Vancomycin Dosing for MRSA Infections
(VIVID Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Hamilton Health Sciences Corporation
Disqualifiers: Vancomycin MIC ≥2ug/mL, Palliative, Dialysis, others
No Placebo Group
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial tests two ways of giving vancomycin to patients with serious MRSA infections. It aims to find out if a simpler dosing method is as effective as a more complex one. Vancomycin is the antibiotic with the most clinical experience for treating MRSA bacteremia.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that you can participate if you are not currently on vancomycin or have been on it for 4 days or less.
What data supports the effectiveness of the drug Vancomycin for MRSA infections?
Research shows that Vancomycin is effective for treating MRSA infections, especially when the drug concentration in the body is carefully monitored and adjusted. Studies suggest that achieving a specific drug concentration (AUC/MIC ratio of ≥400) is linked to better treatment outcomes, reducing the chance of treatment failure.12345
Is vancomycin generally safe for humans?
How is the drug Vancomycin unique in treating MRSA infections?
Vancomycin is unique in treating MRSA infections because it requires careful dosing to achieve specific drug concentration levels in the body, measured by the area under the concentration versus time curve (AUC) divided by the minimum inhibitory concentration (MIC) of the bacteria. This approach helps ensure the drug is effective, especially in critically ill patients, and differs from traditional dosing methods that focus only on trough concentrations.1381011
Eligibility Criteria
Adults with serious MRSA infections confirmed by culture, including blood, lung, brain, bone infections and more. They must join within 4 days of the culture test and can be new to vancomycin treatment or have had it for up to 4 days. Not eligible if they're on dialysis, expected to die within 48 hours, allergic to vancomycin or if their infection resists higher doses of vancomycin.Inclusion Criteria
I am not currently on vancomycin or have been on it for 4 days or less.
I have a serious MRSA infection confirmed by lab tests.
Enrolment within 4 days from date of MRSA culture collection
Exclusion Criteria
History of type 1 hypersensitivity reaction to vancomycin
Vancomycin minimum inhibitory concentration (MIC) ≥2ug/mL
You are receiving end-of-life care and are expected to pass away within the next two days.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive intravenous vancomycin with dosing strategy targeting either a trough level of 10 to 15mg/L or an AUC of 400 to 600 for serious MRSA infections
90 days
Regular monitoring visits for dose adjustments
Follow-up
Participants are monitored for treatment failure, defined as death or microbiologic failure, and other secondary outcomes such as nephrotoxicity and renal replacement therapy
90 days
Treatment Details
Interventions
- Vancomycin (Glycopeptide Antibiotic)
Trial OverviewThis study tests two ways of dosing vancomycin in treating serious MRSA infections: one targets drug levels in the blood (trough level) and the other focuses on how much drug stays in the body over time relative to the bacteria's resistance (AUC/MIC). It checks which method is just as good without being worse by more than a set margin.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Vancomycin targeting trough of 10 to 15mg/LExperimental Treatment1 Intervention
If the patient has not received intravenous vancomycin yet, a loading dose of 25mg/kg (maximum 2g) will be given if the patient is severely ill at the discretion of the physician and pharmacist. The initial dose is 15mg/kg with a maximum dose of 2g. The frequency would be based on creatinine clearance (CrCl) as per the Cockcroft-Gault equation: Q8H if CrCl is \>100mL/min, Q12H if CrCl is 50-100mL/min, Q24H if CrCl is 30- 49mL/min, and Q48H if CrCl is \<30mL/min. Pharmacists can change the initial dose at their own discretion.
Trough level will be done 30 minutes before the 4th dose. For Q48H dosing, a trough level will be done before the second dose. Vancomycin dosing will be adjusted to target trough level of 10 to 15mg/L. If not at target, the pharmacist will adjust the dose based on an assumption of linear pharmacokinetics. Trough will be remeasured before the fourth dose of the new regimen.
Group II: Vancomycin targeting AUC of 400 to 600Active Control1 Intervention
The initial intravenous vancomycin dosing is the same as described above for the trough group.
The AUC target will be 400 to 600, which assumes a MIC of 1ug/mL by broth microdilution.
After the first non-loading dose of vancomycin, patients will have vancomycin level 30 minutes before the next dose. As per the pharmacist's discretion, patient may have an additional vancomycin level one hour after infusion of vancomycin for more accurate estimates. A pharmacist will use a Bayesian software to estimate the AUC and the optimal dose.
Vancomycin is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Vancocin for:
- Severe infections caused by susceptible strains of methicillin-resistant staphylococci
- Enterocolitis caused by Staphylococcus aureus
- Staphylococcal endocarditis
🇪🇺 Approved in European Union as Vancomycin for:
- Severe infections caused by Gram-positive bacteria
- Endocarditis
- Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)
🇨🇦 Approved in Canada as Vancomycin for:
- Severe infections caused by susceptible strains of methicillin-resistant staphylococci
- Enterocolitis caused by Staphylococcus aureus
🇯🇵 Approved in Japan as Vancomycin for:
- Severe infections caused by Gram-positive bacteria
- Endocarditis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McGill University Health CentreMontreal, Canada
Hamilton Health SciencesHamilton, Canada
Kingston Health Sciences CentreKingston, Canada
St. Joseph's Healthcare HamiltonHamilton, Canada
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Who Is Running the Clinical Trial?
Hamilton Health Sciences CorporationLead Sponsor
McMaster UniversityLead Sponsor
Physician Services IncorporatedCollaborator
Canadian Institutes of Health Research (CIHR)Collaborator
The Physicians' Services Incorporated FoundationCollaborator
References
Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid. [2015]The purpose of this study was to determine the clinical cure rate of high-dose vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia (VAP) in critically ill trauma patients. Recent trials suggest that a traditional dose of 1 g q12 hours results in unacceptable cure rates for MRSA VAP. Thus, more aggressive vancomycin dosing has the potential to improve efficacy. Based on pharmacokinetic principles, the goal initial dose at the study center has been 20 mg/kg q12 hours or q8 hours since the 1990s.
Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant Staphylococcus aureus pneumonia. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Vancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend giving an initial loading dose (LD) of 25-30 mg/kg to rapidly increase the serum concentration. However, high-quality evidence for the clinical benefit of LD is lacking. Herein, we aim to examine the association between vancomycin LD and clinical outcome.
Vancomycin pharmacokinetic models: informing the clinical management of drug-resistant bacterial infections. [2017]This review aims to critically evaluate the pharmacokinetic literature describing the use of vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Guidelines recommend that trough concentrations be used to guide vancomycin dosing for the treatment of MRSA infections; however, numerous in vitro, animal model and clinical studies have demonstrated that the therapeutic effectiveness of vancomycin is best described by the area under the concentration versus time curve (AUC) divided by the minimum inhibitory concentration (MIC) of the infecting organism (AUC/MIC). Among patients with lower respiratory tract infections, an AUC/MIC ≥400 was associated with a superior clinical and bacteriological response. Similarly, patients with MRSA bacteremia who achieved an Etest AUC/MIC ≥320 within 48 h were 50% less likely to experience treatment failure. For other patient populations and different clinical syndromes (e.g., children, the elderly, patients with osteomyelitis, etc.), pharmacokinetic/pharmacodynamic studies and prospective clinical trials are needed to establish appropriate therapeutic targets.
Assessment of Appropriateness of an Initial Dosing Regimen of Vancomycin and Development of a New Dosing Nomogram. [2019]Vancomycin is a glycopeptide antibiotic used to treat Gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA). The objectives of this study were to evaluate the appropriateness of the initial dosing regimen of vancomycin, identify factors to be considered in regimen selection and develop a new dosing nomogram. Therapeutic drug monitoring (TDM) data of vancomycin obtained from Seoul National University Hospital from 2011 to 2013 were included in this analysis. The vancomycin trough concentrations at steady-state were estimated using Abbott's PKS software program and then categorized into three levels: subtherapeutic, therapeutic and toxic. The newly developed nomograms were evaluated by analysing the percentage of patients with target vancomycin trough concentration using the data of 2,570 patients of the first TDM cases. Therapeutic level was achieved only in approximately one-fifth of the cases, while 56.0% and 23.8% of the TDMs were considered subtherapeutic and toxic, respectively. As body-weight and creatinine clearance (CrCL) increased, the proportion of patients with a subtherapeutic level increased. Using the newly developed nomogram increased the proportion of patients who achieved therapeutic levels from 23.1% to 45.0% or 13.8% to 36.2% (target, 10-15 and 15-20 mg/L, respectively). These results suggest that the vancomycin concentrations fail to reach the therapeutic level or exceed the safe upper margin of the therapeutic level depending on age, body-weight and CrCL. Considering these factors, the new nomograms provide a strategy to achieve target concentrations of vancomycin more rapidly than existing regimens.
In Silico Pharmacokinetic Study of Vancomycin Using PBPK Modeling and Therapeutic Drug Monitoring. [2021]Vancomycin has been in clinical use for nearly 50 years and remains the first-line treatment option for Gram-positive infections, including methicillin-resistant Staphylococcus aureus (MRSA). There are multiple strategies to monitor therapy and adjust the dose of this antibiotic. AUC24/MIC ratio has been demonstrated to be the best parameter to predict the effectiveness and safety of vancomycin, and a target ratio of ≥400 is recommended. Still, trough and peak serum levels at steady-state conditions have been used in clinical settings as an accurate and practical method to monitor vancomycin.
Vancomycin. A new old agent. [2013]Interest in vancomycin has been rekindled by the emergence of resistant gram-positive pathogens and the improvement in drug purity. The antimicrobial activity, pharmacokinetics, clinical indications, dosing schedules, and adverse reactions of vancomycin are summarized.
Pharmacist-led implementation of a vancomycin guideline across medical and surgical units: impact on clinical behavior and therapeutic drug monitoring outcomes. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Vancomycin is the antibiotic of choice for the treatment of serious infections such as methicillin-resistant Staphylococcus aureus (MRSA). Inappropriate prescribing of vancomycin can lead to therapeutic failure, antibiotic resistance, and drug toxicity.
Evaluation of clinical outcome in children and adolescents receiving vancomycin for invasive infections due to methicillin-resistant Staphylococcus aureus: impact of increasing vancomycin MICs. [2018]Vancomycin is the preferred drug for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in children. In adults, treatment failure with vancomycin has been associated with an area under the curve/24 hrs /MIC (AUC24/MIC) ratio of ≤400 and high minimum inhibitory concentrations (MIC ≥1.0 mg/L). Vancomycin dosing information to ensure optimal AUC24/MIC in the pediatric population remains limited.
Summary of ASHP/IDSA/SIDP vancomycin monitoring recommendations: a focus on osteomyelitis. [2013]Vancomycin has been used extensively for the treatment of Gram-positive bacterial infections, especially in cases of methicillin-resistant Staphylococcus aureus (MRSA). Despite long-term use, many uncertainties have remained regarding appropriate dosing, monitoring, and toxicity risks. In January 2009, a committee representing the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) released recommendations for vancomycin monitoring. As osteomyelitis patients are frequent recipients of vancomycin, this article provides a summary of the recommendations in reference to loading and maintenance doses, trough concentration monitoring, frequency of monitoring, and risk of toxicities.
Vancomycin dosing for pneumonia in critically ill trauma patients. [2022]Vancomycin has been recommended as the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia with a desired trough concentration of 15 to 20 mg/L. The purpose of this study was to evaluate the initial dosing of vancomycin for MRSA pneumonia in critically ill adult trauma patients.
External Validation of a Vancomycin Population Pharmacokinetic Model and Developing a New Dosage Regimen in Neonates. [2022]Label="BACKGROUND AND OBJECTIVE" NlmCategory="OBJECTIVE">Vancomycin is the drug of choice in the treatment of MRSA infections. In a published vancomycin population pharmacokinetic study on neonates in Singapore healthcare institutions, it was found that vancomycin clearance was predicted by weight, postmenstrual age, and serum creatinine. The aim of this study was to externally validate the vancomycin population pharmacokinetic model to develop a new dosage regimen in neonates, and to compare this regimen with the existing institutional and NeoFax® dosage regimens.