Comparison of Continuous and Intermittent IV Infusion
INTRODUCTION
Vancomycin is the mainstay of treatment for multidrug- resistant gram-positive organisms, including methicillin- resistant Staphylococcus aureus (MRSA) and methicillin- resistant coagulase-negative Staphylococcus (MRCNS). Vancomycin exhibits concentration-independent activity, whereby high peak concentrations are not necessary to achieve bacterial killing. Rather, it is thought that serum concentration of the drug should be maintained at 4 to 5 times the minimal inhibitory concentration (MIC) for bactericidal activity. Historically, on the basis of pharmacokinetic studies and anecdotal reports, vancomycin dosing was targeted to achieve peak serum concentrations of 30—40 mg/L and trough concentrations of 5—10 mg/L. More recent clinical guidelines have recommended target trough concentrations of 15—20 mg/L for the treatment of complicated MRSA infections, including bacteremia, meningitis, osteomyelitis, hospital-acquired pneumonia, and endocarditis. Trough concentrations less than 10 mg/L are associated with the development of vancomycin- intermediate S. aureus strains. However, even when a trough level of 15 mg/L is achieved, clinical outcomes do not appear to improve in patients infected with S. aureus strains exhibiting an MIC of 2 mg/L or greater. Furthermore, values for the ratio of area under the concentration—time curve to minimum inhibitory concentration (AUC/MIC) of 400 or greater have been most predictive of clinical efficacy. However, no studies have demonstrated correlation between trough concentration of 15-20 mg/L and AUC/MIC greater than 400.
To achieve the higher recommended serum concentration targets, vancomycin dosages of 15-20 mg/kg every 4-12 h, depending on the patient’s age and renal function, may be required. Some have proposed that continuous IV infusion would be a better dosing strategy to achieve higher serum concentrations of the drug. cialis super active
The theoretical advantages of continuous administration of vancomycin include the ability to consistently maintain drug concentrations above the MIC, without large fluctuations. This may minimize dips in serum concentrations at the end of the dosing interval and avoid potential toxic effects associated with high peak concentrations. However, the correlation between high vancomycin concentrations in serum and nephrotoxicity and ototoxicity is poor.
Pharmacokinetic studies have demonstrated shorter time to and longer duration of target serum concentrations with continuous infusion than with intermittent administration for equivalent total daily doses. However, with continuous infusion, the concentration of vancomycin penetrating into lung tissue was not superior to that achieved by intermittent dosing. Notably, these theoretical benefits have been derived solely from pharmacokinetic studies (but there were method- ologic inconsistencies across these studies, which limited their comparability); whether they will improve clinical outcomes requires evaluation by randomized controlled trials. As such, the ability of continuous infusion to generate higher serum concentrations and better antimicrobial activity against deep- tissue infections remains a subject of debate.
In some studies, use of a continuous-infusion strategy necessitated fewer serum samples for appropriate dosage adjust- ments. Other studies have suggested a lower total dose requirement, decreased pharmacy compounding time, and decreased nursing time. However, these potential advantages have not been confirmed in clinical trials.
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The purpose of this review was to systematically assess the literature comparing continuous infusion and conventional intermittent IV dosing for administration of vancomycin, in terms of efficacy and safety.
Category: Drugs
Tags: continuous infusion, intermittent infusion, vancomycin