Defining the impact of severity of illness on time above the MIC threshold for cefepime in Gram-negative bacteraemia: a ‘Goldilocks’ window

Miglis, Cristina; Rhodes, Nathaniel J.; Kuti, Joseph L.; Nicolau, David P.; Wart, Scott A. Van; Scheetz, Marc H.

doi:10.1016/j.ijantimicag.2017.04.023

Cited by 22 publications

(14 citation statements)

References 20 publications

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“…PK variability of β‐lactams and the association of target attainment with clinical outcomes have been widely reported in critically ill adults, 3,4 but limited data exist in critically ill children. Because β‐lactam antibiotic efficacy depends on the time free drug concentration is above the minimum inhibitory concentration (MIC) of bacteria, it is crucial to ensure appropriate antibiotic doses are given to achieve adequate concentrations in relation to the MIC (termed target attainment).…”

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confidence: 99%

Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of β‐Lactam Antibiotics in Critically Ill Children

Girdwood

Tang

Murphy

et al. 2020

The Journal of Clinical Pharma

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There has been increasing interest in incorporating β‐lactam precision dosing into routine clinical care, but robust population pharmacokinetic models in critically ill children are needed for these purposes. The objective of this study was to demonstrate the feasibility of an opportunistic sampling approach that utilizes scavenged residual blood for future pharmacokinetic studies of cefepime, meropenem, and piperacillin. We aimed to show that opportunistic samples would cover the full concentration‐versus‐time profiles and to evaluate stability of the antibiotics in whole blood and plasma to optimize future use of the opportunistic sampling approach. A prospective observational study was conducted in a single‐center pediatric intensive care unit, where pediatric patients administered at least 1 dose of cefepime, meropenem, or piperacillin/tazobactam and who had residual blood scavenged from samples obtained for routine clinical care were enrolled. A total of 138 samples from 22 pediatric patients were collected in a 2‐week period. For all 3 antibiotics, the samples collected covered the entire dosing intervals and were not clustered around specific times. There was high variability in the free concentrations and in the percentage of drug bound to protein. There was less than 15% degradation for meropenem or piperacillin when stored in whole blood or plasma at 4°C after 6 days. Cefepime degraded by more than 15% after 3 days. The opportunistic sampling approach is a powerful and feasible method to obtain sufficient samples to study the variability of drug concentrations and protein binding for future pharmacokinetic studies in the pediatric critical care population.

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confidence: 99%

Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of β‐Lactam Antibiotics in Critically Ill Children

Girdwood

Tang

Murphy

et al. 2020

The Journal of Clinical Pharma

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“…Literature suggests that higher maximal doses of cefepime, even when renally adjusted, may be more beneficial than standard cefepime dosing [ 32 ]. Because time above MIC is critical for clinical success of cefepime dosing, our study evaluated if the dose was appropriate based on the infection type and renal function [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Infections with Susceptibilities among Levofloxacin, Cefepime, and Carbapenems

Walker

Lee

Klar

2018

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Purpose Highly resistant Gram-negative bacterial infections are associated with high mortality. Increasing resistance to standard therapy illustrates the need for alternatives when treating resistant organisms, especially extended-spectrum beta-lactamase- (ESBL-) producing Enterobacteriaceae. Methods A retrospective chart review at a community hospital was performed. Patients who developed ESBL-producing infections were included. Patients less than eighteen years old, who were pregnant, or who were incarcerated were excluded. The primary outcome was hospital mortality. The secondary outcomes included intensive care unit (ICU) mortality, ICU length of stay, and hospital length of stay. Results 113 patients with ESBL-producing infections met the criteria for review. Hospital mortality: carbapenem (16.6%), cefepime (0%), and levofloxacin (15.3%) (p=0.253). ICU mortality: carbapenem (4.5%), cefepime, (0%), and levofloxacin (3.7%) (p=0.616). Mean ICU and hospital length of stay: carbapenem (9.8 ± 16, 12.1 ± 1 days), cefepime (7.8 ± 6, 11.1 ± 10.5 days), and levofloxacin (5.4 ± 4.1, 11.1 ± 10.4 days) (p=0.805, 0.685). No predictors were clearly found between the source of infection and mortality. Conclusion Cefepime or levofloxacin can be a potential alternative agent for infections with ESBL-producing Enterobacteriaceae, and larger clinical trials investigating these outcomes are warranted.

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“…Although every patient may not require beta-lactam TDM, selection of patients most likely to benefit should become part of standard ICU care of critically ill patients with infections. Achievement of target drug concentrations is one of the most important and modifiable factors in improving infected patient outcomes ( 24 , 25 ).…”

Section: Clinical Application and Future Directionsmentioning

confidence: 99%

Setting the Beta-Lactam Therapeutic Range for Critically Ill Patients: Is There a Floor or Even a Ceiling?

Barreto

Webb

Pais

et al. 2021

Critical Care Explorations

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Defining the impact of severity of illness on time above the MIC threshold for cefepime in Gram-negative bacteraemia: a ‘Goldilocks’ window

Cited by 22 publications

References 20 publications

Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of β‐Lactam Antibiotics in Critically Ill Children

Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of β‐Lactam Antibiotics in Critically Ill Children

Clinical Outcomes of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Infections with Susceptibilities among Levofloxacin, Cefepime, and Carbapenems

Setting the Beta-Lactam Therapeutic Range for Critically Ill Patients: Is There a Floor or Even a Ceiling?

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