JAC Advance Access originally published online on December 21, 2007
Journal of Antimicrobial Chemotherapy 2008 61(2):461-462; doi:10.1093/jac/dkm501
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Research letters |
Treatment of external ventricular drain-associated ventriculitis caused by Enterococcus faecalis with intraventricular daptomycin
1 Department of Medical Microbiology, Frenchay Hospital, Bristol BS16 1LE, UK 2 Department of Neurosurgery, Frenchay Hospital, Bristol BS16 1LE, UK
* Corresponding author. Tel: +44-117-9186590; Fax: +44-117-9571866; E-mail: erwin.brown{at}nbt.nhs.uk
Keywords: neurosurgical infections , ventricular access device , intrathecal
External ventricular drains (EVDs) are essential monitoring devices in neurosurgery, and direct portals for the removal of cerebrospinal fluid (CSF), including the temporary control of raised intracranial pressure, and for the instillation of therapeutic agents. Their benefits must be balanced against the complications associated with their use, the most important of which is infection (ventriculitis). Most patients with EVD-associated ventriculitis can be cured by instilling antibiotics directly into the ventricles.1 We describe here a patient with such an infection treated by administering daptomycin using this route.
A 62-year-old man was admitted to this hospital with a subarachnoid haemorrhage and underwent coil occlusion of an anterior communicating artery aneurysm. Four days later, he became confused and was noted to have raised intracranial pressure; a lumbar drain was inserted. He subsequently became pyrexial and culture of CSF obtained via the lumbar drain yielded Klebsiella pneumoniae. An EVD was inserted and the ventriculitis was successfully treated with a 14 day course of intravenous ceftazidime and intraventricular gentamicin. The intention was to remove the EVD on day 30. However, Gram’s stain examination of a sample of CSF showed Gram-positive cocci, and Enterococcus faecalis, which was susceptible to ampicillin and vancomycin, but exhibited high-level resistance to gentamicin (MIC > 200 mg/L), was isolated. Vancomycin (10 mg) was instilled into the ventricles, but, after 8 days of therapy, E. faecalis was still recovered from the CSF. The MIC of daptomycin for this strain was 2.0 mg/L, as determined by an Etest on Mueller–Hinton agar, and this drug was administered intravenously at a dosage of 1 g (12 mg/kg) once daily. In addition, the EVD was removed and an Ommaya reservoir was implanted. Following a further 4 days of therapy with intraventricular vancomycin, E. faecalis was again recovered from the CSF. It was therefore decided to instil daptomycin into the ventricles at a dosage of 10 mg every third day; consent was obtained from the patient. Trough and peak daptomycin CSF concentrations (determined just before and 30 min after a dose, respectively, by high-performance liquid chromatography at the Department of Medical Microbiology, Southmead Hospital, Bristol, UK) were 23 and 483 mg/L, respectively. The dosage of daptomycin was reduced to 5 mg every third day, and trough and peak daptomycin CSF concentrations at the lower dosage were 9.9 and 139 mg/L, respectively. The CSF became sterile within 3 days of commencing intraventricular daptomycin and remained so throughout the 2 week treatment period. The patient remained well and he was eventually discharged from hospital. However, he was re-admitted 28 days later with symptoms and signs of meningitis. Culture of a sample of CSF yielded E. faecalis with the same antibiogram as the original isolate and treatment with intraventricular daptomycin at a dosage of 5 mg every third day was restarted. In addition, the Ommaya reservoir was replaced with an EVD. Daptomycin was administered for 4 weeks during which time he experienced transient pyrexias after each instillation of daptomycin; this side effect was resolved when the treatment was discontinued. The CSF became sterile, the EVD was removed and he was discharged from hospital 39 days after he had been re-admitted. Clinical and bacteriological cures were sustained after follow-up for more than 1 year.
EVD-associated ventriculitis is one of the most common infections in neurosurgical practice. Until recently, only three antibiotics have been available in formulations suitable for intraventricular use: vancomycin, gentamicin and colomycin. Enterococci are increasingly being recognized as causes of ventriculitis in neurosurgical patients, and some strains exhibit resistance to vancomycin or high-level resistance to the aminoglycosides, thereby limiting treatment options. Linezolid has been used successfully as systemic therapy in such cases.2,3 However, this antibiotic is not bactericidal and prolonged courses increase the risks of adverse effects. Daptomycin is the first of a new class of antibiotics, the cyclic lipopeptides. It has been shown to be rapidly bactericidal against enterococci, including vancomycin-resistant strains.4 Daptomycin penetrates poorly into the CSF compartment when given by the systemic route. In a rabbit model of meningitis caused by Streptococcus pneumoniae, only 5% of the corresponding serum concentration was achieved in the CSF, and the drug failed to sterilize the CSF after 4 days, despite the administration of a high dosage.5 On the other hand, a study involving a rabbit model of Staphylococcus aureus ventriculitis demonstrated that intraventricular daptomycin achieved greater bactericidal activity, more rapid killing kinetics and a longer half-life in the ventricles than intraventricular vancomycin.6 Many years’ experience of managing patients with EVD-associated ventriculitis by instilling antibiotics into the ventricles encouraged us to treat the patient described in this report with intraventricular daptomycin. This present experience suggests that intraventricular daptomycin is an effective therapy of patients with EVD-associated ventriculitis caused by enterococci; it may be equally appropriate as treatment for patients with ventriculitis caused by other Gram-positive bacteria and those with CSF shunt infections. However, additional clinical data are needed to confirm its clinical efficacy and safety in this setting.
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No specific funding was received for this study.
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J. E. and D. P. have nothing to declare. E. B. has served on Novartis advisory boards and received speaker’s fees from Novartis.
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1 Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy. The management of neurosurgical patients with postoperative bacterial or aseptic meningitis or external ventricular drain-associated ventriculitis. Br J Neurosurg (2000) 14:7–12.[CrossRef][Web of Science][Medline]
2 Shaikh ZH, Peloquin CA, Ericsson CD. Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid; case report and literature review. Scand J Infect Dis (2001) 33:375–9.[CrossRef][Web of Science][Medline]
3 Graham PL, Ampofo K, Saiman L. Linezolid treatment of vancomycin-resistant Enterococcus faecium ventriculitis. Pediatr Infect Dis J (2002) 21:798–800.[CrossRef][Web of Science][Medline]
4
Huovinen P, Kotilainen P. In vitro activity of a new cyclic lipopeptide antibiotic, LY146032, against Gram-positive clinical bacteria. Antimicrob Agents Chemother (1987) 31:455–7.
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Cottagnoud P, Pfister M, Acosta F, et al. Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant pneumococci in experimental meningitis. Antimicrob Agents Chemother (2004) 48:3928–33.
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Haworth CS, Sobieski MW, Scheld M, et al. Staphylococcus aureus ventriculitis treated with single-dose vancomycin or daptomycin (LY146032): bacterial and antibiotic kinetics in hydrocephalic rabbits. Antimicrob Agents Chemother (1990) 34:245–51.
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