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

Luque, S.; Grau, Santiago; Álvarez-Lerma, Francisco; Ferrández, Olivia; Campillo, Nuria E.; Horcajada, Juan Pablo; Basas, M.; Lipman, Jeffrey; Roberts, Jason A.

doi:10.1016/j.ijantimicag.2014.07.001

Cited by 48 publications

(43 citation statements)

References 27 publications

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“…Mutations in the rrl gene encoding 23S rRNA confer high-level resistance to oxazolidinones, whereas mutations in the rplC gene encoding ribosomal L4 protein confer low-level resistance. 343 Because these mutations occur spontaneously in only approximately 1 in 10⁸ bacilli, this class has a high genetic barrier to drug resistance. Linezolid, the first drug in this class, has good in-vitro activity against M tuberculosis, and is the best-studied oxazolidinone in tuberculosis.…”

Section: Oxazolidinonesmentioning

confidence: 99%

“…Linezolid also has good pulmonary and cerebrospinal fluid penetration. 343 Linezolid has been used off-label in patients with MDR tuberculosis with promising efficacy in observational studies. 272 The addition of linezolid to a failing regimen in patients with XDR tuberculosis resulted in culture conversion in 87% of patients by 6 months, and resistance emerged in 4 of 38 patients.…”

Section: Oxazolidinonesmentioning

confidence: 99%

See 1 more Smart Citation

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Dheda

Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

521

474

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Section: Oxazolidinonesmentioning

confidence: 99%

Section: Oxazolidinonesmentioning

confidence: 99%

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Dheda

Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

521

474

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“…Only a minority of PK parameters in special disease states have been reported. 23 – 25 PK parameters have not been reported in the CSF of patients who have suffered cerebral hemorrhage after surgical drainage. We analyzed linezolid in this specific patient population to see if the linezolid concentration could achieve an effective therapeutic range while limiting its toxicity and delaying the development of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of linezolid in plasma/cerebrospinal fluid in patients with cerebral hemorrhage after lateral ventricular drainage by Monte Carlo simulation

Tang

Zhang

et al. 2018

DDDT

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ObjectiveWe investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage.Materials and methodsTen patients with cerebral hemorrhage after lateral ventricular drainage with stroke-associated pneumonia who were given linezolid were enrolled. Plasma and cerebrospinal fluid (CSF) samples were taken at appropriate intervals after the first administration of linezolid and assayed by high-performance liquid chromatography (HPLC). Then, PK parameters were estimated, and a Monte Carlo simulation was used to calculate the probability of target attainments (PTAs) for linezolid achieving the PK/PD index at different minimal inhibitory concentrations (MICs).ResultsThe maximum concentration of linezolid in plasma and CSF was reached at 1.00 h and 3.10 h, respectively. The average penetration of linezolid in CSF was 56.81%. If the area under the plasma concentration vs time curve from zero to the final sampling time (AUC0–24 h)/MIC ≥ 59.1 was applied as a parameter, the PTA of linezolid in plasma could provide good coverage (PTA ≥ 90%) only for pathogens with a MIC of ≤2 μg/mL, whereas it could be achieved in CSF with a MIC of ≤1 μg/mL. If %T > MIC ≥ 40% was applied as a parameter, the PTA of linezolid in plasma/CSF could provide good coverage if the MIC was ≤4 μg/mL.ConclusionsFor patients with infection of the central nervous system and who are sensitive to the drug, the usual dosing regimens of linezolid can achieve a good therapeutic effect. However, for critically ill or drug-resistant patients, an increase in dose, the frequency of administration, or longer infusion may be needed to improve the curative effect.

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“…The bactericidal activity of five drugs (MEM, LNZ, PEN, VAN, TMP/SMX) against three isolates was determined using the time-kill method described in the CLSI guidelines [16]. The following concentrations referring to human body pharmacokinetics (Supplemental Table 1) were used for serum and CSF concentrations: MEM 14.6 mg/L and 1.1 mg/L [17][18], LNZ 4 mg/L and 1.8 mg/L [18][19], PEN 21 mg/L and 0.56 mg/L [20], VAN 13.32 mg/L and 10.64 mg/L [21], TMP/SMX 1.3/48.3 mg/L and 0.2/5.9 mg/L [18,22]. The time-kill assays were done and interpreted as described previously [18].…”

Section: Time-kill Assaysmentioning

confidence: 99%

Genetic structure characteristics and treatment for Listeria monocytogenes infections

Huang

Guo

et al. 2020

Preprint

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Background: Invasive Listeria monocytogenes (Lm) carry a high mortality despite antibiotic treatment. The aim of this study was to investigate the mechanism of pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated as well. Methods: Three Lm isolates were collected and 15 antibiotics susceptibility tests were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Furthermore, the effect of meropenem, linezolid, benzylpenicillin, vancomycin, trimethoprim/sulfamethoxazole were determined using the time-kill assay.Results: Two sequence types (STs) were identified for isolate 23949 (ST87), 26530 (ST3), 34096 (ST87), respectively. All isolates were resistant to fosfomycin and daptomycin. The resistant genes fosX, mprF, norB and vgaALC were identified in all isolates. Furthermore, 80 virulence genes were detected and 72 genes were found in all three isolates. There were 26 virulent genes associated with the structure, biosynthesis, motor switch of flagellum. And other virulent genes were involved in chemotaxis, protease, internalin and metabolism. It is of note that 8 genes (inlJ, llsB, llsD, llsG, llsH, llsP, llsX, llsY) were only found in 26530 isolated from cerebrospinal fluid (CSF), 7 of which were associated with haemolysin. Further in vitro time-kill assay found trimethoprim/sulfamethoxazole at serum or CSF concentrations had bactericidal effect (>3.5 log10 CFU/ml) against three tested Lm strains at 24 h. Conclusions: The involved virulence factors were mainly associated with bacterial pathogenicity. Notably, trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm bloodstream infection or intracranial infection.

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

Cited by 48 publications

References 27 publications

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Pharmacokinetics and pharmacodynamics of linezolid in plasma/cerebrospinal fluid in patients with cerebral hemorrhage after lateral ventricular drainage by Monte Carlo simulation

Genetic structure characteristics and treatment for Listeria monocytogenes infections

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