Aminoglycosides: Difference between revisions
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= Dosing = |
== Dosing == |
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== Initial == |
=== Initial === |
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If actual body weight more than 20% higher than ideal body weight, need to calculate adjusted body weight (ABW) |
If actual body weight more than 20% higher than ideal body weight, need to calculate adjusted body weight (ABW) |
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$$ABW = IBW + 0.4 \times (actual BW - IBW)$$ |
$$ABW = IBW + 0.4 \times (actual BW - IBW)$$ |
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== Traditional q8h dosing == |
=== Traditional q8h dosing === |
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* Used for Enterococcus IE, meningitis, septic shock, ascites, AKI/CKD, prefnancy, surgical prophylaxis, burns, osteomyelitis |
* Used for Enterococcus IE, meningitis, septic shock, ascites, AKI/CKD, prefnancy, surgical prophylaxis, burns, osteomyelitis |
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* 1.7mg/kg (5-7.5mg/kg amikacin) |
* 1.7mg/kg (5-7.5mg/kg amikacin) |
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== Extended interval dosing == |
=== Extended interval dosing === |
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* 7mg/kg (15mg/kg amikacin) |
* 7mg/kg (15mg/kg amikacin) |
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* CrCl ≤19 don't use |
* CrCl ≤19 don't use |
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== Dialysis == |
=== Dialysis === |
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* Pre-HD levels with post-HD doses, though this may change |
* Pre-HD levels with post-HD doses, though this may change |
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== Synergy == |
=== Synergy === |
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* 1mg/kg divided q8-12h, peak target 3-5, trough <2 |
* 1mg/kg divided q8-12h, peak target 3-5, trough <2 |
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== Monitoring == |
=== Monitoring === |
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== Peak == |
=== Peak === |
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* 30min after third? dose |
* 30min after third? dose |
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* If below target, increase dose |
* If below target, increase dose |
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== Trough == |
=== Trough === |
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* Prior to 4th dose, or a random level at 24-48h in renal failure |
* Prior to 4th dose, or a random level at 24-48h in renal failure |
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* If above target, increase interval |
* If above target, increase interval |
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== Hartford Nomogram == |
=== Hartford Nomogram === |
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 |
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= Origin = |
== Origin == |
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* Derived from Streptomyces spp (mycins & kacins) or Micromonospora spp (micins) |
* Derived from Streptomyces spp (mycins & kacins) or Micromonospora spp (micins) |
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= Mechanism = |
== Mechanism == |
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* Requires electron transport chain (ETC) to cross over the membrane |
* Requires electron transport chain (ETC) to cross over the membrane |
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* Reversibly binds 30S ribosomal subunit, which stops proofreading and causes accumulation of bad proteins |
* Reversibly binds 30S ribosomal subunit, which stops proofreading and causes accumulation of bad proteins |
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= Spectrum of Activity = |
== Spectrum of Activity == |
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* Good coverage of Gram-negative aerobes |
* Good coverage of Gram-negative aerobes |
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* Can cover Gram-positives if cell wall is disrupted (e.g. by beta-lactam) |
* Can cover Gram-positives if cell wall is disrupted (e.g. by beta-lactam) |
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= Resistance = |
== Resistance == |
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* Altered 50S ribosomal subunit |
* Altered 50S ribosomal subunit |
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* Aminoglycoside-modifying enzymes (Enterococcus) |
* Aminoglycoside-modifying enzymes (Enterococcus) |
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= PK/PD = |
== PK/PD == |
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* Poor membrane penetration, therefore doesn't cross over into lungs and CSF |
* Poor membrane penetration, therefore doesn't cross over into lungs and CSF |
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* Displays concentration-depedent killing with a prolonged post-antibiotic effect (2-13 hours) |
* Displays concentration-depedent killing with a prolonged post-antibiotic effect (2-13 hours) |
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= Side Effects = |
== Side Effects == |
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* Nephrotoxicity (0-50%), usually non-oliguric AKI with decreased Ca/Mg resorption, often reversible |
* Nephrotoxicity (0-50%), usually non-oliguric AKI with decreased Ca/Mg resorption, often reversible |
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* Rarely, neuromuscular blockade |
* Rarely, neuromuscular blockade |
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= Monitoring = |
== Monitoring == |
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* Trough levels |
* Trough levels |
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Revision as of 09:50, 16 August 2019
Dosing
Initial
If actual body weight more than 20% higher than ideal body weight, need to calculate adjusted body weight (ABW)
$$ABW = IBW + 0.4 \times (actual BW - IBW)$$
Traditional q8h dosing
- Used for Enterococcus IE, meningitis, septic shock, ascites, AKI/CKD, prefnancy, surgical prophylaxis, burns, osteomyelitis
- 1.7mg/kg (5-7.5mg/kg amikacin)
Extended interval dosing
- 7mg/kg (15mg/kg amikacin)
- Use Hartford nomogram with a random level (but remember to halve the amikacin level first)
- CrCl ≥60 q24h
- CrCl 40-59 q36h
- CrCl 20-39 q48h
- CrCl ≤19 don't use
Dialysis
- Pre-HD levels with post-HD doses, though this may change
Synergy
- 1mg/kg divided q8-12h, peak target 3-5, trough <2
Monitoring
Peak
- 30min after third? dose
- Response is based on peak:MIC ratio, target is 8-10 times
- If below target, increase dose
Trough
- Prior to 4th dose, or a random level at 24-48h in renal failure
- Side effects are predicted by trough levels
- Tobra <0.5 (extended) or <2 (traditional)
- Amikacin <1 (extended) or <?? (traditional)
- If above target, increase interval
Hartford Nomogram
Origin
- Derived from Streptomyces spp (mycins & kacins) or Micromonospora spp (micins)
Mechanism
- Requires electron transport chain (ETC) to cross over the membrane
- Anaerobes are therefore inherently resistant
- Reversibly binds 30S ribosomal subunit, which stops proofreading and causes accumulation of bad proteins
Spectrum of Activity
- Good coverage of Gram-negative aerobes
- Except Stenotrophomonas and Burkholderia
- Streptomycin also covers mycobacterium
- Some protozoal coverage
- Can cover Gram-positives if cell wall is disrupted (e.g. by beta-lactam)
Resistance
- Altered 50S ribosomal subunit
- Decreased uptake and accumulation (Pseudomonas)
- Decreased membrane permeability
- Efflux (E. coli)
- Aminoglycoside-modifying enzymes (Enterococcus)
PK/PD
- Poor membrane penetration, therefore doesn't cross over into lungs and CSF
- Half-life 2-3 hours (longer in CKD)
- Excreted 99% unchanged in urine
- Displays concentration-depedent killing with a prolonged post-antibiotic effect (2-13 hours)
Side Effects
- Nephrotoxicity (0-50%), usually non-oliguric AKI with decreased Ca/Mg resorption, often reversible
- Decreased protein synthesis
- Decreased cellular respiration
- Increased apoptosis
- Necrosis in proximal tubules
- Ototoxicity (0-60%), irreversible
- Cumulative effect
- Distribute into the perilymph of the ear, and cause free radical formation causing apoptosis of hair cells
- Needs hearing tests, because it can be subclinical
- Monitor audiometry weekly
- Vestibulotoxicity (0-20%), irreversible
- Rarely, neuromuscular blockade
Monitoring
- Trough levels
- Creatinine
- Weekly audiometry
