Is this expensive new therapy worth the cost? Maybe. With a half life of two weeks, once-weekly Dalbavancin might reduce admissions, but it introduces new concerns about antibiotic resistance and high costs.
Is this expensive new therapy worth the cost? Maybe. With a half life of two weeks, once-weekly Dalbavancin might reduce admissions, but it introduces new concerns about antibiotic resistance and high costs.
Patients with extensive cellulitis or large abscesses often require hospital admission for intravenous antibiotics. Most infections are due to Staphylococcus aureus and streptococci, but there are a number of infections that are due to Methicillin-Resistant Staphylococcus Aureus (MRSA), which can be a treatment challenge for many reasons including antibiotic toxicity, bacterial resistance, and/or lack of an oral formulation to treat the infection. This greatly adds to hospitals costs and the other associated risks of inpatient stays. Outpatient treatment of these patients is cost saving and increases patient satisfaction. What if there was a treatment that was as effective as the usual once or twice daily inpatient treatments?
What is Dalbavancin?
This is a lipoglycopeptide antibiotic with activity against gram-positive pathogens including MRSA. The terminal half-life of the antibiotic is 2 weeks. Put simply, this antibiotic is like Vancomycin with a long half-life.
What is the Best Available Evidence for IV Dalbavancin?
A double-blinded, international, multicenter, randomized trial of 1303 patients with pooled analysis of DISCOVER 1 and DISCOVER 2 trials. DISCOVER stands for “Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response.” (Patients who received antibiotics within 14 days before randomization were excluded from this study)
What Were the Arms of the Above Study?
There were 2 arms, each totally 10 – 14 days of therapy:
- IV vancomycin (15 mg/kg) every 12 hours for at least three days with the option to switch to oral linezolid (600 mg) every 12 hours.
- IV dalbavancin (1 g) on day one, followed by 500 mg IV on day 8 (IV or oral placebo given every 12 hours to complete treatment).
What Were the Results of the Above Study?
79.7% of the dalbavancin group and 79.8% of the vancomycin-linezolid group had successful primary outcome at 48 – 72 hours, which was cessation of spread of infection-related erythema and the absence of fever. There were also equivalent outcomes with MRSA infection.
What are some of the Limitations of IV Dalbavancin?
- With such a long half-life, there is going to be a period of time that the antibiotic will not be at therapeutic levels. Will this equate to more resistant bacteria? This is not really clear and only time will really tell. Also consider that once weekly dosing could help with antibiotic compliance issues, which may reduce bacterial resistance.
- When evaluating the patient population of the two studies half these patients met sepsis criteria (i.e. a focus of infection and 2 of the 4 SIRS criteria) and the other half did not. Currently the standard of care for sepsis patients is these patients would all require admission for clinical monitoring and IV antibiotics to ensure there is no progression to oseptic shock and not one dose of IV antibiotics with a discharge home. As for the other half of patients who did not meet SIRS/Sepsis criteria, IV antibiotics would be overkill and an oral regimen of antibiotics would suffice on an outpatient basis without the need for IV antibiotics.
- The cost of the antibiotic has been quoted at about $1100 – $1500 per vial. Each vial is 500mg, so two vials for the first dose and one vial for the second dose would be anywhere from $3300 – $4500 dollars for a full treatment. This may not be a viable option for small EDs or county EDs, but there may be a patient population that this would benefit.
- This is not really a limitation, but it is important to realize that the sponsoring drug company of Dalbavancin (Durata Therapeutics) collected all the data, monitored the study conduct, and performed the statistical analysis. This does not mean that the study is not valid or should be ignored.
What is the Bottom Line for use of IV Dalbavancin?
IV Dalbavancin does appear to be an alternative antibiotic for skin and soft tissue infections that is non-inferior to vancomycin-linezolid. Only time will give us better clarification of cost and future bacterial resistance issues.
Salim Rezaie, MD is the founder and editor of REBEL EM
Editor’s Note:
This study looks at one of many new pharmaceuticals whose sole purpose is to find cost effective ways to balance the risk of outpatient treatment with the high cost of hospitalization. Many patients will fall in the gray zone for the decision to admit and monitor. For example, while it’s true that a low grade fever with an attendant mild tachycardia in a patient with a known focus of infection would currently meet the necessary criteria for admission and monitoring, the question remains: is that the only safe and effective way to treat this patient? With average costs of hospitalization approaching $2000/day, $4500 for a week’s therapy, while expensive, could actually represent a net savings with no significant risk to the patient.
REFERENCE
Boucher, HW et al. Once-Weekly Dalbavancin versus Daily Conventional Therapy for Skin Infection. N Engl J Med 2014; 370:2169-79. PMID: 24897082