Vancomycin: Difference between revisions

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==Background==
= Vancomycin =


*A [[:Category:Glycopeptides|glycopeptide]] antibiotic
== Indications ==


===Mechanism of Action===
* Suspected or confirmed MRSA


*Inhibits cross-linking of peptidoglycans in the cell wall
== Dosing ==


===Mechanisms of Resistance===
* Common dose
** 15mg/kg/dose with timing based on renal function (q12h if normal)
** Titrate based on serum trough drawn within hour before fourth dose
* Target trough
** 10-15 for low-risk infections
** 15-20 for high-risk infections such as osteomyelitis, meningitis, and bacteremia


*Alterations in peptidoglycans conferred by chromosomal or plasmid-mediated ''vanA'', ''vanB'', or ''vanC''
== Adverse Reactions ==


=== Renal Failures ===
===Spectrum of Activity===


*Broadly active against Gram-positive bacteria, including anaerobes
* Risk factors
*Not active against Gram-negative bacteria
** Prolonged courses >21 days
*Notable resistance occurs in:
** Higher trough
**[[Clostridium innocuum]]
** Concomitant nephrotoxic medication
**[[Enterococcus gallinarum]], [[Enterococcus casseliflavus]], and [[Enterococcus flavus]] (chromosomal ''vanC'')
** Older age
**[[Erysipelothrix rhusiopathiae]]
** CKD/AKI
**[[Lactobacillus]], except [[Lactobacillus acidophilus]] and [[Lacobacillus delbrueckii]]
** Liver disease
**[[Leuconostoc]]
** Peritonitis
**[[Pediococcus]]
** Neutropenia
**[[Weissella]]
** Male sex
* Mechanism of injury: oxidative stress in the proximal tubular cells


===Pharmacokinetics and Pharmacodynamics===
=== Red Man Syndrome ===


*Bactericidal
* Rash, pruritis, and hypotension, with onset of vancomycin, resolves on stopping
*Concentration-independent with post-antibiotic effect
* Very high incidence previously
*Efficacy predicted by AUC<sub>24</sub>:MIC
* Histamine-mediated

* Can decrease dose or prolong infusion, prophylactic antihistamines
===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==

=== 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 calculators[[CiteRef::rybak2020th]]
**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

=== 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==

*Primarily include [[Adverse drug reaction::renal failure]] and [[Adverse drug reaction::red person syndrome]]

===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 &gt;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

[[Category:Glycopeptides]]

Latest revision as of 02:09, 10 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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