Ventriculostomy-associated
infections, or ventriculitis, in
critically ill patients are associated with considerable morbidity. Efficacious
antibiotic dosing for the treatment of these
infections may be complicated by altered
antibiotic concentrations in the cerebrospinal fluid due to variable meningeal
inflammation and
antibiotic properties. Therefore, doses used to treat
infections with a higher degree of meningeal
inflammation (such as
meningitis) may often fail to achieve equivalent exposures in patients with
ventriculostomy-associated
infections such as ventriculitis. This paper aims to review the disease burden,
infection rates, and common pathogens associated with
ventriculostomy-associated
infections. This review also seeks to describe the disease- and drug-related factors that influence
antibiotic distribution into cerebrospinal fluid and provide a critical appraisal of current dosing of
antibiotics commonly used to treat these types of
infections. A Medline search of relevant articles was conducted and used to support a review of cerebrospinal fluid penetration of
vancomycin, including critical appraisal of the recent paper by Beach et al. recently published in this journal. We found that in the intensive care unit,
ventriculostomy-associated
infections are the most common and serious complication of external ventricular drain insertion and often result in prolonged patient stay and increased healthcare costs. Reported
infection rates are extremely variable (between 0 and 45%), hindered by the inherent diagnostic difficulty. Both Gram-positive and Gram-negative organisms are associated with such
infections and the rise of multi-drug-resistant pathogens means that effective treatment is an ongoing challenge. Disease factors that may need to be considered are reduced meningeal
inflammation and the presence of
critical illness; drug factors include physiochemical properties, degree of
plasma-protein binding, and affinity to active transporter
proteins present in the blood-cerebrospinal fluid barrier. The relationship between cerebrospinal fluid
antibiotic exposures in the setting of
ventriculostomy-associated
infection and clinical response has not been fully elucidated for many of the
antibiotics commonly used in its treatment. More thorough and clinically relevant investigations are needed to better define blood pharmacokinetic/pharmacodynamics targets and optimal therapeutic exposures for treatment of
ventriculostomy-associated
infections. It is hoped that this future research will be able to provide clearer recommendations for clinicians frequently faced with dosing-related dilemmas when treating patients with these challenging
infections.