Potential Two-Dose Dalbavancin Treatment for Osteomyelitis

Dalbavancin is a lipoglycopeptide antibiotic with potent activity against gram-positive organisms.^1,2 It has a uniquely extended half-life of approximately 346 hours due to its long lipophilic side chain, allowing for once-weekly dosing.¹ Although it is currently approved by the US Food and Drug Administration for the treatment of skin and soft tissue infections, its distinctive pharmacokinetic profile has piqued curiosity regarding its place in therapy for infections requiring long durations of antibiotics, such as osteomyelitis. The results of preliminary pharmacokinetic studies demonstrate sustained levels in the bone well above minimum inhibitory concen­tration values of most gram-positive pathogens for durations of up to 8 weeks.³ While there have been a handful of case reports of dalba­vancin (Dalvance) use in osteomyelitis, Rappo and colleagues are the first to conduct a more robust clinical evaluation.⁴

This open-label trial randomized patients with acute or chronic osteomyelitis in a 7:1 fashion to receive either intra­venous (IV) dalbavancin 1500 mg once weekly for 2 weeks or standard of care (SOC) antibiotics for 4 to 6 weeks. Patients must have had clinical and radiological evidence of osteomyelitis, plus an elevated C-reactive protein. Patients with a history of, or presenting with, multiple sites of osteo­myelitis or those who have a prosthesis at the site of infec­tion were excluded. Other notable exclusion criteria included concomitant infections such as endocarditis, necrotizing fasciitis, gram-negative bacteremia, infections secondary to burn wounds, sacral decubitus ulcers, and septic arthritis in an unrelated portion of the body. The primary outcome was the rate of clinical response, defined as resolution of infec­tion without further need for antibiotics, in the clinically evaluable population at 6 weeks.

Seventy patients were randomized to dalbavancin and 10 patients to SOC treatment. Study participants were predom­inantly white males around 50 years of age. All patients underwent debridement with open biopsy, with the most common sites of infection being the tibia, foot, and femur. Both methicillin-sensitive and resis­tant Staphylococcus aureus, as well as coagulase-negative Staphylococcus spp, were the most common caus­ative organisms. All patients in the SOC arm initially received IV vanco­mycin (Vancocin), and 4 patients transitioned to IV linezolid (Zyvox) or IV levofloxacin (Levaquin) to complete the duration of therapy.

Clinical cure at 6 weeks was achieved in 65/67 (97%) and 7/8 (88%) patients receiving dalba­vancin and SOC, respectively. One clinical failure was noted in the SOC arm due to receiving more than 6 weeks of antibiotic therapy. Rates of clinical cure remained high in both arms, at 6 months and 1 year (Table). As expected, patients in the dalbavancin arm expe­rienced significantly shorter inpatient lengths of stay (15.8 vs 33.3 days) and infusion times (1 vs 101.3 hours) compared with the SOC cohort. Treatment-emergent adverse events were noted in 10/70 (14.3%) dalbavancin patients and in none of the SOC patients. The reported adverse events were not thought to be related to the study drug.

In an era in which focus on outpatient parenteral therapy is steadily increasing, dalbavancin is proving to be a prom­ising agent for difficult and long-standing infections, such as osteomyelitis. Due to its compact dosing regimen, dalbavancin may be ideal for patients intolerant of first-line IV or oral antibiotics or with significant compliance barriers. Although therapy may initially seem cost prohibitive, in theory, dalba­vancin decreases labor associated with daily infusions, lab work for monitoring, and the risks and consequences of central line—associated infections. Until more bioavailable and tolerable oral options arrive on the market, 2 doses of dalba­vancin appear to be a safe and convenient treatment option for osteomyelitis without apparent risk for poor long-term outcomes or treatment-emergent resistance.

References:

1. Dalvance (dalbavancin) [package insert]. Madison, NJ: Allergan; 2018. allergan.com/assets/pdf/dalvance_pi. Accessed December 28, 2018.
2. Pfaller MA, Flamm RK, Castanheira M, Sader HS, Mendes RE. Dalbavancin in-vitro activity obtained against gram-positive clinical isolates causing bone and joint infections in US and European hospitals. Int J Antimicrob Agents. 2018;51(4):608-611. doi: 10.1016/j.ijantimicag.2017.12.011.
3. Dunne MW, Puttagunta S, Sprenger CR, Rubino C, Van Wart S, Baldassarre J. Extended-duration dosing and distribution of dalbavancin into bone and articular tissue. Antimicrob Agents Chemother. 2015;59(4):1849-1855. doi: 10.1128/AAC.04550-14.
4. Rappo U, Puttagunta S, Shevchenko V, et al. Dalbvancin for the treatment of osteomyelitis in adult patients: a randomized clinical trial of efficacy and safety. Open Forum Infectious Disease. 2019;6(1):1-8. academic.oup.com/ofid/article/6/1/ofy331/5235615. Accessed December 28, 2018.