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Is an Expensive New Antibiotic Worth the Cost?

— Once-weekly dalbavancin might reduce admissions, but it introduces new concerns.

MedpageToday

Salim Rezaie, MD, is the founder and editor of . A version of this article originally appeared at .

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?

Dalbavancin 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.

The best available evidence of IV dalbavancin comes from a of 1,303 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.)

There were two arms, each receiving 10 to 14 days of therapy:

  1. IV vancomycin (15 mg/kg) every 12 hours for at least 3 days with the option to switch to oral linezolid (600 mg) every 12 hours
  2. IV dalbavancin (1 g) on day one, followed by 500 mg IV on day eight (IV or oral placebo given every 12 hours to complete treatment)

A total of 79.7% of the dalbavancin group and 79.8% of the vancomycin-linezolid group had successful primary outcome at 48 to 72 hours, which was cessation of spread of infection-related erythema and the absence of fever. There were also equivalent outcomes with MRSA infection.

Limitations of IV Dalbavancin

  1. 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.
  2. When evaluating the patient population of the two studies, half these patients met sepsis criteria (i.e., a focus of infection and two of the four 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 aseptic 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.
  3. The cost of the antibiotic has been quoted at about $1,100 to $1,500 per vial. Each vial is 500 mg, so two vials for the first dose and one vial for the second dose would be anywhere from $3,300 to $4,500 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.
  4. 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.

Intravenous dalbavancin does appear to be an alternative antibiotic for skin and soft tissue infections that is noninferior to vancomycin-linezolid. Only time will give us better clarification of cost and future bacterial resistance issues.