Comparison of Continuous and Intermittent IV Infusion: RESULTS part 4
Level II-3 Evidence
Three studies with level II-3 evidence (i.e., evidence from multiple time series with or without intervention or dramatic results in uncontrolled experiments) were identified. All three studies were retrospective. One involved a pediatric population and 2 involved adult patients.
The concentration of vancomycin in cerebrospinal fluid (CSF) and plasma was evaluated in 13 children receiving the drug by continuous infusion for staphylococcal meningitis (n = 3) and infections of a ventricular shunt (n = 10); 2 of the children had initially received vancomycin by intermittent dosing but were later switched to continuous dosing. Twelve of the patients had coagulase-negative Staphylococcus infections, and one was infected with S. aureus. In the 2 children (aged 17 months and 14 years) treated initially by intermittent administration (20 mg/kg IV q12h infused over 2 h), the serum concentrations of vancomycin were 9 mg/L (trough) and 21 mg/L (peak), whereas the drug was undetectable in the CSF. The duration of intermittent therapy was not described, and these 2 patients were eventually switched to continuous infusion. After 48 h of vancomycin therapy by continuous infusion, the CSF concentration of the drug in both children was above 1 mg/L.
Six of the children received vancomycin by continuous infusion from the beginning of therapy and underwent serial determinations of vancomycin in the serum and CSF during the initial 48 h of treatment. For these children, vancomycin concentration was detectable in the CSF at 48 h. The drug concentration remained stable between day 3 and cessation of therapy (range 1 to 3.2 mg/L), with a median duration of therapy of 3 weeks (range 1 to 4 weeks). Vancomycin became undetectable in the CSF within 24 h of discontinuation. The concentration of vancomycin in plasma ranged from 6 to 50 mg/L. canadian pharmacy cialis
In all 13 patients, no correlation was found between plasma (6-50 ^g/mL) and CSF (1-3.2 ^g/mL) concentrations of the drug (based on 23 plasma and CSF samples drawn concurrently). No complications were associated with continuous infusion of vancomycin, although renal function and adverse events were not reported. All 13 patients survived and were considered cured. One child experienced a recurrence 1 month after discontinuation of therapy.
A retrospective cohort study compared the efficacy of the 2 dosing regimens in 25 critically ill adults with MRSA or MRCNS infection, specifically evaluating the Sepsis-Related Organ Failure Assessment (SOFA) score and white blood cell (WBC) count before and after treatment. Mean patient ages were 70 ± 14 years (continuous therapy) and 63 ± 24 years (intermittent therapy). Two patients in each group had additional mixed infections (Klebsiella pneumoniae and Pseudomonas in both) and received concomitant therapy with monobactams or aminoglycosides. Mean baseline SOFA scores were 6.6 ± 2.2 (continuous therapy) and 4.8 ± 2.5 (intermittent therapy). The mean SOFA score at the end of therapy was significantly lower than baseline in the group that underwent continuous infusion (4.4 ± 3.5; p < 0.05) but was not significantly different from baseline in the group that underwent intermittent dosing (4.0 ± 3.9;p > 0.05). The changes in WBC count after institution of vancomycin therapy were also significant in the continuous infusion group (17 242 ± 12 842 cells/mm3 before therapy versus 10 757 ± 3610 cells/mm3 after therapy) but not in the intermittent dosing group (12 415 ± 5099 cells/mm3 before therapy versus 12 841 ± 6864 cells/mm3 after therapy). Mean serum concentrations of vancomycin were compared between continuous and intermittent dosing, but the statistical significance was not reported (at 2 h, 13.9 ± 5.7 versus 15.0 ± 3.5 mg/L; at 48 h, 17.8 ± 7.6 mg/L versus 22.5 ± 5.6 mg/L; and at 96 h, 4.3 ± 3.9 versus 30.7 ± 6.4 mg/L). No adverse effects were observed in either group. Interestingly, patients assigned to undergo continuous dosing were given an initial dose of 500 mg IV over 10 min. Such rapid administration of vancomycin may increase the risk of infusion-related adverse effects. tadacip 20
The second study involving adults evaluated 26 patients in whom the MIC of vancomycin for all sensitive organisms isolated was less than 4 mg/L. The total daily doses used were highly variable among patients and between the 2 dosing regimens (2.5-4 g/day for continuous infusion and 0.2-2 g/day for intermittent dosing). Twenty-two of the 23 patients who received vancomycin by both modes of administration had higher serum concentrations of the drug with continuous infusion; the one outlier actually received a lower daily dose during the continuous infusion course than the intermittent dosing course. All patients achieved serum concentrations above the MIC with continuous infusion, whereas 4 patients had concentrations below the MIC with intermittent dosing. Three patients experienced adverse drug reactions while receiving vancomycin by continuous infusion (a rash in 2 patients, interstitial nephritis in 1 patient); no adverse reactions were observed during intermittent infusion.
Summary: A pediatric study reported continuous and intermittent administration of vancomycin to children with staphylococcal meningitis and ventricular shunt infections.16 Only administration by continuous infusion resulted in detectable concentrations of the drug in the CSF, and there was no correlation between vancomycin concentrations in the serum and the CSF. In a study of critically ill adults, there was significant improvement in SOFA scores and reduction in WBC counts with continuous infusion of vancomycin, but no significant changes were observed in the intermittent dosing group. However, patients in the continuous dosing group had higher SOFA scores and WBC counts at baseline, which signifies a potentially sicker population than the control group. No adverse effects were reported in either group. In a third study, adult patients treated with vancomycin by continuous infusion achieved higher serum concentrations and consistently maintained concentrations above the MIC. However, the dosing and sampling strategies were highly variable. Cialis Jelly
