Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis

JAMA, Journal Year: 2024, Volume and Issue: 332(8), P. 629 - 629

Published: June 12, 2024

Importance Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients sepsis is uncertain. Objective To evaluate whether vs a antibiotic (piperacillin-tazobactam or meropenem) results decreased all-cause mortality at 90 days critically ill sepsis. Design, Setting, and Participants An international, open-label, randomized clinical trial conducted 104 intensive care units (ICUs) Australia, Belgium, France, Malaysia, New Zealand, Sweden, United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, follow-up completed on April 12, 2023. were adults (≥18 years) treated piperacillin-tazobactam meropenem for Intervention Eligible receive an equivalent 24-hour dose either (n = 3498) 3533) clinician-determined duration treatment until ICU discharge, whichever first. Main Outcomes Measures The primary outcome was within after randomization. Secondary outcomes cure up 14 randomization; new acquisition, colonization, infection multiresistant organism Clostridioides difficile mortality; in-hospital mortality. Results Among 7202 participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements inclusion analysis (97.6%). Within days, 864 3474 (24.9%) assigned had died 939 3507 (26.8%) (absolute difference, −1.9% [95% CI, −4.9% 1.1%]; odds ratio, 0.91 0.81 1.01]; P .08). Clinical higher group (1930/3467 [55.7%] 1744/3491 [50.0%], respectively; absolute 5.7% 2.4% 9.1%]). Other secondary not statistically different. Conclusions Relevance observed difference 90-day between infusions did meet statistical significance analysis. However, confidence interval around effect estimate includes possibility both no important clinically benefit use this patients. Trial Registration ClinicalTrials.gov Identifier: NCT03213990

Language: Английский

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Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock

JAMA, Journal Year: 2024, Volume and Issue: 332(8), P. 638 - 638

Published: June 12, 2024

Importance There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective To determine antibiotic are associated a reduced risk death shock compared intermittent infusions. Data Sources The primary search was conducted MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection Randomized clinical trials comparing (continuous extended) Extraction Synthesis extraction bias were assessed independently by 2 reviewers. Certainty evidence evaluated the Grading Recommendations Assessment, Development Evaluation approach. A bayesian framework used as analysis approach frequentist secondary Main Outcomes Measures outcome all-cause 90-day mortality. Secondary included intensive care unit (ICU) mortality cure. Results From 18 eligible randomized that 9108 (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 (9014 participants) contributed data outcome. pooled estimated ratio for 0.86 (95% credible interval, 0.72-0.98; I = 21.5%; high certainty), 99.1% posterior probability lower Prolonged infusion (risk ratio, 0.84; 95% 0.70-0.97; certainty) an increase cure 1.16; 1.07-1.31; moderate certainty). Conclusions Relevance Among who had shock, use current presents degree certainty clinicians consider standard management Trial Registration PROSPERO Identifier: CRD42023399434

Language: Английский

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Prolonged versus intermittent β-lactam infusion in sepsis: a systematic review and meta-analysis of randomized controlled trials

Annals of Intensive Care, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 18, 2024

Abstract Background The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing to the controversy surrounding effectiveness infusion strategy. We conducted a systemic review and meta-analysis evaluate efficacy safety adult sepsis. Methods systematically searched PubMed, EMBASE, Cochrane Library databases for original randomized controlled trials comparing patients. A random-effects model was used mortality, clinical success, microbiological adverse events. also subgroup analyses explore impact various factors mortality rates. Relative risk (RR) corresponding 95% confidence intervals (CIs) were calculate overall effect sizes dichotomous outcomes. This registered PROSPERO (CRD42023463905). Results assessed 15 involving 2130 In our comprehensive assessment, we found significant reduction all-cause (RR, 0.83; CI 0.72–0.97; P = 0.02) notable improvement success 1.16; 1.03–1.31; group compared group, whereas yield statistically results 1.10; 0.98–1.23; 0.11). No differences events observed between groups 0.91; 0.64–1.29; 0.60). Additionally, remarkable conclusions drawn from including sample exceeding 20 individuals per 0.84; 95%CI 0.72–0.98; 0.03), research post-2010 cases infections predominantly caused by Gram-negative bacteria 0.81; 0.68–0.96; 0.02), as well administration loading dose penicillin 0.61; 0.38–0.98; 0.04). Conclusions Compared infusion, significantly decreases among enhances without increasing

Language: Английский

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Extended-Infusion β-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(7), P. e2418234 - e2418234

Published: July 2, 2024

Importance Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes. Objective To investigate the association EI-BL survival, adverse events, and emergence antibiotic resistance in adults gram-negative bloodstream infections (GN-BSI). Design, Setting, Participants This cohort study consecutive GN-BSI admitted to 24 United States hospitals between January 1, 2019, December 31, receiving were compared same agents as intermittent infusion (II-BL; ≤1-hour infusions). Statistical analysis was performed from October 2023. Exposures (ie, ≥3-hour infusion). Main Outcomes Measures II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression applied PSM outcomes, all censored at day 90. The primary outcome mortality; secondary outcomes included events (≥4-fold increase minimum inhibitory concentration used treat index GN-BSI). Results Among 4861 patients included, 2547 (52.4%) male; median (IQR) age 67 (55-77) years. There 352 group, 1056 group. 1408 patients, 373 (26.5%) died by odds mortality lower group (adjusted ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, survival benefit only identified severe illness or elevated concentrations intermediate range administered). increased catheter complications (aOR, 3.14 1.66-5.96]) discontinuation because (eg, acute kidney injury, cytopenias, seizures) 3.66 1.68-7.95]). Emergence similar 2.9% vs 7.2%, respectively ( P = .35). Conclusions Relevance this GN-BSI, associated reduced those infected nonsusceptible organisms; potential advantages other remain unclear need be balanced events. subsequent warrants investigation larger cohort.

Language: Английский

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Understanding antimicrobial pharmacokinetics in critically ill patients to optimize antimicrobial therapy: A narrative review

Journal of Intensive Medicine, Journal Year: 2024, Volume and Issue: 4(3), P. 287 - 298

Published: Feb. 29, 2024

Effective treatment of sepsis not only demands prompt administration appropriate antimicrobials but also requires precise dosing to enhance the likelihood patient survival. Adequate refers doses that yield therapeutic drug concentrations at infection site. This ensures a favorable clinical and microbiological response while avoiding antibiotic-related toxicity. Therapeutic monitoring (TDM) is recommended approach for attaining these goals. However, TDM universally available in all intensive care units (ICUs) antimicrobial agents. In absence TDM, healthcare practitioners need rely on several factors make informed decisions. These include patient's condition, causative pathogen, impact organ dysfunction (requiring extracorporeal therapies), physicochemical properties antimicrobials. this context, pharmacokinetics vary considerably between different critically ill patients within same over course ICU stay. variability underscores individualized dosing. review aimed describe main pathophysiological changes observed their It provide essential practical recommendations may aid clinicians optimizing therapy among patients.

Language: Английский

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Comparing prolonged infusion to intermittent infusion strategies for beta-lactam antibiotics in patients with gram-negative bacterial infections: a systematic review and meta-analysis

Expert Review of Anti-infective Therapy, Journal Year: 2024, Volume and Issue: 22(7), P. 557 - 567

Published: March 5, 2024

Our objective is to determine whether prolonged infusion (PI) of beta-lactam antibiotics yields superior outcomes compared intermittent (II) in patients with Gram-Negative Bacterial (GNB) infections.

Language: Английский

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Impact of prolonged versus intermittent infusion of meropenem on mortality and clinical outcomes in patients with severe infection: A systematic review and meta-analysis

Journal of Infection and Chemotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 102634 - 102634

Published: Jan. 1, 2025

Language: Английский

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Significant Publications on Infectious Diseases Pharmacotherapy in 2023

Journal of Pharmacy Practice, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Purpose: To provide a summarization of the most significant infectious diseases (ID) pharmacotherapy articles published in peer-reviewed literature 2023. Summary: Members Houston Infectious Diseases Network (HIDN) nominated notable providing contributions to ID Article nominations included those pertaining general and human immunodeficiency virus/acquired syndrome (HIV/AIDS) pharmacotherapy. Out 31 by HIDN members, 22 pertained pharmacotherapy, 9 HIV/AIDS aid selection 2023, survey was created distributed members Society Pharmacists (SIDP). Of 153 SIDP who participated survey, there were 118 recorded votes for top 10 55 article. The publications are summarized. Conclusion: Advances antimicrobial stewardship disease states continue occur. Sustained growth publication ID-related over past year contributed this review’s aim clinicians remaining current on potentially practice-changing from This review provides summary recently literature, including emphasis stewardship, appropriate treatment durations, new antimicrobials, drug-resistant organisms.

Language: Английский

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The characterization of Herbaspirillum huttiense isolated from a uremic patient: virulence and antimicrobial efficacy in the Galleria mellonella model

Letters in Applied Microbiology, Journal Year: 2025, Volume and Issue: 78(2)

Published: Feb. 1, 2025

Herbaspirillum species are typically isolated from plants and known for their role in crop nitrogen fixation. Recently, they have been found to colonize humans cause infections. This study aimed identify characterize two huttiense strains (CLJ01 CLJ02) the blood of a uremic patient, with focus on evaluating pathogenicity antibiotic efficacy. The were identified using VITEK2 system, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry , 16S rRNA gene sequencing, confirming identity as H. huttiense. High-throughput sequencing further revealed presence resistance arnA, which confers polymyxin. For first time, was assessed Galleria mellonella infection model. results demonstrated concentration-dependent virulence, CLJ01 exhibiting slightly higher pathogenicity. Additionally, meropenem showed significant antimicrobial efficacy G. model, particularly under conditions high bacterial load, indicating strong therapeutic potential. In conclusion, this provides experimental evidence supporting correct diagnosis treatment Furthermore, findings underscore importance accurately identifying rare pathogens clinical settings effective treatment.

Language: Английский

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Difficult-to-Treat Pseudomonas aeruginosa Infections in Critically Ill Patients: A Comprehensive Review and Treatment Proposal

Antibiotics, Journal Year: 2025, Volume and Issue: 14(2), P. 178 - 178

Published: Feb. 11, 2025

The management of infections caused by difficult-to-treat Pseudomonas aeruginosa in critically ill patients poses a significant challenge. Optimal antibiotic therapy is crucial for patient prognosis, yet the numerous resistance mechanisms P. aeruginosa, which may even combine, complicate selection an appropriate antibiotic. In this review, we examine epidemiology, mechanisms, risk factors, and available future therapeutic options, as well strategies treatment optimization. Finally, propose algorithm to facilitate decision making based on patterns specific each Intensive Care Unit.

Language: Английский

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