Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial

Read article Submitted by: Submitted by: Dr Chloe Borgas, Dr Celia Cooper Women’s and Children’s Hospital, AdelaideBackground: Staphylococcus aureus bacteremia remains a major global cause of morbidity and mortality in children. Long acting intravenous lipoglycopeptides such as dalbavancin offer a promising alternative to current therapy given their very long-acting pharmacokinetic properties, though robust data is lacking.The DOTS Randomised Controlled Trial randomised 200 people aged over 18 to receive either two-dose intravenous dalbavancin (1,500mg on days 1 and 8) or standard IV therapy (4–8 weeks of cefazolin/penicillin or vancomycin/daptomycin as appropriate) for the maintenance treatment of complicated Staphylococcus aureus bacteremia. Complicated infection was defined as >72 hours of ongoing fever from effective treatment commencement, evidence of metastatic infection, implanted prostheses, endocarditis not excluded or repeat positive blood cultures 2 to 4 days after initial blood cultures.Main Findings: 1. For the composite primary outcome (using Desirability of Outcome Ranking, DOOR), incorporating health related quality of life, safety complications, mortality and infectious complications, dalvabancin was not superior (95 % CI, 39.8–55.7 %) to standard treatment.2. For the secondary outcome assessing clinical efficacy alone outcome (determined by composite measure of clinical failure, infectious complications or mortality) dalbavancin met criteria for non-inferiority relative to standard therapy (dalbavancin: 73/100; standard: 72/100. Difference 1.0%, 95% CI −11.5% to 13.5%).Dalbavancin was well tolerated, with a comparable safety profile to standard therapy. There was interestingly no increased quality of life reported in the adult study population group, however these experiences and preferences may be difficult to extrapolate to paediatric groups which have unique needs.The trial was restricted to adults with modest sample size. The composite DOOR metric has a number of potential pitfalls and interpretation is limited when multiple subjective elements are included. Further, DOOR measures have decreased sensitivity to mortality increases and risk grouping of outcomes of significantly different practical severities into single components.1Critically, in this study dalbavancin was used as a consolidation measure once bacteremia had already been demonstrated cleared, whereas in most paediatric cases, oral antibiotics would be standard recommended therapy at this stage anyway. However, this still represents promising potential for use in remote and low resource settings, poorly compliant patients and those with difficulty tolerating oral medications. This must however be weighed with the increased cost of administering IV medications, which was not examined through this trial.Whilst high quality studies of the same nature have not been published in children, several emerging case studies present promising examples of safe and effective real-world use in paediatric populations, 2,3 which is supported by a recent systematic review by Caselli et al 4.Take home message: Whilst dalbavancin did not outperform standard therapy in DOOR, its comparable efficacy, safety and convenient dosing present a compelling alternative to long term IV antibiotic use. However, in in an era favoring early step down to oral therapy, Dalbavancin may be still searching for its role in management of paediatric complicated S Aureus bacteremia.