Volume 2024, Issue 1 4684986
Research Article
Open Access

Cerebrospinal Pharmacokinetic Analysis and Pharmacodynamic Evaluation of Ceftriaxone in Pediatric Patients with Bacterial Meningitis

Tetsushu Onita

Corresponding Author

Tetsushu Onita

Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo, Shimane 693-8501, Japan shimane-u.ac.jp

Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan hiroshima-u.ac.jp

Search for more papers by this author
Kazuro Ikawa

Kazuro Ikawa

Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan hiroshima-u.ac.jp

Search for more papers by this author
Noriyuki Ishihara

Noriyuki Ishihara

Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo, Shimane 693-8501, Japan shimane-u.ac.jp

Search for more papers by this author
Hiroki Tamaki

Hiroki Tamaki

Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo, Shimane 693-8501, Japan shimane-u.ac.jp

Search for more papers by this author
Takahisa Yano

Takahisa Yano

Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo, Shimane 693-8501, Japan shimane-u.ac.jp

Search for more papers by this author
Norifumi Morikawa

Norifumi Morikawa

Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan hiroshima-u.ac.jp

Search for more papers by this author
Kohji Naora

Kohji Naora

Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo, Shimane 693-8501, Japan shimane-u.ac.jp

Search for more papers by this author
First published: 02 February 2024
Citations: 3
Academic Editor: Seema Saroj

Abstract

What Is Known? and Objective. Ceftriaxone has been widely used to treat bacterial meningitis in pediatric patients. Ceftriaxone dosing regimens of 80–120 mg/kg/day have been recommended for bacterial meningitis in pediatric patients, and the usual duration of therapy is 7–14 days. Although the target site for meningitis is cerebrospinal fluid (CSF), a CSF pharmacokinetic (PK) model in pediatric patients has not been reported. We aimed to develop a CSF PK model of ceftriaxone, using not only serum but also CSF concentration data, and to evaluate the appropriateness of dosing regimens for pediatric patients with bacterial meningitis. Methods. The population PK model was developed by simultaneously fitting serum and CSF data from pediatric patients described in nine published articles. Probabilities of attaining a pharmacodynamic target (100% T > MIC, 100% of time that drug concentrations above the minimum inhibitory concentration) in CSF were estimated for some dosing regimens. Results and Discussion. Twenty-four pediatric patients with meningitis were the subjects for PK modeling (0.52–13 years old, and 3.5–50 kg of body weight). Sixty-eight serum concentrations and 98 CSF samples were used to develop the CSF PK model. The CSF/serum concentration ratio at the same sampling time was 0.0628 ± 0.0689. Age was not a statistically significant covariate in the PK parameter. In the CSF PK model, 40–60 mg/kg q12 h achieved a target attainment probability >90% against causative bacteria for bacterial meningitis. However, 4-h infusion (rather than 0.5-h infusion) dosing regimens were required for efficacy against antimicrobial-resistant bacteria with high MICs. What Is New? and Conclusion. Ceftriaxone-dosing regimens with prolonged infusion times might be reasonably effective for treating antimicrobial-resistant pathogens in empiric therapy.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Data Availability

The data supporting the findings of this study were derived from the resource available in the public domain.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.