Poor central nervous system penetration of tigecycline in a patient with sepsis and ventriculitis caused by multidrug-resistant Klebsiella pneumoniae

Objective: To report the use of tigecycline in a case of ventriculitis and concurrent bacteremia. Case Summary: A 57-year-old African American male with a ruptured brain aneurysm was admitted to the intensive care unit after surgical intervention and external ventricular drainage placement. His hospital course was complicated by myocardial infarction, ventilator-associated pneumonia, ventriculitis, and sepsis, with multidrug-resistant (MDR) Klebsiella pneumoniae isolated from multiple sites, including blood and cerebral spinal fluid (CSF). The patient was treated with high doses of intravenous tigecycline and gentamicin along with intrathecal gentamicin. This combination eradicated infections outside the central nervous system (CNS) within 48 hours, but it took approximately 8 days for the CSF culture to become negative. Timed serum and CSF fluid samples were collected to determine CSF penetration of tigecycline on day 12 of therapy. CSF concentrations obtained 30 minutes after the dose and at the end of the dosing interval remained below the detectable limit of 0.05 μg/mL. Discussion: Although CSF tigecycline concentrations may not represent actual CNS tissue concentrations at the site of infection, the low CSF concentrations observed in our case may be responsible for the slow CSF clearance of infection. It was not clear whether gentamicin therapy alone, administered both intravenously and intrathecally, would have achieved the same outcome and cleared the infection from the CNS in this patient. Conclusions: Until additional clinical data are available, tigecycline should not be used for the management of MDR infections associated with the CNS.