Time to Appropriate Antibiotic Therapy Is an Independent Determinant of Postinfection ICU and Hospital Lengths of Stay in Patients With Sepsis*

Zhang, David; Micek, Scott T.; Kollef, Marin H.

doi:10.1097/ccm.0000000000001140

Cited by 118 publications

(74 citation statements)

References 27 publications

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“…In the presence of sepsis or septic shock, each hour delay in administration of appropriate antimicrobials is associated with a measurable increase in mortality [57,74]. Further, several studies show an adverse effect on secondary end points (e.g., LOS [75], acute kidney injury [76], acute lung injury [77], and organ injury assessed by Sepsis-Related Organ Assessment score [78] with increasing delays. Despite a meta-analysis of mostly poor-quality studies that failed to demonstrate a benefit of rapid antimicrobial therapy, the largest and highest-quality studies support giving appropriate antimicrobials as soon as possible in patients with sepsis with or without septic shock [57,74,[79][80][81].…”

Section: Rationalementioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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Section: Rationalementioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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“…In the United States, P. aeruginosa is the second most frequent cause of ventilator-associated pneumonia and the third most frequent cause of catheterassociated urinary tract infection (8). The MDR nature of P. aeruginosa has been shown to reduce the likelihood of appropriate (active in vitro) initial antimicrobial therapy (10,11). Delaying the initiation of appropriate antimicrobial therapy is well established as being associated with increased morbidity and mortality in patients with severe P. aeruginosa infections (2, 10).…”

Section: Discussionmentioning

confidence: 99%

Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015

Shortridge

Castanheira

Pfaller

et al. 2017

Antimicrob Agents Chemother

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The activity of ceftolozane-tazobactam was compared to the activities of 7 antimicrobials against 3,851 Pseudomonas aeruginosa isolates collected from 32 U.S. hospitals in the Program to Assess Ceftolozane-Tazobactam Susceptibility from 2012 to 2015. Ceftolozane-tazobactam and comparator susceptibilities were determined using the CLSI broth microdilution method at a central monitoring laboratory. For ceftolozane-tazobactam, 97.0% of the isolates were susceptible. Susceptibilities of the other antibacterials tested were: amikacin, 96.9%; cefepime, 85.9%; ceftazidime, 85.1%; colistin, 99.2%; levofloxacin, 76.6%; meropenem, 81.8%; and piperacillintazobactam, 80.4%. Of the 699 (18.1%) meropenem-nonsusceptible P. aeruginosa isolates, 87.6% were susceptible to ceftolozane-tazobactam. Six hundred seven isolates (15.8%) were classified as multidrug resistant (MDR), and 363 (9.4%) were classified as extensively drug resistant (XDR). Only 1 isolate was considered pandrug resistant, which was resistant to all tested agents, including colistin. Of the 607 MDR isolates, 84.9% were ceftolozane-tazobactam susceptible, and 76.9% of XDR isolates were ceftolozane-tazobactam susceptible. In vitro activity against drug-resistant P. aeruginosa indicates ceftolozane-tazobactam may be an important agent in treating serious bacterial infections.

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“…We hypothesized that active TDM versus non-TDM will decrease median ICU LOS from 7 to 6 days (baseline 7 ± 3.5, data of five hospitals ICU LOS [28,29]). With alpha level of 0.05, and power of 0.80, the sample size is calculated as 192 per group.…”

Section: Sample Size Calculationmentioning

confidence: 99%

The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial

et al. 2020

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Background: Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of betalactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. Methods: A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and costeffectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included.Discussion: No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM?

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Time to Appropriate Antibiotic Therapy Is an Independent Determinant of Postinfection ICU and Hospital Lengths of Stay in Patients With Sepsis*

Cited by 118 publications

References 27 publications

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015

The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial

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