Disease relevance of linezolid

• Linezolid resistance in a clinical isolate of Staphylococcus aureus [1].
• Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid [2].
• Clinical trials confirm the activity of linezolid in the setting of pneumonia, skin and soft-tissue infections, and infections due to vancomycin-resistant enterococci [3].
• We have characterised an MRSA isolate resistant to linezolid that was recovered from a patient treated with this agent for dialysis-associated peritonitis [1].
• A derivative of Mycobacterium smegmatis, which carries only one functional rRNA (rrn) operon, was used to isolate mutants resistant to the ribosome-targeted antibiotic linezolid [4].

Psychiatry related information on linezolid

• By univariate analysis, four variables were associated with the occurrence of anaemia: age >58 years, alcohol abuse, diabetes mellitus and low haemoglobin before linezolid treatment [5].
• The following day, the patient developed anxiety, panic attacks, tremors, tachycardia, and hypertension that persisted throughout linezolid treatment [6].

High impact information on linezolid

• Introduction of mutant rrl2447T into M. smegmatis rrn- resulted in a linezolid-resistant phenotype, demonstrating a cause-effect relationship of the 2447G --> T alteration [4].
• In contrast, ribosomes from class II mutants show wild-type susceptibility to a linezolid derivative in vitro, pointing to a non-ribosomal mechanism of resistance [4].
• Introduction of a wild-type ribosomal RNA operon into linezolid-resistant strains restored linezolid sensitivity in class I mutants, indicating that resistance (i) maps to the rRNA and (ii) is recessive [4].
• Linezolid and rifampin: Drug interaction contrary to expectations [7]?
• Examination of the linezolid pharmacokinetics as a function of age revealed that CL increased rapidly during the first week of life and as a function of postnatal age [8].

Chemical compound and disease context of linezolid

• Improved outcomes with linezolid for methicillin-resistant Staphylococcus aureus infections: better drug or reduced vancomycin susceptibility [9]?
• The susceptibilities of clinical vancomycin-intermediate Staphylococcus aureus (VISA), heterogeneous VISA, and laboratory-generated linezolid-resistant S. aureus strains to the new oxazolidinone AZD2563 were assessed by agar dilution MIC determination [10].
• U-100592 and U-100766 are potent oxazolidinones active against antibiotic-susceptible and -resistant gram-positive pathogens in experimental systemic and soft tissue infections [11].
• The activity of WCK 771 was superior to those of moxifloxacin, vancomycin, and linezolid in a mouse cellulitis model of infection caused by one MSSA and two MRSA strains, with effective doses of 2.5 and 5 mg/kg for the MSSA strain and 10-fold higher effective doses for MRSA strains [12].
• Comparative efficacies of quinupristin-dalfopristin, linezolid, vancomycin, and ciprofloxacin in treatment, using the antibiotic-lock technique, of experimental catheter-related infection due to Staphylococcus aureus [13].

Biological context of linezolid

• In addition, three more linezolid-resistant mutants were identified among the previously isolated mutants of H. halobium containing mutations in either 16 S or 23 S rRNA genes [14].
• Clinical failures of linezolid and implications for the clinical microbiology laboratory [15].
• Clustering of linezolid-resistance mutations within this region strongly suggests that the binding site of the drug is located in the immediate vicinity of the peptidyl transferase center [14].
• The use of H. halobium, which possess only one chromosomal copy of rRNA operon, allowed isolation of a number of linezolid-resistance mutations in rRNA [14].
• Two members of the family, linezolid and XA043, were examined for their effects on translational fidelity using a lacZ reporter gene in vivo [16].

Anatomical context of linezolid

• Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections [17].
• The intracellular penetration and activity of linezolid in human polymorphonuclear leukocytes and tissue-cultured cells (McCoy) were evaluated [18].
• The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five neurointensive care patients with staphylococcal ventriculitis was studied [19].
• Linezolid achieved a high concentration in the middle ear during experimental OM [20].
• Therefore, linezolid should be tested for use as empirical treatment for complicated urinary tract infections due to gram-positive uropathogens in an appropriate clinical trial [21].

Associations of linezolid with other chemical compounds

• A new representative of oxazolidinone antibiotics, linezolid, was found to be active against bacteria and against the halophilic archaeon Halobacterium halobium [14].
• Our results demonstrate that linezolid clearly reduced bacterial numbers in the methicillin-resistant S. aureus hematogenous infection model and significantly improved the survival rate of immunocompromised mice infected with vancomycin-insensitive S. aureus compared with vancomycin and teicoplanin [22].
• In vitro antimicrobial activities and spectra of U-100592 and U-100766, two novel fluorinated oxazolidinones [23].
• In a randomized crossover study, 12 volunteers (6 males, 6 females) received a single oral dose of 600 mg of linezolid or 500 mg of ciprofloxacin to assess the concentrations in plasma (up to 24 h), urinary excretion (by high-pressure liquid chromatography), and bactericidal titers in urine (UBT) at intervals up to 120 h [21].
• High concentrations of fluoroquinolones, macrolides, clindamycin, chloramphenicol, rifampin, tetracycline, and linezolid during 48 h of incubation inhibited proliferation and metabolic activity, whereas aminoglycosides and inhibitors of bacterial cell wall synthesis did not [24].

Gene context of linezolid

• Linezolid is metabolized via morpholine ring oxidation, which is independent of the cytochrome P450 (CYP450) enzyme system; as a result, linezolid is unlikely to interact with medications that stimulate or inhibit CYP450 enzymes [25].
• Because linezolid also competitively inhibits human monoamine oxidase-A (MAO-A; Ki = 55 microM), we monitored its effects on the cardiovascular responses to tyramine and amine cold remedies in comparison with standard MAO inhibitors [26].
• Quinupristin/dalfopristin and linezolid show good activity against both mecA-positive and -negative CNS [27].
• OBJECTIVE: This study used pharmacoeconomic modeling to evaluate the costs and outcomes associated with the use of i.v. vancomycin compared with p.o. linezolid in the treatment of MRSS-infected patients [28].
• No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD [29].

Analytical, diagnostic and therapeutic context of linezolid

• Blood samples (2 to 10 per patient; median, 4) were obtained and assayed for linezolid by high-performance liquid chromatography [30].
• Linezolid was measured in plasma by a high-pressure liquid chromatography (HPLC) technique and in BAL specimens and AC by a combined HPLC-mass spectrometry technique [31].
• As a result of these 2 factors, the proportion of mutant : wild-type 23S rRNA genes increased in association with an increase in the minimum inhibitory concentration of linezolid [32].
• Linezolid is fully bioavailable following oral administration when compared with intravenous administration [33].
• Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units [34].

References