Vancomycin Dosing and Monitoring 2 Years After the Guidelines

Ben M Lomaestro

Expert Rev Anti Infect Ther. 2011;9(6):657-667.

Five-year View

Increased use of rapid diagnostic techniques such as PCR may allow prompt discontinuation of vancomycin when not indicated. Further development of alternative antimicrobials may also lessen its use. If novel biomarkers and anti-oxidants provide improved monitoring or some protection against renal injury, more aggressive dosing might be more accepted. Clarification of differences between generic sources of the drug may also clarify potency and safety issues. Despite a mere 2 years since the vancomycin guidelines were first published, further data has questioned some of our long-held tenets of efficacy, toxicity and monitoring and directed areas for future research to optimize vancomycin usage while identifying risk factors for toxicity.

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Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Cite this: Vancomycin Dosing and Monitoring 2 Years After the Guidelines - Medscape - Jun 01, 2011.

Table 1. Summary of vancomycin monitoring guidelines recommendations.
Variable	Recommendation	Level of evidence
Optimal monitoring parameter	Serum trough concentration most practical	IIB
Timing of troughs	Troughs should be obtained at steady state: approximately prior to the fifth dose	IIB
Optimal trough concentrations	Should be >10 mg/l at a minimum to avoid development of resistanceFor a pathogen MIC of 1 mg/l, the trough should be at least 15 mg/l to attain an AUC/MIC of 400	IIIB
Optimal trough concentrations: complicated infections (endocarditis, osteomyelitis, meningitis, hospital-acquired pneumonia caused by Staphylococcus aureus)	Trough concentrations of 15–20 mg/l recommended to improve penetration, increase probability of target attainment and improve clinical outcomes	IIIB
Dosing regimen to achieve optimal trough	Daily doses of 15–20 mg/kg (using actual bodyweight) given every 8–12 h recommended for most patients with normal renal function and when organism MIC is <1 mg/lTarget of AUC/MIC >400 is not possible with conventional dosing in patients with normal renal function when MIC is >2.0 mg/l	IIIB
Loading doses: complicated infections	In seriously ill patients, loading dose of 25–30 mg/kg (based on actual bodyweight) can be used to facilitate rapid attainment of target trough concentration	IIIB
Continuous versus intermittent administration	Continuous infusion unlikely to improve patient outcome when compared with intermittent dosing	IIA
Monitoring for nephrotoxicity	A minimum of two or three consecutive documented increases in serum creatinine concentrations (0.5 mg/dl or >50% increase from baseline, whichever is greater) after several days of vancomycin therapy	IIB
Criteria for monitoring	Data do not support serum peak concentration monitoring for nephrotoxicityTrough monitoring recommended when aggressive dosing (to achieve trough of 15–20 mg/l) and in patients at high risk (i.e., concurrent nephrotoxins)Monitoring recommended for patients with unstable renal function or prolonged treatment courses (>3–5 days)	IIBIIIBIIB
Frequency of monitoring	Frequent monitoring (more than one trough before the fourth dose) for short course or lower intensity dosing (trough below 15 mg/l) is not recommendedPatients on prolonged courses of vancomycin (>3–5 days) should have at least one steady-state trough prior to the fifth dose and repeated as deemed clinically appropriateThere are limited data supporting the safety of sustained trough concentrations of 15–20 mg/lOnce-weekly monitoring of trough concentration is recommended in hemodynamically stable patientsMore frequent monitoring is recommended in hemodynamically unstable patients	IIBIIBIIIB
Monitoring for ototoxicity	Monitoring for ototoxicity is not recommended for patients receiving vancomycin monotherapyMonitoring should be considered for patients receiving concurrent ototoxins such as aminoglycosides	IIIBIIIB

AUC: Area under the curve.
Adapted with permission from [1].

Box 1. Continuing issues with vancomycin.
Why not use continuous infusion? Is a Staphylococcus aureus MIC of 2.0 mg/l always associated with treatment failure? What is the significance of MSSA or MRSE with a vancomycin MIC of 2.0 mg/l? Was there enough data to support the area under the curve/MIC target and inferred troughs recommended in the guidelines? Is it always correct to dose based on actual bodyweight? Do clinicians really want to wait for a steady state (approximately prior to the fifth dose) prior to obtaining a trough? Are there additional risks of toxicity (or more acute development of toxicity) associated with aggressive loading doses? Are differences in efficacy and/or toxicity due to differing generic products? Alternatives to vancomycin all have issues of their own such as expense, a lack of superiority in trials, toxicities and insufficient data for several indications.

MRSE: Methicillin-resistant Staphylococcus epidermidis; MSSA: Methicillin-susceptible Staphylococcus aureus.

Box 2. Approach to vancomycin dosing at Albany Medical Center Hospital.
Target more aggressive dosing to bacteremia, osteomyelitis, meningitis, pneumonia and endocarditis Limit loading doses to 2.0 g or less. Can repeat at first scheduled maintenance interval if desired Give 1 g over 1 h and larger doses at 500 mg/h Draw the trough before the third dose to make sure regimen is adequate. Note: this will be prior to steady-state Monitor all patients on standing vancomycin of regimens >1 day until discontinued

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