New Antibiotic Dalbavancin: Should we use this in the ED?

New Antibiotic Dalbavancin: Should we use this in the ED?

2016-11-11T19:18:19+00:00

antibiotic ivA new antibiotic will soon be approved for skin and soft tissue infections (SSTIs): dalbavancin. The company behind the drug will likely begin marketing heavily to emergency physicians as many patients with SSTIs seek care in the Emergency Department (ED). However, should we seriously consider dalbavancin as an addition to an ED’s arsenal against SSTIs and should it change our practice?

Since we are talking about a new medication, my disclaimer: I have no conflicts of interest to disclose.

Dalbavancin: About the Drug

  • Bacterial coverage: Think of it as vancomycin – great at covering gram + bacteria (including MRSA)
  • Dosing: Two-dose regimen given once weekly as a 30 minute infusion
  • Adverse events: Similar to any antibiotic (nausea, vomiting, diarrhea, rash)

Evidence Thus Far*

Two phase III trials were just completed (DISCOVER 1 and DISCOVER 2), where DISCOVER stands for “Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response.”

These non-inferiority trials have not been published in a peer reviewed journal at the time of writing this, but the data has been submitted to the FDA for approval.

Population Mostly white patients (~90%) needing at least 3 days of IV antibiotic therapy for SSTI (locations: North America, Europe, South Africa, Asia)
Intervention Randomized double-blind once weekly dalbavancin x 2 weeks
Comparison IV vancomycin for at least 3 days with an option to switch to linezolid PO to complete 10-14 days of therapy
Outcome (primary) Halt of lesion spread and resolution of fever at 72 hours
Conclusions Dalbavancin is non-inferior to IV vancomycin +/- linezolid

Should we use dalbavancin in the ED?

The patients in DISCOVER 1 and 2 trials were all deemed to need 3 days of intravenous antibiotics. From an ED perspective, these patients are sick enough to be admitted. It is unlikely that emergency physicians will discharge a potentially septic patient with an obvious skin source regardless of the antibiotic’s week-long pharmacokinetics. We might be tempted to treat less sick SSTIs with dalbavancin – even those we would treat with POs and discharge home. However, in a patient with a stable SSTI we really shouldn’t be using ANY IV antibiotics, as I posted on ALiEM earlier.

Once weekly dosing of dalbavancin is attractive and could potentially eliminate some compliance issues with 10-14 days of BID-QID oral antibiotic therapy that we currently use. However, dalbavancin will require a second ED visit for a second infusion. It could be argued that patients with very poor compliance are just as unlikely to return to the ED for a follow up second infusion-visit as they are to take their oral antibiotics, especially if they defervesced and are feeling much better after three days.

One of the biggest factors, especially for county hospitals taking care of underserved or uninsured patients, is the cost. Pricing is still a secret; however, my colleagues and I have been quoted different prices, ranging from $1,000-2,500 per infusion, not accounting for costs of two ED visits and other non-medication related charges. The DISCOVER 1 and 2 trials have only shown that dalbavancin is non-inferior to standard care for admitted SSTIs: much less expensive IV vancomycin followed by an oral antibiotic. Although linezolid was the subsequent oral antibiotic studied in these trials, there is no reason why using bug susceptibilities to choose another inexpensive oral antibiotic (like trimethoprim/sulfamethoxazole) would be inferior.

There may be a place for dalbavancin in the treatment of gram positive infections, but just not in the ED. Although no data exists yet on osteomyelitis, dalbavancin could theoretically spare patients from central line placements and prolonged home antibiotic infusions.

Final Thoughts

Antibiotics are not high-profit medications. Any company who invests resources to study a new antibiotic in the age of multi-drug-resistant bugs should be commended. That being said: Dalbavancin is not an antibiotic that should be first or second line treatment for SSTIs in the ED. Even if the company adjusts the price to <$100 per dose, hospital antimicrobial stewardship programs need to rationalize and limit the use of this new antibiotic for cases when cheaper non-inferior treatments have failed. Advertisers’ persuasion of better compliance for “high-risk patients,” convenience, and non-inferiority, are not enough to challenge the standard care of SSTIs in the ED.

Would love to hear your thoughts.

Reference

*The available data on dalbavancin is limited as it is not published. The PICO was synthesized using limited information available from the manufacturer’s abstract posters.


Zlatan Coralic, PharmD

Zlatan Coralic, PharmD

Assistant Clinical Professor
Emergency Department Clinical Pharmacist
University of California, San Francisco (UCSF)
  • hl88

    Interesting post. You have good points.

    However, I am not sure that your conclusion are right for the following reasons. 1) Dalbavancin(Dalba) is a potent antibiotic against S. aureus and other target pathogens, including MRSA; 2)Dalba Efficacy of once-weekly dosing regimen in Patients who were significantly ill and the skin infections studied are established in multiple Phase III studies; 3) Once-weekly dosing regimen of Dalba is easier and more compliant than other oral medications of 10-14 days. 4)According to Jauregui, et al. Clin. Infect. Dis. 2005;41:1407-1415, Dalba can potentially save up to $12,187 when hospital admission is avoided for many SSTI patients compared to 5 days of inpatient treatment with vancomycin or daptomycin.

    • Zlatan Coralic

      Hi hl88,

      Thank you for your feedback. To address some of your
      comments:

      1) Dalbavancin could be a good antibiotic against gram-positive infections. In the age of multi-drug resistant organisms, we are very happy to see another option available to clinicians.

      2) The two most recent phase III that were submitted to the FDA are cited above. All other preceding trials were not strong enough to gain FDA approval.

      3) Theoretically, once weekly dosing of dalbavancin appears to be more convenient and has the potential to improve compliance; however, no credible published data exists, and I hesitate making any conclusions about compliance in patients outside of controlled clinical trials. Further, for a stable SSTI each dalbavancin infusion would require an ED visit, a potentially very long wait in the waiting room of a busy department, initiation of an IV line, medication preparation, thirty minute infusion, monitoring, and discharge – times two; and a very very expensive bill for the two ED visits. I am not sure how much easier this is for the ED patient or the provider compared to a $4 generic efficacious oral antibiotic. Nevertheless, the bottom line in all of this is the proven clinical efficacy – and at best, dalbavancin is as good (not better) as the current standard care of admitted patients.

      4) The cited article is from 2005 and has many limitations, including the inherent bias as it was sponsored and written by Vicuron pharmaceuticals (makers of dalbavancin at that time). Few years after this article, Pfizer acquired the rights to the drug and quickly dropped it due to feedback from “regulators who were unconvinced by the data offered for its support;” data that I assume included this large 2005 trial. (source: http://bit.ly/1so4Z9d) Further, I am unable to find the potential savings of $12,187 in the article that you cite. Only the following conclusion is made about the cost by the authors, “… the impact of dalbavancin’s weekly dosing schedule on patient compliance, hospitalization, or health care costs cannot be ascertained from our study.” That $ amount was frequently used in the pitches to investors by the company and inappropriately referenced (http://bit.ly/1rc919d). In my search I was unable to find the detailed methods on how this cost was derived. Any guidance would be much appreciated.

      Thanks for the feedback and the discussion!

      • Guest

        An update on cost…