Penetration of Ceftaroline Into Cerebrospinal Fluid(CSF) (Ceftaroline)

Open and Exploratory Trial to Investigate the Pharmacokinetic of Ceftaroline in Patients With CSF Device

Ceftaroline is a piece of new cephalosporin very active on resistant staphylococci in methicillin (SEMR: Staphylococcus Epidermidis Resistant in Methicillin, SMAR: Staphylococcus Aureus Resistant in Methicillin)and/or in vancomycin ; Ceftaroline is also very active on pneumococci resistant in penicillin and/or 3rd generation of cephalosporins.

Ceftaroline was approved by the European Medicines Agency for the treatment of complicated skin and soft tissue infections and community-acquired pneumonia.

Scientific literature describes a good efficiency in septicemy and/or SAMR endocarditis.

Besides, a study on animal shows the efficiency of ceftaroline in meningeal infections with gram-negative Bacilli.

The rationale of this study is based on the antibacterial spectra of ceftaroline that could be used for the antibacterial treatment (curative and prophylactic) of CSF shunt associated infections.

To validate this hypothesis, it is necessary to evaluate the concentration of ceftaroline in meningeal compartment after treatment.

Study Overview

• Status: Completed
• Conditions: Meningitis; Ventriculitis
• Intervention / Treatment: Drug: Ceftaroline fosamil

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21079
    • CHU Dijon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (≥ 18 years)

  • Provision of informed consent prior to any study specific procedures
  • Female patients of childbearing potential may be entered if pregnancy testing is negative and the patient agrees to abstain from procreational sexual intercourse or must use double-barrier contraceptive measures for the duration of the study
• Presence of an indwelling external cerebrospinal fluid (CSF) access device (ventriculostomy or lumbar drain)
• Presence of inflamed meninges as a result of documented or suspected meningitis or ventriculitis. Patients with both clinical symptoms (fever, headache, meningismus, and altered mentation) and laboratory parameters (CSF leukocytosis, defined as a CSF white blood cell count [WBC] of >10 3, elevated CSF protein, defined as CSF protein of >1g/l, reduced CSF glucose, defined as CSF glucose of <0.3g/l, or a positive CSF Gram stain or culture) indicative of CNS infection were deemed to have definitive bacterial meningitis/ventriculitis. Inflamed meninges were defined as the presence of >5 leukocytes/mm3 of CSF.

Exclusion Criteria:

• Patient has documented history of hypersensitivity or allergic reaction (urticaria, angiooedema, anaphylaxis, desquamative rash) to any β-lactam antimicrobial including cephalosporins (contraindication to cephalosporins)
• Patient is pregnant or lactating and intends to continue breastfeeding
• Severe renal insufficiency defined as creatinine clearance < 50 mL/min.
• Patients with conditions known or suspected to alter pharmacokinetics (i.e., burn or cystic fibrosis patients)
• Refusal to participate
• Person not affiliated with the social security

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftaroline fosamil; 600mg 1 hour intravenous infusion ZINFORO	Drug: Ceftaroline fosamil; 600mg IV infusion; Other Names: ZINFORO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ceftaroline serum concentration	before infusion, at 0.5h, 1h, 3h, 6h, 12h, 24h after infusion
Ceftaroline cerebrospinal fluid concentration	before infusion, at 0.5h, 1h, 3h, 6h, 12h, 24h after infusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Publications and helpful links

General Publications

• Chauzy A, Nadji A, Combes JC, Defrance N, Bouhemad B, Couet W, Chavanet P. Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with an external ventricular drain. J Antimicrob Chemother. 2019 Mar 1;74(3):675-681. doi: 10.1093/jac/dky489.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2015
• Primary Completion (Actual): October 24, 2016
• Study Completion (Actual): October 24, 2016

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 16, 2016
• First Posted (Estimated): June 21, 2016

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuroinflammatory Diseases; Meningitis; Anti-Infective Agents; Anti-Bacterial Agents; Ceftaroline fosamil
• Other Study ID Numbers: Chavanet AZ 2014