Loading
Sepsis Diagnosis and Treatment · Journal article
Pharmacotherapy the Journal of Human Pharmacology and Drug Therapy · August 14, 2026
Well-designed and adequately powered for the question it asks.
This focused update meta-analysis of 28 RCTs strengthens the evidence base for prolonged-infusion beta-lactams in severely ill adults, demonstrating moderate certainty that prolonged infusion reduces mortality (RR 0.91, 95% CI 0.85–0.97) and improves clinical cure (RR 1.11, 95% CI 1.06–1.17) compared to short infusion, with Bayesian posterior probabilities of benefit exceeding 98%. The recommendation to use prolonged-infusion therapy with loading doses is reinforced by pooled and Bayesian evidence, though certainty remains moderate for mortality and low for clinical cure.
Systematic review and meta-analysis of randomized controlled trials with Bayesian meta-analyses. Severely ill adult patients enrolled in randomized controlled trials comparing prolonged-infusion versus short-infusion beta-lactam antibiotics. Intervention: Prolonged-infusion beta-lactam antibiotics, including use of loading doses before continuous infusion. Compared with: Short-infusion beta-lactam dosing. International; specific geographic distribution of included RCTs not stated in abstract.
Mortality: RR 0.91 (95% CI 0.85–0.97) across 28 RCTs with 98.76% posterior probability of benefit Clinical cure: RR 1.11 (95% CI 1.06–1.17) across 21 RCTs with 99.97% posterior probability of benefit Certainty of evidence strengthened to moderate for mortality and low for clinical cure
Absolute risk reduction for mortality not reported; relative risk reduction alone limits clinical quantification Mortality: RR 0.91 (95% CI 0.85–0.97) across 28 RCTs with 98.76% posterior probability of benefit
Clinicians should use prolonged-infusion beta-lactams over short-infusion dosing in severely ill adult patients, with a loading dose administered before initiation of continuous infusion, based on moderate certainty evidence for mortality reduction and low certainty evidence for improved clinical cure. This represents a strengthened recommendation compared to the 2023 guideline that cited very low certainty of evidence.
Systematic review and meta-analysis of 28 RCTs with moderate certainty of evidence showing prolonged-infusion beta-lactams reduce mortality (RR 0.91, 95% CI 0.85–0.97) and improve clinical cure (RR 1.11, 95% CI 1.06–1.17) in severely ill adults, supported by Bayesian analyses.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should use prolonged-infusion beta-lactams over short-infusion dosing in severely ill adult patients, with a loading dose administered before initiation of continuous infusion, based on moderate certainty evidence for mortality reduction and low certainty evidence for improved clinical cure. This represents a strengthened recommendation compared to the 2023 guideline that cited very low certainty of evidence.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
In 2023, international consensus recommendations suggested the use of prolonged-infusion beta-lactam antibiotics over short-infusion dosing in severely ill adult patients to improve mortality or clinical cure, although the certainty of evidence was very low. With the availability of several new randomized controlled trials (RCTs), this focused update re-evaluates the efficacy of prolonged versus short infusion among severely ill adult patients. The original Population, Intervention, Comparator, and Outcome (PICO) question VII was separated into two questions addressing mortality (VIIa) and clinical cure (VIIb). Methods used for study identification, screening, and evidence grading were consistent with the original guideline, with the addition of Bayesian meta-analyses. A total of 28 RCTs evaluating mortality in severely ill adults were analyzed, with pooled estimates favoring prolonged infusion (RR 0.91; 95% confidence interval 0.85 to 0.97), supported by Bayesian analyses demonstrating a 98.76% posterior probability of benefit. Across 21 RCTs evaluating clinical cure, prolonged infusion improved outcomes compared with short infusion (RR 1.11; 95% confidence interval 1.06 to 1.17), supported by Bayesian analyses demonstrating a 99.97% posterior probability of benefit. Certainty of evidence was strengthened to moderate for mortality and low for clinical cure. Consistent with the original recommendation (PICO X), subgroup analyses evaluating loading doses suggested improved outcomes when a loading dose is used before continuous infusion. Overall, the cumulative evidence reinforces and strengthens the recommendation for use of prolonged-infusion beta-lactam therapy in severely ill adult patients to improve survival and clinical cure. Continued use of loading doses when initiating continuous-infusion therapy is suggested. Future research should identify subpopulations most likely to benefit, clarify optimal prolonged-infusion strategies, and define the role of therapeutic drug monitoring.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.