Intermittent Infusion Of Vancomycin Research Articles

Comparison of the Areas Under the Curve of Vancomycin Continuous vs. Intermittent Infusion in Critically Ill Pediatrics: A Randomized Clinical Trial

Background: Providing data on the superior efficacy of vancomycin administered based on the area under the curve over 24 hours to the minimum inhibitory concentration of vancomycin (AUC24/MIC) is crucial. However, data on dosing and monitoring of vancomycin pharmacokinetics in the pediatric population are limited. Previous findings have suggested that intermittent infusion of vancomycin (IIV) may not achieve the desired levels. Continuous infusions of vancomycin (CIV) reach the desired serum concentration faster than IIV and are associated with reduced nephrotoxicity. Objectives: This study aimed to compare the concentrations, AUC24, clinical variables, and adverse effects of two vancomycin administration methods in the pediatric population. Methods: This study was a double-blind, randomized, controlled clinical trial conducted at a tertiary children's teaching hospital. Inclusion criteria were age between 2 months and 15 years and weight less than 67 kilograms, with exclusion criteria including renal impairment. Participants were divided into CIV and IIV groups following distinct administration protocols. Demographic, clinical, and laboratory data, including vancomycin serum concentrations, were compiled. Assessments included pediatric mortality risk, pediatric sequential organ failure assessment, and regular temperature monitoring. Pharmacokinetic analysis was conducted using Monolix software 2023R1. Primary endpoints were vancomycin serum levels and AUC24 between cohorts on day three, with nephrotoxicity and additional adverse drug responses evaluated. Results: Sixty-eight patients in the pediatric intensive care unit (PICU) were allocated to either CIV (33) or IIV (35) for vancomycin treatment. In the CIV group, 82% of patients achieved an AUC24 ≥ 400 mg.h/L, compared to 23% in the IIV group. Continuous infusions of vancomycin demonstrated a greater AUC24 (587.7 ± 184.4 mg.h/L vs. 361.9 ± 113.2 mg.h/L, P < 0.05) compared to IIV. Two cases of nephrotoxicity were reported, one in each group, with mortality and adverse events being comparable between the two groups. Conclusions: This study demonstrated that continuous vancomycin infusion has a higher success rate in safely achieving therapeutic vancomycin levels in PICU patients compared to intermittent vancomycin infusion.

769: CONTINUOUS VERSUS INTERMITTENT VANCOMYCIN INFUSION IN ICU PATIENTS WITH AUGMENTED RENAL CLEARANCE

Introduction: Augmented renal clearance (ARC) has been associated with sub-optimal antibiotic concentrations. Administering vancomycin as a continuous infusion may be a strategy to achieve therapeutic levels faster with less monitoring. The purpose of this study was to compare the safety and efficacy of continuous infusion vancomycin (CIV) versus intermittent infusion vancomycin (IIV) in critically ill patients with ARC. Methods: This was a single-center, retrospective study of adult patients admitted to the ICU at Stanford Health Care. Patients were included if they received intravenous vancomycin and had ARC (creatinine clearance > 130 ml/min calculated by Cockroft-Gault equation). Patients were excluded if they received vancomycin for surgical prophylaxis. From January 2020 – March 2021, patients received IIV targeting a vancomycin area-under-the-curve (AUC) of 400-600 mg*h/L calculated by the trapezoidal method (using peak and trough levels). From April 2021 – March 2022, patients received CIV with a target level of 17-25 mcg/mL (representing an AUC of 408-600 mg*h/L) drawn at least 24 hours after initiation. The primary outcome was the time to achieve target levels for each dosing strategy. Secondary outcomes included the incidence of acute kidney injury (AKI) define by the RIFLE criteria and number of vancomycin levels collected. Results: Fifty-one patients were included for analysis (38 in IIV group and 13 in CIV group). Median treatment duration was 3.8 days for IIV and 3 days in the CIV group (p=0.2). Median daily dose was 34 and 44 mg/kg in the IIV and CIV group respectively (p=0.06). Median time to target level was 1.4 days in the IIV vs 1.1 days in the CIV group (p=0.26). Initial vancomycin levels were therapeutic in 42% in the IIV group vs 61% in the CIV group (p = 0.27). Incidence of AKI was 24% in for IIV vs 8% for CIV (p=0.21) despite higher total daily doses in the CIV group. Median number of levels drawn was 3 vs. 2 in the IIV and CIV groups respectively (p=0.01). Conclusions: Administration of vancomycin as a continuous infusion may be an alternative dosing strategy in critically ill patients with ARC. Given this study was underpowered, larger studies are warranted to further explore the efficacy and safety of continuous infusion vancomycin.

1862. Time to Therapeutic Goal is Faster with Continuous Infusion Vancomycin for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Abstract Background Continuous infusion vancomycin (CIV) is an attractive alternative to intermittent infusion vancomycin (IIV) as it may result in more rapid attainment of target serum drug concentrations, provide ease of monitoring, and decreased risk of nephrotoxicity. At our institution CIV has been the preferred infusion method for over 20 years. The purpose of this study was to examine the time to therapeutic goal among patients receiving IIV compared to CIV for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Secondary objectives included all-cause readmission, relapse, and mortality 30 days after completion of therapy. Methods This was a single-center, retrospective study of patients who received vancomycin for MRSA bacteremia between January 2018 and December 2021. Included patients were ≥ 18 years of age, had ≥ 1 blood culture positive for MRSA, received vancomycin for > 10 days, and had follow-up in the outpatient parenteral antimicrobial therapy clinic. Patients who were pregnant, received vancomycin for ≤ 10 days, or were diagnosed at an outside hospital were excluded. All patients were started on IIV then transitioned to CIV. Patients on IIV with an appropriately drawn trough between 15-20 mcg/mL were considered therapeutic. For patients on CIV, a single random level between 17-25 mcg/mL, corresponding to an AUC/MIC of 400-600 mcg·h/mL, was considered therapeutic. Results Sixty-three patients with 65 MRSA bacteremia episodes were included. Significantly fewer patients achieved a therapeutic goal on IIV compared to patients on CIV (52.3% vs. 83.1%, p-value < 0.01). Of the 31 patients who did not reach the IIV trough goal, 87.1% became therapeutic when switched to CIV. Patients on IIV took 3.6 days, on average, to reach the target goal, compared to 1.9 days when patients were switched to CIV (95% confidence interval 0.50 – 2.96, p-value < 0.01). No patients experienced relapse or mortality 30 days after completion of therapy. Six patients (9.2%) were readmitted 30 days after completion of therapy. Conclusion CIV enabled patients with MRSA bacteremia to achieve the AUC/MIC goal significantly faster than when receiving IIV. Patients who were unable to achieve a therapeutic goal on IIV became therapeutic once switched to CIV. Disclosures Martha Carvour, MD, PhD, The Suga Project/The Suga Project Foundation: I provide consultation and support but do not receive compensation.

Continuous infusion versus intermittent infusion of vancomycin in critically ill patients undergoing continuous venovenous hemofiltration: a prospective interventional study

BackgroundA prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices.MethodsThis prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC).ResultsOverall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P < 0.05) or AUC24/MIC (53.2% vs. 28.6%; P < 0.05). There were no significant differences in clinical success (72.2% vs. 50.0%; P = 0.183) and microbiological success (83.3% vs. 75.0%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (0.0% vs. 4.4%; P = 0.462), and mortality between the two modalities was also not significant different (21.7% vs. 17.9%; P = 0.728). Correlation analysis showed a weak to moderately inverse correlation of EFR with observed concentration (r = − 0.3921, P = 0.01) and AUC24/MIC (r = − 0.3811, P = 0.013) in the II group, whereas the correlation between EFR and observed concentration (r = − 0.5711, P < 0.001) or AUC24/MIC (r = − 0.5458, P < 0.001) in the CI group was stronger.ConclusionAs compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, the inverse correlation of PK/PD indices with EFR was stronger among patients treated with CI of vancomycin.Trial registration The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393).

Continuous vancomycin infusion versus intermittent infusion in critically Ill patients: The research protocol

Background: Methicillin‐resistant Staphylococcal and Enterococcal infections are important problems in intensive care units (ICUs). Vancomycin is a drug of choice, and continuous administration has long been proposed as an alternative method with better therapeutic benefits. This study aims to examine information on the benefits of continuous vancomycin infusion (CVI) compared with the intermittent vancomycin infusion (IVI) method. Method: A quasi-experimental study with a propensity score-matched historical control involves adult patients in medical or surgical ICUs. In the experimental group, 31 patients for whom vancomycin is indicated will be enrolled to receive CVI for at least 48 hours with therapeutic drug monitoring according to the study protocol. For the historical control group, data of patients who received IVI between January 2018 and October 2020 will be retrospectively reviewed. Capability to achieve serum vancomycin therapeutic target within 48 hours, 96 hours, the incidence of supra- and subtherapeutic level, treatment successfulness, mortality, and incidence of acute kidney injury (AKI) between the two infusion methods will be analyzed before and after one-to-two propensity score matching. Ethics and dissemination: The study was approved by the institutional review boards of Faculty of Medicine Siriraj Hospital, Mahidol University (COA no. Si 027/2021). We plan to disseminate the results in peer-reviewed critical care medicine or infectious disease-related journals and national and international conferences. Trial registration: TCTR20210122005. Registered on January 22, 2021, with Thai Clinical Trials Registry

When There Is No Trough: Use and Outcomes of Continuous-Infusion Vancomycin at a Free-Standing Children's Hospital.

There is minimal published literature regarding the use of continuous-infusion vancomycin (CIV) in children. The objective of this study was to describe the use, dosing requirements, and outcomes of CIV at a free-standing children's hospital. This is a retrospective review of patients who received CIV while admitted to Nationwide Children's Hospital between July 1, 2010, and June 30, 2020. The total daily dose (TDD) of vancomycin required to attain a target serum vancomycin concentration (SVC) was compared between CIV and intermittent-infusion vancomycin (IIV) administration regimens. Safety outcomes and treatment failure were also explored. Fourteen patients (77% male) with a median age of 7 years (IQR = 1, 10 years) were included. Most patients (71%) were started on CIV in anticipation of outpatient parenteral antimicrobial therapy. The median TDD required to achieve a target SVC was higher with IIV compared with CIV (82.4 mg/kg/day vs 50.5 mg/kg/day; p = 0.02). Despite higher TDD with IIV, median SVC with IIV was similar to SVC with CIV (16.6 mg/L vs 17.6 mg/L; p = 2.00). There were no safety concerns or therapeutic failures identified with CIV. Continuous-infusion vancomycin was a well-tolerated and effective alternative to IIV for the patients included in this study. The TDD of vancomycin required to achieve a target SVC was lower in patients receiving CIV compared with those receiving IIV.

Efficacy and Safety of Continuous Infusion of Vancomycin in Children: A Systematic Review.

Vancomycin is used to treat a wide variety of infections within the pediatric population. In adults, continuous infusion of vancomycin (CIV) has been evaluated as an alternative to intermittent infusion of vancomycin (IIV) with potential advantages. In children, the use of CIV is increasing; however, data is currently limited. The objective is to provide efficacy and safety evidence for CIV within this population. The review was carried out following PRISMA guidelines. A bibliographic search was performed for studies on PubMed and EMBASE. Clinical trials and observational studies that reported clinical efficacy and/or target attainment of CIV in pediatrics were included. Articles were reviewed to assess their design and target population, characteristics of vancomycin treatment and the main findings in terms of safety and efficacy. A total of 359 articles were identified, of which seven met the inclusion criteria. All of them evaluated the target attainment, six assessed safety but only three assessed clinical efficacy. The best administration method for this antibiotic within the pediatric population is still unknown due to limited evidence. However, studies conducted thus far suggest pharmacokinetic advantages for CIV. Further investigation is required, in particular for studies comparing IIV with CIV for clinical efficacy and toxicity outcomes.

Continuous infusion of vancomycin improved therapeutic levels in term and preterm infants.

Growing evidence suggests that continuous infusion of vancomycin (CIV) is superior to intermittent infusion of vancomycin (IIV) in neonates. This quality improvement (QI) project aimed to transition from IIV to CIV with earlier and improved attainment of therapeutic vancomycin levels. The Model for Improvement framework with Plan Do Study Act cycles was used. Prospective data were collected during three phases: IIV, CIV-1 and CIV-2. A QI team developed a CIV drug monograph and a multidisciplinary education package. Using IIV, 36% (9/25) of first vancomycin levels were within target range. CIV achieved therapeutic levels twice as quickly as IIV (p < 0.05) with improved first vancomycin target levels (IIV36%, 9/25;CIV-1 55%, 16/29; CIV-2 61%, 14/23) and total therapeutic levels (IIV 44%, 37/84;CIV-1 56%, 55/98; CIV-2 69%, 79/114). This QI project demonstrated a successful transition from IIV to CIV with reduced time to achieve target vancomycin and an increased proportion of therapeutic levels.

Validation of Vancomycin Dosing Guidance During Transition of Care.

Vancomycin is an antibiotic commonly used to treat serious gram-positive infections. Patients requiring prolonged therapy in Singapore routinely receive intermittent vancomycin infusion in the hospital and are switched to continuous infusion for outpatient parenteral antibiotic therapy. During this transition of care, there may be a risk of not achieving therapeutic targets. We evaluated the performance of a model-based dosing algorithm in achieving a therapeutic target within 7 days of care transition. A published population pharmacokinetic model was used as the foundation to guide vancomycin dosing when discharging inpatients on intermittent infusion to outpatient care on continuous infusion. Selected demographic variables (age, weight, and creatinine clearance) were used to devise initial dosing. Patients with guided dosing were compared with historic controls (dosing by clinicians alone). The primary outcome of the study was to achieve vancomycin steady-state concentration of 20-25mg/L. Compared with historic controls, the proportion of patients attaining a therapeutic target by day 7 was significantly improved (6 of 19 [31.6%] vs 12 of 17 [70.6%], P = .04). Our model-based approach could guide customized dosing to facilitate switching patients from intermittent to continuous infusion during transition of care. Further validation in a larger patient cohort is warranted.

Exposure Variability and Target Attainment of Vancomycin: A Systematic Review Comparing Intermittent and Continuous Infusion

Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered. Moreover, due to large differences in the design and efficacy end points in these studies, a meta-analysis of the currently available data is not feasible. Therefore, this systematic review aimed to compare the exposure variability and target attainment with vancomycin during InI and CoI. A literature search was performed, and clinical studies reporting on vancomycin-treated populations were selected. After exclusion of reviews, case reports, and articles not published in the English language, 505 articles were screened for reported data on vancomycin serum concentrations. A total of 34 studies were included in the review. Relative standard deviations reported in the included studies were assessed, and vancomycin serum concentration variability and target attainment were compared between vancomycin InI and CoI. The variability in serum concentrations was significantly larger for InI than for CoI (relative standard deviations 46.5% and 32.1%, respectively; P = 0.001). Notably, variability appeared to be independent of the study population or design. Studies directly comparing target attainment between both modes of administration denoted higher and faster target attainment with CoI in all instances. In conclusion, CoI was associated with lower variabilities in the serum concentration and favorable target attainment rates compared with InI. These findings are important because vancomycin exposure is considered a major predictor of the patients' clinical outcomes. However, the role of lower serum concentration variability and higher target attainment rates in achieving better clinical outcomes needs to be evaluated in patients treated with vancomycin CoI compared with InI.

Retrospective multicentre matched cohort study comparing safety and efficacy outcomes of intermittent-infusion versus continuous-infusion vancomycin.

Patients with good renal function receiving intermittent-infusion vancomycin (IIV) may require total daily doses ≥4 g to achieve trough concentrations of 15-20 mg/L, increasing the risk of vancomycin-associated nephrotoxicity. Continuous-infusion vancomycin (CIV) may be associated with a lower risk of vancomycin-associated nephrotoxicity compared with IIV, but studies comparing safety of both dosing strategies are lacking. To compare the risk of nephrotoxicity with CIV versus IIV when target concentration ranges were the same with both dosing modalities. A retrospective multicentre matched cohort study of admitted patients between 1 January 2010 and 31 December 2016 was completed. Adult patients who received ≥48 h of vancomycin with at least one steady-state vancomycin concentration were eligible. The primary outcome was to compare the rates of nephrotoxic risk and renal injury, defined by the RIFLE criteria, between CIV and IIV. Of 2136 patients who received vancomycin during the study period, 146 CIV patients were eligible and matched to 146 IIV patients. After adjustment of potential confounders, CIV was found to have a lower odds of developing nephrotoxic risk (OR 0.42, 95% CI 0.21-0.98, P = 0.025) and renal injury (OR 0.19, 95% CI 0.05-0.59, P = 0.004). CIV is associated with a lower odds of nephrotoxicity compared with IIV when targeting the same concentration range and should be an alternative dosing strategy for patients who will receive prolonged therapy or require >4 g/day to achieve therapeutic levels.

Intermittent vs. continuous vancomycin infusion for gram-positive infections: A systematic review and meta-analysis

ObjectiveThe clinical use of intermittent infusion of vancomycin (IIV) and continuous infusion of vancomycin (CIV) is controversial. The aim of this study was to assess the effectiveness and safety of IIV and CIV by using a meta-analysis for cohort studies and randomized controlled trials. MethodsWe compared the probabilities of target attainment (PTA) for the measured concentration (Cm) ≥the target concentration (Ct), the PTA for the area under the drug concentration curve/minimal inhibitory concentration (AUC/MIC) ≥400, the duration of treatment, nephrotoxicity, and overall mortality after vancomycin treatment as reported in PubMed, Embase, Cochrane, and Web of Science. ResultsA total of 14 studies with 1640 patients were included in the meta-analysis. For IIV, the PTA of Cm≥Ct (RR=0.72, 95% CI=0.60–0.88), and nephrotoxicity (RR=1.70, 95% CI=1.34–2.14) were significantly different from those of CIV. The treatment duration (SMD=0.08, 95% CI=−0.08–0.25), the PTA of AUC/MIC ≥ 400 (RR=0.84, 95% CI=0.70–1.00) and mortality (RR=0.94, 95% CI=0.72–1.25) were not significantly different from those of CIV. ConclusionsThe results showed that CIV was easier to achieve Ct and safer than IIV. Additional randomized controlled trials focusing on the concentration of vancomycin are needed for further analysis.

A rapid and simple UPLC method for serum vancomycin determination in pediatric patients undergoing continuous infusion or intermittent infusion of vancomycin

Vancomycin is a glycopeptide antibiotic widely used against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus. Several studies have found that in adults, continuous infusions of vancomycin showed earlier attainment of desired target drug concentrations and reduced nephrotoxicity relative to intermittent infusion. In the pediatric population, there is no consensus on the best vancomycin infusion method. The present study developed and validated a simple and cost-effective UPLC method to determine serum vancomycin levels in pediatric patients and applied it to the therapeutic drug monitoring of vancomycin in children who were treated with either continuous infusion or intermittent infusion of vancomycin. The sample preparation procedure involves only protein precipitation and filtration, and the UPLC method takes 5 min/sample. The assay was linear from 5 mg/L to 100 mg/L (R2 = 0.999). The precision and accuracy were determined at 4 concentration levels. The intraday variability (%CV) ranged from 1.23% to 6.01% (n = 6), and the interday variability ranged from 3.02% to 9.75% (n = 18). The accuracies were good and ranged from 91.21% to 112.63%. Serum vancomycin was stable at room temperature for 12 h or for 3 freeze/thaw cycles, and the processed sample was stable in an autosampler within 15.5 h.

Experience with Continuous Infusion Vancomycin Dosing in a Large Pediatric Hospital.

There is a paucity of data on dosing of continuous infusion of vancomycin (CIV) in pediatric patients, despite it being an attractive treatment option for limiting escalating doses of intermittent infusion of vancomycin. The purpose of this study was to determine the total daily dose of CIV required to attain therapeutic serum vancomycin concentrations (SVCs) in pediatric patients according to age (≥31 days to <2 years, 2 to <8 years, and 8 to <18 years). We retrospectively evaluated patients who were transitioned from intermittent infusion of vancomycin to CIV between January 2013 and December 2016. Demographic data, vancomycin data (indication, dosing, steady-state SVCs, and time to reach goal SVC), and adverse-effect data (infusion reactions and serum creatinine level) were collected. Of the 240 patients included, 76 had a goal SVC of 10 to 15 µg/mL and 164 had a goal of 15 to 20 µg/mL. The dose of CIV required to reach an SVC of 10 to 15 µg/mL in the youngest age group was 48.4 mg/kg per day versus 45.6 and 39.4 mg/kg per day in the older age groups (P < .005). The 2 younger age groups of patients with a goal SVC of 15 to 20 µg/mL required 50.2 and 50.6 mg/kg per day, respectively, whereas patients aged ≥8 years required 44.7 mg/kg per day (P = .008). One patient experienced renal injury, and 1 experienced renal failure. CIV is an effective method for attaining a therapeutic SVC in pediatric patients. Patients <8 years of age require higher dosing than older pediatric patients to reach the goal SVCs of 10 to 15 and 15 to 20 µg/mL.

Vancomycin Intermittent Dosing versus Continuous Infusion for Treatment of Ventilator-associated Pneumonia in Trauma Patients

Current guidelines for the empiric treatment of ventilator-associated pneumonia (VAP) recommend that vancomycin is dosed 15 mg/kg and administered twice daily for a target trough level of 15 to 20 μg/mL. This study compared conventional intermittent vancomycin infusion (IVI) with continuous vancomycin infusion (CVI). Our prospective, randomized study compared CVI with IVI in trauma patients with suspected VAP. The primary outcome measure was a serum vancomycin level within the target level 48 hours after initiation of therapy. Treatment groups were compared using standard statistical methods. The study included 73 patients, 36 IVI and 37 CVI. Eighteen patients were withdrawn from the study as a result of discontinuation of the drug before 48 hours or failure to draw levels at the appropriate time, resulting in 27 IVI and 28 CVI study patients. There were no differences between treatment groups in gender (P = 0.97), Injury Severity Score (P = 0.70), total body weight (P = 0.36), or age (P = 0.81). The mean serum vancomycin level for the IVI group was 8.9 ± 3.9 μg/mL, and the CVI level was 19.8 ± 6.13 μg/mL (P < 0.0001). Two patients in the IVI group (7.4%) were in the therapeutic range compared with 16 (57.1%) in the CVI group (P < 0.0001). Six patients in the CVI group (21.4%) and none of the IVI patients had supratherapeutic levels. Four patients developed renal insufficiency, three IVI (11.1%) and one CVI (3.6%) (P = 0.36). The current American Trauma Society dosing recommendations for vancomycin for presumptive VAP treatment are inadequate. Continuous vancomycin infusion should be adopted as the standard dosing strategy.

Review of Continuous-Infusion Vancomycin

To evaluate the efficacy and safety of administering vancomycin as a continuous infusion. Literature was accessed through MEDLINE (1977-September 2012), Embase (1977-September 2012), and Google Scholar, using the terms vancomycin, continuous, discontinuous, infusion, pharmacokinetics, pharmacodynamics, and nephrotoxicity. In addition, reference citations from publications identified were reviewed. All English-language articles identified from the data sources were evaluated. Studies including more than 30 adults were included in the safety and efficacy review. Infections due to methicillin-resistant Staphylococcus aureus (MRSA) carry a significant risk of morbidity and mortality. Vancomycin is commonly prescribed for invasive MRSA infections and has been traditionally administered as an intermittent infusion. Administering vancomycin as a continuous infusion is a novel approach to improving its efficacy and safety profile. Fourteen clinical trials were reviewed (2 prospective, 1 meta-analysis, 11 retrospective). The pharmacodynamic profiles between continuous-infusion vancomycin and intermittent-infusion vancomycin were comparable. Continuous-infusion therapy did not significantly improve the efficacy of vancomycin in the treatment of invasive MRSA infections. Conflicting results exist regarding the safety profile of continuous-infusion compared with intermittent-infusion vancomycin. The only published prospective randomized clinical trial comparing continuous infusion with intermittent therapy found no significant difference in the rates of nephrotoxicity. The data from retrospective studies are heterogeneous and show variable rates of nephrotoxicity. In general, compatibility information for administering vancomycin as a continuous infusion is unavailable. Overall, currently available evidence is insufficient to conclude whether an improvement in vancomycin efficacy exists when it is administered as a continuous infusion. The risk of nephrotoxicity associated with continuous-infusion vancomycin requires further investigation in prospective randomized trials. Specific patient populations that would benefit from continuous-infusion vancomycin have yet to be determined.

Evaluation of a pediatric continuous-infusion vancomycin therapy guideline

An institutional guideline for converting pediatric patients to continuous-infusion vancomycin (CIV) therapy if therapeutic targets are not achieved with intermittent i.v. dosing was evaluated. All patients within a specified age range (>6 months but <19 years) who were converted to CIV therapy for pneumonia or osteomyelitis during the 2 years after guideline implementation were included in the evaluation. The guideline calls for conversion to CIV therapy if goals for trough serum vancomycin concentration (SVC) are not attained with escalating intermittent-infusion vancomycin (IIV) dosing. Primary outcome measures included the rate of attainment of the goal steady-state trough SVC (15-20 mg/L), preferably within 24-48 hours, the adequacy of an empirical dosing strategy, and adverse events. Secondary study outcomes included final vancomycin doses and the time to attainment of therapeutic SVCs. Within 24-48 hours after conversion to CIV therapy, the mean initial plateau SVC in the evaluated cases (n = 15) was 20.2 mg/L; the mean of all SVCs was 19.1 mg/L. The range of dosages required to achieve a plateau SVC of 15 mg/L was 23.8-65.4 mg/kg/day (median, 41 mg/kg/day). The mean ± S.D. vancomycin dosage at the end of CIV therapy was 44.3 ± 12.8 mg/kg/day. Monitoring of serum creatinine, urine output, and glomerular filtration rate indicated that no patients developed nephrotoxicity during CIV therapy. Conversion from IIV to CIV therapy in selected pediatric patients appeared to be safe and well tolerated, with few adverse effects noted. Using the institutional CIV dosing guideline, goal plateau SVC values were attained in most patients within 24-48 hours.

Efficacy of continuous infusion of vancomycin for the outpatient treatment of methicillin-resistant Staphylococcus aureus infections

Recently published guidelines on the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend against administering vancomycin by continuous infusion on the basis of insufficient studies comparing this with intermittent infusion. We compared outcomes of patients treated with continuous infusion and intermittent infusion of vancomycin. Data for outpatients treated with continuous infusion and intermittent infusion of vancomycin were compared utilizing rates of clinical failure defined as the need for unplanned re-admission, change of antibiotics or extension of therapy. A total of 244 patients met the inclusion criteria, with 188 receiving continuous infusion and 56 intermittent infusion of vancomycin. The endpoint occurred in 21.3% and 30.4% of those receiving continuous infusion and intermittent infusion, respectively (relative risk 0.701, 95% CI 0.432-1.136, P = 0.159). Patient characteristics differed slightly between the two groups; however, logistic regression to adjust for differences in age, co-morbidity, subtherapeutic levels and prosthetic devices did not substantially alter this result. No difference in rates of clinical failure of continuous infusion and intermittent infusion of vancomycin was observed in this outpatient cohort.

Intermittent versus continuous infusion of vancomycin in neonates

ObjectiveTo compare the effectiveness of intermittent and continuous vancomycin infusions in achieving target concentrations in neonates and to assess the implications for clinical practice.MethodsThe study involved infants who required treatment...

Continuous intravenous administration of vancomycin in medical intensive care unit patients

PurposeThe aim of this study was to evaluate continuous vancomycin infusion (contV) in intensive care unit patients. Materials and MethodsA retrospective study in 164 patients treated with contV was conducted. They were compared with 75 patients treated with intermittent vancomycin infusion. ResultsThe median duration of vancomycin therapy in the contV group was 6 (5%-95% percentile range, 2-21) days. The median daily vancomycin dose in the contV group was 960 (526-1723) mg, resulting in a median serum vancomycin plateau concentration of 19.8 (9.8-29.4) mg/L (target: 15-25 mg/L). The contV administration regime was sufficient regarding achievement of the target serum vancomycin concentration. However, in the contV group, serum vancomycin levels were frequently in a subtherapeutic range on treatment days 1 (44%), 2 (29%), and 3 (23%). In the contV group, serum vancomycin concentration determinations per treatment day were performed significantly less often compared with the intermittent vancomycin infusion group (0.38 [0.15-0.75] vs 0.43 [0.22-1.00], P = .041). ConclusionsIn medical intensive care unit patients, contV is sufficient to achieve target serum vancomycin concentrations. Because contV frequently resulted in subtherapeutic drug levels on the first days of therapy, a higher loading or starting dose might be necessary.