Dalbavancin has submitted FDA approval to join Oritavancin as a single dose antibiotic for skin and soft tissue infections, so lets take a look at this $6,000 / dose drug – that is only reimbursed as an outpatient (ie, if the patient is admitted, you can not give the drug, you’re out $6,000).
Dalbavancin 1.5 grams as a single IV dose was compared to 1 gram followed by 500mg seven days later. This was carried out at 60 centers (double blind, but pharmacist unblinded – 1:1 in blocks of 4) from April 2014-March 2015 across US, Europe, Russia, and South Africa. Patients were required to have at least 75 cm^2 of erythema, and included not just plain ol’ cellulitis (48% of patients), but also “major abscess” (abscess that required an I&D with 5cm erythema in all directions beyond central induration – 25% of patients) and traumatic wounds/surgical site infections (defined as >5cm of erythema from wound margins – 27% of patients). Patients were also required to have one of the following: wbc >12 (37% of patients), >10% immature neutrophils (15%), or temp >38C within the last 24 hrs (82%), and to have been antibiotic naive except for a one time dose of a short acting antibiotic. Those with catheter infections, infected devices, diabetic foot ulcerations, decubitus ulcers, or perirectal abscesses were excluded. 11.5% of patients were diabetics, 30% were IV drug users, and 16% had HepC.
Primary endpoint was >20% reduction in erythema at 48-72 hours, with resolution or improvement of signs/symptoms was performed at day 14 and 28.
Here’s the rub: In addition to being antibiotic naive, empirically, Flagyl was allowed for suspected anaerobes as well as aztreonam (or for gram-negative pathogens identified post-culture). Aztreonam was given 3.4% of the time for the single dose regimen, and 6.6% of the time for the two dose regimen. Flagyl was used 6.6% and 4.3% of patients through day 14 for the single and 2 dose regimens, respectively. So, about 10% of patients received additional antibiotics. They had initially only planned to sample 410 patients, only to find on interim analysis they needed to boost their sample size to attempt to reach “the assumption of a 90% response rate.” – which they still did not reach. Plus, I have to wonder how they were able to figure out if a patient actually had a temp within the last 24 hours or if “they felt warm yesterday.”
Clinical response at 48-72 hours was 81.4% vs 84.2% for the one time and 2 dose regimen respectively. Response rates for IV drug users for the same time frame was 89.5% and 86%.
More rub: 45.6% of patients were hospitalized – with the median duration being 8 days, even though the outcome rates (at 48-72hrs) were similar (83.3% vs 82.4%) vs those treated as an outpatient (82.1% vs 82.7%).
More more rub: no organism had an MIC to vancomycin >2 ug / ml.
Plus side: for those with Staph Aureus bacteremia, all 7 patients in the two dose regimen and 7/8 patients in the single dose cleared their bacteremia on repeat cultures. ADRs were minimal, with only nausea reported >2% of the time
I think there are certain instances for this drug to be used– for the patient that has used 1 or 2 other antibiotics and wants to avoid an admission, or the patient that can not fill their antibiotic script – but dalbavancin just simply is not tested in this type of patient. An 80-90% clinical cure rate is simply not acceptable for such an expensive medication, particularly when local antibiograms may yield cheaper alternatives, and when less expensive alternatives such clindamycin or bactrim have shown ~80-90% clinical cure rates for skin and soft tissue infections