Pharmacokinetics and protein binding of linezolid in cerebrospinal fluid and serum in a case of post-neurosurgical bacterial meningitis

Tsuji, Yasuhiro; Hiraki, Yoichi; Matsumoto, Kana; Mizoguchi, Akiko; Sadoh, Shinichi; Kobayashi, Tsutomu; Takemura, Yusuke; Sakamoto, Seisaburo; Morita, Kunihiko; Kamimura, Hidetoshi; Karube, Yoshiharu

doi:10.3109/00365548.2011.600327

Cited by 16 publications

(16 citation statements)

References 15 publications

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“…In this study, the linezolid concentrations in plasma and CSF were much lower than those reported in most other PK studies performed in critically ill patients [12][13][14][15]25].…”

Section: Discussioncontrasting

confidence: 63%

“…In one case study of linezolid in meningitis, the authors reported similar drug concentrations in plasma and CSF and suggested that plasma concentrations are a suitable indicator of CSF penetration [15]. This is unsurprising as drug penetration in meningitis should be greater than in patients with non-inflamed meninges.…”

Section: Discussionmentioning

confidence: 99%

“…A c c e p t e d M a n u s c r i p t [4,[12][13][14][15][16]. This population can develop severe pathophysiological changes (e.g.…”

Section: Page 5 Of 31mentioning

confidence: 99%

“…When considering an MIC of 2 mg/L, optimal pharmacokinetic/pharmacodynamic (PK/PD) targets in plasma and CSF were achieved in the majority of the previously described experiences [12][13][14][15]. However, using an MIC of 4 mg/L, a value for less susceptible strains [20], these PK/PD ratios were only achieved in two studies [12,15].…”

Section: Page 5 Of 31mentioning

confidence: 99%

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Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections

Luque¹,

Grau²,

Álvarez-Lerma³

et al. 2014

International Journal of Antimicrobial Agents

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“…In this study, the linezolid concentrations in plasma and CSF were much lower than those reported in most other PK studies performed in critically ill patients [12][13][14][15]25].…”

Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

“…A c c e p t e d M a n u s c r i p t [4,[12][13][14][15][16]. This population can develop severe pathophysiological changes (e.g.…”

Section: Page 5 Of 31mentioning

confidence: 99%

Section: Page 5 Of 31mentioning

confidence: 99%

See 2 more Smart Citations

Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections

Luque¹,

Grau²,

Álvarez-Lerma³

et al. 2014

International Journal of Antimicrobial Agents

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“…Linezolid has been shown to have good penetration into the CSF 61,117. Linezolid has also been used to treat CNS infections caused by resistant organisms, including by VRE118 and by PRP,119 including treatment of PRP after failure of vancomycin 120.…”

Section: Efficacy Studiesmentioning

confidence: 99%

Clinical update on linezolid in the treatment of Gram-positive bacterial infections

Gould¹

2012

IDR

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Gram-positive pathogens are a significant cause of morbidity and mortality in both community and health care settings. Glycopeptides have traditionally been the antibiotics of choice for multiresistant Gram-positive pathogens but there are problems with their use, including the emergence of glycopeptide-resistant strains, tissue penetration, and achieving and monitoring adequate serum levels. Newer antibiotics such as linezolid, a synthetic oxazolidinone, are available for the treatment of resistant Gram-positive bacteria. Linezolid is active against a wide range of Gram-positive bacteria and has been generally available for the treatment of Gram-positive infections since 2000. There are potential problems with linezolid use, including its bacteriostatic action and the relatively high incidence of reported adverse effects, particularly with long-term use. Long-term use may also be complicated by the development of resistance. However, linezolid has been shown to be clinically useful in the treatment of several serious infections where traditionally bacteriocidal agents have been required and many of its adverse effects are reversible on cessation. It has also been shown to be a cost-effective treatment option in several studies, with its high oral bioavailability allowing an early change from intravenous to oral formulations with consequent earlier patient discharge and lower inpatient costs.

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Clinical Pharmacokinetics of Antibacterials in Cerebrospinal Fluid

Paolo

Gori

Tascini³

et al. 2013

Clin Pharmacokinet

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In the past 20 years, an increased discrepancy between new available antibacterials and the emergence of multidrug-resistant strains has been observed. This condition concerns physicians involved in the treatment of central nervous system (CNS) infections, for which clinical and microbiological success depends on the rapid achievement of bactericidal concentrations. In order to accomplish this aim, the choice of drugs is based on their disposition toward the cerebrospinal fluid (CSF), which is influenced by the physicochemical characteristics of antibacterials. A reduced distribution into CSF has been documented for beta-lactams, especially cephalosporins and carbapenems, on the basis of their hydrophilic nature. However, they represent a cornerstone of the majority of combined therapeutic schemes for their ability to achieve bactericidal concentrations, especially in the presence of inflamed meninges. The good tolerability of beta-lactams makes possible high daily dose intensities, which may be associated with increased probability of cure. Furthermore, the adoption of continuous infusion seems to be a fruitful option. Fluoroquinolones, namely moxifloxacin, and antituberculosis drugs, together with the agents such as linezolid, reach the highest CSF/plasma concentration ratio, which is greater than 0.8, and for most of these drugs it is near 1. For all drugs that are currently used for the treatment of CNS infections, the evaluation of pharmacokinetic/pharmacodynamic parameters, on the basis of dosing regimens and their time-dependent or concentration-dependent pattern of bacterial killing, remains an important aspect of clinical investigation and medical practice.

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Pharmacokinetics and protein binding of linezolid in cerebrospinal fluid and serum in a case of post-neurosurgical bacterial meningitis

Cited by 16 publications

References 15 publications

Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections

Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections

Clinical update on linezolid in the treatment of Gram-positive bacterial infections

Clinical Pharmacokinetics of Antibacterials in Cerebrospinal Fluid

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