Comparison of Continuous and Intermittent IV Infusion: DISCUSSION
Limited evidence is currently available to evaluate the clinical efficacy and safety of vancomycin by continuous infusion relative to conventional intermittent infusion. Published trials were highly heterogeneous in terms of study design, dosing regimens, and serum monitoring strategies, and evaluated a vast array of outcomes that rendered comparison across trials difficult. Although both adult and pediatric populations were of interest, only one pediatric study met the inclusion criteria for this review.
A common limitation to the existing literature is the relatively small sample populations used for individual studies. Sample size was generally less than 30, and the largest trial involved only 119 patients. That randomized controlled trial is the largest comparison of continuous and intermittent administration of vancomycin published to date and has been frequently cited by other authors. However, because it did not meet the prespecified sample size of 320 (and thus had only 23% power to assess its primary outcome), its results should be interpreted with caution. Unfortunately, that study also used different prespecified target concentrations of vancomycin for the intermittent and continuous infusion groups. Therefore, the results reflected not only the 2 modes of vancomycin administration but also a discrepancy in target serum concentrations. The other 8 studies that were identified and analyzed here did not report a priori sample size calculations. It was also unclear whether they were designed to be superiority, non- inferiority, or equivalence studies.
Some studies assessed only pharmacokinetic and pharmacodynamic outcomes. Although continuous infusion was hypothesized to shorten the time to reach target serum concentrations (defined as time of administration of the first dose to time when target concentration is reached) and lengthen the 7>MIC at equivalent doses, these assumptions were not supported by 2 of the 3 studies. Moreover, a shorter time to target concentration is not a compelling benefit because it can be achieved with a loading dose, regardless of the dosing regimen.
Other studies included in this review focused on whether continuous vancomycin dosing would improve clinical efficacy and safety rather than on surrogate pharmacokinetic outcomes. Two prospective controlled trials were identified, one randomized controlled trial involving critically ill patients with a variety of MRSA and MRCNS infections (level I evidence) and one nonrandomized controlled trial in patients with chronic MRSA and MRCNS osteomyelitis (level II-1 evidence). In neither study were there significant differences in rates of treatment failure, overall mortality, or infection-related mortality between the 2 treatment regimens. levitra 20 mg
As noted earlier, one of these studies was significantly underpowered to assess treatment failure, and the other did not report the required sample size a priori, so it remains unclear whether it had adequate power to assess cure rate.
A study of chronic osteomyelitis was designed primarily to evaluate standard-dose versus high-dose vancomycin, with the high-dose group further divided into continuous and intermittent dosing. Unfortunately, the authors did not report comparative data for continuous and intermittent administration of high-dose therapy, and the data pertaining to continuous dosing were limited, both of which restrict the contribution of this study to the analysis presented here. The other retrospective study revealed a link between continuous infusion and higher frequency of serum concentrations above the MIC.18 However, many potential confounding factors might have affected serum concentrations of vancomycin, including dosage, serum sampling times, pathogens isolated and their level of resistance, and experience of the clinicians making the dosage adjustments. Only the lowest recorded serum concentrations of vancomycin were reported, so these data did not capture whether target concentrations were sustained throughout the course of treatment or whether supratherapeutic concentrations were observed.
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Only one study evaluated the cost-effectiveness of the 2 dosing regimens, estimating a cost saving of US$133 per 10-day course with the continuous infusion regimen. This saving may be negligible in light of the substantial costs associated with admission to hospital and related care. It would be useful to assess the satisfaction of nurses and patients, potential administration challenges (e.g., line access, IV compatibility), and receptiveness in the outpatient setting for these 2 modes of administration. It might be argued that continuous infusion is more labour-intensive, but this end point is highly subjective. It is also important to note that cost estimates should be interpreted with caution as they are subject to variation according to dosage adjustments and serum monitoring protocols of the institution.
Overall, the studies included in this review had inconsistent findings. They were highly heterogeneous in terms of methodologic design, patient population, dosing and sampling strategies, and outcomes evaluated. Common limitations to these studies were small sample size, poor reporting of adverse drug reactions, and insufficient consideration of potential confounding factors that might bias outcomes. For example, timely and accurate diagnosis and initiation of antibiotics have been shown to improve mortality in the intensive care unit. Potential confounders, such as severity of illness, comorbid conditions, multipathogen infections, and other interventions (e.g., surgical debridement), were seldom addressed in the current literature but are likely to affect outcome measures to a larger extent than would the mode of vancomycin administration. In light of these limitations, there appears to be a lack of sound evidence to support the use of continuous infusion of vancomycin for treating multidrug-resistant gram-positive infections. Furthermore, continuous infusion does not appear to reduce costs relative to traditional intermittent dosing.
This systematic review had some limitations. Only articles published in English and French were included. As a result, 3 potentially relevant articles (2 in Spanish and 1 in Japanese) were excluded. Only studies that directly compared continuous with intermittent vancomycin infusion were eligible for review. Studies evaluating pharmacokinetic characteristics and clinical efficacy of continuous infusion alone were not included. tadalis sx
CONCLUSIONS
Current evidence does not support routine administration of vancomycin by continuous infusion for various multidrug- resistant gram-positive infections. Although this review does not negate the potential role of continuous vancomycin infusion in unique therapeutic circumstances, such specific cases warrant individualized clinical judgement based on patient-specific parameters and evaluation of the potential benefits and risks of each administration modality.
