The annual sepsis update, delivered by Meshell Johnson, MD, ATSF, professor of medicine at the University of California in San Francisco, distilled a year’s worth of high-impact evidence into practice-ready guidance for busy hospitalists. Below are highlights of the pivotal trials, clinical pearls, and future directions that should inform bedside care today.
β‑lactam delivery: intermittent dosing still king—at least for now
The 7,031-patient BLING III trial compared continuous to intermittent β-lactam infusions in 104 ICUs. Continuous dosing trimmed absolute 90-day mortality by 1.9 percentage points (24.9% versus 26.8%) but failed to reach statistical significance. A parallel Journal of the American Medical Association meta-analysis pooling 9,108 critically ill adults echoed the signal: a 14% relative mortality reduction and better “clinical cure” with prolonged infusions, yet confidence intervals crossed unity. Practical barriers—dedicated lines, pharmacy compounding, and pump time—remain. Until the mortality advantage is unequivocal, experts advised sticking with intermittent dosing outside research protocols, while recognizing that continuous infusion may benefit the sickest or those with organisms having higher minimum inhibitory concentrations.
Right drug, shorter course: biomarker-guided stewardship and the seven-day rule
A 2,760-patient U.K. randomized controlled trial tested whether procalcitonin (PCT) or C-reactive protein could safely truncate antibiotic courses. PCT guidance shaved therapy to 9.8 days versus 10.7 days under usual care without excess 28-day mortality; C-reactive protein offered no advantage. Key caveat: use PCT to stop antibiotics, not to start them. Meanwhile, a landmark 3,608-patient New England Journal of Medicine trial demonstrated non-inferiority of seven versus 14 days of therapy for gram-negative and other non-Staphylococcus aureus bloodstream infections, with identical 90-day mortality. One in four “short‑course” patients still received treatment beyond a week, underscoring the cultural inertia hospitalists must overcome. Together, these studies support a stewardship mantra: order PCT if unsure when to de-escalate and feel comfortable capping most bacteremia at seven days, barring endovascular foci, severe immunosuppression, or staphylococcal bugs.
Vasopressor timing and steroid selection: precision over escalation
When norepinephrine requirements climb, clinicians often delay a second agent, yet reinforcement‑learning analysis of 14,453 septic shock cases suggests earlier vasopressin, within four hours and at norepinephrine doses of roughly 0.2 µg/kg/min, could cut mortality by 19% and halve dialysis risk. Only 31% of real-world patients received vasopressin, and typically much later. Separately, a network meta-analysis of 95,841 patients ranked hydrocortisone plus fludrocortisone as the regimen most likely to improve 28-day survival with acceptable rates of superinfection and gastrointestinal bleeding, outperforming hydrocortisone alone. Given low cost and biologic plausibility, Dr. Johnson leaned toward pairing 50 mg IV hydrocortisone every six hours with 50 µg oral fludrocortisone daily in refractory shock unless contraindications exist.
Emerging adjuncts and clinician behavior
Methylene blue (six randomized controlled trials, 302 patients) showed promise for vasoplegia by inhibiting nitric‑oxide signaling, but data remain under‑powered, unblinded, and short on adverse‑event reporting. A survey of 550 critical‑care clinicians revealed that fluid volume already administered, more than lactate or respiratory status, drives resuscitation decisions; most give 2 to 3 L crystalloid and increasingly start vasopressors peripherally. These insights reinforce guideline trends toward conservative fluids plus early pressors. Pneumonia continues to account for 70% of septic shock, and subgroup analyses hint at a mortality benefit from stress‑dose steroids in acute respiratory distress syndrome of infectious origin, though definitive trials are pending.
Artificial intelligence and the Sepsis ImmunoScore™
The U.S. Food and Drug Administration‑authorized Sepsis ImmunoScore™, trained on 2,366 admissions and validated externally (area under the curve approximately 0.81), stratifies patients into four risk tiers within 24 hours of arrival using 22 routinely collected variables—PCT, respiratory rate, and systolic blood pressure being most influential. Very‑high-risk patients had an 18% in-hospital mortality versus less than 2% in the medium‑risk group. Implementation challenges include electronic health record integration (Epic’s proprietary algorithm guards its turf) and the perennial absence of a gold standard for early sepsis diagnosis. Still, the tool exemplifies a future in which machine learning augments clinician judgment, flags occult sepsis sooner, and personalizes therapy intensity.
Although the lecture hall for this SHM Converge 2025 session sat just off the Las Vegas Strip, the real gamble in 2025 is postponing evidence-based changes that could shave hours off antibiotic exposure, pressor doses, and mortality curves. By updating protocols now, hospitalists can tilt the odds decisively in favor of their patients.
Key Takeaways
- Stick with intermittent β-lactam infusions unless pharmacy bandwidth and local antibiograms justify continuous delivery
- Leverage procalcitonin to shorten antibiotic duration and adopt seven-day courses for uncomplicated bacteremia, keeping a tighter audit on therapy creep
- Add vasopressin early—think at 14 µg/min in a 70 kg patient—rather than escalating norepinephrine alone, and couple hydrocortisone with fludrocortisone in persistent shock
- Balance fluids judiciously, recognizing cumulative volume, and keep methylene blue in the “rescue therapy” toolbox until higher-quality evidence emerges
- Advocate for electronic-health-record‑embedded sepsis prediction models that are transparent, validated in your population, and that trigger actionable care bundles
Dr. Migliore is an assistant professor of medicine at Columbia University College of Physicians and Surgeons, director of general medicine perioperative and consult services, and medical director of surgery and surgical step-down at Columbia University Medical Center in New York.