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Penetration of antimicrobial treatments into the cerebrospinal fluid is essential to successfully treat infections of the central nervous system. This penetration is hindered by different barriers, including the blood–brain barrier, which is the most impermeable. However, inflammation may lead to structural alterations of these barriers, modifying their permeability. The impact of blood–brain barrier disruption on linezolid and tedizolid (antibiotics that may be alternatives to treat nosocomial meningitis) penetration in cerebrospinal fluid (CSF) remains unknown. The aim of this study is to evaluate the impact of blood brain barrier disruption on CSF penetration of linezolid and tedizolid. Female C57BI/6 J mice were used. Blood–brain barrier disruption was induced by an intraperitoneal administration of lipopolysaccharide. Linezolid (40 mg/kg) or tedizolid‐phosphate (20 mg/kg) were injected intraperitoneally. All the plasma and CSF samples were analyzed with a validated UPLC‐MS/MS method. Pharmacokinetic parameters were calculated using a non‐compartmental approach based on the free drug concentration. The penetration ratio from the plasma into the CSF was calculated by the AUC0‐8h (Area Under Curve) ratio (AUC0‐8hCSF/AUC0‐8hplasma). Linezolid penetration ratio was 46.5% in control group and 46.1% in lipopolysaccharide group. Concerning tedizolid, penetration ratio was 5.5% in control group and 15.5% in lipopolysaccharide group. In conclusion, CSF penetration of linezolid is not impacted by blood–brain barrier disruption, unlike tedizolid, whose penetration ratio increased.

We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage. Ten 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). The 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 (AUC )/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. For 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.

Poor penetration of many anti-tuberculosis (TB) antibiotics into the central nervous system (CNS) is thought to be a major driver of morbidity and mortality in TB meningitis (TBM). While the amount of a particular drug that crosses into the cerebrospinal fluid (CSF) varies from person to person, little is known about the host factors associated with interindividual differences in CSF concentrations of anti-TB drugs. In patients diagnosed with TBM from the country of Georgia (n = 17), we investigate the association between CSF concentrations of anti-TB antibiotics and multiple host factors including serum drug concentrations and CSF concentrations of metabolites and cytokines. We found > 2-fold differences in CSF concentrations of anti-TB antibiotics from person to person for all drugs tested including cycloserine, ethambutol, imipenem, isoniazid, levofloxacin, linezolid, moxifloxacin, pyrazinamide, and rifampin. While serum drug concentrations explained over 30% of the variation in CSF drug concentrations for cycloserine, isoniazid, linezolid, and pyrazinamide (adjusted R 2  ≥ 0.3, p < 0.001 for all), there was no significant association between serum concentrations of imipenem and ethambutol and their respective CSF concentrations. CSF concentrations of carnitines were significantly associated with concentrations of ethambutol and imipenem (q < 0.05), and imipenem was the only antibiotic significantly associated with CSF cytokine concentrations. These results indicate that there is high interindividual variability in CSF drug concentrations in patients treated for TBM, which is only partially explained by differences in serum drug concentrations. With the exception of imipenem, there was no association between CSF drug concentrations and concentrations of cytokines and chemokines.

Highlights Retrospective study evaluating linezolid in 99 TBM patients. Linezolid significantly reduced CSF protein levels, especially in critically ill patients. Similar adverse event rates between groups. Relevant literature reviews were reviewed. Background Tuberculous meningitis (TBM) is the most severe form of tuberculosis, with high morbidity and mortality. This retrospective study evaluates the clinical efficacy of linezolid in patients with TBM. Methods We analyzed 99 TBM patients treated at the Shanghai Public Health Clinical Center from June 2013 to March 2020. Patients were divided into two groups: those receiving standard therapy ( n  = 43) and those receiving standard therapy plus linezolid ( n  = 56). Clinical outcomes, cerebrospinal fluid parameters, and adverse events were assessed. Results Of the included patients, 42.4% were female, and the median age was 24.00 (7.00–44.00) years. Baseline characteristics between the two groups were comparable. After six months of treatment, both groups showed improvements in cerebrospinal fluid parameters, with no significant differences in intracranial pressure, white blood cell count, glucose, or chloride levels (all P  > 0.05). Adding linezolid significantly reduced cerebrospinal fluid protein levels compared to the standard therapy group (0.873 [0.228–1.591] g/L vs. 0.172 [-0.691–0.559] g/L, P  = 0.018), correlating with better 6-month survival (adjusted OR 1.850, 95% CI 1.111–3.081, P  = 0.018), with a stronger effect in critically ill patients (1.010 [0.257–2.019] g/L vs. 0.121 [-0.556–0.510] g/L, P  = 0.004). Although intracranial lesion resolution rates were higher in the linezolid group, they were not statistically significant ( P  > 0.05). Adverse event rates were similar between groups (16.1% vs. 18.6%, P  = 0.392). Conclusion Linezolid appears to offer clinical benefits in managing TBM, particularly in critically ill patients, warranting further prospective studies to optimize treatment protocols.

Tuberculosis is a challenging and severe infection among solid organ transplant recipients. Contezolid, a new oxazolidinone antimicrobial, has exhibited potent activity against Mycobacterium tuberculosis with a safety profile superior to linezolid, which is constrained by adverse effects such as myelosuppression and peripheral neuropathy. We present here a case of a renal recipient who suffered from allograft tuberculosis and tuberculous meningitis. A contezolid-included regimen successfully treated him with no drug-related adverse effects and drug-drug interaction. Concentration of contezolid in serum and cerebrospinal fluid at various time points during treatment was monitored. Given the increased risk of TB in patients with organ transplantation and limited evidence of contezolid for tuberculous meningitis, further clinical studies are needed to investigate the appropriate dosage and application of contezolid in patients with the most devastating type of extra-pulmonary TB. Clinical trial number Not applicable.

Tuberculous meningitis is a devastating brain infection that is caused by Mycobacterium tuberculosis and is notoriously difficult to diagnose and treat. New technologies characterising the transcriptome, proteome, and metabolome have identified new molecules and pathways associated with tuberculous meningitis severity and poor outcomes that could offer novel diagnostic and therapeutic targets. The next-generation GeneXpert MTB/RIF Ultra assay, when used on CSF, offers diagnostic sensitivity for tuberculous meningitis of approximately 70%, although it is not widely available and a negative result cannot rule out tuberculous meningitis. Small trials indicate that clinical outcomes might be improved with increased doses of rifampicin, the addition of linezolid or fluoroquinolones to standard antituberculosis therapy, or treatment with adjunctive aspirin combined with corticosteroids. Large phase 3 clinical trials are underway worldwide to address these and other questions concerning the optimal management of tuberculous meningitis; these studies also form a platform for studying pathogenesis and identifying novel diagnostic and treatment strategies, by allowing the implementation of new genomic, transcriptomic, proteomic, and metabolomic technologies in nested substudies.

Acute bacterial meningitis is still considered one of the most dangerous infectious diseases in children. To investigate the prevalence and antibiotic resistance profiles of cerebrospinal fluid (CSF) pathogens in children with acute bacterial meningitis in Southwest China, CSF samples from 179 meningitis patients (3 days to 12 years old) with positive culture results were collected from 2012 to 2015. Isolated pathogens were identified using the Vitek-32 system. Gram stain results were used to guide subcultures and susceptibility testing. The antimicrobial susceptibility of isolates was determined using the disc diffusion method. Of the isolates, 50.8% were Gram-positive bacteria, and 49.2% were Gram-negative bacteria. The most prevalent pathogens were E. coli (28.5%), Streptococcus pneumoniae (17.8%), Staphylococcus epidermidis (10.0%), Haemophilus influenzae type b (9.5%), and group B streptococcus (7.2%). In young infants aged ≤3 months, E. coli was the organism most frequently isolated from CSF (39/76; 51.3%), followed by group B streptococcus (13/76; 17.1%) and Streptococcus pneumoniae (8/76; 10.5%). However, in young infants aged >3 months, the most frequently isolated organism was Streptococcus pneumoniae (24/103; 23.3%), followed by Staphylococcus epidermidis (18/103; 17.5%) and Haemophilus influenzae type b (16/103; 15.5%). Antimicrobial susceptibility tests indicated that for E. coli isolates, the susceptibility rates to aminoglycosides ranged from 56.8% to 100.0%, among them, amikacin was identified as the most effective against E. coli. As for cephalosporins, the susceptibility rates ranged from 29.4% to 78.4%, and cefoxitin was identified as the most effective cephalosporin. In addition, the susceptibility rates of piperacillin/tazobactam and imipenem against E. coli were 86.3% and 100%. Meanwhile, the susceptibility rates of Streptococcus pneumoniae isolates to penicillin G, erythromycin, chloramphenicol, ceftriaxone and tetracycline were 68.8%, 0.0%, 87.5%, 81.3% and 0.0%, respectively. Gentamycin, ofloxacin, linezolid and vancomycin were identified as the most effective antibiotics for Streptococcus pneumoniae, each with susceptibility rates of 100%. It was notable that other emerging pathogens, such as Listeria monocytogenes and group D streptococcus, cannot be underestimated in meningitis.

This study conducted a meta-analysis comparing vancomycin and linezolid for treating central nervous system (CNS) infections, addressing the lack of comprehensive evaluations in existing research on antibiotic therapy for CNS infections. We systematically searched databases, including the PubMed, Embase, Web of Science, Cochrane Library and Chinese databases, up to April 22, 2025. All eligible randomized controlled trials and cohort studies of vancomycin or linezolid were included. The clinical success rate was the primary outcome of interest. The secondary outcomes of interest were cerebrospinal fluid (CSF) parameters, systemic inflammatory markers and the occurrence of adverse drug reactions (ADRs). Two reviewers independently extracted the data and assessed the study quality (NOS/ROB 2.0). The meta-analysis employed random/fixed-effects models to calculate pooled dichotomous outcomes (ORs) and continuous outcomes (SMDs) with 95% CIs via RevMan 5.4. This meta-analysis included 17 studies (6 head-to-head). Clinical cure rates were not significantly different between vancomycin (84.7%, 222/262) and linezolid (79.7%, 200/251), with a pooled OR of 1.29 (95% CI: 0.55-2.99; p =0.56), while substantial heterogeneity existed (I = 58%). The secondary outcomes showed no differences but suffered extreme heterogeneity (I² >90%). Safety analysis revealed a significantly greater ADR with vancomycin (21.0% vs. 15.1%; OR 1.63, 95% CI: 1.01-2.65; p = 0.05) with low heterogeneity (I² = 15%). Vancomycin and linezolid have similar effectiveness in CNS infection from current available evidences, but vancomycin is associated with a greater risk of ADR. Treatment selection should be based on patients' individual characteristics, such as risk of thrombocytopenia, renal function, and availability of therapeutic drug monitoring.

Pretomanid is a nitroimidazole antimicrobial active against drug-resistant Mycobacterium tuberculosis and approved in combination with bedaquiline and linezolid (BPaL) to treat multidrug-resistant (MDR) pulmonary tuberculosis (TB). However, the penetration of these antibiotics into the central nervous system (CNS), and the efficacy of the BPaL regimen for TB meningitis, are not well established. Importantly, there is a lack of efficacious treatments for TB meningitis due to MDR strains, resulting in high mortality. We have developed new methods to synthesize 18 F-pretomanid (chemically identical to the antibiotic) and performed cross-species positron emission tomography (PET) imaging to noninvasively measure pretomanid concentration-time profiles. Dynamic PET in mouse and rabbit models of TB meningitis demonstrates excellent CNS penetration of pretomanid but cerebrospinal fluid (CSF) levels does not correlate with those in the brain parenchyma. The bactericidal activity of the BPaL regimen in the mouse model of TB meningitis is substantially inferior to the standard TB regimen, likely due to restricted penetration of bedaquiline and linezolid into the brain parenchyma. Finally, first-in-human dynamic 18 F-pretomanid PET in six healthy volunteers demonstrates excellent CNS penetration of pretomanid, with significantly higher levels in the brain parenchyma than in CSF. These data have important implications for developing new antibiotic treatments for TB meningitis. Pretomanid has been approved for use in cases of multi-drug resistant pulmonary tuberculosis, yet the penetration of this antibiotic into other target tissues is not well established. Authors provide insight on pretomanid pharmacokinetics in the central nervous system, using positron emission tomography in animal models, and human studies.