Continuous 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.

Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients.

Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R2 = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.

Dosing and Exposure of Vancomycin With Continuous Infusion: A Retrospective Study.

Vancomycin continuous infusion (CI) has suggested benefits over intermittent infusion: reduced nephrotoxicity, higher target attainment, and simpler therapeutic drug monitoring (TDM). Empiric dosing regimens range from 30-60 mg/kg/day and it is unclear which regimen results in optimal exposure. This study evaluates whether a dosing regimen of 45 mg/kg/day after a 20 mg/kg loading dose for patients with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min results in adequate exposure. We retrospectively analyzed plasma concentrations from patients treated with vancomycin CI as routine clinical care between February and October 2021. Patients under 18 years old, with renal replacement therapy, reduced creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration < 50 mL min/1.73 m2 ) or outpatient antibiotic therapy were excluded. Dose, renal function, and blood draw procedures were assessed for each measured vancomycin sample. Initially, 121 samples were included. Subsequently, 7 samples, 6 of which with concentrations ≥ 40 mg/L, were verified to be incorrectly drawn and excluded. With doses of 40-50 mg/kg/day concentrations ranged from 18.4-61.0 mg/L. Only 25% were within the target window of 17-25 mg/L and 15% were ≥ 40 mg/L. Supratherapeutic concentrations were observed in 89% of samples from patients dosed 40-60 mg/kg/day with eGFR 50-80 mL/min. Concluding, an empiric dosing regimen of 45 mg/kg results in too high vancomycin exposure and thus we recommend lower doses and differentiation according to renal function. Additionally, when measuring concentrations over 40 mg/L incorrect sampling must be excluded before dose adjustment and the large variability in exposure between patients, warrants the need for swift TDM.

Evaluation of Continuous Infusion Vancomycin in a Pediatric Hematology/Oncology Population.

Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients. A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV. Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort (P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m2 (P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%). CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

'The Year of Living Dangerously': Successful Rhodococcus Equi Therapy in an Immunosuppressed Patient with Minimal Toxicity by One Year of Continuous Intravenous Vancomycin Therapy Combined with Oral Levofloxacin And Rifampicin.

Rhodococcus equi is a Gram-positive microorganism that causes infections, particularly in immunocompromised patients. Treatment duration can be prolonged. While vancomycin is an effective drug in this scenario, its use may lead to renal damage. Studies have shown that continuous vancomycin infusion appears to be a safe strategy in terms of adverse effects compared to bolus administration. We present the case of a 71-year-old female liver transplant recipient. After being diagnosed with a mediastinal infection caused by Rhodococcus equi with poor response to initial therapy, she required 12 months of continuous intravenous domiciliary infusion of vancomycin combined with oral levofloxacin and rifampicin. There was no drug-related complication throughout the follow-up. The use of continuous vancomycin infusion has emerged as a safer, more efficient, and cost-effective alternative to intermittent administration. We want to emphasise the uniqueness of this case, where despite the unprecedented treatment duration, no adverse effects occurred. Vancomycin therapy based on continuous infusion represents a safer and cheaper strategy than classic intermittent administration.The use of continuous infusion facilitates the management of complex infections with outpatient antimicrobial therapy.

P09 Lancashire and South Cumbria Critical Care Network Vancomycin Project

Abstract Background This project was a collaborative piece of work across a critical care network that included specialist advice from colleagues including aseptic/technically trained pharmacists and microbiology to optimize care for critical care patients in Lancashire and South Cumbria. We used several members of our workforce including pharmacists, nursing staff, microbiologists, rotational doctors and consultants to work towards a harmonized guideline. Methods During our initial meeting, we identified that different centres were using different glycopeptides and administering them differently: East Lancashire Hospitals (ELHT)—continuous vancomycin infusion; Blackpool Cardiac and Blackpool General—continuous vancomycin infusion, with no formal guideline in place but adopted from ELHT; Lancashire Teaching Hospitals—intermittent vancomycin infusions; and University Hospitals Morecambe Bay—teicoplanin is glycopeptide of choice. Our consultant microbiologist discussed the use of glycopeptides and what infections they are used for in critical care. The pharmacokinetics of vancomycin and the benefit of using a continuous infusion was also discussed. We decided to undertake a clinical audit of our vancomycin guidelines at ELHT to ensure that we had an evidence base to implement our guideline and provide assurance to the working group. We agreed to reconvene the working group after this audit was completed and after the concerns of colleagues had been addressed. Results and conclusions We presented the results of our audit and highlighted the opportunities harmonizing this guideline would provide. We discussed various scenarios such as stepping up from a ward protocol to a continuous infusion and the different methods of calculating creatinine clearance and if this would influence the first 24 h of the infusion. One comment was concerning the administration of vancomycin and the number of times nurses will be changing bags for patients requiring higher doses, i.e. the majority of patients would usually be on 3 g/day or more depending on concentrations. This would mean changing the bag more than twice a day; as much as there is a therapeutic benefit to continuous vancomycin infusions, considering the max. concentration for peripheral and central lines allows for larger volumes, it would be beneficial (except in fluid restricted cases) to have a slightly larger volume to reduce the number of bag changes and plastic consumption. We considered this comment and discussed it with our aseptic services lead pharmacist. We attended a meeting of the ICS Aseptics Working Party across Lancashire and South Cumbria. WE discussed the proposed guideline and requested that aseptic units across Lancashire and South Cumbria developed worksheets to manufacture 5 g in 600 mL or 10 g in 1.2 L for central use to stop breaking the line when changing a bag and reducing plastic consumption. We also met with critical care practice educators across the network to discuss how we can promote this guideline and ensure nursing staff and prescribers are aware of how to prescribe and administer continuous vancomycin infusions. One of our units noted that they have had a few incidents with incorrect concentrations of vancomycin being made up for patients. We developed an e-learning package to educate our workforce.

Vancomycin and Gentamicin Removal with the HA380 Cartridge during Experimental Hemoadsorption

Introduction: Hemoadsorption has emerged as an adjunctive therapy for sepsis, but its impact on antibiotic levels remains poorly defined. We conducted an in vivo experimental study to investigate the removal of vancomycin and gentamicin during hemoadsorption using the HA380 cartridge, a novel styrene-divinylbenzene copolymer cartridge. Methods: Six surgically prepared sheep were administered 2 g of vancomycin and 400 mg of gentamicin over 30 min, followed by a continuous infusion of vancomycin (20 mg/h). Hemoadsorption was implemented with a styrene-divinylbenzene copolymer HA380 cartridge at a blood flow of 120 mL/min. The removal ratio, sorbent-based clearance, and the mass removal rate were calculated for each time point. Results: The mean 10-min vancomycin removal ratio exceeded 90% and declined to 68.0% at 30 min; 52.8% at 60 min, and 28.0% by 4 h. Due to constant plasma flow, clearance varied proportionally with the removal ratio. Over 4 hours, the total mass removal was 556 mg (SD 106.3). For gentamicin, the mean 10-min removal ratio was 96.9% and the final ratio at 4 h remained 53.0%, with clearances changing proportionately. The total mass removal of gentamicin was 138 mg (SD 26.6) over 4 h. The sorbent-based clearance of vancomycin was significantly lower than that of gentamicin (P_group < 0.0001). Conclusion: The novel HA380 sorbent cartridge appears safe and achieves significant vancomycin and gentamicin removal over a four-hour period. This information can be used by clinicians to guide their prescription and consider the additional dosing of at least an extra 25–35% amount in patients receiving HA380 hemoadsorption therapy during sepsis.

The pharmacokinetics and pharmacodynamics of continuous infusion vancomycin in adult people with cystic fibrosis.

The American Thoracic Society Guidelines recommend vancomycin as first line option for treatment of methicillin-resistant Staphylococcus aureus. Two studies have described the pharmacokinetics (PK) of intermittent intravenous (IV) vancomycin in adult people with cystic fibrosis (PwCF). Currently, there have not been any studies describing the PK of continuous infusion vancomycin in PwCF. Our study aimed to describe the PK of continuous infusion vancomycin in adult PwCF. Included patients were adult PwCF, who were admitted to University of Utah Hospital between May 11, 2014 and August 31, 2020, and received continuous infusion vancomycin for the treatment of an pulmonary exacerbations. The primary outcome was to describe vancomycin clearance rate (CLvanco ) and total daily dose (TDD). Secondary outcomes included rates of acute kidney injury (AKI), liver injury, and infusion-related reactions. Twenty patients were included in this study. The mean CLvanco was 5.08 L/h on Day 3 and 4.58 L/h on Day 7 (p = .04), and the TDD increased from 2444 mg on Day 3 to 2556 on Day 7, although not statistically significant (p = 0.26). Zero patients experienced an AKI, two patients experienced liver injury, and no patients experienced infusion-related reactions. This study demonstrates that continuous infusion vancomycin PK, namely CLvanco , is similar to previously reported CLvanco for intermittent dosed IV vancomycin in adult PwCF. This study suggests that continuous infusion vancomycin is likely safe to use in adult PwCF.

Feasibility of individualised patient modelling for continuous vancomycin infusions in outpatient antimicrobial therapy, a retrospective study.

The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter for dosing vancomycin continuous infusion in methicillin-resistant Staphylococcus aureus (MRSA) infection. Individualised pharmacokinetic-pharmacodynamic (PK/PD) calculation of AUC24 may better represent therapeutic dosing than current Therapeutic Drug Monitoring (TDM) practices, targeting a Steady State Concentration of 15-25mg/L. To compare real world TDM practice to theoretical, individualised, PK/PD target parameters utilising Bayesian predictions to steady state concentrations (Css) for outpatients on continuous vancomycin infusions. A retrospective single centre study was conducted at a tertiary hospital on adult patients, enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program, receiving vancomycin infusions for MRSA infection. Retrospective Bayesian dosing was modelled to target PK/PD parameters and compared to real world data. Fifteen patients were evaluated with 53% (8/15) achieved target CSS during hospitalisation, and 83% (13/15) as outpatient. Median Bayesian AUC/MIC was 613mg.h/L with CSS 25mg/L. Patients suffering an Acute Kidney Injury (33%) had higher AUC0-24/MIC values. Retrospective Bayesian modelling demonstrated on median 250mg/24h lower doses than that administered was required (R2 = 0.81) which achieved AUC24/MIC median 444.8 (range 405-460) mg.h/L and CSS 18.8 (range 16.8-20.4) mg/L. Bayesian modelling could assist in obtaining more timely target parameters at lower doses for patients receiving continuous vancomycin infusion as part of an OPAT program, which may beget fewer adverse effects. Utilisation of personalised predictive modelling may optimise vancomycin prescribing, achieving earlier target concentrations as compared to empiric dosing regimens.

P30 Evaluating vancomycin continuous infusion protocol compliance and gauging therapeutic target attainment in neonates

Abstract Background Vancomycin is commonly indicated to treat neonatal late-onset sepsis. At St. George’s Hospital, neonates with central-line access are administered vancomycin by continuous infusion. A protocol instructs a 1-hour 15 mg/kg-loading dose, followed by a creatinine clearance- (CLCR)/weight–based maintenance dose. Due to vancomycin’s narrow therapeutic margin, daily therapeutic drug monitoring (TDM) of serum concentrations is necessary to obtain safe/effective therapy. Concentrations between 15 and 25 μg/mL act as a surrogate therapeutic target extrapolated from adult data.1 Methods A locally approved service evaluation retrospectively analysed 78 courses of vancomycin from 46 patient’s electronic prescribing and medicine administration (ePMA) records (July 2021–March 2022). Data on vancomycin administration/TDM were analysed using descriptive statistics. Results Individual loading and maintenance doses were calculated correctly in 83% (65/78) and 97% (75/77) of records. 72% (33/46) of patients received both correctly calculated loading/maintenance doses. A gap greater than 1 hour between loading and maintenance doses was recorded in 32% (24/75) of courses. 61% (41/67) of courses had appropriately taken serum concentrations within 22–26 hours of treatment initiation. In correctly dosed patients, therapeutic vancomycin courses increased from 43% (23/54) to 53% (19/36) and 55% (17/31) between 24–48–72-hour timepoints. In pre-term neonates &amp;lt; 28 weeks gestational age (GA), subtherapeutic courses were consistent between 38% (15/40)–42% (11/26)–36% (8/22) at 24–48–72-hour timepoints. Supra-therapeutic courses decreased from 20% (8/40)–0% (0/26)–5% (1/22), respectively. In term neonates &amp;gt; 37 weeks GA, subtherapeutic courses increased from 33% (3/9)–43% (3/7)–50% (3/6) between 24–48–72-hour timepoints. As did respective supra-therapeutic courses from 11% (1/9)–14% (1/7)–17% (1/6). Insufficient course data (5) were available for neonates between 28–32/32–37 weeks GA. Conclusions Non-therapeutic treatment worsened over 72 hours for neonates &amp;gt; 37 weeks GA, whereas toxic concentrations decreased over time despite consistent subtherapeutic concentrations in neonates &amp;lt; 28 weeks. Neonatal pharmacokinetic (PK) variability due to evolving renal function/distribution volume/non-blood protein-bound vancomycin concentrations, likely contributed to non-therapeutic concentrations. As did limitations of sample size/non-capture of dosing amendment impact. Population PK–derived dosing based on covariates explaining vancomycin PK variability could be used to improve neonatal target attainment. Whereas, neonatal area under the vancomycin concentration time curve targets supported by clinical data are needed to benchmark the therapeutic target. This will provide insight into if lower concentrations adequately treat common infections with coagulase-negative organisms.1 A quality improvement project addressing protocol ePMA interface issues and implementing a dose-amendment nomogram may improve dose calculation/monitoring. Delays between manually input loading/maintenance dose administration times onto the ePMA system require investigation before dosing revisions. Aspects of protocol compliance require improvement. Therapeutic target attainment was erratic, but reflective of the literature.1 Optimized dosing is required for specific neonatal subgroups.

Pursuing the Real Vancomycin Clearance during Continuous Renal Replacement Therapy in Intensive Care Unit Patients: Is There Adequate Target Attainment?

Introduction: Vancomycin is used in intensive care unit (ICU) patients for the treatment of infections caused by gram-positive bacteria. The vancomycin pharmacokinetic/pharmacodynamic index is a ratio of the area under the concentration to the minimum inhibitory concentration ≥400–600 h*mg/L. This target can generally be achieved by a plasma concentration of 20–25 mg/L. Together with the pathophysiological alterations and pharmacokinetic variability associated with critical illness, the use of continuous renal replacement therapy (CRRT) may complicate the attainment of adequate vancomycin concentrations. The primary objective was the prevalence of attainment of vancomycin concentrations 20–25 mg/L after 24 h in adult ICU patients receiving CRRT. Secondary outcomes were to evaluate target attainment at days 2 and 3 and to calculate vancomycin clearance (CL) by CRRT and residual diuresis. Methods: We performed a prospective observational study in adult ICU patients on CRRT, which received at least 24 h continuous infusion of vancomycin. Between May 2020 and February 2021, daily vancomycin residual blood gas and dialysate samples were collected from 20 patients, every 6 h and if possible vancomycin urine samples. Vancomycin was analysed with an immunoassay method. The CL by CRRT was calculated by a different approach correcting for the downtime and providing insight into the degree of filter patency. Results: The proportion of patients with vancomycin concentrations <20 mg/L was 50% 24 h after starting vancomycin (n = 10). No differences were observed in patient characteristics. The target vancomycin concentration 20–25 mg/L was only achieved in 30% of the patients. On days 2 and 3, despite the use of TDM and albeit in lower percentages, sub- and supratherapeutic levels were still observed. Taking downtime and filter patency into account resulted in lower vancomycin CL. Conclusions: 50% of the studied ICU patients on CRRT showed subtherapeutic vancomycin concentrations 24 h after starting therapy. The results reveal that optimization of vancomycin dosage during CRRT therapy is needed.

P14 Improving adherence to and effectiveness of an adult critical care vancomycin continuous infusion protocol: a pilot quality improvement and administration data accuracy project

Abstract Background Vancomycin treats serious Gram-positive infections. In St George's Hospital (SGH) intensive care unit (ICU) settings, vancomycin is administered intravenously by continuous infusion. Steady-state serum concentrations are monitored daily with a 20–25 mg/L therapeutic target. Non-therapeutic concentrations are associated with patient harm and prolonged stay.1 A service evaluation revealed variable adherence to/effectiveness of the vancomycin prescribing/administration/monitoring protocol. Electronic prescribing and medicine administration (ePMA) system interface issues may have contributed.2 Consequently, multifaceted interventions were devised and piloted on General ICU. Objectives To (i) improve combined protocol prescribing/administration/monitoring adherence; (ii) enhance therapeutic protocol dosing; and (iii) ascertain accuracy of patients’ paper drug administration (PDA) charts compared with the ePMA system. Methods The quality improvement project (QIP) was approved by SGH clinical governance/audit teams. Over a 9 month period (September 2021 to May 2022) system/person-focused interventions were implemented. Protocol dosing2 was revised; introducing a &amp;gt;90 kg patient 2 g loading dose, new renal-function categories and an increased maintenance dose for creatinine clearance (CLCR) &amp;gt;90 mL/min. Protocol accessibility was increased via ePMA and CliniBee/Microguide app integration. Educational protocol presentations were incorporated into medical/nursing induction training. Vancomycin prescribing/administration/monitoring data for non-renal replacement patients during the intervention period, was extracted retrospectively from the ePMA system. This was compared with baseline informing ICU data collected July 2020 to July 2021.2 Patient's drug administration accuracy data (PDA charts/ePMA system) was extracted retrospectively from January to May 2022 and analysed. Results Compared with baseline, the proportion of patients receiving per protocol prescribing/administration of vancomycin loading/maintenance doses with daily monitoring increased [39% (7/18) to 68% (15/22)]. Within 48 h 54% (7/13) of vancomycin serum concentrations in all patients were therapeutic, demonstrating a baseline increase of 21% (3/9 to 7/13). In per protocol treated patients, serum concentrations increased 16% (2/7 to 4/9) therapeutically, decreased 20% (3/7 to 2/9) supra-therapeutically and increased 4% (2/7 to 3/9) sub-therapeutically. Supra-therapeutic concentrations were associated with CLCR &amp;lt;50 mL/min. Sub-therapeutic concentrations were associated with CLCR &amp;gt;90 mL/min and obesity. Compared with the ePMA system, there was 38% (5/13) less PDA charts recording both loading/maintenance doses. Administration time differences &amp;gt;60 min were recorded for 38% (3/8) of loading and 31% (4/13) maintenance doses. Discussion Staff turnover periods were associated with decreased protocol compliance. Further education is required around prescribing/administration of standardized vancomycin infusion bags, with associated rate changes. Integration of pharmacists into daily Microbiology ward rounds may alleviate these issues. Higher 20 mg/kg loading doses for &amp;gt;100 kg patients and maintenance dose revisions may reduce non-therapeutic concentrations.3 Multidirectional variation in vancomycin administration timings recorded between PDA charts/ePMA system, requires further investigation. Infusion-pump data may offer the most accurate administration time for calculating pharmacokinetic variables. Conclusions Multifaceted interventions were successful at improving adherence to/effectiveness of the vancomycin protocol. Findings will inform QIP roll-out across all three SGH ICUs, which will incorporate infusion-pump data collection to facilitate pharmacokinetic modelling. This will inform local dosing strategies and research into patient variability.

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.

Continuous Vancomycin Infusion versus Intermittent Infusion in Critically Ill Patients.

Vancomycin is the best-choice medication for methicillin-resistant staphylococcal and enterococcal infections, which are major problems in intensive care units (ICUs). Intermittent infusion is standard for vancomycin, although delayed therapeutic target achievement and supra- and subtherapeutic levels are concerns. A recently proposed alternative with superior therapeutic target achievement is continuous infusion. To compare the benefits of continuous (CVI) and intermittent (IVI) vancomycin infusion. This quasi-experimental study used propensity score-matched historical controls and adult patients in medical and surgical ICUs for whom vancomycin was indicated. The experimental group received CVI for ≥ 48 hours. Data on patients receiving IVI between January 2018 and October 2020 were reviewed. Capability to achieve serum vancomycin therapeutic targets (48 and 96 hours), episodes of supra- and subtherapeutic levels, treatment success, mortality, and incidence of acute kidney injury (AKI) were analyzed before and after one-to-two propensity score matching. The CVI group had 31 patients, while the unmatched IVI group had 125. More CVI patients achieved the therapeutic target within 48 hours (54.8% vs 25.6%; P=0.002). CVI patients had a higher median number of supratherapeutic episodes (2 vs 1; P=0.007) but a lower median for subtherapeutic episodes (0 vs 1; P=0.003). Other outcomes demonstrated no differences. After propensity score matching, target achievement within 48 hours (54.8% vs 22.6%; P=0.002) and fewer subtherapeutic episodes (0 vs 1; P=0.014) remained significant. CVI's rapid therapeutic target achievement and fewer subtherapeutic episodes make it superior to IVI. No differences in treatment success, mortality, or AKI are evident.

Improving adherence to and effectiveness of a vancomycin continuous infusion protocol, a pilot quality improvement project

Abstract Introduction Vancomycin treats serious Gram-positive infections such as methicillin-resistant Staphylococcus aureus. In St George’s University Hospital’s (SGH) intensive care unit (ICU) settings, vancomycin is administered by continuous infusion. Steady-state serum concentrations are measured daily with a 20-25 mg/L target. Non-therapeutic concentrations are associated with adverse drug reactions/prolonged length of stay.1 A SGH service-evaluation conducted across all three ICUs, revealed variable adherence to/effectiveness of its vancomycin prescribing/administration/monitoring protocol.2 Consequently, multifaceted interventions were devised using the Institute-for-Healthcare-Improvement’s model Plan-Do-Study-Act (PDSA) cycles and piloted on General ICU (GICU). Aim (1) To improve adherence to/effectiveness of the vancomycin protocol. (2) To ascertain administration accuracy of paper-fluid-balance-charts compared to the electronic-prescribing-and-medicines-administration (ePMA) system to assist with identifying per protocol treated patients. Methods PDSA Cycle-1 was conducted over a 9-month period (09/2021-05/2021) in which a mix of system/person-focused interventions were implemented. Protocol dosing2 was revised, introducing a &amp;gt;90kg patient 2g loading dose, renal-function category revision and increased maintenance dose for creatinine clearance (CLCR) &amp;gt;90ml/min. Protocol accessibility was increased via integration into an ePMA prescribing interface, plus CliniBee/Microguide apps. Educational slides on relevant protocol aspects were incorporated into medical/nursing induction training. Data relating to vancomycin prescribing/administration/monitoring for all non-renal replacement patients was extracted retrospectively from the ePMA system between 09/2021-05/2022. This data was compared to baseline GICU data (07/2020-07/2021).2 The project and associated interventions were approved by Trust Clinical Governance and Audit Teams. Data was collected by pharmacists directly involved in patient’s care and stored/analysed on the Trust’s secure server in line with Data Protection Act principles. Due to local generalisability, ethics approval wasn’t required. Results Compared to baseline, the proportion of patients receiving per protocol prescribing/administration of loading/maintenance doses with daily monitoring, nearly doubled (39% (7/18) to 68% (15/22)). 48-hour vancomycin serum concentrations in all patients increased therapeutically by 21% (3/9 to 7/13). In per protocol treated patients, concentrations increased 15% (2/7 to 4/9) therapeutically, decreased 21% (3/7 to 2/9) supra-therapeutically and increased 4% (2/7 to 3/9) sub-therapeutically. Supra-therapeutic concentrations were associated with CLCR&amp;lt;50ml/min. Sub-therapeutic concentrations were associated with CLCR&amp;gt;90ml/min and obesity. Compared to the ePMA system, there was 36% (8/22) less paper-fluid-balance-charts recording both loading/maintenance doses. Maintenance dose administration times in 9% (2/22) of cases differed by &amp;gt;60 minutes. Discussion/Conclusion Staff-turnover periods were associated with decreased protocol compliance. Observations suggest further education is required around prescribing/administration of standardised infusion bags for maintenance dosing. Pharmacist integration into daily Microbiology ward rounds may increase protocol compliance. Higher 20mg/kg loading doses for obese patients and maintenance dose revision should be considered to reduce non-therapeutic concentrations.3 Limitations include heterogenous/small sample sizes due to data paucity and vancomycin requirement. This can be addressed by involving all ICU’s in PDSA Cycle-2. Due to disparities, both the ePMA system and paper-fluid-balance-charts should be used to identify protocol adherence. Utilisation of digital-infusion-pump data to quantify administration accuracy may offer a promising solution. Piloted multifaceted interventions were successful at improving adherence to/effectiveness of the vancomycin protocol. Findings have informed further interventions and data capture methods for PDSA Cycle-2 implementation across all ICUs.

The OBTAINS study: A nationwide cross-sectional survey on the implementation of extended or continuous infusion of β-lactams and vancomycin among neonatal sepsis patients in China.

Background: Dosing strategies of β-lactams and vancomycin should be optimized according to pharmacokinetic/pharmacodynamic principles. However, there is no available data indicating the implementation of extended infusion (EI) or continuous infusion (CI) administration in the management of neonatal sepsis. Methods: A nationwide cross-sectional survey was conducted and the pediatricians from 31 provinces in China were enrolled. A multidisciplinary team created the questionnaire, which had three sections and a total of 21 questions with open- and closed-ended responses. The survey was then conducted using an internet platform in an anonymous way. The data was eventually gathered, compiled, and examined. To identify the risk factors associated with the implementation of EI/CI, logistic regression was carried out. Results: A total of 1501 respondents answered the questionnaires. The implementation of EI/CI of β-lactams and vancomycin were only available to one-third of the respondents, and the prolonged strategy was primarily supported by guidelines (71.25%) and advice from medical specialists (55.18%). A significant fraction (72.94%–94.71%) lacked a strong understanding of the infusions’ stability. Additionally, it was discovered that more frequent MDT discussions about antibiotic use and the appropriate time pediatricians worked in the neonatal ward were associated with an increase in the use of the EI/CI strategy. Conclusion: The EI/CI strategy in neonatal sepsis was not well recognized in China, and it is necessary to establish a solid MDT team with regularly collaborates. In the near future, guidelines regarding prolonged infusion management in neonatal sepsis should be developed.

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).

Systematic Comparison of Hospital-Wide Standard and Model-Based Therapeutic Drug Monitoring of Vancomycin in Adults.

We aimed to evaluate the predictive performance and predicted doses of a single-model approach or several multi-model approaches compared with the standard therapeutic drug monitoring (TDM)-based vancomycin dosing. We performed a hospital-wide monocentric retrospective study in adult patients treated with either intermittent or continuous vancomycin infusions. Each patient provided two randomly selected pairs of two consecutive vancomycin concentrations. A web-based precision dosing software, TDMx, was used to evaluate the model-based approaches. In total, 154 patients contributed 308 pairs. With standard TDM-based dosing, only 48.1% (148/308) of all of the second concentrations were within the therapeutic range. Across the model-based approaches we investigated, the mean relative bias and relative root mean square error varied from −5.36% to 3.18% and from 24.8% to 28.1%, respectively. The model averaging approach according to the squared prediction errors showed an acceptable bias and was the most precise. According to this approach, the median (interquartile range) differences between the model-predicted and prescribed doses, expressed as mg every 12 h, were 113 [−69; 427] mg, −70 [−208; 120], mg and 40 [−84; 197] mg in the case of subtherapeutic, supratherapeutic, and therapeutic exposure at the second concentration, respectively. These dose differences, along with poor target attainment, suggest a large window of opportunity for the model-based TDM compared with the standard TDM-based vancomycin dosing. Implementation studies of model-based TDM in routine care are warranted.

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

Clinical Efficacy and Safety of Vancomycin Continuous Infusion in Patients Treated at Home in an Outpatient Parenteral Antimicrobial Therapy Program.

Vancomycin is commonly used in outpatient parenteral antimicrobial therapy (OPAT) of Gram-positive infections. Therapeutic drug monitoring and adverse event monitoring pose a challenge. Outcome data of vancomycin in OPAT (vOPAT) are limited. The study aim was to report the safety and efficacy of a structured vOPAT program implemented in the University Hospitals Leuven. The program provides continuous elastomeric infusion of vancomycin at home with biweekly follow-up at the outpatient clinic. Demographics, clinical, biochemical and treatment parameters, target attainment parameters and clinical outcomes were recorded. An e-survey was conducted to assess patient satisfaction. Thirty-five vOPAT episodes in 32 patients were included. During 206 follow-up consultations, 203 plasma concentration measurements were registered with a median vancomycin plasma concentration of 22.5 mg/L (range 6.6–32.0). The majority of concentrations (68.5%) were within the therapeutic range (20.0–25.0 mg/L). Adverse event rates, including drug- (5.7%) and catheter-related (5.7%) events, were low. For 32 vOPAT episodes, a clinical cure rate of 100% was observed. All patients who completed the e-survey were satisfied with their vOPAT course. These findings show that a structured vOPAT program with rigorous follow-up provides safe and effective ambulatory treatment of patients with vancomycin in continuous infusion.