A concise route to benzofused macrolactones via ynolides: cycloproparadicicol.

A new facile synthesis has been developed for nanomolar Hsp90 inhibitor, cycloproparadicicol (2). Our approach relied on cobalt-complexation promoted RCM, in combination with tandem Diels-Alder/retro-Diels-Alder reactions to assemble the resorcycinylic macrolactone.

Cerebrospinal fluid penetration of imipenem and cilastatin (primaxin) in children with central nervous system infections.

Cerebrospinal fluid (CSF) penetration of imipenem-cilastatin was evaluated in 20 children (aged 4 months to 11 years) with central nervous system infections. A total of 10 children received a single 25-mg/kg intravenous dose, and 10 received three 25-mg/kg intravenous doses at 6-h intervals. Blood and CSF were obtained 1.5 to 2.5 h after the last dose during the early (days 1 to 3) and the late (days 7 to 10) stages of infection. Imipenem concentrations after single-dose infusion in serum and CSF during the early phase of treatment (8.59 +/- 0.95 and 1.36 +/- 0.32 micrograms/ml, respectively) were similar to those during the late phase (9.96 +/- 2.36 and 2.08 +/- 1.14 micrograms/ml, respectively). Concentrations of imipenem in serum and CSF after multiple-dose infusion during the early phase (11.97 +/- 2.03 and 1.87 +/- 0.29 micrograms/ml, respectively) were similar to those during the late phase (9.57 +/- 1.76 and 1.22 +/- 0.11 micrograms/ml, respectively). There were no significant differences in the serum or CSF imipenem concentrations between the single- and multiple-dose groups during the early or late treatment stages. Cilastatin concentrations in serum and CSF were similar in all groups with the exception of the multiple-dose, early- versus late-phase evaluation of CSF cilastatin concentration. There was no correlation between age or absolute CSF neutrophil count and the serum or CSF concentrations of imipenem or cilastatin. We found a mean CSF penetration of 15 to 27% for imipenem and 16 to 66% for cilastatin in children. These findings suggest that imipenem-cilastatin sufficiently penetrates into CSF in children to warrant further investigation of this compound in pediatric central nervous system infections.

Penetration of imipenem and cilastatin into cerebrospinal fluid of patients with bacterial meningitis.

The penetration of imipenem and cilastatin into the cerebrospinal fluid (CSF) was determined in patients with bacterial meningitis. Four 1000 mg doses [corrected] of both imipenem and cilastatin were infused intravenously over 20-30 min at 6 h intervals, first between days 2 and 4, and again, whenever possible, between days 11 to 20, in 12 patients with bacterial meningitis undergoing treatment with other antibiotics. Concentrations of imipenem and cilastatin in serum and cerebrospinal fluid samples obtained either at 60, 90 or 120 min following the fourth dose were measured by high pressure liquid chromatography. Concentrations of imipenem in CSF ranged from 0.5 to 11 mg/1 and concentrations of cilastatin ranged from 1.1 to 10.5 mg/1, depending on the sampling time and the time elapsed since the onset of the disease.