What are the guidelines for using intraventricular antibiotics, such as gentamicin (an aminoglycoside) or vancomycin, in neonates with ventriculitis or central nervous system (CNS) infections?

Intraventricular Antibiotics in Neonates with CNS Infections

Intraventricular antibiotics are not recommended as routine treatment for neonatal CNS infections due to increased mortality risk, and should be reserved only for specific cases of treatment-refractory ventriculitis with multidrug-resistant organisms under specialist consultation. 1, 2

General Principles for CNS Infections in Neonates

• For neonatal meningitis and ventriculitis, intravenous (IV) vancomycin is the recommended first-line therapy for suspected or confirmed MRSA infections 3
• Standard IV vancomycin dosing for neonates is 15 mg/kg as an initial dose, followed by 10 mg/kg every 12 hours for neonates in the 1st week of life and every 8 hours thereafter up to 1 month of age 4
• Each vancomycin dose should be administered over at least 60 minutes to minimize infusion-related reactions 4
• For MRSA CNS infections, some experts recommend adding rifampin (15-20 mg/kg/day divided every 12 hours) to vancomycin to improve CNS penetration 3
• Alternative therapies for CNS infections include linezolid (10 mg/kg/dose PO/IV every 8 hours, not exceeding 600 mg/dose) or TMP-SMX (5 mg/kg/dose IV every 8-12 hours) 3

Evidence Against Routine Intraventricular Antibiotics

• A landmark multicenter controlled trial found that infants receiving intraventricular gentamicin plus systemic antibiotics had a significantly higher mortality rate (42.9%) compared to those receiving systemic antibiotics alone (12.5%) 2
• A Cochrane systematic review concluded that intraventricular antibiotics in addition to IV antibiotics resulted in a three-fold increased risk of mortality compared to IV antibiotics alone 1
• Based on this evidence, intraventricular antibiotics as tested in these trials should be avoided for routine treatment 1

Special Considerations for CNS Shunt Infections

• For CNS shunt infections, shunt removal is strongly recommended, and the shunt should not be replaced until CSF cultures are repeatedly negative 3
• Surgical drainage of focal abscesses and removal of any foreign body should be performed whenever possible 3
• The duration of antibiotic therapy for CNS infections is typically 2 weeks for uncomplicated meningitis and 4-6 weeks for brain abscess, subdural empyema, or spinal epidural abscess 3

Limited Exceptions for Intraventricular Antibiotics

• Intraventricular antibiotics may be considered in highly selected cases of treatment-refractory ventriculitis caused by multidrug-resistant organisms 5, 6, 7
• When used, intraventricular gentamicin dosing of 1 mg every 24-36 hours has been reported in older case series for treatment of resistant infections 7
• Any use of intraventricular antibiotics should be done in consultation with infectious disease specialists and neurosurgeons 5, 6
• Recent case reports suggest combining intraventricular endoscopic surgery with intraventricular antibiotics may be beneficial in select cases of multiloculated hydrocephalus with ventriculitis 6

Pharmacokinetic Considerations

• CSF penetration of vancomycin is poor (1-5%), with maximum CSF concentrations of 2-6 μg/mL 3
• Linezolid has better CSF penetration (up to 66%), with CSF peak and trough concentrations of 7-10 μg/mL and 2.5-6.0 μg/mL, respectively 3
• TMP-SMX has CSF penetration of 13-53% for TMP and 17-63% for SMX 3
• Rifampin has CSF penetration of approximately 22% and can achieve bactericidal concentrations in CSF 3

Monitoring and Follow-up

• Close monitoring of serum vancomycin concentrations is recommended in neonates to ensure therapeutic levels while minimizing toxicity 4
• In premature infants, vancomycin clearance decreases as postconceptional age decreases, potentially requiring longer dosing intervals 4
• Follow-up CSF cultures should be obtained to document clearance of infection, particularly before replacement of any CSF shunt 3

Remember that the evidence strongly discourages routine use of intraventricular antibiotics in neonates with CNS infections due to increased mortality risk. Treatment should focus on appropriate systemic antibiotics with good CNS penetration, surgical intervention when indicated, and specialist consultation for complex cases.