Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy

Pfausler, Bettina; Spiss, Heinrich; Beer, Ronny; Kampl, Andreas; Engelhardt, K.; Schober, Maria; Schmutzhard, Erich

doi:10.3171/jns.2003.98.5.1040

Cited by 126 publications

(84 citation statements)

References 26 publications

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“…In some cases, several attempts are necessary in order to establish a functioning, uninfected shunt, and in such cases, there is evidence of poorer outcome. Intravenous administration of most of the common antimicrobials does not reliably lead to therapeutic antibiotic levels in the CSF (1,19,23,24). Intraventricular antibiotic administration involves a risk of introduction of infection, and administration of some antibiotics by this route is not possible due to neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Action of Linezolid or Vancomycin on Biofilms in Ventriculoperitoneal Shunts In Vitro

Bayston

Ullas

Ashraf

2012

Antimicrob Agents Chemother

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Cerebrospinal fluid (CSF) shunts used to treat hydrocephalus have an overall infection rate of about 10% of operations. The commonest causative bacteria are Staphylococcus epidermidis, followed by Staphylococcus aureus and enterococci. Major difficulties are encountered with nonsurgical treatment due to biofilm development in the shunt tubing and inability to achieve sufficiently high CSF drug levels by intravenous administration. Recently, three cases of S. epidermidis CSF shunt infection have been treated by intravenous linezolid without surgical shunt removal, and we therefore investigated vancomycin and linezolid against biofilms of these bacteria in vitro. A continuous-perfusion model of shunt catheter biofilms was used to establish mature (1-week) biofilms of Staphylococcus aureus, Staphylococcus epidermidis (both methicillin resistant [MRSA and MRSE]), Enterococcus faecalis, and Enterococcus faecium. They were then "treated" with either vancomycin or linezolid in concentrations achievable in CSF for 14 days. The biofilms were then monitored for 1 week for eradication and for regrowth. Enterococcal biofilms were not eradicated by either vancomycin or linezolid. Staphylococcal biofilms were eradicated by both antibiotics after 2 days and did not regrow. No resistance was seen. Linezolid at concentrations achievable by intravenous or oral administration was able to eradicate biofilms of both S. epidermidis (MRSE) and S. aureus (MRSA). Neither vancomycin at concentrations achievable by intrathecal administration nor linezolid was able to eradicate enterococcal biofilms. It is hoped that these in vitro results will stimulate further clinical trials with linezolid, avoiding surgical shunt removal.

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Section: Discussionmentioning

confidence: 99%

Action of Linezolid or Vancomycin on Biofilms in Ventriculoperitoneal Shunts In Vitro

Bayston

Ullas

Ashraf

2012

Antimicrob Agents Chemother

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“…Elimination halflives appear to be longer after injection into the lumbar than into the ventricular CSF: the CSF elimination half-life of a hydrophilic radioactive compound ( 111 indium-diethylene triamine pentaacetic acid [ 111 In-DTPA]) injected into the lumbar CSF space was estimated to be 12.4 to 131.1 h (median, 31.7 h) (167). Conversely, the elimination half-life of the large hydrophilic drug vancomycin after intraventricular injection ranged from 3.0 to 20.5 h (median, 5.2 h) (191,192,204).…”

Section: Physiology Of the Exchange Of Drugs Between Blood And The DImentioning

confidence: 99%

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

2010

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SUMMARY The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.

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“…Our study also confirms the relative delay in CSF linezolid peak concentrations (240 min versus 60 min for plasma after bolus infusion), which is in agreement with the amphiphilic properties of the substance (6). In addition, recent studies demonstrated that tissue penetration of antimicrobial agents is markedly determined by the presence of local or systemic inflammation (12,19). Therefore, the severity of inflammation of the ventricular ependyma could influence the penetration of linezolid into the CSF.…”

mentioning

confidence: 99%

“…However, EVDs are not without complications, the most significant of which is infection resulting in ventriculitis or ventriculomeningitis (2,4,14) caused predominantly by gram-positive bacteria, especially multiresistant coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA) (7). Standard antimicrobial therapy with vancomycin has major limitations: the penetration of vancomycin in the cerebral spinal fluid (CSF), even through inflamed meninges and ventricular ependyma, is poor (1,19). Adverse effects, mainly its nephrotoxicity, often represent contraindications for vancomycin therapy in critically ill patients.…”

mentioning

confidence: 99%

Pharmacokinetics of Intravenous Linezolid in Cerebrospinal Fluid and Plasma in Neurointensive Care Patients with Staphylococcal Ventriculitis Associated with External Ventricular Drains

Beer

Engelhardt

Pfausler

et al. 2007

Antimicrob Agents Chemother

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The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five neurointensive care patients with staphylococcal ventriculitis was studied. The mean area under concentration-time curve (؎ standard deviation) was 63 ؎ 18.9 mg · h/liter, with a CSF-to-plasma ratio of 0.8 ؎ 0.3. Times above MIC in CSF were 99.8% and 57.2% for pathogens with MICs of 2 mg/liter and 4 mg/liter, respectively.

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Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy

Abstract: Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.

Cited by 126 publications

References 26 publications

Action of Linezolid or Vancomycin on Biofilms in Ventriculoperitoneal Shunts In Vitro

Action of Linezolid or Vancomycin on Biofilms in Ventriculoperitoneal Shunts In Vitro

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

Pharmacokinetics of Intravenous Linezolid in Cerebrospinal Fluid and Plasma in Neurointensive Care Patients with Staphylococcal Ventriculitis Associated with External Ventricular Drains

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