Successful treatment of ventriculostomy-associated meningitis caused by multidrug resistant coagulase-negative Staphylococcus epidermidis using low-volume intrathecal daptomycin and loading strategy.

OBJECTIVE: To report successful use of low-volume intrathecal (IT) daptomycin and loading strategy for the treatment of ventriculostomy-associated meningitis. CASE SUMMARY: A 23-year-old man with a history of multiple ventriculoperitoneal shunt revisions resulting from multidrug-resistant Staphylococcus epidermidis shunt infection presented with meningitis despite suppressive antibiotic therapy. After source control surgery, the patient improved with intravenous daptomycin plus IT vancomycin. Then, 4 days later, significant ventriculostomy output occurred, and the S epidermidis was confirmed to be intermediately sensitive to vancomycin (MIC = 8 µg/mL) and susceptible to daptomycin (MIC = 2 µg/mL). IT vancomycin was changed to IT daptomycin 5 mg in 3 mL normal saline (NS) every 24 hours for 3 days, then every 72 hours for 18 days. The cerebrospinal fluid (CSF) was sterile after 1 day of IT daptomycin and remained so. Creatine kinase remained normal throughout the course of treatment. The patient was discharged on hospital day 50 without antibiotics. DISCUSSION: IT daptomycin has been reported for adult doses ranging from 5 to 10 mg once every 24 to 72 hours in volumes ranging from 5 to 10 mL; drug accumulation has been seen after the third dose of once every 24 hours dosing, and delayed improvement has been seen with once every 72 hours dosing. We planned for rapid load and CSF sterilization and extended the dosing interval once drug accumulation was expected to have occurred. CONCLUSIONS: IT daptomycin 5 mg diluted to 3 mL in NS and dosed in a loading strategy was effective and without adverse sequelae.

Regulation of cortical dendrite development by Rap1 signaling.

Rap1 is a small GTP-binding protein that has been implicated in intracellular signaling and cytoskeletal control. Here, we show that Rap1 is expressed in rat cortical neurons and plays a critical role in dendritic development. Inhibition of Rap1 signaling either by expressing dominant negative mutant of Rap1 or Rap1GAP in cortical neurons reduced dendritic complexity. In contrast, expression of a constitutively active mutant of Rap1 (Rap1V12) induced dendritic growth and branching. Membrane depolarization, which induces dendritic growth via calcium influx, led to a rapid activation of Rap1 via cAMP and cGMP signaling. A CREB-dependent mechanism is involved in depolarization-induced dendritic growth in cortical neurons. Rap1 function contributed to depolarization induced CREB activation, and inhibition of CREB suppressed dendritic growth induced by Rap1V12. These observations identify Rap1 as a key mediator of calcium regulation of CREB-dependent transcription and dendritic development.