Use of therapeutic drug monitoring to characterize cefepime‐related neurotoxicity

Venugopalan, Veena; Casaus, Danielle; Kainz, Leonie; Slaton, Cara N; Hurst, Natalie; Bruzzone, Maria; Hu, Calvin; Sword, Gabriel; Cherabuddi, Kartikeya; Iovine, Nicole M.; Liu, Jiajun; Scheetz, Marc H.; Rhodes, Nathaniel J; Maranchick, Nicole; Peloquin, Charles A.; Klinker, Kenneth P.; Al‐Shaer, Mohammad H.

doi:10.1002/phar.2744

Cited by 12 publications

(16 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…Dose-dependent neurotoxicity with cefepime has been observed in approximately 5% of patients. 33,47 Several limitations exist with this study which must be considered. Key subpopulations were excluded such as those treated with extracorporeal membrane oxygenation or kidney replacement therapy who are known to have profound PK derangements.…”

Section: Discussionmentioning

confidence: 99%

“…Safety must be simultaneously considered alongside effectiveness outcomes including clinical and microbiologic cure. Dose‐dependent neurotoxicity with cefepime has been observed in approximately 5% of patients 33,47 …”

Section: Discussionmentioning

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%

See 3 more Smart Citations

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

et al. 2023

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

confidence: 99%

See 2 more Smart Citations

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

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the incidence has been highly variable among different reports, ranging from 4% to 23% in diverse settings. 16 …”

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

View full text Add to dashboard Cite

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.

show abstract

Acute kidney injury is associated with abnormal cefepime exposure among critically ill children and young adults

Pavia,

Girdwood,

Paice

et al. 2024

Pediatr Nephrol

View full text Add to dashboard Cite

Background Elevated cefepime blood concentrations can cause neurotoxicity in adults. The consequences of elevated cefepime concentrations among pediatric patients are unknown. Future exploration of such effects requires first identifying patients at risk for elevated cefepime exposure. We investigated the role of acute kidney injury as a risk factor for increased cefepime concentrations in critically ill children. Methods This was a retrospective analysis at a single pediatric intensive care unit. Analyzed patients received at least 24 h of cefepime and had at least two opportunistic samples collected for total cefepime concentration measurement. Individual pharmacokinetic (PK) profiles during treatment courses were reconstructed using Bayesian estimation with an established population PK model. Elevated trough concentration (Cmin) was defined as ≥ 30 mg/L based on adult toxicity studies. The effect of kidney dysfunction on cefepime PK profiles was interrogated using a mixed-effect model. Results Eighty-seven patients were included, of which 13 (14.9%) had at least one estimated Cmin ≥ 30 mg/L. Patients with elevated Cmin were more likely to have acute kidney injury (AKI) during their critical illness (92% vs. 57%, p = 0.015 for any AKI; 62% vs. 26%, p = 0.019 for severe AKI). Patients who had AKI during critical illness had significantly higher cefepime exposure, as quantified by the area under the concentration–time curve over 24 h (AUC24h) and Cmin. Conclusions Among critically ill children, AKI is associated with elevated cefepime concentrations. Identifying these high-risk patients is the first step toward evaluating the clinical consequences of such exposures. Graphical abstract

show abstract

Use of therapeutic drug monitoring to characterize cefepime‐related neurotoxicity

Cited by 12 publications

References 35 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

Acute kidney injury is associated with abnormal cefepime exposure among critically ill children and young adults

Contact Info

Product

Resources

About