Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen

Georges, Bernard; Conil, Jean‐Marie; Cougot, P.; Decun, J. F.; Archambaud, M.; Seguin, Thierry; Chabanon, G.; Virenque, C; Houin, Georges; Saivin, Sylvie

doi:10.5414/cpp43360

Cited by 87 publications

(91 citation statements)

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“…Research has shown that improved antibiotic exposure can be obtained via three general approaches: (1) increasing the antibiotic dose; (2) increasing the frequency of antibiotic dosing or; (3) by utilizing EI or CI [67,85,86,106,151,[164][165][166][167][168][169][170][171][172][173][174][175]. However, increasing the antibiotic dose has been shown to be less effective to adequately maintain effective drug concentration during a dosing period.…”

Section: Beta-lactam Antibiotics and Their Pharmacokinetic And Pharmamentioning

confidence: 99%

“…Numerous clinical comparative studies have been conducted with beta-lactams testing various dosing strategies in various patient populations including critically ill patients [85,86,151,166,169,171,172,[241][242][243][246][247][248][249][250][251][252], patients receiving extracorporeal renal circuit [244,245,253], trauma patients [254], patients with malignant diseases [255], patients with intra-abdominal infections [256], patients with chronic obstructive pulmonary disease (COPD) [257,258] and nonspecific hospitalized patients [173,[259][260][261][262] (Table 1-2). These studies have not shown whether alternative dosing approaches (i.e., CI and EI) are advantageous nor which patient groups may benefit.…”

Section: Clinical Outcomesmentioning

confidence: 99%

“…A number of articles have also discussed the potential advantages and disadvantages of CI [13][14][15][16][17][263][264][265]. A recent systematic review of the published literature by Abdul-Aziz et al, [13] found no statistically significant differences in critically ill patients with regards to mortality rate [151,172,243,248], clinical cure [172,243,266], time to normalization of leukocytosis or pyrexia [248,254], mechanical ventilation [172,243,254,266], hospital or ICU length of stay [172,243,254,266] and adverse events [266] between CI and IB dosing. In addition, three meta-analyses have been published to determine if any clinical benefits of CI beta-lactams can be found from the combined clinical data of the present studies [217,240,267].…”

Section: Clinical Outcomesmentioning

confidence: 99%

“…The duration of mechanical ventilation has been compared in several studies (Table 3- To date, no significant difference has been reported in length of hospital [243,254,298,374,375] or ICU stay [172,243,254,266,274,375] between patients receiving CI or IB of beta-lactam antibiotics (Table 3-3). Studies are often underpowered to detect any significant difference and the studied outcome is usually confounded by several factors other than the intervention given [264].…”

Section: Mechanical Ventilationmentioning

confidence: 99%

“…The diverse range of patient groups include critically ill patients with sepsis [151,172,243,248,261,262,266], trauma patients (86), patients with abdominal infections [256,407], COPD patients [257,258], cancer [255] and non-specific hospitalized infections [173]. Thus, meta-analyses have evaluated heterogeneous patient groups and any potential benefits of CI or IB that may exist in a particular patient group were not assessed.…”

Section: Heterogeneous Patient Populationsmentioning

confidence: 99%

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Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

Abdul‐Aziz¹,

Mohd²

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Severe sepsis is a major burden in the intensive care unit (ICU) with persistently high mortality rates. Optimization of antibiotic dosing has been suggested as an intervention to improve clinical outcomes for critically ill patients with severe sepsis. However, current antibiotic dosing guidelines may not be appropriate for these patients, as they rarely consider the altered physiology and illness severity associated with this population. Optimizing antibiotic dosing using pharmacokinetic (PK) and pharmacodynamic (PD) principles can address these critical illness-related changes and promote therapeutic success. Due to their wide spectrum of antibiotic activity and excellent safety profile, beta-lactam antibiotics are commonly used for severe infections in the ICU. Two alternative dosing approaches to traditional intermittent bolus (IB) dosing, namely continuous infusion (CI) and extended infusion (EI), have been suggested to maximize the therapeutic potential of these antibiotics in critically ill patients. Collectively, the two dosing approaches can also be referred as prolonged infusion (PI).This Thesis aims to better characterize the pharmacokinetics/pharmacodynamics (PK/PD) of betalactam antibiotics to determine whether there is any therapeutic advantage associated with PI dosing (CI and/or EI) as compared to IB dosing. This Thesis comprises of eight chapters. Chapter 1 is an introductory chapter which provides an overview of the published literature on the area of research. The discussion in Chapter 1 presents a theoretical framework behind the Thesis objectives. Chapter 1 concludes with the specific aims of this Thesis.Chapter 2 reports the findings of a prospective PK study which aimed to describe the population PK of doripenem in critically ill patients with sepsis and perform dosing simulations to develop clinically relevant dosing guidelines for these patients. Twelve critically ill participants receiving 500 mg of doripenem 8-hourly as a 1-hr infusion were enrolled. The volume of distribution (Vd) and clearance (CL) of doripenem in this patient cohort were substantially different than those usually described in non-critically patients. As current dosing guidelines were mostly derived from the non-critically ill, findings from this study suggest that the licensed "one-dose-fits-all" dosing for doripenem is unlikely to achieve optimal exposures in critically ill patients. Empirical use of PI dosing should be considered to account for PK and illness severity differences, particularly when less-susceptible pathogens are involved.ii Chapter 3 incorporates a published systematic review which compares the PK/PD data and clinical outcomes between CI and IB dosing to describe any potential merits supporting either of the two dosing approaches for critically ill patients. The findings suggest that beta-lactam CI may not be advantageous for all critically ill patients and may be beneficial in patients with severe infections.Chapter 4 describes the findings of a post hoc analysis on the Defining...

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Section: Beta-lactam Antibiotics and Their Pharmacokinetic And Pharmamentioning

confidence: 99%

Section: Clinical Outcomesmentioning

confidence: 99%

Section: Clinical Outcomesmentioning

confidence: 99%

Section: Mechanical Ventilationmentioning

confidence: 99%

Section: Heterogeneous Patient Populationsmentioning

confidence: 99%

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Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

Abdul‐Aziz¹,

Mohd²

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Resolving the Dilemma on Continuous vs Intermittent β-Lactam Antibiotics in Sepsis

Wiersinga,

van Agtmael

2024

JAMA

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

Abdul-Aziz,

Hammond,

Brett

et al. 2024

JAMA

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ImportanceThere is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock.ObjectiveTo determine whether prolonged β-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions.Data SourcesThe primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024.Study SelectionRandomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of β-lactam antibiotics in critically ill adults with sepsis or septic shock.Data Extraction and SynthesisData extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach.Main Outcomes and MeasuresThe primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure.ResultsFrom 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of β-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty).Conclusions and RelevanceAmong adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock.Trial RegistrationPROSPERO Identifier: CRD42023399434

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Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen

Cited by 87 publications

References 0 publications

Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

Resolving the Dilemma on Continuous vs Intermittent β-Lactam Antibiotics in Sepsis

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

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