A 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.
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.
*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.