Continuous Infusion of Piperacillin/Tazobactam in Septic Critically Ill Patients—A Multicenter Propensity Matched Analysis

Gonçalves-Pereira, João; Oliveira, Bruno; Janeiro, Sérgio; Estilita, J.; Monteiro, Catarina; Salgueiro, Andrea; Vieira, Alfredo; Gouveia, João; Paulino, Carolina; Bento, Luís; Póvoa, Pedro

doi:10.1371/journal.pone.0049845

Cited by 24 publications

(19 citation statements)

References 38 publications

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“…Grant et al reported that days of therapy were similar with both treatment groups (7.3 ± 4.8 days for continuous infusion versus 8.7 ± 7.1 days for conventional intermittent infusion, P = 0.26) [ 21 ]. This finding was also found by Patel et al [ 25 ], Lorente et al [ 26 ], Yost et al [ 29 ] and Pereira et al [ 30 ]. However, Lodise et al found that the median duration of hospital stay was significantly shorter in patients who received extended infusion therapy compared to conventional intermittent therapy (21 days versus 38 days, P = 0.02) [ 24 ].…”

Section: Discussionsupporting

confidence: 84%

“…Higher clinical cure rate for the extended infusion approach was found in our study, which is an important result, indicating the merit of using the extended or continuous infusion instead of the conventional intermittent infusion approach in clinical practice. The reason for which the extended or continuous infusion leads to increased clinical cure rate may be related to the increase in the time that the drug concentrations exceed the MIC since piperacillin/tazobactam is a time-dependent antimicrobial [ 1 ], [ 12 – 14 ], [ 17 ], [ 19 ], [ 24 ], [ 30 ], [ 33 ], [ 34 ]. However, Falagas et al concluded no difference in clinical cure rate between extended and conventional intermittent infusion strategy after their meta-analysis [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

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Clinical Outcomes with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis

et al. 2015

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ObjectivesA better dosing strategy can improve clinical outcomes for patients. We sought to compare the extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam, investigating which approach is better and worthy of recommendation for clinical use.MethodsArticles were gathered from PubMed, Web of Science, ProQuest, Science Direct, Cochrane, two Chinese literature databases (CNKI, Wan Fang Data) and related ICAAC and ACCP conferences. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently extracted and investigated the data. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated.ResultsFive randomized controlled trials and nine observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significantly higher clinical cure rate (OR 1.88, 95% CI 1.29-2.73, P = 0.0009) and a lower mortality rate (OR 0.67, 95% CI 0.50-0.89, P = 0.005). No statistical difference was observed for bacteriologic cure (OR 1.40, 95% CI 0.82-2.37, P = 0.22) between the two dosing regimens. The sensitivity analysis showed the results were stable.ConclusionsOur systematic review and meta-analysis suggested that the extended or continuous infusion strategy of piperacillin/tazobactam should be recommended for clinical use considering its higher clinical cure rate and lower mortality rate in comparison with conventional intermittent strategy. Data from this study could be extrapolated for other β-lactam antimicrobials. Therefore, this dosing strategy could be considered in clinical practice.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis

et al. 2015

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“…Fifteen of the included studies reported length of hospital stay (13,14,31,(33)(34)(35)37,15,16,18,23,24,26,29,30). Pooling of studies showed that patients receiving C/PI had a significantly shorter length of hospital stay (2101 patients; OR -1.27, 95% C.I -2.45-0.08, P = 0.04; Fig.…”

Section: Length Of Hospital Staymentioning

confidence: 99%

Comparing Clinical Outcomes of Piperacillin-Tazobactam Administration and Dosage Strategies in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis

Fawaz¹,

Barton²,

Nabhani‐Gebara³

2020

Preprint

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Background: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically-ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Methods: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Results: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (OR 1.56, 95% C.I 1.28-1.90, P = 0 .0001), lower mortality rates (OR 0.68, 95% C.I 0.55-0.84, P = 0 .0003), higher microbiological success rates (OR 1.52, 95% C.I 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (OR -1.27, 95% C.I -2.45—0.08, P = 0.04) in critically ill patients. Conclusion: There is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. Therefore, this alternative infusion strategy could be recommended in clinical practice.

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“…In spite of the well-known PK benefits of this strategy, studies have repeatedly failed to show a significant impact on mortality [12,13]. As a result further clinical studies are needed to assess the impact of this strategy, continuous infusion of b-lactams, on patient outcomes.…”

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confidence: 99%

Antibiotic dosing in the critically ill: asking the same questions but expecting different answers

2014

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The approach of severe sepsis and septic shock has three fundamental steps: early recognition, hemodynamic resuscitation and early empiric antibiotic therapy with focus control if appropriate. Empiric antibiotic therapy involves two decisions: the choice of antibiotics, which depends on the presumed focus and pathogens, and dosing of antibiotics, which should be appropriate along with a correct route and mode of administration [1].In a recent issue of Intensive Care Medicine, Jan De Waele et al. [2] presented data from the Defining Antibiotic Levels in Intensive care unit patients (DALI) study looking at patient characteristics predictive of non-attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets, namely f T [ MIC of the suspected pathogen for at least 50 and 100 % of the dosing interval, in intensive care unit (ICU) patients receiving eight different b-lactams. The DALI project [3] is an international prospective, multicentre, pharmacokinetic point prevalence study involving 68 hospitals, ten countries, with a total of 343 patients, of whom 259 had infection. In the present study, 57 % of patients received penicillins, 27 % carbapenems, and 16 % cephalosporins. Dosing was at the discretion of the treating clinician.In the present study, antibiotics were given for treatment of infection in 75.5 % of patients; however, there was no information on the rate of microbiological documentation or on the bacterial antibiotic susceptibility. The aim of the study was to evaluate target non-attainment neither for the actual infection nor for the microbiological agents, but envisioning an empirical situation where the least susceptible organism was potentially causing the infection. To overcome this weakness, recognized by the authors, they assume that the concentrations obtained in the DALI study were also the concentrations that would be reached during empirical dosing. Accordingly, the authors calculate the non-attainment of PK/PD targets using the highest European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC90 data breakpoint for the administered antibiotic among all potential pathogens. The rationale for this choice was that empiric antibiotic dose selection is based on the 'worst-case' scenario in terms of bacterial susceptibility.The authors showed that free antibiotic concentrations remained below the least susceptible MIC during 50 and 100 % of the dosing interval in 66 (19.2 %) and 142 (41.4 %) patients, respectively. By multivariate analysis, they found that intermittent infusion (vs. extended or Intensive

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Continuous Infusion of Piperacillin/Tazobactam in Septic Critically Ill Patients—A Multicenter Propensity Matched Analysis

Cited by 24 publications

References 38 publications

Clinical Outcomes with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis

Clinical Outcomes with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis

Comparing Clinical Outcomes of Piperacillin-Tazobactam Administration and Dosage Strategies in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis

Antibiotic dosing in the critically ill: asking the same questions but expecting different answers

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