DOTS trial data support dalbavancin for Staph aureus bacteremia
According to Megan Klatt, PharmD, BCIDP, DPLA, infectious diseases and antimicrobial stewardship clinical pharmacist at the University of Kansas Health System, 2 studies from the past year stand out for antimicrobial stewardship teams. The DOTS trial (NCT04775953) evaluated dalbavancin (Dalvance, AbbVie) as an alternative to prolonged intravenous therapy for complicated Staphylococcus aureus bacteremia.1
Complicated S aureus bacteremia typically requires 4 to 6 weeks of intravenous antibiotic therapy, carrying risks of catheter complications and added nursing and laboratory costs. Carbapenem-sparing options for extended-spectrum beta-lactamase (ESBL) producing Enterobacterales remain a stewardship priority as carbapenem use drives further resistance. Both questions have persisted since the original MERINO trial linked piperacillin-tazobactam to a mortality disadvantage against meropenem in 2018.2
The phase 2b DOTS trial randomized 200 adults with complicated S aureus who had cleared their baseline blood cultures before assignment to dalbavancin or 4 to 6 weeks of standard intravenous antibiotic therapy.1 Investigators dosed dalbavancin recipients with two 1500-mg infusions one week apart, leveraging the drug's fourteen-day half-life to sustain effective plasma concentrations without ongoing central-line access.1 The primary outcome, desirability of outcome ranking at day 70, yielded a 47.7% probability of a more desirable outcome with dalbavancin, missing the trial's prespecified superiority threshold against standard care.1
Despite the headline non-superiority result, event rates for treatment failure and adverse outcomes were similar across both arms, according to Platt, suggesting dalbavancin remains a reasonable option for patients who complete initial intravenous therapy and clear their bacteremia. The recent approval of a generic dalbavancin formulation is expected to widen access to the 2-dose regimen, sparing eligible patients weeks of catheter-dependent infusion therapy and the associated nursing and laboratory costs.
"Event rates were very similar between the 2 arms, so this would suggest dalbavancin may be considered a treatment option for these patients with complicated Staph aureus bacteremia," Platt told Contagion.
PeterPen interim results reopen piperacillin-tazobactam debate for ESBL infections
A separate interim analysis from the PeterPen trial (NCT03671967), presented at the ESCMID Global 2026 meeting in Munich, Germany, revisited whether piperacillin-tazobactam can safely treat bloodstream infections caused by ESBL-producing organisms.
The original MERINO trial linked piperacillin-tazobactam to higher 30-day mortality than meropenem among patients with ceftriaxone-resistant E coli or Klebsiella pneumoniae bloodstream infections, prompting many centers to shift toward carbapenem-first therapy for ESBL-producing organisms.2 The trial was stopped early after an interim analysis of roughly 340 patients showed a mortality signal, leaving it underpowered, and investigators did not use extended infusion dosing for piperacillin-tazobactam.2
Frequently Asked Questions
What did the DOTS trial show about dalbavancin for Staph aureus bacteremia?
The trial found dalbavancin was not superior to four to six weeks of standard intravenous therapy for the primary endpoint, but event rates were similar between arms, supporting its use as a treatment option after initial bacteremia clearance.
How does the PeterPen trial differ from the original MERINO trial?
PeterPen uses extended infusion dosing for both piperacillin-tazobactam and meropenem and remains enrolling, while the original MERINO trial stopped early without extended infusion dosing and reported a mortality disadvantage for piperacillin-tazobactam.
Why does extended infusion dosing matter for piperacillin-tazobactam trials?
Extended infusion dosing improves pharmacokinetic and pharmacodynamic target attainment against ESBL-producing organisms, potentially explaining why earlier trials without this dosing strategy found worse outcomes for piperacillin-tazobactam.
The PeterPen trial was designed to retest the comparison using extended infusion dosing for both agents, with co-primary endpoints of 30-day mortality and day-7 treatment failure.3
An interim analysis of the PeterPen trial found extended infusion piperacillin-tazobactam was noninferior to extended infusion meropenem for day-7 treatment failure.3 Klatt noted enrollment is ongoing and cautioned against overinterpreting interim data, but said the findings could eventually spare more patients carbapenem exposure. If confirmed in the final analysis, the results would support extended infusion piperacillin-tazobactam as a carbapenem-sparing option for select ESBL bloodstream infections.
“PeterPen essentially sought to replicate the Merino study, and their internal analysis was published or released at ESCMID and they found that in those clinical outcomes piperacillin-tazobactam was comparable to meropenem, and that there wasn't a significant difference in treatment failure between those two arms, so this is huge,” Klatt said. “They're still actively enrolling patients in this study, but if these findings and data continue to pan out, it would shift or swing that pendulum back towards mainly using more piperacillin-tazobactam in these patients, and would spare a lot of patients carbapenem therapy, which, of course, as stewards, we all would love that.”
ESCMID guidelines already caution against reflexive carbapenem use for non-severe ESBL infections, and additional trials evaluating extended infusion beta-lactams and newer beta-lactam-beta-lactamase inhibitor combinations are underway to further define carbapenem-sparing strategies.
Staying Up With the Study Literature
Klatt says there are a couple of strategies to keep clinicians up to to date on the latest literature in antimicrobial treatment.
“We as ID pharmacists are really seen as the experts in terms of keeping up to date on primary literature, and so I would say, if you have the opportunity to round with a provider, and have those individual patient-level discussions. I think that's the best way to really incorporate primary literature. We call it planning the seed, right? You come to rounds, and you have that paper, and you can say, ‘Hey, we're talking about this patient, I've seen that there's this paper that sampled this patient population. What do you think? What are the pros and cons? And then you can have a nuanced conversation in the moment, but then the clinician hopefully will read that after the fact and have a more balanced assessment,” Klatt said.
And when not able to do rounds, she recommends creating ID journal clubs, which can incorporate primary literature into the antimicrobial stewardship committees. This allows ID clinicians to bring up the primary literature to colleagues.
References
1.DOTS Trial Investigators. Dalbavancin for treatment of Staphylococcus aureus bacteremia: the DOTS randomized clinical trial. JAMA. Published online August 13, 2025. ClinicalTrials.gov identifier: NCT04775953.
2.Harris PNA, Tambyah PA, Lye DC, et al. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA. 2018;320(10):984-994.
3.Paul M, Rodríguez-Baño J. The trial run: treatment of ESBL bacteraemia (off to never-never land). Presented at: ESCMID Global 2026; April 20, 2026; Munich, Germany. ClinicalTrials.gov identifier: NCT03671967.
