ppi-0903 and Meningitis--Bacterial

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.. To investigate ceftaroline CSF pharmacokinetics in ICU patients with an external ventricular drain (EVD).. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Cerebral Ventricles; Cerebral Ventriculitis; Cerebrospinal Fluid; Chromatography, Liquid; Drainage; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meningitis, Bacterial; Middle Aged; Models, Theoretical; Neurosurgical Procedures; Postoperative Complications; Tandem Mass Spectrometry; Young Adult

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Female; Humans; Meningitis, Bacterial; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Staphylococcal Infections; Surgical Wound Infection; Treatment Outcome

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Cerebrospinal Fluid; Humans; Meningitis, Bacterial; Plasma; Ventriculoperitoneal Shunt

The only clinically available cephalosporin with in vivo and in vitro activity against methicillin-resistant Staphylococcus aureus is ceftaroline, which is approved for the treatment of soft tissue infection and community-acquired pneumonia in doses of 600 mg intravenously every 12 hours for 2 weeks or less. However, many clinicians use ceftaroline to treat more serious infections and dose more frequently (every 8 hours) for longer periods of time.. A retrospective medication safety assessment was performed at two centers where agranulocytosis was observed in four patients (two at each center) who were treated with ceftaroline. The cases were reviewed by the treating physicians for common features, and the frequency of agranulocytosis was calculated based on the total number of treated patients.. We report four cases of agranulocytosis associated with ceftaroline use, highlighted by prolonged use (more than 14 days) and 8-hour dosing intervals or 12-hour dosing intervals with concomitant clindamycin therapy. When ceftaroline (600 mg every 12 hours) and clindamycin (900 mg every 8 hours) were coadministered for more than 2 weeks, the frequency of agranulocytosis was 18% (2 of 18 patients treated). When ceftaroline alone was administered for more than 2 weeks at 600 mg every 8 hours, agranulocytosis occurred in 5.4% (2 of 37 treated patients). No cases of ceftaroline-related agranulocytosis were seen that did not have these features. In these patients, granulocyte-colony stimulating factor therapy usually resulted in rapid myeloid recovery.. Clinicians should have a heightened awareness of agranulocytosis when using ceftaroline in such settings and monitor complete blood counts at least once/week.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Clindamycin; Drug Therapy, Combination; Female; Fournier Gangrene; Humans; Male; Meningitis, Bacterial; Middle Aged; Retrospective Studies; Staphylococcal Infections; Surgical Wound Infection; Young Adult

A female patient 23 years old was admitted to the medical intensive care unit due to sudden loss of consciousness and seizures. At the time of admition observed lack of consciousness, seizures and severe critical condition was observed. Meningitis and septic shock were diagnosed. Based on computed tomography performed on the first day--inflammation of the sinuses soft tissues was diagnosed. Suspected cause of infection was performed 6 weeks earlier surgical correction of the nasal septum. In the next stage of treatment on the seventh day after admission the functional endoscopic sinus surgery was performed. Due to massive tissue hypoperfusion the necrosis in the skin of the lower limbs occurred. Due to the lack of effectiveness antimicrobial therapy use of intravenous ceftaroline was administrated. Effective treatment allowed in day 11 to wean the patient from the ventilator. At the day 26 the patient was transferred to a hospital in the place of residence.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Female; Humans; Intensive Care Units; Meningitis, Bacterial; Nasal Septum; Nasal Surgical Procedures; Postoperative Complications; Shock, Septic; Young Adult