Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis*

Rhodes, Nathaniel J.; Liu, Jiajun; O’Donnell, John M.; Dulhunty, Joel M.; Abdul‐Aziz, Mohd H.; Berko, Patsy Y.; Nadler, Barbara; Lipman, J; Roberts, Jason A.

doi:10.1097/ccm.0000000000002836

Cited by 95 publications

(86 citation statements)

References 42 publications

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“…20,21 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. 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).…”

Section: Discussionsupporting

confidence: 54%

“…While EI strategies improve the probability of pharmacodynamic target attainment in critically ill patients, various issues (eg, intravenous access, staff education, and transitions of care) create potential barriers to wider adoption . 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 .…”

Section: Discussionmentioning

confidence: 83%

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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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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 83%

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

Self Cite

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“…The target levels were most frequently missed in the q6 dosage regimen, presumably due to augmented renal clearance in those patients. For them, other dosing regimens like continuous infusion are necessary to achieve the target [50]. Richter et al reported higher rates of target attainment and reduced mortality in patients treated with continuous piperacillin infusion in contrast to a short infusion regimen [51].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

et al. 2020

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Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The extent to which therapeutic drug monitoring (TDM) in clinical practice can reduce insufficient antibiotic concentrations is an ongoing matter of investigation. We retrospectively evaluated routine meropenem and piperacillin measurements in critically ill patients who received antibiotics as short infusions in the first year after initiating a beta-lactam TDM program. Total trough concentrations above 8.0 mg/L for meropenem and above 22.5 mg/L for piperacillin were defined as the breakpoints for target attainment. We included 1832 meropenem samples and 636 piperacillin samples. We found that 39.3% of meropenem and 33.6% of piperacillin samples did not reach the target concentrations. We observed a clear correlation between renal function and antibiotic concentration (meropenem, r = 0.53; piperacillin, r = 0.63). Patients with renal replacement therapy or creatinine clearance (CrCl) of <70 mL/min had high rates of target attainment with the standard dosing regimens. There was a low number of patients with a CrCl >100 mL/min that achieved the target concentrations with the maximum recommended dosage. Patients with impaired renal function only required TDM if toxic side effects were noted. In contrast, patients with normal renal function required different dosage regimens and TDM-guided therapy to reach the breakpoints of target attainment.

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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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Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis*

Abstract: Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients.

Cited by 95 publications

References 42 publications

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

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

Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

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

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