Implementing Extended-Infusion Cefepime as Standard of Care in a Children’s Hospital

Nichols, Kristen R.; Karmire, Lauren C.; Cox, Elaine G.; Kays, Michael B.; Knoderer, Chad A.

doi:10.1177/1060028014566447

Cited by 16 publications

(11 citation statements)

References 20 publications

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“…[17][18][19] The feasibility of implementing cefepime PI in pediatric patients has been described in the literature. 20 A comparison of clinical outcomes in pediatric patients receiving cefepime, piperacillin-tazobactam, or meropenem via PI or SI infusions was recently published but did not identify any significant differences in length of stay, hospital readmission, or mortality. 21 Additional PK differences in pediatric patients with CF specifically increased lean body mass to adipose tissue ratio and decreased lung penetration of antibiotics, are expected to further reduce PTA in children with CF.…”

mentioning

confidence: 99%

Evaluation of the safety of cefepime prolonged infusions in pediatric patients with cystic fibrosis

Imburgia

Engdahl

Pettit

2022

Pediatric Pulmonology

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Objective: Pediatric cystic fibrosis (CF) patients possess unique pharmacokinetics and may benefit from prolonged beta-lactam infusions to optimize pharmacodynamics. This study compared adverse drug event (ADE) rates with cefepime prolonged (PI) and standard infusions (SI).Methods: This retrospective study included pediatric patients treated with cefepime for CF exacerbations between 2009 and 2019. One encounter per patient was analyzed with prioritization of SI encounters given sample size limitations. Baseline lab abnormalities, seizure disorders, and bleeding were exclusion criteria. The primary outcome was a composite safety endpoint (acute kidney injury [AKI], hepatotoxicity, hematologic toxicity, neurotoxicity, and hypersensitivity).Results: Of 188 patients, 135 received PI and 53 received SI. Baseline characteristics were similar between groups. More PI patients used CF transmembrane conductance regulator (CFTR) modulators (25% vs. 0%, p < 0.01) or had antibiotic allergies (62% vs. 38%, p = 0.02). Difference in rates of composite safety endpoint was not statistically significant between PI and SI (21 [15.6%] vs. 6 [11.3%] p = 0.46) nor was incidence of AKI (16 [11.8%] vs. 6 [11.3%], p = 0.92). Other ADEs were rarely observed. Length of stay (12.2 vs. 10.1 days, p = 0.06), change in discharge ppFEV1 from admission (13 vs. 12, p = 0.91) or from baseline (−4 vs. −6.5, p = 0.33), and time to next exacerbation (249.7 vs. 192.5 days, p = 0.93) were similar. Conclusions:No difference in risk of ADEs including AKI was seen with cefepime PI in pediatric CF patients. Clinical outcomes were not significantly different between groups, but sample size may have limited comparison. PI cefepime may be considered in pediatric CF patients to optimize pharmacodynamics.

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confidence: 99%

Evaluation of the safety of cefepime prolonged infusions in pediatric patients with cystic fibrosis

Imburgia

Engdahl

Pettit

2022

Pediatric Pulmonology

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“…Mathematical modeling studies have questioned the ability of conventional cefepime regimens with doses administered over 30 minutes to achieve adequate f T > MIC, and they support either increased administration frequency or prolonged infusion time to optimize pharmacodynamic target attainment . These findings have promoted the use of extended‐infusion (EI) cefepime in clinical practice . Immediate‐infusion cefepime pharmacokinetics have been described in various detail for patients receiving one of the three more common CRRT modalities: continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF); however, to our knowledge, no studies have been identified that evaluate EI cefepime in patients receiving CRRT .…”

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confidence: 99%

“…[16][17][18][19][20][21][22] These findings have promoted the use of extended-infusion (EI) cefepime in clinical practice. [22][23][24] Immediate-infusion cefepime pharmacokinetics have been described in various detail for patients receiving one of the three more common CRRT modalities: continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF); however, to our knowledge, no studies have been identified that evaluate EI cefepime in patients receiving CRRT. [25][26][27][28][29][30] Furthermore, previous literature suggests that cefepime dose reductions are required in patients receiving CRRT; however, more recent data highlight prevalent antibiotic underdosing in patients receiving CRRT and recommend aggressive dosing to minimize the risk of antibiotic failure due to lack of achievement of the pharmacodynamic target.…”

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confidence: 99%

Pharmacokinetics and Pharmacodynamics of Extended‐Infusion Cefepime in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Prospective, Open‐Label Study

et al. 2019

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Study Objective To evaluate extended‐infusion (EI) cefepime pharmacokinetics (PK) and pharmacodynamic target attainment in critically ill patients receiving continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD). Design Prospective, open‐label, PK study. Setting Intensive care units at a large, academic, tertiary‐care medical center. Patients Ten critically ill adults who were receiving cefepime 2 g intravenously every 8 hours as a 4‐hour infusion while receiving CVVH (eight patients) or CVVHD (two patients). Intervention Two sets of five serum cefepime concentrations were collected for each patient to assess pharmacokinetics before and during presumed steady state. Concurrent serum and CRRT effluent samples were collected at hours 1, 2, 3, 4, and 8 after the first cefepime dose and after either the fourth, fifth, or sixth (steady‐state) cefepime doses. Measurements and Main Results Reversed‐phase high‐performance liquid chromatography was used to determine free cefepime concentrations. PK analyses included CRRT clearance, half‐life, and sieving coefficient or saturation coefficient. Cefepime peak (4 hrs) concentrations, trough (8 hrs) concentrations (Cmin), and minimum inhibitory concentration breakpoint of 8 µg/ml for the pathogen (MIC8) were used to evaluate attainment of pharmacodynamic targets: 100% of the dosing interval that free drug remains above MIC8 (100% fT > MIC8), 100% fT > 4 × MIC8 (optimal), percentage of time fT > 4 × MIC8 (%fT > 4 × MIC8) at steady state, and ratio of Cmin to MIC8 (fCmin/MIC8). Total CRRT effluent flow rate was a mean ± SD of 30.1 ± 5.4 ml/kg/hr, CRRT clearance was 39.6 ± 9.9 ml/min, and half‐life was 5.3 ± 1.7 hours. Sieving coefficient or saturation coefficient were 0.83 ± 0.13 and 0.69 ± 0.22, respectively. First and steady‐state dose Cmin were 23.4 ± 10.1 µg/ml and 45.2 ± 14.6 µg/ml, respectively. All patients achieved 100% fT > MIC8 on first and steady‐state doses. First and steady‐state dose 100% fT > 4 × MIC8 were achieved in 22% (2/9 patients) and 87.5% (7/8 patients) of patients, respectively. The mean %fT > 4 × MIC8 at steady state was 97.5%. The fCmin/MIC8 was 2.92 ± 1.26 for the first dose and 5.65 ± 1.83 at steady state. Conclusion Extended‐infusion cefepime dosing in critically ill patients receiving CRRT successfully attained 100% fT > MIC8 in all patients and an appropriate fCmin/MIC8 for both first and steady‐state doses. All but one patient achieved 100% fT > 4 × MIC8 at steady state. No significant differences were observed in PK properties between first and steady‐state doses among or between patients. It may be reasonable to initiate an empiric or definitive regimen of EI cefepime in critically ill patients receiving concurrent CRRT who are at risk for resistant organisms. Further research is needed to identify the optimal dosing regimen of EI cefepime in this patient population.

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“…To date, no studies evaluated the impact of administering cefepime as prolonged infusion, among the pediatric population. Descriptive evidence published by Nichols et al, suggests that implementing extended-infusion of cefepime as standard of care is feasible and not related to major complications, in children with a median age of six years admitted to several pediatric departments, excluding intensive care units [72]. However, comparison of outcomes with patients receiving conventional intermittent infusions were beyond the scope of their study.…”

Section: Clinical Outcomesmentioning

confidence: 95%

Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?

et al. 2020

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Optimizing the use of antibiotics has become mandatory, particularly for the pediatric population where limited options are currently available. Selecting the dosing strategy may improve overall outcomes and limit the further development of antimicrobial resistance. Time-dependent antibiotics optimize their free concentration above the minimal inhibitory concentration (MIC) when administered by continuous infusion, however evidences from literature are still insufficient to recommend its widespread adoption. The aim of this review is to assess the state-of-the-art of intermittent versus prolonged intravenous administration of antibiotics in children and neonates with bacterial infections. We identified and reviewed relevant literature by searching PubMed, from 1 January 1 2000 to 15 April 2020. We included studies comparing intermittent versus prolonged/continuous antibiotic infusion, among the pediatric population. Nine relevant articles were selected, including RCTs, prospective and retrospective studies focusing on different infusion strategies of vancomycin, piperacillin/tazobactam, ceftazidime, cefepime and meropenem in the pediatric population. Prolonged and continuous infusions of antibiotics showed a greater probability of target attainment as compared to intermittent infusion regimens, with generally good clinical outcomes and safety profiles, however its impact in terms on efficacy, feasibility and toxicity is still open, with few studies led on children and adult data not being fully extendable.

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Implementing Extended-Infusion Cefepime as Standard of Care in a Children’s Hospital

Abstract: Because 93.0% of the patients who initially received EIC remained on EIC, implementation of EIC as the standard dosing strategy was feasible in this pediatric hospital.

Cited by 16 publications

References 20 publications

Evaluation of the safety of cefepime prolonged infusions in pediatric patients with cystic fibrosis

Evaluation of the safety of cefepime prolonged infusions in pediatric patients with cystic fibrosis

Pharmacokinetics and Pharmacodynamics of Extended‐Infusion Cefepime in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Prospective, Open‐Label Study

Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?

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