Clinical Pharmacokinetics and Pharmacodynamics of Cefepime

Pais, Gwendolyn; Chang, Jack; Barreto, Erin F.; Stitt, Gideon; Downes, Kevin J.; Al‐Shaer, Mohammad H.; Lesnicki, Emily; Panchal, Vaidehi; Bruzzone, Maria; Bumanglag, Argyle V.; Burke, Sara N.; Scheetz, Marc H.

doi:10.1007/s40262-022-01137-y

Cited by 38 publications

(29 citation statements)

References 170 publications

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“…Use of invasive mechanical ventilation was protective in the %ƒT > 32 analysis (i.e., associated with a higher %ƒT > 32) (Table S7, Table S8). Using the individual concentration‐time curves from the PK model, no patients had cefepime trough concentrations that exceeded 35 mg/L or higher in the first 24 h, a threshold that has been associated with an increased risk for neurotoxicity 23,32,33 …”

Section: Resultsmentioning

confidence: 99%

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Adequacy of cefepime concentrations in the early phase of critical illness: A case for precision pharmacotherapy

et al. 2023

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Study ObjectiveIn critically ill patients, adequacy of early antibiotic exposure has been incompletely evaluated. This study characterized factors associated with inadequate cefepime exposure in the first 24 h of critical illness.DesignProspective cohort study.SettingAcademic Medical Center.PatientsCritically ill adults treated with cefepime. Patients with acute kidney injury or treated with kidney replacement therapy or extracorporeal membrane oxygenation were excluded.InterventionNone.MeasurementsA nonlinear mixed‐effects pharmacokinetic (PK) model was developed to estimate cefepime concentrations for each patient over time. The percentage of time the free drug concentration exceeded 8 mg/L during the first 24 h of therapy was calculated (%ƒT>8; appropriate for the susceptible breakpoint for Pseudomonas aeruginosa). Factors predictive of low %ƒT>8 were explored with multivariable regression.Main ResultsIn the 100 included patients, a one‐compartment PK model was developed with first‐order elimination with covariates for weight and estimated glomerular filtration rate based on creatinine and cystatin C (eGFRSCr‐CysC). The median (interquartile range) %ƒT>8 for cefepime in the first 24 h of therapy based on this model was 85% (66%, 100%). Less than 100% ƒT>8 during first 24 h of therapy occurred in 70 (70%) individuals. Lower Sequential Organ Failure Assessment score (p = 0.032) and higher eGFRSCr‐CysC (p < 0.001) predicted a lower %ƒT>8. Central nervous system infection source was protective (i.e., associated with a higher %ƒT>8; p = 0.008).ConclusionsDuring early critical illness, cefepime concentrations were inadequate in a significant proportion of patients. Antimicrobial optimization is needed to improve the precision of pharmacotherapy in the critically ill patients.

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Section: Resultsmentioning

confidence: 99%

“…Using the individual concentration-time curves from the PK model, no patients had cefepime trough concentrations that exceeded 35 mg/L or higher in the first 24 h, a threshold that has been associated with an increased risk for neurotoxicity. 23,32,33…”

Section: Predictors Of the Percent Time The Free Drug Concentration E...mentioning

confidence: 99%

Adequacy of cefepime concentrations in the early phase of critical illness: A case for precision pharmacotherapy

et al. 2023

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“…The drug was first approved in the United States in 1996. 11 , 12 The potential neurotoxic effects of cefepime were first reported in 1999 in a patient with end-stage renal disease undergoing hemodialysis. The patient developed an altered mental status, myoclonus, and generalized tonic–clonic seizures with an elevated serum cefepime concentration.…”

Section: Discussionmentioning

confidence: 99%

Cefepime-induced encephalopathy in an older patient with polypharmacy and renal insufficiency: a case report

Tsai,

Wang

2024

J Int Med Res

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The world population is rapidly aging. Societal aging poses many challenges for individuals, families, nations, and the global healthcare system. Therefore, geriatric care is a crucial issue that demands our attention. In this case report, we describe a woman in her early 70s with multiple comorbidities, polypharmacy, and renal insufficiency who developed cefepime-induced encephalopathy with moderate to severe cerebral dysfunction during treatment of a urinary tract infection. The patient’s consciousness level gradually improved, and no further seizures were observed following the discontinuation of cefepime for several days. This case report underscores the fact that polypharmacy and medication safety are significant concerns that are often overlooked when caring for older patients. The report also highlights the increased susceptibility of older individuals to antibiotic-associated adverse reactions during the management of infectious diseases. Therefore, optimization of antibiotic therapy for older patients is a critical issue that requires thorough investigation and consideration in geriatric care.

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“…Unsurprisingly, given the newness of the process, pharmacist feedback indicated a desire for a reference document to enhance recognition of both “normal” ranges and potential toxic levels. In response, the BL steering committee reviewed recent literature 1,39,41 and consulted with an international expert to develop updated thresholds for toxicity, as well as an infographic to support this educational need which was posted to the internal web resource.…”

Section: Lessons Learnedmentioning

confidence: 99%

“…38 Once patient specific culture data became available, clinical pharmacists adapted the goal to the highest MIC of the isolated organism(s). To account for the potential for dosedependent BL neurotoxicity, 39 we initially included calculator prompts for dose re-evaluation when trough concentrations exceeded 64 mcg/ mL for cefepime, 124 mcg/mL for piperacillin, and 16 mcg/mL for meropenem (i.e., 8 times the P.aeruginosa susceptible breakpoint). 10 These were later revised slightly.…”

Section: Pharmacokinetic/pharmacodynamic Targetmentioning

confidence: 99%

“How to” guide for pharmacist‐led implementation of beta‐lactam therapeutic drug monitoring in the critically ill

Ausman

Moreland‐Head

Saleh

et al. 2023

J Am Coll Clin Pharm

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Beta‐lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes in critically ill patients, but has not been implemented widely in the United States. Mayo Clinic recently implemented a beta‐lactam TDM program. This single‐center experience forms the basis of the manuscript which outlines practical considerations involved with beta‐lactam TDM implementation, including the pharmacist's role as a leader. Our implementation effort focused on three primary domains. First, we aimed to ensure a supportive organizational infrastructure. Early leadership engagement by the pharmacist‐led core team facilitated advocacy for the clinical need, allocation of resources, and assay development. Second, core clinical workflows were developed that addressed the preferred patient population for use, desirable pharmacokinetic and pharmacodynamic targets, and the preferred sampling strategy. Clinical tools to guide pharmacists in interpreting the results (e.g., pharmacokinetics calculator) and documenting decisions were developed. Third, stakeholders were offered repeated exposure to evidence and expertise to facilitate understanding and application of the new practice. This act of ‘individual internalization’ seems to be uniquely important to beta‐lactam TDM implementation compared with the implementation of other antimicrobial TDM programs. Educational strategies and supportive materials that were developed were focused on providing substantive and varied information tailored to the stakeholders' role in the process. For pharmacists, this included both clinical and operational considerations. A continuous improvement plan to support management of the process was instituted to address necessary updates and changes that inevitably emerged. In summary, the described approach to implementation of a pharmacist‐led beta‐lactam TDM program could be used as a roadmap to aid other institutions that aim to develop such a program.

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Clinical Pharmacokinetics and Pharmacodynamics of Cefepime

Cited by 38 publications

References 170 publications

Adequacy of cefepime concentrations in the early phase of critical illness: A case for precision pharmacotherapy

Adequacy of cefepime concentrations in the early phase of critical illness: A case for precision pharmacotherapy

Cefepime-induced encephalopathy in an older patient with polypharmacy and renal insufficiency: a case report

“How to” guide for pharmacist‐led implementation of beta‐lactam therapeutic drug monitoring in the critically ill

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