Dalbavancin in Bone and Joint Infections: A Systematic Review

Abstract

Background: Approved for acute bacterial skin and skin structure infections, dalbavancin (DBV) has gradually acquired over the years a role as an off-label treatment for several infections caused by Gram-positive bacteria even in other anatomical sites. Osteoarticular (OA) infections are one of the most difficult-to-treat infections and, since the absence of recommendations, clinicians use different and heterogenic DBV dosing schedule regimens for the off-label treatment of osteomyelitis, spondylodiscitis, and septic arthritis. Our aim is to systematically review the current literature to describe DBV administration schedules and their outcome in OA infections.

Methods: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the use of DBV in OA infections were included. We conducted a literature search on PubMed and Cochrane Controlled Trials.

Results: A total of 23 studies and 450 patients were included, prevalently male (144/195, 73.8%) and diabetic (53/163, 32.5%). Overall, 280 (280/388, 72.2%) osteomyelitis, 79 (79/388, 20.4%) spondylodiscitis, and 29 (29/388, 7.5%) septic arthritis were considered. Staphylococcus aureus (164/243, 67.5%) was the most common pathogen isolated. A previous treatment failure (45/96, 46.9%) was the main reason for a switch to a long-acting antibiotic. Most patients were successfully cured with DBV (318/401, 79.3%). A source control was performed in most patients with a favourable outcome (80.4%), while MRSA was prevalently isolated in people with an unfavourable outcome (57%). While a higher percentage of success was found in people who received three doses of DBV 1 week apart (92.3%), a higher rate of treatment failure was recorded in cases of when the DBV cycle was composed of less than two or more than four doses (27.8%).

Conclusions: DBV has shown to be effective as a treatment for OA infections. The most favourable outcome was found in patients receiving three doses of DBV and with an adequate surgical management prior to antibiotic treatment. Although a rigorous administration schedule does not exist, DBV is a viable treatment option in the management of OA infections.

Keywords: DBV; Gram-positive; Systematic review; arthritis; bone; dalbavancin; joints; osteoarticular infections; osteomyelitis; review; spondylodiscitis.

Figure 1

Research term combinations and flow-chart of the study selection process. Acronym used—PJIs: prosthetic joint infection, ABSSSIs: acute bacterial skin and soft tissues infections, BSIs: bloodstream infections.

Figure 2

Venn diagrams comparing the prescription of antimicrobials before starting a DBV treatment (up) and while administering DBV (down). Every circle represents a combination of antibiotic molecules pooled based on their antibacterial spectrum of activity. The sizes of the circles are proportional to the number of patients that were prescribed with the corresponding therapeutic regimen. Combination therapies were considered for their global antibacterial spectrum. Percentages refer to the single category. Grouping was assessed as follows: anti-Gram-positive (cefazolin, oxacillin, amoxicillin/clavulanic acid); anti-MRSA po (rifampin, linezolid, tedizolid, clindamycin); anti-MRSA IV (vancomycin, daptomycin, teicoplanin, ceftaroline); anti-MRSA and anti-Gram-negative po (TMP/SMX, tetracycline, quinolone Anti-MRSA); and anti-Gram-negative IV (ceftriaxone, ertapenem, meropenem, gentamycin, fosfomycin, piperacillin/tazobactam).

Figure 3

Favourable versus unfavourable outcomes in different administration schedules of DBV: in the histogram every column represents the total number of patients treated with a specific number of doses of DBV, regardless of the interval of administration. The percentages represented in red and blue refer, respectively, to unfavourable and favourable outcomes.