with vancomycin toxicity?
- advanced age
- dehydration
- pre-existing renal dysfx
- pre-existing oto dysfx
- co-administration of other nephro- or oto-toxic drugs
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What are the sx of redman's syndrome d/t vancomycin?
- hypotension
- flushing or rash on the face, neck, chest, and/or upper extremities
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How can you prevent red man's syndrome with vancomycin?
slow infusion down to 15 mg/min or less and/or pre-medicate with an antihistamine
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How is vancomycin monitored?
- trough-only
- 30 min before administration
-
What are the nomograms used for vancomycin dosing?
-
How should vancomycin doses be rounded?
to the nearest 250mg
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