What side effects are associated with this type of intervention?

The most common treatments for Staphylococcus aureus, particularly intravenous vancomycin, are associated with several side effects. Vancomycin can cause nephrotoxicity, which is a significant concern, and infusion-related reactions such as 'red man syndrome.' Teicoplanin, another glycopeptide, tends to be better tolerated but can still cause nephrotoxicity and infusion reactions. Telavancin, a lipoglycopeptide, has a higher rate of toxicity, including taste disturbances, nausea, vomiting, and renal dysfunction, and is also associated with teratogenicity. Linezolid, an oxazolidinone, can cause myelosuppression, peripheral neuropathy, and lactic acidosis with prolonged use.

What prior FDA approvals exist?

FDA-approved treatments for Staphylococcus aureus, particularly MRSA, include vancomycin, which inhibits cell wall synthesis. Similar treatments include linezolid, which inhibits protein synthesis, daptomycin, which disrupts cell membrane function, and ceftaroline, a fifth-generation cephalosporin with broad-spectrum activity. These drugs are used in cases where vancomycin is ineffective or resistance is present.

What other types of research exist?

Promising novel alternatives to intravenous vancomycin for treating Staphylococcus aureus include linezolid, ceftaroline, daptomycin, telavancin, and oritavancin. These agents have shown efficacy in clinical trials and studies, with some demonstrating comparable or superior outcomes to vancomycin.

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Glycopeptide Antibiotic

Vancomycin Dosing for MRSA Infections (VIVID Trial)

Q: What is the mechanism of action of this treatment?

The most common treatments for Staphylococcus aureus infections include vancomycin, daptomycin, linezolid, and ceftaroline. Vancomycin inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of cell wall precursors, preventing proper cell wall formation. Daptomycin disrupts cell membrane function by inserting into the bacterial membrane and causing rapid depolarization, leading to cell death. Linezolid inhibits protein synthesis by binding to the bacterial 50S ribosomal subunit, preventing the formation of a functional 70S initiation complex. Ceftaroline, a beta-lactam antibiotic, also inhibits cell wall synthesis by binding to penicillin-binding proteins. These mechanisms are crucial for effectively treating Staphylococcus aureus infections, especially in cases of methicillin-resistant Staphylococcus aureus (MRSA), as they target essential bacterial processes, leading to bacterial cell death and resolution of the infection.

N/A

Recruiting

Led By Anthony D Bai, MD

Research Sponsored by Hamilton Health Sciences Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adult patients with serious MRSA infections based on culture results including bacteremia, pneumonia, pleural space infection, central nervous system infection, bone infection, septic arthritis, prosthetic joint infection, and deep abscess

Be older than 18 years old

Must not have

Patients on intermittent hemodialysis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 90 days

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

This 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.

What are the potential side effects?

Vancomycin may cause kidney damage, hearing problems, low white blood cell counts leading to increased infection risk, allergic reactions like rashes or anaphylaxis (severe), infusion-related reactions such as redness or pain at injection site.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have a serious MRSA infection confirmed by lab tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am on intermittent hemodialysis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 90 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~90 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 90 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Treatment failure

Secondary study objectives

Day 3 AUC

Major adverse kidney events

Renal replacement therapy

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Vancomycin

2020

Completed Phase 4

~7920

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Staphylococcus aureus infections include vancomycin, daptomycin, linezolid, and ceftaroline. Vancomycin inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of cell wall precursors, preventing proper cell wall formation. Daptomycin disrupts cell membrane function by inserting into the bacterial membrane and causing rapid depolarization, leading to cell death. Linezolid inhibits protein synthesis by binding to the bacterial 50S ribosomal subunit, preventing the formation of a functional 70S initiation complex. Ceftaroline, a beta-lactam antibiotic, also inhibits cell wall synthesis by binding to penicillin-binding proteins. These mechanisms are crucial for effectively treating Staphylococcus aureus infections, especially in cases of methicillin-resistant Staphylococcus aureus (MRSA), as they target essential bacterial processes, leading to bacterial cell death and resolution of the infection.

Telavancin: TD 6424, TD-6424.