Vancomycin Therapeutic Drug Monitoring

[Pages:7]VANCOMYCIN

Vancomycin is a glycopeptide antibiotic with activity against Gram-positive infections such as Staphylococcus including MRSA, Streptococcus and Enterococcus for the treatment of intravascular catheter related blood stream infection, MRSA sepsis, skin and soft tissue infections. It is also an alternative to penicillin in patients who have a history of serious penicillin allergy.

Vancomycin shows a time-dependant and concentration-independent killing above the minimum inhibitory concentration (MIC). Therefore vancomycin works most effectively when the level of the drug remains above the MIC for the target organism(s) at all times.

High peaks are not associated with improved bactericidal effects and may be associated with increased toxicity. Serum levels need to be monitored because it is potentially nephrotoxic, and also to ensure that therapeutic serum concentrations are maintained (pre-dose level of 10-15mg/L, 15-20mg/L for severe MRSA infections).

Oral vancomycin is NOT absorbed and should not be given for systemic infections unless it is required for Clostridium difficile infection (see Regimens for specific confirmed infections).

Dose recommendations

A loading dose should be given to all patients starting on Vancomycin. This is then followed by maintenance dose based on patient's Creatinine Clearance (CrCl) estimated using the Cockcroft and Gault equation below:

Male

CrCl = 1.23 (140 ? age) x Weight* (kg) Serum Creatinine (mol/L)

Female CrCl = 1.04 (140 ? age) x Weight* (kg) Serum Creatinine (mol/L)

*IBW for male (kg) = 50 + (2.3 x height in inches over 5 ft)

*IBW for female (kg) = 45.5 + (2.3 x height in inches over 5 ft)

For underweight patients use actual body weight

For obese patients (>20% of IBW) use adjusted body weight = IBW + 0.4 (ABW-IBW)

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Cockcroft and Gault equation will not work for Muscle wasting (patient's CrCl will be overestimated) Oedematous patients (use IBW) Ascites (use IBW and consider dilutional effect on serum creatinine) Acute renal failure. This may represent non-steady state serum creatinine

levels and may underestimate the level of renal impairment.

The following chart tabulates height against ideal body weight, and indicates the weight above which the patient is defined as being obese:

Height (ft) 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 5.10 5.11 6.0 6.1 6.2 6.3 6.4

MEN

IBW (kg) Obese if >kg

50

61

52.3

63

54.6

66

56.9

69

59.2

72

61.5

74

63.8

77

66.1

80

68.4

83

70.7

85

73

88

75.3

91

77.6

94

79.9

96

82.2

99

84.5

102

86.8

105

WOMEN

IBW (kg) Obese if > kg

45.5

55

47.5

58

50.1

61

52.4

63

54.7

66

57

69

59.3

72

61.6

74

63.9

77

66.2

80

68.5

83

70.8

85

73.1

88

75.4

91

77.7

94

80.0

96

82.3

99

Administration

Dilute in Sodium Chloride 0.9% or Glucose 5% to a maximum concentration of 5mg/ml (e.g 1g in 250ml or 500mg in100ml) over at least 60 minutes.

Maximum infusion rate: 10mg/min (e.g 1g over 100 min or 500mg over 1hour)

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Vancomycin Regimens

Vancomycin can be given as: 1. Intermittent dosing (standard) ? (see page 4-5) 2. Continuous infusion (ITU patients only) ? (see page 5

Do not dose at midday or midnight

Aim for

(10am and 10pm) or (6am and 6pm) for 12 hourly dosing

(10am or 2pm) for 24 hourly/ 48 hourly dosing

General rules for Vancomycin Monitoring

Aim for pre-dose (trough) level: 10-15 mg/L. Below 10mg/L is subtherapeutic. Level should be maintained above 10mg/L to avoid resistance

Higher trough level (15 -20 mg/L) may be required in serious infection (i.e. enterococcal and MRSA endocarditis) ? discuss with consultant microbiologist

Take a trough serum level before giving the third or fourth dose

Document clearly on the request form: time dose was administered and time sample taken

The Blood Sciences laboratory (ESH) will process samples received between 08:00 and 20:00 daily. Therefore, take the assays so that the results will be available in time for necessary changes to the regimen

Antibiotic assays should NEVER be taken via an intravenous catheter that is used for the administration of the antibiotic

The dose can be given after trough level is taken if serum creatinine is normal with good urine output

After any dose adjustment, re-check level just before the 3rd or 4th dose on the new regimen.

If levels are normal and patient's renal function is stable, twice weekly monitoring of pre-dose level is recommended

Routine peak level monitoring is unnecessary

Daily serum creatinine and urea is recommended for patients on IV vancomycin

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1. Vancomycin IV Intermittent Dosing i) Starting regimen

Table 1: Loading dose

Actual

Loading dose

Body

(mg)

Weight (kg)

>90

2000

60-90

1500

120

1000mg

42

CVVH

1000mg

42

iii) Continued daily dose

The daily dose should be adjusted according to serum levels shown below.

Vancomycin level Adjustment to daily dose Infusion rate adjustment

(mg/L)

25 ? 29.9

Decrease by 500mg*

Reduce to next level down

in table

>30

Stop infusion for at least 6 According to review, restart

hours and review by doctor at a reduced rate

*If current dose is 500 mg/day, the dose should be decreased to 250mg/day

iv) Monitoring

A serum level (gold top vacuette) must be taken at 06.00 (with the routine blood tests) every day to enable determination of daily dose. Testing is done in Blood Sciences laboratory at ESH.

Aim for a serum level of 15-25mg/L. If the level is outside this range, change the infusion rate to give the desired dose (mg/hr) until the infusion is complete (table 2). When making up the next infusion add the appropriate dose for the whole 24 hours.

v. Changing back to intermittent dosing

On leaving ICU the prescription needs to be changed back to IV intermittent dosing regimen as per Table 2 in section 6.2.1(ii). Advice should be taken from a Consultant Microbiologist if necessary.

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References 1. A.H.Thomson, C.E.Staatz, C.M. Tobin, M.Gall and A.M Lovering.

Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. Journal of Antimicrobial Chemotherapy (2009) 63, 1050-1057. 2. Michael Rybak, Ben Lomastro, John C Rotschafer, Rober Moellering Jr., William Craig, Marianne Billeter, Joseph R Dalovisio and Donald P. Levine. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm. (2009) 66:82-98.

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