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Linezolid

Manufactured by Pfizer
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Linezolid is a synthetic antimicrobial agent that inhibits bacterial protein synthesis. It is used in the treatment of infections caused by Gram-positive bacteria, including those resistant to other antibiotics.

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Lab products found in correlation

Vancomycin, by Merck Group (4 mentions) Gentamicin, by Merck Group (4 mentions) Daptomycin, by Novartis (4 mentions) Tigecycline, by Pfizer (3 mentions) Moxifloxacin, by Bayer (2 mentions) Oxacillin, by Merck Group (2 mentions) Crisaborole, by Pfizer (1 mentions) Mannitol salt agar, by bioMérieux (1 mentions) Nutriselect plus, by Merck Group (1 mentions) Al2o3 nanowires, by Merck Group (1 mentions) Pooled human liver microsome, by Xenotech (1 mentions) Sesamin, by Merck Group (1 mentions) Nadph, by Merck Group (1 mentions) Pooled human intestinal microsomes, by Corning (1 mentions) Emetine, by Merck Group (1 mentions) 10 cm petri dishes, by BD (1 mentions) Vitek 2 system, by bioMérieux (1 mentions) Vancomycin van, by Merck Group (1 mentions) Teicoplanin, by Merck Group (1 mentions) Amoxicillin, by Merck Group (1 mentions)

27 protocols using linezolid

1

Linezolid Dose Effects on Mice

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Doses of 0.6 or 3.0 mg/kg/day linezolid (Pfizer) or vehicle (saline) were injected intraperitoneally (ip) for 4 weeks (n ¼ 5 in each linezolid and each control group). General clinical condition was monitored daily. Body weight was measured at the baseline (before the treatment) and every week afterwards for each mouse. At the end of the experiment, mice were deeply anaesthetized and sacrificed by decapitation.
# The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com J Antimicrob Chemother 2016; 71: 685 -691 doi:10.1093/jac/dkv386 Advance Access publication 26 November 2015
Bobylev I., Maru H., Joshi A.R, & Lehmann H.C. (2016). Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy. The Journal of antimicrobial chemotherapy, 71(3).
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2

Crisaborole and Linezolid Formulation

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Crisaborole (2% ointment) and linezolid were provided by Pfizer. linezolid was prepared in 0.5% methylcellulose in water (vehicle) at a final concentration of 10 mg/ml, as previously described.36 (link)
Youn C., Dikeman D.A., Chang E., Liu H., Nolan S.J., Alphonse M.P., Joyce D.P., Liu Q., Meixiong J., Dong X., Miller L.S, & Archer N.K. (2022). Crisaborole efficacy in murine models of skin inflammation and Staphylococcus aureus infection. Experimental dermatology, 32(4), 425-435.
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3

Antimicrobial Susceptibility Testing of S. aureus

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The clinical and laboratory standard guidelines were followed to assess the tested agents minimum inhibitory concentration (MIC) [8 ]. In brief, some isolated colonies of S. aureus were recovered from mannitol salt agar (bioMérieux, Marcy I'Etoile, France) and subsequently resuspended in tryptic soy broth (NutriSelect® Plus, Sigma-Aldrich, Schnelldorf, Germany) to an optical density of 0.5 McFarland (ca 1.5 × 108 colony forming [CFU] units per mL). This suspension was then dispersed in a 96-well microplate containing serial twofold dilutions of the testing molecules to a final concentration of 105 CFU/mL. MIC values were visually assessed after 48 h. The following antibacterial agents were assessed against the planktonic form of S. aureus: (1) vancomycin (Vianex, Greece); (3) Al2O3 nanowires (diameter × L 2–6 nm × 200–400 nm; Sigma); (3) TiO2 nanoparticles (Nanografi, Turkey); daptomycin (Accord Healthcare SLU); Fucidic Acid (LEO Pharmaceutical); linezolid (Pfizer, Hellas A.E.). The above compounds were diluted in a twofold fashion with NaCL 0.9%.
Tsikopoulos K., Meroni G., Kaloudis P., Pavlidou E., Gravalidis C., Tsikopoulos I., Drago L., Romano C.L, & Papaioannidou P. (2023). Is nanomaterial- and vancomycin-loaded polymer coating effective at preventing methicillin-resistant Staphylococcus aureus growth on titanium disks? An in vitro study. International Orthopaedics, 47(6), 1415-1422.
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4

Metabolic Profiling of Linezolid Analogues

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Linezolid and cyp3cide were from the Pfizer sample bank. (S)-8,8-dimethyl-2-oxo-7,8-dihydro-2H,6H-pyrano[3,2-g]chromen-7-yl (E)-3-(4-nitrophenyl)acrylate (LKY-047) was prepared according to the method of Phuc et al. (2017) . 1-(3-chlorophenyl)-3-phenylurea was prepared using the method of Mohd Siddique et al., (2016) . 2-HydroxyLinezolid and desethyleneLinezolid were biosynthesized using female rabbit liver microsomes in the approach described by Walker et al. (2014) . Sesamin, NADPH, and a-naphthoflavone were from Sigma (St. Louis, MO). Ketoconazole was from Research Biochemicals International (Natick, MA). Montelukast was from Sequoia Research Products (Pangbourne, UK). Quinidine was from Fluka (St. Gallen, Switzerland). Pooled human liver microsomes (N = 54, mixed sex) were prepared under contract by Xenotech (Lenexa, KS). Recombinant heterologously expressed human cytochrome P450 enzymes and pooled human intestinal microsomes were from Corning/Gentest (Woburn, MA).
Obach R.S. (2022). Linezolid Metabolism Is Catalyzed by Cytochrome P450 2J2, 4F2, and 1B1. Drug metabolism and disposition: the biological fate of chemicals, 50(4).
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5

Quantitative Mitochondrial Protein Synthesis

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HEK293 cells were grown in 10‐cm petri dishes (BD Falcon) in DMEM with 10% FBS to 80% confluence, washed, and incubated for 30 min in DMEM without methionine. Media were exchanged to DMEM without methionine supplemented with 100 μM emetine (Sigma‐Aldrich) and incubated for 15 min. The medium was replaced with 500 μl methionine‐free DMEM supplemented with 2 μl of 35S‐methionine and 100 μM emetine, and cells were incubated for 2 h at 37°C. The supernatant was carefully aspirated, and cells were detached by pipetting with 1 ml of PBS. The cells were washed 2 times with PBS and resuspended in 200 μl of 1× SDS loading buffer. The samples were analyzed on a 15% SDS–PAGE. The gel was fixed, dried, and exposed on a phosphor‐imager screen and scanned with the FLA‐5100 laser scanner. A pilot experiment was performed to control that emetine effectively inhibited cytosolic protein synthesis and that the residual protein synthesis reflects mitochondrial translation as shown by susceptibility to linezolid (Pfizer) (Appendix Fig S3G).
Akbergenov R., Duscha S., Fritz A., Juskeviciene R., Oishi N., Schmitt K., Shcherbakov D., Teo Y., Boukari H., Freihofer P., Isnard‐Petit P., Oettinghaus B., Frank S., Thiam K., Rehrauer H., Westhof E., Schacht J., Eckert A., Wolfer D, & Böttger E.C. (2018). Mutant MRPS5 affects mitoribosomal accuracy and confers stress‐related behavioral alterations. EMBO Reports, 19(11), e46193.
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6

Synergistic Antimicrobial Activity of Linezolid and Fosfomycin Against MRSA

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In the previous study, we found 98.04% synergy of the combination of linezolid and fosfomycin against 102 planktonic MRSA strains by fractional inhibitory concentration index (FICI) in vitro [7 (link)]. Therefore, 3 MRSA strains with numbers 154311, 152898, and 159228 were randomly selected from the 102 strains for both in vitro and in vivo studies. The strains were clinically isolated from PLA General Hospital and were identified by the automated VITEK-2 system (bioMérieux, Marcy l'Etoile, France) with a rapid latex agglutination test. Staphylococcus aureus ATCC 25923 was used as the quality control strain.
Fosfomycin, rifampin, and levofloxacin (National Institute for Food and Drug Control, Beijing, China) were used for the in vitro study. Fosfomycin sodium (Northeast Pharm, Shenyang, China) and linezolid (for injection, Pfizer, Madison, USA) were used in the biofilm-infection rat model.
Chai D., Liu X., Wang R., Bai Y, & Cai Y. (2016). Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus. BioMed Research International, 2016, 6413982.
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7

Antibiotic Treatment for MRSA Infection in Mice

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Mice were i.p. injected with a therapeutic dose (100 mg/kg) of gentamicin at 3 h after MRSA infection and then followed by 50 mg/kg/d (Espersen et al., 1994 (link)). In some experiments, mice were treated s.c. with 50 mg/kg/d linezolid (Pfizer Inc.) or 150 mg/kg/d vancomycin beginning 2 h after MRSA infection (Reyes et al., 2011 (link); Niska et al., 2013 (link); Schuch et al., 2014 (link)). Control mice received PBS. All antibiotic treatment and sham injections continued through day 10 after MRSA infection.
Sun K., Yajjala V.K., Bauer C., Talmon G.A., Fischer K.J., Kielian T, & Metzger D.W. (2016). Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia. The Journal of Experimental Medicine, 213(9), 1851-1864.
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8

Antibacterial Agents Characterization

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Antimicrobial agent Vancomycin (VAN) was purchased from Sigma Aldrich (St. Louis, MO, USA), and Linezolid (LNZ) was supplied by Pfizer (Rome, Italy). BTZ2e was freshly synthesized and characterized at the Department of Pharmacy of University “A. Moro” of Bari. BTZ2e purity was analytically estimated to be > 99% by performing elemental analysis as reported in Franchini et al. [21 (link)].
Muraglia M., Schiavone B.I., Rosato A., Clodoveo M.L, & Corbo F. (2023). Antimicrobial Synergistic Effects of Linezolid and Vancomycin with a Small Synthesized 2-Mercaptobenzothiazole Derivative: A Challenge for MRSA Solving. Molecules, 28(17), 6348.
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9

Antimicrobial Susceptibility of Bacterial Isolates

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Ceftobiprole was provided by Basilea Pharmaceutica International Ltd. (Basel, Switzerland); ceftaroline, linezolid and tigecycline by Pfizer Inc. (New York, NY, USA); daptomycin by Novartis (Basel, Switzerland). Penicillin, ampicillin, amoxicillin, imipenem, vancomycin, teicoplanin, gentamicin and streptomycin were purchased commercially (Sigma Chemical Co., ST. Louis, MO, USA). MICs were determined by broth microdilution and interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints (http://www.eucast.org/clinical_breakpoints/) (EUCAST, 2021 ). In the absence of EUCAST clinical breakpoints, those of the Clinical and Laboratory Standards Institute were applied (Clinical and Laboratory Standards Institute, 2021 ).
Lazzaro L.M., Cassisi M., Stefani S, & Campanile F. (2022). Impact of PBP4 Alterations on β-Lactam Resistance and Ceftobiprole Non-Susceptibility Among Enterococcus faecalis Clinical Isolates. Frontiers in Cellular and Infection Microbiology, 11, 816657.
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10

Antibiotic-loaded Bone Cement with Biodegradable Polymer

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The formulations of acrylic bone cements were loaded with two new-generation antibiotics, linezolid (Pfizer, Peapack, NJ, USA) and daptomycin (Cubist Pharmaceutical Incorporation, Kenilworth, NJ, USA), individually or in combination with vancomycin. The composition of the solid phase of commercial bone cement Palacos R® (Heraeus Medical, Wehrheim, Germany) was modified by incorporating microspheres of a biodegradable copolymer, PLGA, as described in our previous study [11 (link)].
García-García J., Azuara G., Fraile-Martinez O., García-Montero C., Álvarez-Mon M.A., Ruíz-Díez S., Álvarez-Mon M., Buján J., García-Honduvilla N., Ortega M.A, & De la Torre B. (2022). Modification of the Polymer of a Bone Cement with Biodegradable Microspheres of PLGA and Loading with Daptomycin and Vancomycin Improve the Response to Bone Tissue Infection. Polymers, 14(5), 888.
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