Vancomycin: Difference between revisions

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*A [[:Category:Glycopeptides|glycopeptide]] antibiotic
  
*A [[:Category:Glycopeptides|glycopeptide]] antibiotic
   
−
===Mechanism of action===
 +
===Mechanism of Action===
   
 
*Inhibits cross-linking of peptidoglycans in the cell wall
  
*Inhibits cross-linking of peptidoglycans in the cell wall
   
  +
===Mechanisms of Resistance===
−
===Pharmacodynamics===
  
   
  +
*Alterations in peptidoglycans conferred by chromosomal or plasmid-mediated ''vanA'', ''vanB'', or ''vanC''
−
*Efficacy predicted by AUC to MIC ratio
  
   
  +
===Spectrum of Activity===
−
==Indications==
  
   
  +
*Broadly active against Gram-positive bacteria, including anaerobes
−
*Suspected or confirmed MRSA
  
  +
*Not active against Gram-negative bacteria
  +
*Notable resistance occurs in:
  +
**[[Clostridium innocuum]]
  +
**[[Enterococcus gallinarum]], [[Enterococcus casseliflavus]], and [[Enterococcus flavus]] (chromosomal ''vanC'')
  +
**[[Erysipelothrix rhusiopathiae]]
  +
**[[Lactobacillus]], except [[Lactobacillus acidophilus]] and [[Lacobacillus delbrueckii]]
  +
**[[Leuconostoc]]
  +
**[[Pediococcus]]
  +
**[[Weissella]]
  +
  +
===Pharmacokinetics and Pharmacodynamics===
  +
  +
*Bactericidal
  +
*Concentration-independent with post-antibiotic effect
  +
*Efficacy predicted by AUC<sub>24</sub>:MIC
  +
  +
===Clinical Breakpoints===
  +
{| class="wikitable"
  +
! rowspan="2" |Species
  +
! colspan="3" |Breakpoints (μg/mL)
  +
|-
  +
!S
  +
!I
  +
!R
  +
|-
  +
|[[Staphylococcus aureus]]
  +
|≤2
  +
|4-8
  +
|≥16
  +
|-
  +
|[[Staphylococcus]] species other than [[Staphylococcus aureus]]
  +
|≤4
  +
|8-16
  +
|≥32
  +
|-
  +
|[[Enterococcus]]
  +
|≤4
  +
|8-16
  +
|≥32
  +
|-
  +
|[[Streptococcus pneumoniae]]
  +
|≤1
  +
|—
  +
|—
  +
|-
  +
|[[β-hemolytic streptococci]]
  +
|≤1
  +
|—
  +
|—
  +
|}
   
 
==Dosing==
  
==Dosing==
   
  +
=== Intermittent Infusion ===
 
*Common dose
  
*Common dose
 
**Loading dose of 25-30 mg/kg given once for serious infections
  
**Loading dose of 25-30 mg/kg given once for serious infections
 
**15 mg/kg/dose with timing based on renal function (q12h if normal)
  
**15 mg/kg/dose with timing based on renal function (q12h if normal)
 
**Titrate based on monitoring parameters (below)
  
**Titrate based on monitoring parameters (below)
−
**Adjustments assume linear pharmacokinetics,so a doubling of the daily dose, for example, should double the trough or AUC:MIC
 +
**Adjustments assume linear pharmacokinetics, so a doubling of the daily dose, for example, should double the trough or AUC:MIC
   
−
===Obesity===
 +
==== Renal Dosing ====
  +
  +
* CrCl >100 mL/min: 15-20 mg/kg q8-12h
  +
* CrCCl 50 to 100: 15-20 mg/kg q12h
  +
* CrCl 20-49: 15-20 mg/kg q24h
  +
* CrCl <20: 15-20 mg/kg q48h
  +
* '''Hemodialysis:''' target pre-dialysis levels of 15 to 20
  +
** If next HD in 1 day, give 15 mg/kg
  +
** If next HD in 2 days, give 25 mg/kg
  +
** If next HD in 3 days, give 35 mg/kg
  +
** Give at rate of 15 mg/min over the last 120 minutes of HD to coincide with the end of dialysis
  +
**Alternatively:
  +
***< 70 kg: 1000mg IV x 1, then 500mg post-dialysis
  +
***70 –100kg: 1250mg IV x 1, then 750mg post-dialysis
  +
***>100 kg: 1500mg IV x 1, then 1000mg post-dialysis
  +
* CAPD: 7.5 mg/kg q48-96h
  +
* CRRT: 10-15 mg/kg q24-48h
  +
  +
====Obesity====
   
 
*Dosing should use actual body weight, with a maximum loading dose of 3 g
  
*Dosing should use actual body weight, with a maximum loading dose of 3 g
   
−
===Monitoring===
 +
====Monitoring====
   
 
*Based on PK/PD modelling, the '''trough level''' was previously used to dose vancomycin
  
*Based on PK/PD modelling, the '''trough level''' was previously used to dose vancomycin
Line 36: Line 105:
 
**Use peak 60 min after infusion and trough 1 to 60 minutes before next dose, and record times accurately
  
**Use peak 60 min after infusion and trough 1 to 60 minutes before next dose, and record times accurately
 
**Target AUC/MIC<sub>BMD</sub> ratio of 400 to 600 for serious [[Staphylococcus aureus]] infections
  
**Target AUC/MIC<sub>BMD</sub> ratio of 400 to 600 for serious [[Staphylococcus aureus]] infections
  +
  +
=== Continuous Infusion ===
  +
  +
* Particularly useful in the following patients:
  +
** Total daily doses of 4 g or higher, since it will lower the total dose and therefore associated toxicitynephro
  +
** Home antibiotic therapy, to simplify drug monitoring
  +
* At least as safe and effective as intermittent infusion
  +
* Limited by pump availability and IV access
  +
* Consider '''loading dose''' in patients who are not already on intermittent infusion and who are hemodynamically unstable
  +
* Initial dose based on creatinine clearance and weight
  +
  +
{| class="wikitable"
  +
!TBW (kg)
  +
!CrCl (mL/min)
  +
!Load (mg)
  +
!Maintenance (mg/24h)
  +
|-
  +
|<100
  +
| rowspan="3" |≥90
  +
|1000
  +
|2000
  +
|-
  +
|100-119
  +
|1500
  +
|2500
  +
|-
  +
|≥120
  +
|2000
  +
|3000
  +
|-
  +
! colspan="4" |Obesity and Renal Failure
  +
|-
  +
| rowspan="5" |100-115
  +
|70-89
  +
|1000
  +
|1750
  +
|-
  +
|50-69
  +
|1000
  +
|1250
  +
|-
  +
|40-49
  +
|1000
  +
|1000
  +
|-
  +
|30-39
  +
|1000
  +
|750
  +
|-
  +
|20-29
  +
|1000
  +
|500
  +
|-
  +
| rowspan="5" |116-139
  +
|70-89
  +
|1250
  +
|2000
  +
|-
  +
|50-69
  +
|1250
  +
|1500
  +
|-
  +
|40-49
  +
|1250
  +
|1250
  +
|-
  +
|30-39
  +
|1250
  +
|1000
  +
|-
  +
|20-29
  +
|1250
  +
|750
  +
|-
  +
| rowspan="5" |140-159
  +
|70-89
  +
|1500
  +
|2500
  +
|-
  +
|50-69
  +
|1500
  +
|1750
  +
|-
  +
|40-49
  +
|1500
  +
|1500
  +
|-
  +
|30-39
  +
|1500
  +
|1250
  +
|-
  +
|20-29
  +
|1500
  +
|750
  +
|-
  +
| rowspan="5" |160-179
  +
|70-89
  +
|1500
  +
|2750
  +
|-
  +
|50-69
  +
|1500
  +
|2000
  +
|-
  +
|40-49
  +
|1500
  +
|1500
  +
|-
  +
|30-39
  +
|1500
  +
|1250
  +
|-
  +
|20-29
  +
|1500
  +
|1000
  +
|-
  +
| rowspan="5" |180-199
  +
|70-89
  +
|1750
  +
|3000
  +
|-
  +
|50-69
  +
|1750
  +
|2500
  +
|-
  +
|40-49
  +
|1750
  +
|2000
  +
|-
  +
|30-39
  +
|1750
  +
|1500
  +
|-
  +
|20-29
  +
|1750
  +
|1000
  +
|}
  +
  +
==== Monitoring ====
  +
  +
* Random vancomycin levels
  +
** First level is 24 hours after starting
  +
** Monitor weekly, any time the patient is unstable, and 24 hours after any dose adjustments
  +
** Target levels are typically 15 to 20
  +
* Serum creatinine should be measured twice weekly
  +
* CBC monitored weekly
   
 
==Adverse Reactions==
  
==Adverse Reactions==
Line 43: Line 258:
 
===Renal Failures===
  
===Renal Failures===
   
  +
*Dose-dependent risk, with significant increase with trough over 15
−
*Risk factors
  
  +
*Lower risk with AUC-based dosing, which promotes lower dosing, and with continuous infusion
−
**Prolonged courses &gt;21 days
  
  +
*Risk factors: prolonged courses &gt;21 days, higher troughs, concomitant nephrotoxic medication, older age, [[CKD]]/[[AKI]], [[liver disease]], [[peritonitis]], [[neutropenia]], and male sex
−
**Higher trough
  
  +
*Mechanism of injury: either AIN or ATN from oxidative stress in the proximal tubular cells
−
**Concomitant nephrotoxic medication
  
  +
**May be able to detect it early with serum Kim-1 elevation, or NGAL elevation (though less specific)
−
**Older age
  
−
**CKD/AKI
  
−
**Liver disease
  
−
**Peritonitis
  
−
**Neutropenia
  
−
**Male sex
  
−
*Mechanism of injury: oxidative stress in the proximal tubular cells
  
   
 
===Red Person Syndrome===
  
===Red Person Syndrome===

Latest revision as of 22:09, 9 October 2022

Background

Mechanism of Action

  • Inhibits cross-linking of peptidoglycans in the cell wall

Mechanisms of Resistance

  • Alterations in peptidoglycans conferred by chromosomal or plasmid-mediated vanA, vanB, or vanC

Spectrum of Activity

Pharmacokinetics and Pharmacodynamics

  • Bactericidal
  • Concentration-independent with post-antibiotic effect
  • Efficacy predicted by AUC24:MIC

Clinical Breakpoints

Species Breakpoints (μg/mL)
S I R
Staphylococcus aureus ≤2 4-8 ≥16
Staphylococcus species other than Staphylococcus aureus ≤4 8-16 ≥32
Enterococcus ≤4 8-16 ≥32
Streptococcus pneumoniae ≤1 — —
β-hemolytic streptococci ≤1 — —

Dosing

Intermittent Infusion

  • Common dose
    • Loading dose of 25-30 mg/kg given once for serious infections
    • 15 mg/kg/dose with timing based on renal function (q12h if normal)
    • Titrate based on monitoring parameters (below)
    • Adjustments assume linear pharmacokinetics, so a doubling of the daily dose, for example, should double the trough or AUC:MIC

Renal Dosing

  • CrCl >100 mL/min: 15-20 mg/kg q8-12h
  • CrCCl 50 to 100: 15-20 mg/kg q12h
  • CrCl 20-49: 15-20 mg/kg q24h
  • CrCl <20: 15-20 mg/kg q48h
  • Hemodialysis: target pre-dialysis levels of 15 to 20
    • If next HD in 1 day, give 15 mg/kg
    • If next HD in 2 days, give 25 mg/kg
    • If next HD in 3 days, give 35 mg/kg
    • Give at rate of 15 mg/min over the last 120 minutes of HD to coincide with the end of dialysis
    • Alternatively:
      • < 70 kg: 1000mg IV x 1, then 500mg post-dialysis
      • 70 –100kg: 1250mg IV x 1, then 750mg post-dialysis
      • >100 kg: 1500mg IV x 1, then 1000mg post-dialysis
  • CAPD: 7.5 mg/kg q48-96h
  • CRRT: 10-15 mg/kg q24-48h

Obesity

  • Dosing should use actual body weight, with a maximum loading dose of 3 g

Monitoring

  • Based on PK/PD modelling, the trough level was previously used to dose vancomycin
    • Serum trough drawn within hour before fourth dose
    • 10-15 for low-risk infections
    • 15-20 for high-risk Staphylococcus aureus infections such as osteomyelitis, meningitis, and bacteremia
  • Current guidelines recommend AUC:MIC monitoring using Bayesian calculators1
    • Use peak 60 min after infusion and trough 1 to 60 minutes before next dose, and record times accurately
    • Target AUC/MICBMD ratio of 400 to 600 for serious Staphylococcus aureus infections

Continuous Infusion

  • Particularly useful in the following patients:
    • Total daily doses of 4 g or higher, since it will lower the total dose and therefore associated toxicitynephro
    • Home antibiotic therapy, to simplify drug monitoring
  • At least as safe and effective as intermittent infusion
  • Limited by pump availability and IV access
  • Consider loading dose in patients who are not already on intermittent infusion and who are hemodynamically unstable
  • Initial dose based on creatinine clearance and weight
TBW (kg) CrCl (mL/min) Load (mg) Maintenance (mg/24h)
<100 ≥90 1000 2000
100-119 1500 2500
≥120 2000 3000
Obesity and Renal Failure
100-115 70-89 1000 1750
50-69 1000 1250
40-49 1000 1000
30-39 1000 750
20-29 1000 500
116-139 70-89 1250 2000
50-69 1250 1500
40-49 1250 1250
30-39 1250 1000
20-29 1250 750
140-159 70-89 1500 2500
50-69 1500 1750
40-49 1500 1500
30-39 1500 1250
20-29 1500 750
160-179 70-89 1500 2750
50-69 1500 2000
40-49 1500 1500
30-39 1500 1250
20-29 1500 1000
180-199 70-89 1750 3000
50-69 1750 2500
40-49 1750 2000
30-39 1750 1500
20-29 1750 1000

Monitoring

  • Random vancomycin levels
    • First level is 24 hours after starting
    • Monitor weekly, any time the patient is unstable, and 24 hours after any dose adjustments
    • Target levels are typically 15 to 20
  • Serum creatinine should be measured twice weekly
  • CBC monitored weekly

Adverse Reactions

Renal Failures

  • Dose-dependent risk, with significant increase with trough over 15
  • Lower risk with AUC-based dosing, which promotes lower dosing, and with continuous infusion
  • Risk factors: prolonged courses >21 days, higher troughs, concomitant nephrotoxic medication, older age, CKD/AKI, liver disease, peritonitis, neutropenia, and male sex
  • Mechanism of injury: either AIN or ATN from oxidative stress in the proximal tubular cells
    • May be able to detect it early with serum Kim-1 elevation, or NGAL elevation (though less specific)

Red Person Syndrome

  • Rash, pruritis, and hypotension, with onset of vancomycin, resolves on stopping
  • Very high incidence previously
  • Histamine-mediated
  • Can decrease dose or prolong infusion, prophylactic antihistamines

References

  1. ^  Michael J Rybak, Jennifer Le, Thomas P Lodise, Donald P Levine, John S Bradley, Catherine Liu, Bruce A Mueller, Manjunath P Pai, Annie Wong-Beringer, John C Rotschafer, Keith A Rodvold, Holly D Maples, Benjamin M Lomaestro. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy. 2020. doi:10.1093/ajhp/zxaa036.

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