Clinical trial NCT02806882: Penetration of Ceftaroline Into Cerebrospinal Fluid(CSF)
Official title: Open and Exploratory Trial to Investigate the Pharmacokinetic of Ceftaroline in Patients With CSF Device
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Meningitis
Ventriculitis
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2016-06-21
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Ceftaroline serum concentration
timeFrame: before infusion, at 0.5h, 1h, 3h, 6h, 12h, 24h after infusion
measure: Ceftaroline cerebrospinal fluid concentration
timeFrame: before infusion, at 0.5h, 1h, 3h, 6h, 12h, 24h after infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Dijon
country: France
facility: CHU Dijon
Study officials:
References:
citation: 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.