Central Nervous System Infection
Conditions
Interventions
1:Blood samples were collected at the following times: 1) within -3h before the first dose (blank) or at screening
2) within 48-72h after the first dose, 6 points were collected within one dosing interval: in the case of intravenous infusion for 2 h: sampling time was 1h (during infusion) after the start of intrav
2) within 48-72h after the first dose, 2ml cerebrospinal fluid samples were collected at the same time as PK blood samples, and cerebrospinal fluid samples were collected at 0-1h, 1-2h, 2-2.5h, 2.5-3h
3) 2ml cerebrospinal fluid samples were collected at the same time as PK blood samples collected at the last dose, and cerebrospinal flui
Sponsors
Huashan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be included in the study: Obtain the subject or his/her legal representative voluntarily sign the informed consent form approved by the Ethics Committee before the start of the study; Aged 18 to 70 years, male or female; Patients after neurosurgery; Patients who are clinically suspected or confirmed as having central nervous system infection after neurosurgery and receive Ceftobiprole alone for anti-infection as assessed by the physician (see Appendix 1 for the detailed basis for the diagnosis of central nervous system infection); Patients requiring continuous drainage of cerebrospinal fluid due to disease condition (including external ventricular drainage or lumbar drainage); Patients who have received antimicrobial therapy for more than 48 hours before enrollment, but whose symptoms and signs of infection have not been relieved, and whose cerebrospinal fluid culture remains positive may also be enrolled.
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria could not be included in the study: 1) Known or suspected hypersensitivity to active substances or any excipients listed in [Ingredients], cephalosporin antibiotics, other types of ß-lactam antibiotics (such as penicillin, monoamides or carbapenems) and other serious hypersensitivity; 2) Unstable vital signs or inability to obtain cerebrospinal fluid samples; 3) Ommaya capsule and other devices are estimated not to be removed or replaced during the whole treatment process, and permanent indwelling is required; 4) Drug can not control status epilepticus, or may affect the compliance of the program mental illness, or suicide risk; 5) History of alcohol abuse; 6) Having a history of illicit drug abuse; 7) Patients with cerebrospinal fluid culture for Enterococcus faecium or ESBL-producing Enterobacteriaceae; 8) According to the doctor 's judgment, Ceftobiprole Medocaril Sodium alone could not control the infection; 9) Patients with moderate and severe renal dysfunction, i.e., endogenous creatinine clearance (CrCL) = 50 mL/min; endogenous creatinine clearance (male) = (140-age) × body weight (kg)/[0.818 × serum creatinine value (µmol/L)] endogenous creatinine clearance (female) = endogenous creatinine clearance (male) × 0.85 10) Abnormal liver function tests: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 5 times the upper limit of the reference value 3 days before enrollment, and total bilirubin 2 times the upper limit of the reference value 3 days before enrollment; 11) Patients with any known disease that seriously affects the immune system, such as: history of human immunodeficiency virus (HIV) infection; or advanced hematological malignancies; or splenectomy; 12) Female pregnancy (blood or urine pregnancy test positive), lactation patients; 13) Any condition that the investigator considers may increase the risk of the subject or interfere with the clinical study; 14) Patients who have participated in this clinical study and used the study drug before inclusion;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Blood PK(Pharmacokinetics) parameters: Cmax, ss (maximum concentration at steady state), Cmin, ss (trough concentration at steady state), Cav, ss (plateau concentration at steady state), AUCPlasma 0-6h, ss (area under the concentration-time curve from 0 to 6h at steady state), Tmax (time to maximum concentration), T1/2 (elimination half-life), CLss (clearance at steady state), Vss (volume of distribution at steady state);Cerebrospinal fluid PK(Pharmacokinetics) parameters: Cmax, ss(maximum concentration at steady state), Cmin, ss (trough concentration at steady state), AUCCSF 0-6h, ss (area under the concentration-time curve from 0 to 6h at steady state), Tmax (time to maximum concentration), T1/2(elimination half-life), CLss(clearance at steady state), segmented cerebrospinal fluid output and excretion rate, cumulative cerebrospinal fluid output and cumulative excretion rate.;Penetration evaluation: The drug concentration ratio (CCSF, ss/CPlasma, ss), AUC ratio (AUCCSF 0-8h, ss/AUC0-8h, ss) and peak drug concentration ratio (Cmax-CSF, ss/Cmax-Plasma, ss) of ceftobiprole in cerebrospinal fluid at different time points were calculated to evaluate the penetration of ceftobiprole 500 mg q6h in cerebrospinal fluid at steady state after infusion.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Laboratory tests, vital signs, 12-lead ECG and physical examination, etc. Incidence of adverse events and serious adverse events.;Clinical response assessments: analyses of early clinical response, clinical response at end of treatment (EOT), cure assessment (TOC), and all-cause mortality at 28 days after start of study drug administration. Microbiological response assessment (if data allowed): Clear, presumed clear, not clear, presumed not clear, uncertain. ;Correlation analysis of biomarkers (central nervous system S100 protein, neuron-specific enolase NSE, etc.) in blood and cerebrospinal fluid with brain injury and cerebrospinal fluid penetration of ceftobiprole.; | — |
Countries
China
Contacts
Public ContactMao Ying/ Zhang Jing
Huashan Hospital, Fudan University
Outcome results
None listed