Extended Infusion of Beta-Lactams Is Associated With Improved Outcomes in Pediatric Patients

Overview

Journal J Pediatr Pharmacol Ther

Specialty Pediatrics

Date 2021 Feb 19

PMID 33603583

Citations 11

Authors

Tracy N Zembles

Rachael Schortemeyer

Evelyn M Kuhn

Glenn Bushee

Nathan E Thompson

Michelle L Mitchell

Affiliations

Soon will be listed here.

Abstract

Objective: The pharmacokinetics of beta-lactam antibiotics favor administration via an extended infusion. Although literature supporting extended infusion beta-lactams exists in adults, few data are available to guide the practice in pediatrics. The purpose of this study was to compare clinical outcomes between extended and standard infusions in children.

Methods: This retrospective chart analysis included hospitalized patients 0 to 18 years old who received at least 72 hours of cefepime, piperacillin-tazobactam, or meropenem between October 1, 2017, and March 31, 2019. Clinical outcomes of care included hospital length of stay, readmission within 30 days, and all-cause mortality.

Results: A total of 551 patients (258 extended infusion, 293 standard infusion) met criteria for evaluation. Clinical outcomes among the entire population were similar. A subanalysis of select populations demonstrated decreased mortality in critical care patients (2.1% vs 19.6%, p = 0.006) and decreased 30-day readmission rates in bone marrow transplant patients (0% vs 50%, p = 0.012) who received the extended infusion compared with a standard infusion.

Conclusions: Outcomes were similar between extended and standard infusions in children. Subgroup analyses suggest a possible mortality benefit in the critically ill and decreased readmission rate in bone marrow transplant patients.

Citing Articles

Continuous versus intermittent infusion of beta-lactam antibiotics: where do we stand today? A narrative review.

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Extended-Infusion β-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections.

Karaba S, Cosgrove S, Lee J, Fiawoo S, Heil E, Quartuccio K JAMA Netw Open. 2024; 7(7):e2418234.

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Extended Infusion of Beta-Lactams and Glycopeptides: A New Era in Pediatric Care? A Systematic Review and Meta-Analysis.

Burch A, von Arx L, Hasse B, Neumeier V Antibiotics (Basel). 2024; 13(2).

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Extended infusion of β-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis.

Budai K, Timar A, Obeidat M, Mate V, Nagy R, Harnos A EClinicalMedicine. 2023; 65:102293.

PMID: 38021371 PMC: 10651452. DOI: 10.1016/j.eclinm.2023.102293.

Optimization of β-Lactam Dosing Regimens in Neonatal Infections: Continuous and Extended Administration versus Intermittent Administration.

Leegwater E, Wewerinke L, de Grauw A, van Veen M, Storm B, Kruizinga M Clin Pharmacokinet. 2023; 62(5):715-724.

PMID: 36972008 DOI: 10.1007/s40262-023-01230-w.

References

Shabaan A, Nour I, Elsayed Eldegla H, Nasef N, Shouman B, Abdel-Hady H . Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis: A Randomized Controlled Trial. Pediatr Infect Dis J. 2016; 36(4):358-363. DOI: 10.1097/INF.0000000000001445. View

Roberts D, Roberts J, Roberts M, Liu X, Nair P, Cole L . Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study. Crit Care Med. 2012; 40(5):1523-8. DOI: 10.1097/CCM.0b013e318241e553. View

Roberts J, Paul S, Akova M, Bassetti M, De Waele J, Dimopoulos G . DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients?. Clin Infect Dis. 2014; 58(8):1072-83. DOI: 10.1093/cid/ciu027. View

Roberts J, Abdul-Aziz M, Davis J, Dulhunty J, Cotta M, Myburgh J . Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials. Am J Respir Crit Care Med. 2016; 194(6):681-91. DOI: 10.1164/rccm.201601-0024OC. View

Falagas M, Tansarli G, Ikawa K, Vardakas K . Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2012; 56(2):272-82. DOI: 10.1093/cid/cis857. View

Turnidge J . The pharmacodynamics of beta-lactams. Clin Infect Dis. 1998; 27(1):10-22. DOI: 10.1086/514622. View

Cotrina-Luque J, Gil-Navarro M, Acosta-Garcia H, Alfaro-Lara E, Luque-Marquez R, Beltran-Garcia M . Continuous versus intermittent piperacillin/tazobactam infusion in infection due to or suspected pseudomonas aeruginosa. Int J Clin Pharm. 2015; 38(1):70-9. DOI: 10.1007/s11096-015-0208-y. View

Nichols K, Karmire L, Cox E, Kays M, Knoderer C . Implementing extended-infusion cefepime as standard of care in a children's hospital: a prospective descriptive study. Ann Pharmacother. 2015; 49(4):419-26. DOI: 10.1177/1060028014566447. View

Udy A, Varghese J, Altukroni M, Briscoe S, McWhinney B, Ungerer J . Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2011; 142(1):30-39. DOI: 10.1378/chest.11-1671. View

10.

Craig W . Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998; 26(1):1-10; quiz 11-2. DOI: 10.1086/516284. View

11.

Bauer K, West J, OBrien J, Goff D . Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2013; 57(7):2907-12. PMC: 3697364. DOI: 10.1128/AAC.02365-12. View

12.

Dulhunty J, Roberts J, Davis J, Webb S, Bellomo R, Gomersall C . A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. Am J Respir Crit Care Med. 2015; 192(11):1298-305. DOI: 10.1164/rccm.201505-0857OC. View

13.

Pollack M, Patel K, Ruttimann U . The Pediatric Risk of Mortality III--Acute Physiology Score (PRISM III-APS): a method of assessing physiologic instability for pediatric intensive care unit patients. J Pediatr. 1997; 131(4):575-81. DOI: 10.1016/s0022-3476(97)70065-9. View

14.

Vardakas K, Voulgaris G, Maliaros A, Samonis G, Falagas M . Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2017; 18(1):108-120. DOI: 10.1016/S1473-3099(17)30615-1. View

15.

Nichols K, Knoderer C, Cox E, Kays M . System-wide implementation of the use of an extended-infusion piperacillin/tazobactam dosing strategy: feasibility of utilization from a children's hospital perspective. Clin Ther. 2012; 34(6):1459-65. DOI: 10.1016/j.clinthera.2012.05.005. View

16.

Knoderer C, Karmire L, Andricopulos K, Nichols K . Extended Infusion of Piperacillin/Tazobactam in Children. J Pediatr Pharmacol Ther. 2017; 22(3):212-217. PMC: 5473395. DOI: 10.5863/1551-6776-22.3.212. View

17.

MacVane S, Kuti J, Nicolau D . Prolonging β-lactam infusion: a review of the rationale and evidence, and guidance for implementation. Int J Antimicrob Agents. 2013; 43(2):105-13. DOI: 10.1016/j.ijantimicag.2013.10.021. View

18.

Teo J, Liew Y, Lee W, Kwa A . Prolonged infusion versus intermittent boluses of β-lactam antibiotics for treatment of acute infections: a meta-analysis. Int J Antimicrob Agents. 2014; 43(5):403-11. DOI: 10.1016/j.ijantimicag.2014.01.027. View

19.

Walker M, Lam W, Manasco K . Continuous and extended infusions of β-lactam antibiotics in the pediatric population. Ann Pharmacother. 2012; 46(11):1537-46. DOI: 10.1345/aph.1R216. View

20.

Winstead E, Ratliff P, Hickson R, Mueller J, Judd W . Evaluation of an alternative extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections. Int J Clin Pharm. 2016; 38(5):1087-93. DOI: 10.1007/s11096-016-0334-1. View