The following is an archived discussion of a featured article nomination. Please do not modify it. Subsequent comments should be made on the article's talk page or in Wikipedia talk:Featured article candidates. No further edits should be made to this page.

The article was promoted by Karanacs 20:41, 21 July 2009 [1].

Nominator(s): Fvasconcellos (t·c) 19:40, 14 July 2009 (UTC)[reply]

Linezolid is a very expensive drug of last resort used to treat serious "superbug" infections—the subject matter of WP:PHARM articles may not be very exciting, but this one sure seemed exciting to me :) I first stumbled across this article a year ago, found it to be in pretty good shape for a stub, and decided to make a project out of it. Since only two other articles on drugs are featured—Bupropion and Sertraline—I didn't have much of a template to look at, and chose to follow WP:MEDMOS and WP:MEDRS as closely as possible instead. For a drug with less than a decade of marketing experience, there is (thankfully) plenty of literature on linezolid, and I've tried to use the best and highest-quality sources available (thanks to II, Tim Vickers, and the kind folks at the Resource Exchange for helping out in this area).

The article passed WP:GA two months ago without a hitch, and I chose to forgo Peer review and ask for an independent copyedit instead (thank you, Outriggr!). I now believe the article meets all of the Featured article criteria. Here's hoping you'll agree with me. Fvasconcellos (t·c) 19:40, 14 July 2009 (UTC)[reply]

Support. An excellent effort at giving an interesting compound the most thorough treatment. I believe it is currently up to FA standards. I would, however, thoroughly welcome any attempt to make the introduction (and possibly some other sections) slightly more readable for the layperson. This may require short explanations and expansion on technical terms (e.g. Gram positive). JFW | T@lk 20:29, 14 July 2009 (UTC)[reply]

• I've added a brief explanation of what "Gram-positive" means in the "Spectrum of activity" section; "Resistance" may need some de-jargoning later. I'm wary of explaining more in the introduction because it is quite long already. Do you have any suggestions on which areas of the lead need to be more lay-friendly? Fvasconcellos (t·c) 20:53, 14 July 2009 (UTC)[reply]

I agree with Jfdwolff; it's an excellent and thorough summary, the sourcing is exemplary, and it's practically monograph-worthy. The only flaw I see is the one Jfdwolff identified: it's written in fairly technical language, and seems to assume the reader has a basic familiarity with medical and pharmacologic terminology. I think this is a minor issue and one we can readily fix, and otherwise it seems to exemplify some of Wikipedia's best work, as FA's ought to do. MastCell ^Talk 21:35, 14 July 2009 (UTC)[reply]

• OK, I'm trying some generous application of WP:MTAA. Fvasconcellos (t·c) 23:03, 14 July 2009 (UTC)[reply]
  • I've explained some of the more esoteric concepts, such as post-antibiotic effect and what it means for a drug to have 100% oral bioavailability. Fvasconcellos (t·c) 02:12, 16 July 2009 (UTC)[reply]

• Support. I agree with JFW and MastCell that the prose could be a tad more lay-readable, even now, but wow! this article is first class all the way. Eubulides (talk) 10:09, 15 July 2009 (UTC)[reply]

• Support. This is fantastic—beautifully written and relatively accessible considering the complexity of the topic. I made a couple changes but didn't really find anything to complain about. For some reason, the ALT text in the infobox images is not working. The alt text just displays the file name. A code problem with the infobox perhaps? --Laser brain (talk) 17:31, 15 July 2009 (UTC)[reply]
  • A little help, Eubulides? :) Fvasconcellos (t·c) 01:59, 16 July 2009 (UTC)[reply]
• Comment I'm asking mostly out of curiosity since I wouldn't know where to look to find the answer: would it be reasonably correct when discussing the similarity with rivaroxaban to say that the pharmacophore in rivaroxaban is the morpholinone-phenyl group whereas the morpholine group is accessory in linezolid? Circeus (talk) 20:50, 15 July 2009 (UTC)[reply]
  • Not likely; PMID 16161994 should have the answer. Rivaroxaban is probably devoid of antimicrobial activity because of the bulky chlorothiophene group "attached" to the acetamide. Even minor deviations from the 5-acetamidomethyl group (for instance, adding a single extra carbon atom) pretty much destroy antibiotic potential; reference 4 (Brickner, 1996) explains this in detail. Unfortunately, trying to explain this in the article would veer into WP:OR territory. Fvasconcellos (t·c) 01:59, 16 July 2009 (UTC)[reply]
    • Thanks, I'll look into it when I next get on campus. I'm not clear whether mentioning the similarity without discussing the source of differences is all that useful, though. Circeus (talk) 17:50, 16 July 2009 (UTC)[reply]

Image review with two one concerns:

• File:Linezolid.svg: I do not think "2D structure of antibiotic drug linezolid" is accurate... what kind of structure (surely the drug's 2D physical appearance does not look like that, heh)? Sorry, I am not good with chemical terminologies (might mess the description up); otherwise I would have just done this myself.
  • Actually, that's accurate. See chemical structure and skeletal formula. Fvasconcellos (t·c) 01:59, 16 July 2009 (UTC)[reply]
    • Umm, not quite. If I understand nothing of chemistry, "2D structure" would mean to me that the drawing is a physical representation of the subject (i.e. what it looks like to the naked eye). Your links above, however, allowed me to do this, which clarifies the description for anyone. Jappalang (talk) 03:47, 16 July 2009 (UTC)[reply]
      • I'm sorry, I have a terrible, terrible habit of presuming things of the reader. Yours is actually the wording I use in all the structural formulae I upload. Fvasconcellos (t·c) 03:49, 16 July 2009 (UTC)[reply]
• File:CDC-10046-MRSA2.JPG: why is this used when the larger sized version (File:CDC-10046-MRSA.jpg) is available. This image is applicable for speedy deletion in commons under commons:Commons:Deletion policy#Duplicates.
  • Hmm, that change was made by Materialscientist (talk · contribs) with an edit summary of "loading too slowly". I personally find it unadvisable to switch images for downsampled or lower-resolution equivalents because of file size concerns, but I'm on a good computer and a very fast broadband connection, so page loading times are rarely an issue for me; perhaps users with a dial-up connection, for instance, are having trouble loading the page. Fvasconcellos (t·c) 01:59, 16 July 2009 (UTC)[reply]
    • That is because the image was used in its full size, instead of as a thumbnail (which renders in the smaller size). I have been bold and used {{Multiple image}} with the larger image, tagging the smaller with Duplicate.

Just two concerns that should be very easily resolved. Images are verifiably in public domain or appropriately licensed. Jappalang (talk) 01:40, 16 July 2009 (UTC)[reply]

• Fossil-coming-back-from-the-dead support for this excellent article. I have a few very minor suggestions for you to accept, ignore, or tell me how my recommendations violate the WP:MOSOMGWTFBBQ policy adopted in my absence.

• From the lead, the sentence "Although many antibiotics have similar mechanisms of action, that of linezolid appears to be unique." strikes me as slightly awkward, since we aren't told anything about how it differs until near the end of the article.
  • I thought it was important to mention mechanism of action in the lead, and it had to be in the second paragraph as that's when I introduce the oxazolidinones. The article body, however, follows WP:MEDMOS section ordering, with pharmacokinetics/dynamics all the way towards the bottom (not least because more technical content is usually left to the end of the article). Do you think it should be dropped from the lead? Fvasconcellos (t·c) 03:28, 16 July 2009 (UTC)[reply]
    • I'm mostly nitpicking the prose, not the overall article structure. If you don't follow the mechanisms link and/or don't understand that there are multiple ways to inhibit protein synthesis, it reads like the unique feature is the protein synthesis inhibition. Opabinia regalis (talk) 04:01, 17 July 2009 (UTC)[reply]
      • OK, I see what you mean. I'll see what I can do about this. Fvasconcellos (t·c) 23:34, 18 July 2009 (UTC)[reply]
• In some areas you use "as of 2009", in another "as of June 2009".
  • Hmm, slip-up. I've changed all to "As of 2009" for consistency. Fvasconcellos (t·c) 03:28, 16 July 2009 (UTC)[reply]
• In the chemistry section, the acetamide is listed as a desirable structural characteristic, but it's colored blue in the image?
  • Ah, yes. The 5-acetamidomethyl group is the best substituent, and it is essential for good activity (as noted in the caption), but several bioisosteric groups retain activity (with much higher MICs, though). Fvasconcellos (t·c) 03:28, 16 July 2009 (UTC)[reply]
    • Hmm, maybe the caption wording needs adjusting? The text as written clearly groups "essential core" vs the acetamide, fluorine, and morpholine. Opabinia regalis (talk) 04:01, 17 July 2009 (UTC)[reply]
      • This is a touchy one... I'll tweak the wording. Fvasconcellos (t·c) 23:34, 18 July 2009 (UTC)[reply]
• It looks like the quinupristin/dalfopristin article is the only 'comparable' antibiotic that lacks structural images... hint, hint :) Speaking of which, is there anything interesting to the fact that the molecule is so much smaller than most of the others in the 'comparable' list?
  • I've been meaning to add an image to that article for quite some time now, but I'd like it to be a nice PyMol picture of both streptogramins interacting in their conformation... and I can't find the article where I first saw that! I think it was J Biol Chem, but some laziness on my part has contributed as well. Most protein synthesis inhibitors are quite small molecules (the macrolides are a notable exception, of course), but linezolid probably has a very "concise" structure because it's fully synthetic, and you have to remember the discovery of oxazolidinones as antibiotics was serendipitous; like the quinolones, they're not even "antibiotics" in the Waksman sense of the word (but that's another story, for another article I have in the works... :).
    • Looking forward to it! Now what's that you were saying about concise structures? I was just reading about this guy... Opabinia regalis (talk) 04:01, 17 July 2009 (UTC)[reply]

Fvasconcellos (t·c) 03:28, 16 July 2009 (UTC)[reply]

• • • • Ah, the glitz and glamour of organic synthesis... Fvasconcellos (t·c) 23:34, 18 July 2009 (UTC)[reply]
• Maybe add a picture of the linezolid/ribosome structure? (As a side note, that ribosome cartoon is very pretty, but why no E site?) Opabinia regalis (talk) 03:00, 16 July 2009 (UTC)[reply]
  • Adding a picture of the linezolid–ribosome complex was one of my first considerations, but the linezolid molecule looks so tiny; I could add a sort of picture-in-picture close-up or I could just add an image of the binding site, but neither option seemed ideal so I just let it go. As for the translation picture, you'll have to take it up with the very talented Mariana Ruiz. Fvasconcellos (t·c) 03:28, 16 July 2009 (UTC)[reply]
    • I like the picture/inset idea, but it's not crucial. I'd take a whack at it myself, but... part of the reason I'm killing time on Wikipedia again is that my good home computer is broken, I'm using my netbook, and therefore I can't get any real work done! Opabinia regalis (talk) 04:01, 17 July 2009 (UTC)[reply]
      • I'll play with PyMol/QuteMol a bit when I get a chance and see what I can do. You can always do article work on a netbook, you know :) Isn't that what they're made for? Fvasconcellos (t·c) 23:34, 18 July 2009 (UTC)[reply]
• Thank you so much for supporting, but I'm most glad to see you come out of retirement—you've been missed! :) Fvasconcellos (t·c) 03:28, 16 July 2009 (UTC)[reply]

• Support - This is spooky, I read this article for real-life reasons without noticing it was an FA candidate! I found all the answers to the questions that were on my mind, such as spectrum, mode of action, resistance and cost. I didn't know much about the problems with extended use, and in this regard, the article was particularly enlightening. It is beautifully written in a style that helps the reader—well this one—to remember the salient points without having to re-read sections. I fully support its promotion to FA and will recommend it to my students and colleagues, well done. Graham Colm ^Talk 07:44, 16 July 2009 (UTC)[reply]

Support with COI I did the GA review. In my view it is now fully worthy of FA status Jimfbleak - talk to me? 07:45, 16 July 2009 (UTC)[reply]

Support Looks pretty comprehensive to me. Meodipt (talk) 09:37, 16 July 2009 (UTC)[reply]

• Support. Since I've read the article, I might as well. I fixed a rather obvious typo along the line, so it might be a good idea to ask a third if they wouldn't mind giving it a reading, but I nonetheless do think it ranks amongst our best stuff. Circeus (talk) 17:50, 16 July 2009 (UTC)[reply]
  • Ouch, thanks for catching that one. A spell checker is all but useless in an article with so many technical terms, so I guess I'll go over it manually once again. Fvasconcellos (t·c) 00:58, 17 July 2009 (UTC)[reply]
• Support. Along with a few minor questions on linking: (1) Does "Gram-positive bacteria" in the lead need two adjacent links? If I needed to look up 'bacteria', I'm pretty sure I'd need to look up 'Gram-positive' as well. Why not make it a single link to Gram-positive bacteria? (2) There's another link to Gram-positive bacteria in " Spectrum of activity". Although I think a duplicate link is useful when it's well-separated from the first, don't you think in this case it's too close? Possibly Indication (medicine), Methicillin-resistant Staphylococcus aureus, Vancomycin-resistant enterococcus and resistant as well. (3) Does the article benefit from links to Skin, Headache and U.S. Dollar? You are sensibly using a lot of wikilinks to help explain technical terms, and links to commonly-understood terms rather dilute the value of the useful ones. --RexxS (talk) 00:12, 17 July 2009 (UTC)[reply]
  • OK, most of your suggestions are in line with WP:LINK, so I've gone ahead and implemented them. Thanks :) Fvasconcellos (t·c) 00:57, 17 July 2009 (UTC)[reply]
• This article is excellent. Definitely FA worthy. Well done -- Samir 22:52, 18 July 2009 (UTC)[reply]

• Comments - sources look okay, links checked out with the link checker tool. Ealdgyth - Talk 16:06, 19 July 2009 (UTC)[reply]

• Comments from Axl:-

From the lead section, paragraph 2: "Although many antibiotics have similar mechanisms of action, that of linezolid appears to be unique." Other oxazolidinone antibiotics are in development. Presumably they also have the same mechanism of action?

Yes, I've tweaked this (also at Opabinia's request), is it any better now? Fvasconcellos (t·c) 12:07, 20 July 2009 (UTC)[reply]

Thanks, that's good. Axl ¤ [Talk] 17:41, 20 July 2009 (UTC)[reply]

From "Therapeutic uses", paragraph 2: "In the United States, the FDA-approved indications for linezolid use are: vancomycin-resistant Enterococcus infection, with or without bacterial invasion of the bloodstream." The latter part of this sentence seems to me to be redundant. I previously removed it, but Fvasconcellos restored it.

I wonder if this picture (left) would be helpful in the "Chemistry" section?

It was my original idea, but I'm wary of making the article too structure-heavy—chemical structures aren't exactly reader-friendly. I would like to include it, though; I'll try to find a way. Fvasconcellos (t·c) 12:07, 20 July 2009 (UTC)[reply]

From "Pharmacokinetics", paragraph 2: "Peak serum concentrations (Cmax) are reached one to two hours after administration of the drug, and are around 13 mg/L after a single dose and 16–19 mg/L after repeated administration; trough concentrations (Cmin) are 4–8 mg/L." Presumably this is following the default dose: 600 mg twice a day? Our guideline suggests that drug doses should not be included in Wikipedia articles. Therefore I question the value of including serum concentrations.

This was a lead-in to explaining concentrations in CSF and bronchial fluid, which play an important role in the efficacy of linezolid for CNS infections and pneumonia. Do you think it's meaningless if dosage information is not included? Fvasconcellos (t·c) 12:07, 20 July 2009 (UTC)[reply]

Exactly. Without knowing the dose, there's no value in the serum concentration. If these serum concentrations are supposed to lead to a discussion of CSF/bronchial concentrations, there should be CSF/bronchial concentrations included. Overall, I think that the article would be better without these values. Axl ¤ [Talk] 17:46, 20 July 2009 (UTC)[reply]

Axl ¤ [Talk] 18:34, 19 July 2009 (UTC)[reply]

Hmm. I see your point. Fvasconcellos (t·c) 00:07, 22 July 2009 (UTC)[reply]

Comment - Fvasconcellos, overall, I think you have done a great job with this article! However, while I was reading it, I noticed that semicolons are used a fair amount. With that being said, I am not an expert on the topic, but are all of those semicolons necessary and/or being used properly? Regardless, again, great job. ---kilbad (talk) 22:32, 19 July 2009 (UTC)[reply]

I do tend to use a lot of semicolons when writing. Do you feel any are used incorrectly? Are there any particular sentences you feel could be reworded for improved flow? Fvasconcellos (t·c) 12:07, 20 July 2009 (UTC)[reply]

The only sentence that I personally would like to see re-worded a bit (and this is a very minor issue!) is "It does so by preventing the formation of the initiation complex, composed of the 30S and 50S subunits of the ribosome, tRNA, and mRNA; the oxazolidinones are the only drugs that inhibit this particular step of the process." Perhaps it would read a little better if broken up, and expanded into two sentences? ---kilbad (talk) 17:45, 21 July 2009 (UTC)[reply]

Done. Fvasconcellos (t·c) 00:07, 22 July 2009 (UTC)[reply]

• Note to reviewers: I am in the middle of a very, very serious family matter (suffices to say a relative of mine with a history of psychiatric disorders has gone missing) and I will be editing sporadically over the next few days. Nevertheless, rest assured that I will address any further issues that are raised—don't go closing my FAC! :) Fvasconcellos (t·c) 00:07, 22 July 2009 (UTC)[reply]

The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.