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Article

Pharmacokinetics and Pharmacodynamics of Cefepime in Adults with Hematological Malignancies and Febrile Neutropenia after Chemotherapy

by 1,2,‡, 1,2,3,*,†,‡, 2,4,‡, 2,4,5,‡, 2,3,‡, 4,‡, 2,3,‡, 1,2,3,‡ and 1,5,‡
1
Facultad de Medicina, Universidad Nacional de Colombia, 111321 Bogotá, Colombia
2
Grupo en Enfermedades Infecciosas en Cáncer y Alteraciones Hematológicas (GREICAH), Universidad Nacional de Colombia, 111321 Bogotá, Colombia
3
Instituto Nacional de Cancerología (INC)—Empresa Social del Estado, 111511 Bogotá, Colombia
4
Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, 111321 Bogotá, Colombia
5
Grupo de Investigación en Enfermedades Infecciosas, Facultad de Medicina, Universidad Nacional de Colombia, 111321 Bogotá, Colombia
*
Author to whom correspondence should be addressed.
Current address: Carrera 45 N° 26-85, Edificio Uriel Gutiérrez, 111321 Bogotá, Colombia.
These authors contributed equally to this work.
Academic Editors: Philipp Simon and David P. Nicolau
Received: 23 March 2021 / Revised: 17 April 2021 / Accepted: 21 April 2021 / Published: 29 April 2021
(This article belongs to the Special Issue Optimizing Antibiotic Treatment: Pharmacokinetics and Clinical Trials)
Patients with chemotherapy-induced febrile neutropenia (CIFN) may have changes in the pharmacokinetics (PK) compared to patients without malignancies or neutropenia. Those changes in antibiotic PK could lead to negative outcomes for patients if the therapy is not adequately adjusted to this. In this, open-label, non-randomized, prospective, observational, and descriptive study, a PK model of cefepime was developed for patients with hematological neoplasms and post-chemotherapy febrile neutropenia. This study was conducted at a cancer referral center, and study participants were receiving 2 g IV doses of cefepime every 8 h as 30-min infusions. Cefepime PK was well described by a two compartment model with a clearance dependent on a serum creatinine level. Using Monte Carlo simulations, it was shown that continuous infusions of 6g q24h could have a good achievement of PK/PD targets for MIC levels below the resistance cut-off point of Enterobacteriaceae. According to the simulations, it is unnecessary to increase the daily dose of cefepime (above 6 g daily) to increase the probability of target attainment (PTA). Cumulative fraction of response (CFR) using interment dosing was suboptimal for empirical therapy regimens against K. pneumoniae and P. aeruginosa, and continuous infusions could be used in this setting to maximize exposure. Patients with high serum creatinine levels were more likely to achieve predefined PK/PD targets than patients with low levels. View Full-Text
Keywords: cefepime; cephalosporins; pharmacokinetics; chemotherapy-induced febrile neutropenia; hematologic neoplasms cefepime; cephalosporins; pharmacokinetics; chemotherapy-induced febrile neutropenia; hematologic neoplasms
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MDPI and ACS Style

Álvarez, J.C.; Cuervo, S.I.; Silva, E.; Díaz, J.A.; Jiménez, L.L.; Parra, D.S.; Gómez, J.C.; Sánchez, R.; Cortés, J.A. Pharmacokinetics and Pharmacodynamics of Cefepime in Adults with Hematological Malignancies and Febrile Neutropenia after Chemotherapy. Antibiotics 2021, 10, 504. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050504

AMA Style

Álvarez JC, Cuervo SI, Silva E, Díaz JA, Jiménez LL, Parra DS, Gómez JC, Sánchez R, Cortés JA. Pharmacokinetics and Pharmacodynamics of Cefepime in Adults with Hematological Malignancies and Febrile Neutropenia after Chemotherapy. Antibiotics. 2021; 10(5):504. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050504

Chicago/Turabian Style

Álvarez, José C., Sonia I. Cuervo, Edelberto Silva, Jorge A. Díaz, Lorena L. Jiménez, Daniel S. Parra, Julio C. Gómez, Ricardo Sánchez, and Jorge A. Cortés 2021. "Pharmacokinetics and Pharmacodynamics of Cefepime in Adults with Hematological Malignancies and Febrile Neutropenia after Chemotherapy" Antibiotics 10, no. 5: 504. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050504

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