Dalbavancin is a semisynthetic lipoglycopeptide antibiotic which received FDA approval in 2014 for skin and soft tissue infections.1 It has also been used recently for treatment of osteomyelitis with positive results, although FDA approval has not been given for this indication as of 2020.2,3 Dalbavancin targets gram-positive organisms, most notably methicillin-resistant Staphylococcus aureus (MRSA), as it has a mechanism of action that breaks up cell wall synthesis by targeting the terminal d-alanyl-d-alanine residues of the cell wall.1 In fact, some studies have found it to be superior to vancomycin due to its increased interaction and binding affinity toward this target, which allows for more potent bactericidal activity, particularly towards staphylococcus species.1,4 It also boasts a significantly longer half-life allowing for less frequent dosing compared to agents such as vancomycin, giving it an advantage to other IV medications in the outpatient setting.5 Additionally, Dalbavancin is generally well tolerated, with no reported differences in adverse events in clinical trials vs comparator groups.1
Due to its long half-life, improved efficacy, and lack of adverse events, Dalbavancin provides an attractive option for treating infections where longer durations of outpatient therapy are required, particularly for patients where continued IV access may represent a challenge. Given the data that exists for efficacy in osteomyelitis, the drug may be similarly potent against primary bloodstream infections (BSI) or infective endocarditis (IE), both of which often require sustained inpatient IV antibiotic therapy. While significant data exists to support the use of other glycopeptide derivatives to treat BSI or IE, data specifically for Dalbavancin is lacking, though limited retrospective data indicates promise. Bryson-Cahn et al. reviewed the use of Dalbavancin in intravenous drug users (IVDU) with serious methicillin-sensitive Staphylococcus aureus (MSSA) infections and found that over half of the patients demonstrated clinical response.6 Hidalgo-Tenorio et al looked at the use of Dalbavancin as consolidation therapy for IE or BSI and found that once stabilized, patients had favorable outcomes completing therapy with Dalbavancin.7 Another study looked at the use of Dalbavancin for more serious infections, though again, limited primarily to patients already stabilized on routine therapy at the start of treatment.8 The lack of data supporting Dalbavancin is indicative of its infrequent usage for BSI and IE despite its potential advantages to the standard of care.
One area where Dalbavancin is being used off-label for Staphylococcus IE or primary BSI is with patients who are leaving against medical advice (AMA), or in patients who are refusing necessary medical procedures for long term intravenous antibiotic therapy such as a peripherally inserted central catheter (PICC). Historically speaking, patients who leave AMA have a statistically significant increased risk of 30-day readmittance to the hospital.9 These same patients were also found to have increased rates of homelessness, comorbidity, and mortality at one-year follow-up.10 For these severe infections such as endocarditis and bacteremia, especially with gram positive organisms such as MRSA, even full course effective IV treatment with vancomycin or daptomycin have poor outcomes with high mortality rate.11,12 Therefore, patients who plan to leave AMA with such infections have even worse outcomes with further increased mortality.13,14 While studies are ongoing on how to combat these disparities, these patients represent increased financial and workload burden on the hospital system and healthcare workers.13 Due to its aforementioned long half-life, providing patients with a dose of Dalbavancin prior to leaving AMA reduces the need for a PICC line while also decreasing hospital length. If efficacious, transitioning IV antibiotic care to the outpatient setting in patients who would leave AMA without proper follow up may be a more elegant solution for the increased cost and mortality seen in this population. For skin and soft tissue infections, outpatient antibiotic programs have demonstrated their ability to improve cost by greater than 53%.15
Another potential population that could benefit from the use of Dalbavancin are patients who are not ideal candidates for IV access or prolonged hospital stays. Most notably, this would be for patients who have a history of IVDU or who cannot tolerate PICC placement for other reasons. Historically speaking, patients who inject drugs have been discouraged from receiving IV access in the outpatient setting, due to the potential increased risk of drug use through the catheter, or increased risk of catheter related complications such as infections.16 While updated literature reviews seem to suggest this risk may be overstated, IV drug users still have an increased risk of readmittance with outpatient enteral antibiotic therapy compared to non-users.17 Discharging these patients with the long-acting therapy of Dalbavancin without the increased risk of outpatient IV access may mitigate this concern for abuse, while also providing significant cost savings compared with prolonged inpatient stay and inpatient antibiotics.17 Other than IV drug users, some patients cannot tolerate PICC access due to recent catheter infection, immunosuppression, or simply inability of healthcare staff to gain access. These patients would also benefit from outpatient Dalbavancin therapy due to its excellent toleration and long half-life.
Given previous retrospective studies showing effectiveness of Dalbavancin, as well as high morbidity and financial implications associated with inpatient antibiotic therapy, this retrospective chart analysis was performed to analyze the effectiveness of Dalbavancin in primary bloodstream infections and infective endocarditis in patients who did not tolerate long term IV antibiotic therapy.