Failure of linezolid therapy for post-neurosurgical meningitis due to Enterococcus faecium

Abstract

Nosocomially acquired intracranial infections may be caused by a wide array of microorganisms, including staphylococci, enterococci, Gram-negative bacilli and yeasts. In the presence of prosthetic devices, the treatment of choice for infections caused by Gram-positive organisms is removal of the device and iv administration of vancomycin. However, experimental and clinical data suggest that the penetration of vancomycin into CSF is poor and sometimes unpredictable in cases without severe meningeal inflammation. Some authors have reported that in patients with meningitis, continuous intravenous administration of vancomycin may lead to higher penetration, though in patients without meningitis CSF concentrations usually remain below 4 mg/L. 2 The breakpoint concentration for susceptible organisms may not be achieved consistently in patients without severe meningeal inflammation, even when high daily doses of up to 4 g are used. Therefore, some authors advocate intrathecal administration of vancomycin, although a comprehensive evaluation of the benefits has yet to be made and the associated risks, such as ototoxicity, remain unclear. 2 Treatment of ampicillin-resistant enterococcal infections is further complicated by the fact that the activity of vancomycin is bacteriostatic. The CSF may not be sterilized unless bactericidal activity is established by the addition of gentamicin. 1 These factors, and the desire to avoid further surgery to establish intrathecal access, made linezolid an attractive treatment option for our patient. Linezolid is the first licensed member of the oxazolidinone class of antibiotics with activity against almost all Gram-positive pathogens. Excellent tissue penetration and 100% oral bioavailability are notable properties of linezolid and it is approved in Europe and the USA for the treatment of nosocomial pneumonia, skin and soft tissue infections and, in the USA, vancomycin-resistant E. faecium and methicillin-resistant Staphylococcus aureus (MRSA) infections. 3 Linezolid has also been shown to have good penetration into the CNS. 4 A 2007 review of the evidence regarding the use of linezolid for the treatment of patients with CNS infections identified 42 relevant cases. In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin-non- susceptible Streptococcus pneumoniae (7; 17.9%), vancomycin-resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%) and MRSA (3; 7.7%). Of the 42 patients treated with linezolid, 38 were either cured or showed clinical improvement. 5 Case reports of other authors have found that enterococci disappeared from the CSF after as little as 2 days of iv linezolid treatment. 6