Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with an external ventricular drain.

BACKGROUND: Owing to its antibacterial properties, ceftaroline could be attractive for prevention or treatment of bacterial post-neurosurgical meningitis/ventriculitis. However, few data are available concerning its meningeal concentrations. OBJECTIVES: To investigate ceftaroline CSF pharmacokinetics in ICU patients with an external ventricular drain (EVD). METHODS: Patients received a single 600 mg dose of ceftaroline as a 1 h intravenous infusion. Blood and CSF samples were collected before and 0.5, 1, 3, 6, 12 and 24 h after the end of the infusion. Concentrations were assayed in plasma and CSF by LC-MS/MS. A two-step compartmental pharmacokinetic analysis was conducted. Ceftaroline plasma data were first analysed, and thereafter plasma parameters estimated and corrected for protein binding of 20% were fixed to fit unbound CSF concentrations. In the final model, parameters for both plasma and CSF data were simultaneously estimated. RESULTS: Nine patients with an EVD were included. The Cmax was 18.29 ± 3.33 mg/L in plasma (total concentrations) and at 0.22 ± 0.17 mg/L in CSF (unbound concentration). The model-estimated CSF input/CSF output clearance ratio was 9.4%, attesting to extensive efflux transport at the blood-CSF barrier. CONCLUSIONS: Ceftaroline CSF concentrations are too low to ensure prophylactic protection against most pathogens with MICs between 1 and 2 mg/L, owing to its limited central distribution.

[Risk factors for the acquisition of Pseudomonas aeruginosa in a surgical intensive care unit]. / Facteurs de risque d'acquisition de Pseudomonas aeruginosa dans un service de réanimation chirurgicale et traumatologique.

OBJECTIVES: To investigate the risk factors for the acquisition (infection and/or colonization) of Pseudomonas aeruginosa, which is frequently associated with nosocomial infections, in a surgical intensive care unit in Dijon. METHOD: A retrospective case-control study was performed on 57 cases matching with 114 controls, between December 1996 and February 1999. The statistical method used was a conditional multiple logistic regression model. RESULTS: Three groups of variables were studied (patient characteristics--invasive procedures--previous administration of antibiotics). The multiple logistic regression analysis confirmed 3 risk factors: duration of sedation, infection with another bacteria and cranio-encephalic trauma. These factors are commonly involved in nosocomial infections. CONCLUSION: This study confirms the interest of infection control measures and the prevention of nosocomial infections, especially in cranio-encephalic trauma. The hypothetical relationship between acquisition of Pseudomonas aeruginosa and previous administration of antibiotics was not confirmed. A more powerful study would perhaps specify this relationship.