Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials

Vardakas, Konstantinos Z.; Voulgaris, Georgios L; Maliaros, Athanasios; Samonis, George; Falagas, Matthew E.

doi:10.1016/s1473-3099(17)30615-1

Cited by 268 publications

(258 citation statements)

References 74 publications

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“…However, evidence regarding the impact of target attainment on clinical effect remains limited in this population, and the data are inconsistent. In two recent systematic reviews and meta‐analysis, the authors identified a significant benefit in survival and clinical cure for prolonged infusion of β‐lactams compared with IA in critically ill patients. Conversely, Tamma et al .…”

Section: Discussionmentioning

confidence: 99%

Piperacillin pharmacokinetics and target attainment in children with cancer and fever: Can we optimize our dosing strategy?

Maarbjerg

Thorsted

Kristoffersson

et al. 2019

Pediatric Blood & Cancer

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Background Data on piperacillin–tazobactam pharmacokinetics and optimal dosing in children with cancer and fever are limited. Our objective was to investigate piperacillin pharmacokinetics and the probability of target attainment (PTA) with standard intermittent administration (IA), and to simulate PTA in other dosing regimens. Procedure This prospective pharmacokinetic study was conducted from April 2016 to January 2018. Children with cancer receiving empiric piperacillin–tazobactam to treat infections were included. Piperacillin–tazobactam 100 mg/kg was infused over 5 min every 8 hours (IA). An optimized sample schedule provided six blood samples per subject for piperacillin concentration determination. The evaluated targets included: (1) 100% time of free piperacillin concentration above the minimum inhibitory concentration (fT > MIC) and (2) 50% fT > 4× MIC. MIC50 and MIC90 were defined based on an intrainstitutional MIC range. Results A total of 482 piperacillin concentrations were obtained from 43 children (aged 1–18 years) during 89 fever episodes. Standard IA resulted in insufficient target attainment, with significant differences in piperacillin pharmacokinetics for different body weights. Median fT > MIC was 61.2%, 53.5%, and 36.3% for MIC50 (2.0 mg/L), MIC90 (4.0 mg/L), and breakpoint for Pseudomonas aeruginosa (16.0 mg/L), respectively. Correspondingly, the median fT > 4× MIC was 43%, 36.3%, and 20.1%. Simulations showed that only continuous infusion reached a PTA of 95% for MIC = 16.0 mg/L, while extended infusion lasting half of the dosing interval reached a PTA of 95% for MIC ≤ 8 mg/L. Conclusions Our data revealed insufficient PTA with standard IA of piperacillin–tazobactam in children with cancer and fever. Alternative dosing strategies, preferably continuous infusion, are required to ensure adequate PTA.

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Section: Discussionmentioning

confidence: 99%

Piperacillin pharmacokinetics and target attainment in children with cancer and fever: Can we optimize our dosing strategy?

Maarbjerg

Thorsted

Kristoffersson

et al. 2019

Pediatric Blood & Cancer

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“…One possible approach may be to optimize the pharmacodynamics of the agents used as much as possible. For example, using continuous or extended infusions of β‐lactams improves pharmacodynamic target attainment and may be associated with improved efficacy . More research is needed in the area of prescribing alternative dosing of agents susceptible to changes as a result of ARC (e.g., would greater than 4 g/day of levetiracetam or 6 g/day of cefepime be more effective but still be safe in patients with ARC?…”

Section: Identifying Patients At Risk For Arcmentioning

confidence: 99%

Augmented Renal Clearance

2019

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Augmented renal clearance (ARC) is a phenomenon in critically ill patients characterized by increased creatinine clearance and elimination of renally eliminated medications. Patients with severe neurologic injury, sepsis, trauma, and burns have been consistently identified as at risk of ARC, with mean creatinine clearances ranging from 170 ml/minute to more than 300 ml/minute. Several potential mechanisms may contribute to the occurrence of ARC including endogenous responses to increased metabolism and solute production, alterations in neurohormonal balance, and therapeutic maneuvers such as fluid resuscitation. Augmented renal clearance is associated with suboptimal exposure to critical medications, including β‐lactams and vancomycin, increasing the risk of treatment failure. Although definitive screening tools are not yet known, critical care pharmacists must be vigilant in recognizing when ARC may be a contributing factor affecting expected treatment outcomes in individual patients. Optimizing dosing strategies in critically ill patients with ARC remains a goal of continued research. The current review discusses the clinical characteristics and methods of identifying patients at risk of ARC, potential mechanisms for ARC, and describes pharmacotherapy dosing considerations in patients with ARC.

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“…A systematic review and meta‐analysis of 18 studies found prolonged piperacillin/tazobactam infusions were associated with reduced mortality and improved clinical cure rates in severely ill patients . These findings mirror results from a large meta‐analysis evaluating clinical outcomes in septic patients across a range of intravenous beta‐lactams . Prospective trials evaluating alternative beta‐lactam regimens found mixed results, perhaps because of small sample sizes, diverse infections and causative pathogens, inconsistent dosing regimens, and heterogeneity or uncertainty of organism minimum inhibitory concentration (MIC) .…”

Section: Discussionmentioning

confidence: 93%

“…22 These findings mirror results from a large meta-analysis evaluating clinical outcomes in septic patients across a range of intravenous beta-lactams. 23 Prospective trials evaluating alternative beta-lactam regimens found mixed results, perhaps because of small sample sizes, diverse infections and causative pathogens, inconsistent dosing regimens, and heterogeneity or uncertainty of organism minimum inhibitory concentration (MIC). [24][25][26][27][28][29][30] Infectious diseases and CC pharmacists could improve selection of patient-specific, evidence-based strategies for critically ill patients requiring beta-lactam therapy and encouraging discovery of patients' true beta-lactam exposure through TDM.…”

Section: Discussionmentioning

confidence: 99%

Perceptions and practices for beta‐lactam antibiotic dosing, administration, and monitoring in critically ill patients: Current views and use among critical care and infectious diseases pharmacists

Hammond

McCreary

Rech

et al. 2019

J Am Coll Clin Pharm

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Purpose To elucidate considerations that infectious diseases (ID) and critical care (CC) pharmacists have regarding beta‐lactam antibiotics in critically ill adult patients in order to identify areas for practice improvement and future research. Materials and Methods A 17‐item survey was distributed to ID and CC pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables were compared using χ2 or Fisher's exact test, as appropriate. Results Ninety‐five of 834 ID pharmacists (11.4%) and 221 of 1436 CC pharmacists (15.4%) participated. Compared with ID pharmacists, more CC pharmacists would administer renally‐excreted beta‐lactams in critically ill patients with reduced renal function without dosage adjustment for 24 hours (17% vs 34%, P = 0.002). Most respondents believed therapeutic drug monitoring would be somewhat/very important in all surveyed scenarios. ID pharmacists more frequently believed antimicrobial stewardship teams should conduct prospective audits for definitive beta‐lactam therapy (98% vs 86%, P = 0.001), develop protocols for beta‐lactam use (95% vs 85%, P = 0.019), recommend beta‐lactam dosing (98% vs 85%, P < 0.001), and recommend empirical beta‐lactam selection (95% vs 81%, P = 0.001) compared with CC pharmacists. Conclusion Beta‐lactam dosing and monitoring recommendations in critically ill adults were frequently similar between pharmacy specialties. Research should be conducted in areas where opinions differ between specialties.

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Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials

Cited by 268 publications

References 74 publications

Piperacillin pharmacokinetics and target attainment in children with cancer and fever: Can we optimize our dosing strategy?

Piperacillin pharmacokinetics and target attainment in children with cancer and fever: Can we optimize our dosing strategy?

Augmented Renal Clearance

Perceptions and practices for beta‐lactam antibiotic dosing, administration, and monitoring in critically ill patients: Current views and use among critical care and infectious diseases pharmacists

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