The Pulse - November 2025

Greetings Readers! In this monthly edition, we examine 3 practice changing studies.

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1. From OPAT Marathon to DOTS Sprint: Simplifying MRSA Bacteremia

   The highly-anticipated DOTS trial evaluated whether a simplified dalbavancin regimen could safely replace standard 4–8 week OPAT in adults with Staphylococcus aureus bacteremia who had cleared their bloodstream infection after 3–10 days of initial therapy. Two doses of dalbavancin 1500 mg, given one week apart, were noninferior to conventional prolonged IV therapy with respect to a composite endpoint of clinical success, infectious complications, safety, mortality, and quality of life at day 70. The majority of patients had soft-tissue infections, septic arthritis, or nonvertebral osteomyelitis, while more complex infections, such as left-sided endocarditis, were excluded. Safety and survival outcomes were comparable between groups, supporting dalbavancin as a viable stepdown, particularly for MRSA bacteremia, while beta-lactams remain preferred for methicillin-susceptible strains. This trial validates a practice many ID clinicians had already adopted, demonstrating that a short-course, long-acting agent can safely streamline care. Turner NA et al. JAMA 2025 Aug

   Study Type: open-label, multi-center (US and Canadian) RCT of 200 hospitalized patients with complicated Staph aureus bacteremia (including both MRSA and MSSA) who achieved blood culture clearance following at least 72 hours but no more than 10 days of initial antibiotic therapy. Patients were randomized 1:1 to 2 doses of IV dalbavancin or 4-8 total weeks of standard IV therapy. Patient with retained infected prosthetic material, left-sided endocarditis, CNS infection or severe immune compromised were excluded.

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2. A-Lines or A-Little Less?

   A large French trial delivered a surprising reality check: routine early arterial catheterization in shock didn’t improve mortality at 28 or 90 days compared with noninvasive monitoring. Patients managed noninvasively avoided most line-related complications but paid for it with more frequent arterial punctures and greater monitoring discomfort. Meanwhile, the invasive group had a modest bleeding/hematoma rate but very low infection risk, reinforcing that A-lines are generally safe but not benign. Overall, the findings suggest clinicians can safely delay arterial catheter placement in many early-shock patients without compromising outcomes. For those with refractory or severe shock, however, an arterial line remains a reasonable and practical escalation. Muller G et al. N Engl J Med 2025 Oct.

   Study Type: French multi center, open-label, noninferiority RCT of patients with shock admitted to ICU randomized to early insertion (<4 hours after randomization) of arterial lines (invasive) vs non-invasive monitoring (brachial cuff).

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3. Buffering the Blow: Targeted Bicarb Infusions in Severe AKI

   Severe acidemia is a frequent and consequential companion of critical illness, yet evidence for IV sodium bicarbonate has long been inconclusive and supported only by a weak Surviving Sepsis recommendation—largely built on a subgroup signal from the original BICARICU trial. BICARICU-2 directly tested that signal by enrolling 640 critically ill patients with pH ≈7.15 and moderate-to-severe AKI, randomizing them to targeted alkali therapy vs. no bicarbonate. The trial was underpowered for the 90-day mortality endpoint and ultimately showed a neutral effect, with confidence intervals wide enough to accommodate both modest benefit and modest harm. However, the reduction in renal replacement therapy (35% vs. 50%) and delayed time to initiation mirrors the biologically plausible hypothesis that correcting severe acidemia can prevent clinicians from crossing the dialysis threshold—acknowledging that open-label design and clinician behavior may contribute. Practically, BICARICU-2 doesn’t confirm a mortality advantage, but it supports short-term bicarbonate as a safe, reasonable tool for stabilizing severe acidemia in AKI, especially when the alternative is dialysis. Jung B et al. JAMA 2025 Oct

   Study Type: multi center, French, open-label RCT of 640 patients (59% men, mean age 67) with severe academic and moderate-to-severe AKI across 43 ICUs. Patients randomized 1:1 to either receive sodium bicarbonate or not to target an arterial pH of 7.30 or higher. Patient all-cause mortality followed for 90 days.
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