Continuous vs Intermittent Vancomycin Infusion for Infections

Overseen By Aaron M Cook, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Aaron Cook

Must be taking: Vancomycin

Disqualifiers: Chronic kidney disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

56 Participants Needed

Trial Summary

What is the purpose of this trial?

Hospitalized adult participants prescribed vancomycin by their treating physician will be randomized to receive vancomycin via continuous or intermittent infusion and measures of kidney function and injury will be collected.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on how vancomycin is given, so it's best to ask the trial team for guidance.

What data supports the effectiveness of the drug Vancomycin when used for infections?

Research suggests that continuous infusion of vancomycin may reach effective drug levels faster and with fewer side effects compared to intermittent dosing. This method also requires fewer blood tests and may shorten the treatment duration, making it potentially more efficient for treating infections. ^{1 2 3 4 5}

Is continuous or intermittent vancomycin infusion safe for humans?

Continuous infusion of vancomycin may be safer for the kidneys compared to intermittent infusion, as it is associated with a lower risk of kidney damage (nephrotoxicity). However, more large-scale studies are needed to confirm these findings. ^{1 5 6 7 8}

How does continuous vancomycin infusion differ from intermittent infusion for treating infections?

Continuous vancomycin infusion is unique because it achieves therapeutic levels faster and more consistently than intermittent infusion, reducing the time to reach effective drug levels and the number of blood samples needed. It also results in less kidney damage compared to intermittent infusion, making it a potentially safer option for critically ill patients. ^{1 3 5 6 9}

Research Team

Aaron M Cook, PharmD

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for hospitalized adults at the University of Kentucky who need vancomycin treatment, are over 18 years old, and can give consent. It's not for those with chronic kidney disease, recent acute kidney injury, prior vancomycin use within 72 hours (except loading dose), allergy to iohexol, uroepithelial tumors, prisoners, pregnant women or individuals with end-stage kidney disease.

Inclusion Criteria

My doctor has prescribed me two or more doses of vancomycin.

I can sign or have someone legally allowed to sign for me.

I am 18 years old or older.

Exclusion Criteria

I have chronic kidney disease with a GFR under 60.

My kidneys are in the final stage of failure.

I have a bladder cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive vancomycin via continuous or intermittent infusion with kidney function and injury biomarkers collected

5 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of major adverse kidney events

Up to 17 days

Treatment Details

Interventions

• Vancomycin

Trial Overview The study compares two ways of giving vancomycin: a continuous infusion versus an intermittent infusion. Participants will be randomly assigned to one method and their kidney function will be monitored to see which method is safer and more effective.

Participant Groups

Group I: Vancomycin continuous infusion Active Control 1 Intervention

Continuous infusion of Vancomycin

Group II: Vancomycin intermittent infusion Active Control 1 Intervention

Intermittent infusion of vancomycin

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

Who Is Running the Clinical Trial?

Aaron Cook

Lead Sponsor

Trials

2

Recruited

80+

Alexander Flannery

Lead Sponsor

Trials

2

Recruited

90+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Findings from Research

In a study of 150 trauma ICU patients, continuous infusion of vancomycin led to a significantly faster time to reach therapeutic drug levels (2.5 days) compared to intermittent dosing (3.8 days), with a higher success rate in achieving target levels (60% vs 40%).

Continuous infusion also resulted in fewer blood samples needed (1 vs 3 per patient) and reduced nephrotoxicity (21% vs 43%), suggesting it may be a safer and more efficient method for administering vancomycin in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Continuous Infusion Vancomycin Administration in a Critically Ill Trauma Population. Bissell, BD., Riggi, G., Morrison, C.[2021]

In a study of 12 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, both continuous and intermittent infusion of vancomycin effectively eradicated the infections after 10 days of treatment, demonstrating the efficacy of both methods.

No adverse events related to vancomycin were observed during the study, indicating that both infusion methods are safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of continuous infusion versus intermittent infusion of vancomycin in patients with methicillin-resistant Staphylococcus aureus. Jaruratanasirikul, S., Julamanee, J., Sudsai, T., et al.[2013]

Continuous infusion (CoI) of vancomycin significantly reduces the risk of nephrotoxicity compared to intermittent infusion (InI), with a relative risk of 0.6 based on one randomized clinical trial and five observational studies.

There was no significant difference in overall mortality between CoI and InI, indicating that while CoI may be safer regarding kidney function, its impact on survival rates needs further investigation through randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. Cataldo, MA., Tacconelli, E., Grilli, E., et al.[2022]

A review of 9 studies, including 1 pediatric and 8 adult populations, found that while continuous infusion of vancomycin may offer pharmacodynamic advantages, the overall clinical efficacy compared to intermittent dosing remains inconsistent.

The highest quality studies showed some benefits for continuous infusion in pharmacokinetics, but mixed results in clinical outcomes suggest that continuous infusion is not routinely recommended for treating multidrug-resistant gram-positive infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Continuous and Intermittent IV Infusion of Vancomycin: Systematic Review. Man, SS., Carr, RR., Ensom, MH.[2021]

Continuous vancomycin infusion is as effective as intermittent infusion based on a systematic review of six studies, with some evidence suggesting it may be more effective for patients with osteomyelitis.

Continuous infusion is associated with a lower risk of rapid nephrotoxicity and offers advantages such as lower costs and simpler serum level monitoring, potentially allowing for quicker hospital discharges and easier home care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Continuous and intermittent infusion of vancomycin equally effective: review of the literature]. van Maarseveen, EM., Man, WH., Touw, DJ., et al.[2018]

In a study of 129 critically ill patients receiving continuous vancomycin infusion, 29.5% developed acute kidney injury (AKI), indicating a significant risk associated with this treatment method.

Risk factors for AKI included higher body weight, presence of diabetes, increased need for vasopressors, and prolonged treatment duration, especially when vancomycin levels exceeded 30 μg/mL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients. Spapen, HD., Janssen van Doorn, K., Diltoer, M., et al.[2021]

Continuous infusion (CI) of vancomycin may reduce the risk of kidney injury compared to intermittent infusion (II), based on a meta-analysis of six studies, although some studies showed mixed results.

CI allows for more reliable monitoring of steady-state serum concentrations, which may improve dosing accuracy compared to the traditional trough level monitoring used in II, making it a potentially better option for vancomycin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion. Waineo, MF., Kuhn, TC., Brown, DL.[2015]

An updated meta-analysis of seven studies suggests that continuous infusion (CI) of vancomycin may be associated with a non-significant trend towards reduced nephrotoxicity compared to intermittent infusion, although the results were not statistically significant (risk ratio=0.799).

Despite the potential benefits of CI in reducing kidney damage, further research, particularly a large randomized controlled trial, is needed to confirm these findings and establish clear guidelines for vancomycin administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion. Hanrahan, T., Whitehouse, T., Lipman, J., et al.[2022]

Continuous vancomycin infusion (CVI) significantly improves the ability to achieve therapeutic drug levels within 48 hours compared to intermittent infusion (IVI), with 54.8% of CVI patients reaching targets versus only 25.6% of IVI patients.

CVI results in fewer subtherapeutic episodes (0 vs 1) while having a higher number of supratherapeutic episodes (2 vs 1), but overall, there are no differences in treatment success, mortality, or acute kidney injury between the two methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous Vancomycin Infusion versus Intermittent Infusion in Critically Ill Patients. Maluangnon, C., Tongyoo, S., Permpikul, C.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Continuous Infusion Vancomycin Administration in a Critically Ill Trauma Population. [2021]

2. Thailand pubmed.ncbi.nlm.nih.gov

Comparison of continuous infusion versus intermittent infusion of vancomycin in patients with methicillin-resistant Staphylococcus aureus. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

Comparison of Continuous and Intermittent IV Infusion of Vancomycin: Systematic Review. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

[Continuous and intermittent infusion of vancomycin equally effective: review of the literature]. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion. [2015]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Continuous Vancomycin Infusion versus Intermittent Infusion in Critically Ill Patients. [2023]