Section: CME Category: Medicine & Pharmacology

Quinolones: Friend or Foe

Mark Kosinski, DPM

Mark Kosinski, DPM discusses strengths, bioavailability, Drug-Drug interactions, as well as spectrum of action of quinolones. Dr Kosinski also highlights common adverse events associated with quinolone use and ways to report adverse Drug reactions.

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Goals and Objectives
  1. Review the strengths of quinolones including bioavailability and spectrum
  2. Recognize common drug-drug interactions
  3. Recognize common adverse events, including tendinopathy, neuropathy and CNS effects
  4. List ways to report an adverse drug reaction as well as how to access the FDA Adverse Event Reporting System
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  • CPME (Credits: 0.75)

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  • Lecture Transcript
  • TAPE STARTS – [00:00]


    Male Speaker: So next to the podium, Dr. Mark Kosinski is coming and he practices in New York, over 36 years, affiliated with Foot Clinics of New York and the Metropolitan Hospital Center in New York. Graduated from NYCPM in 1983 and is licensed to practice in New York. He's going to spend some time this afternoon with us talking about quinolones, a friend or foe?

    So please give a warm welcome to Dr. Kosinski.

    Mark Kosinski: Don't push the bottom one, which is now I want to push them. Thank you everybody for staying. I know the real reason you're staying is because you have to swipe out in two more lectures.

    Yeah, it really – it's always nice to come back and see you all my old friends, all the classmates, all the students who I helped train over the years. It's nice to see everybody and that everybody is doing well and looks younger than I even remember them.

    So if I can remember the clicker. So we're going to talk about quinolones today. And here's my – here's my conflict of interest slide. And I'm really not sure if it is a conflict of interest, but on the interest of full transparency, I was invited to one advisory board yesterday in Cutanea Life Sciences and they're looking at topical non-fluorinated quinolone. Well, it's not going to be mentioned in this lecture. I received no sponsorship for this lecture for many company. I work solely at the college where I'm paid weekly, very weekly. Yes.

    These are the jokes. So anyway, I like old sci-fi movies. And these, you know, when I said conflict of interest and full transparency, I thought of this movie. And if anybody remembers this movie, it's a 1960 sci-fi movie called the Amazing Transparent Man. And if you're not old enough to remember that, if you're younger, you might have seen it on Comedy Central, where it was reviewed in Mystery Science Theatre 3000.

    [02:04]

    So I thought – I thought a good topic for this, rather a good name for this lecture would be The Good, the Bad and the Weird sort of taking off from The Good, the Bad and the Ugly. And there actually is a movie that was called The Good, the Bad and the Weird when I looked up to see if I could find a title slide. And that sort of dovetails into the learning objectives that we're going to have today because we're going to look at the good things about quinolones, right, all the good things, the reason why we would prescribe them. The bad things, all the class effects and FDA warnings. And we're going to look – and I say this respectively, at the weird. We're going to look into the floxed community if we have time, of people who have sustained a permanent neuromuscular damage due to fluoroquinolone using. You can see it does get a little weird.

    So why this topic? So on the morning that we were asked if we wanted to give a lecture at Superbones, Dr. Trepel had sent out this mass emailing to the faculty and the student body on the latest FDA warning on aortic dissection in quinolones. And like one of the nice things about being at the college is that you're up to date. Like we send each other articles and we send each other updates and things like that and PDF files of newly published articles, so that was kind of cool.

    So I thought this would be a topic that we could all, you know, we could all use because we all prescribe antibiotics and a lot of us still prescribe quinolones and it's their go-to drug. I'm not telling you not to prescribe quinolones, let me tell you this at the outset, although it might seem that way. I'm just saying if you prescribe quinolones, just do so with caution.

    So basically, here are the quinolones that we would find ourselves are using. Ciprofloxacin came out in 1987. And I remember as a clinician in the medicine department that distinctly I'm in the hallway, and one of the clinicians – I don't remember who it was, it was years ago – prescribing ciprofloxacin for some green-tinged macerated tissue in an interest space.

    [04:02]

    So even back then, it was starting to be overused.

    So ciprofloxacin, first generation fluoroquinolone, we think of first generation fluoroquinolone as being heavy on the grim, negative spectrum. Levofloxacin is the levo isomer of ofloxacin – ofloxacin or floxin was introduced about the same time as ciprofloxacin. They found out that the levo isomer was the more active isomer of all floxacin. So they made a drug called levofloxacin and that's why it's named the way it is.

    Moxifloxacin came out in 1999. Moxifloxacin's claim to fame is that it had some anaerobic coverage in terms of B. frag. And then you probably heard of delafloxacin which came out FDA approved in 2017 and are probably available for use in, like, 2018. It's claim to fame is that it's active against MRSA.

    Fluoroquinolones are among the most widely prescribed class of antibiotics in the world. In the United States alone, 32 million prescriptions of fluoroquinolones are written for each year. And as you would suspect, ciprofloxacin and levofloxacin are responsible for about 80% of those prescriptions.

    Now all those prescriptions aren't written by podiatrists, right? You don't have 15,000 podiatrists writing for, you know, 30 million prescriptions of quinolones. Most of the prescriptions for quinolones come from primary care docs, et cetera. And they're written for UTIs, because of the spectrum of activity there, they're heavy on the gram-negative aside. So they're written for UTIs, sinusitis, bronchitis and even viral upper respiratory tract infection. So a lot of prescriptions for quinolones are written inappropriately.

    So let's talk at some of the good things about quinolones. Well, the two good things about quinolones are its spectrum of activity and it's bioavailability. I've written for a lot of quinolones for a lot of patients and, knock wood, I really haven't had any of the adverse events that we're going to be talking about now.

    [06:00]

    But I've written a quinolone prescriptions because of its spectrum of activity and quinolones in general are the – basically the only class of antibiotic that's available in oral form to treat pseudomonas, not that I was treating pseudomonas at the time, but that's one of the good spectrums of activity of quinolones. And also quinolones tend to have very high bioavailability.

    So if you think about spectrum of activity versus generation of quinolone, it's sort of the inverse of what you see in cephalosporin. So with cephalosporins, first generation cephalosporins have a more gram-positive activities, you go up the spectrum, you have more gram-negative activity. But with quinolones, it's reversed. So early generation quinolones, heavier on the gram-negatives.

    So nalidixic acid, even though it's a quinolone, you wouldn't think it's a quinolone, because it's named nalidixic acid. Well, it's a quinolone but it's not a fluorinated quinolones, a non-fluorinated quinolone. It's trade name is NegGram, which just reinforces the gram-negative activity of early quinolones.

    Ciprofloxacin, even though it's a second generation quinolones, it's a first generation fluoroquinolone, tends to be more heavy on the gram-negative side. Levofloxacin, a little bit more gram-positive activity. Moxifloxacin, as we said before, anaerobic coverage in addition to above. And delafloxacin, it's claim to fame is it's active against MRSA.

    We tend to think of quinolones as being good pseudomonas killers. Good gram-negative killers in general, good pseudomonas killers in particular.

    This was a CNS report that was a sent to me by a friend of mine in Coney Island Hospital. And take a look, this is pseudomonas and this is the susceptibility report. Take a look at the two antibiotics that the strain of pseudomonas is resistant to. It's resistant to ciprofloxacin and levofloxacin. It's resistant to quinolones. It's susceptible to everything else.

    So 32 million prescriptions every year has had one of its tolls resistance.

    [08:01]

    They're an overused, overprescribed class of antibiotics. Want to treat your urinary tract infection? Use a quinolone. But why can't I use trimethoprim-sulfamethoxazole to kill the gram-negatives? So there are other drugs to use that all falls under the heading of antibiotic stewardship.

    So quinolones are some of the most bioavailable antibiotics around. Safe for the oxazolidinone, like linezolid and tedizolid.

    So levofloxacin has a 99% bioavailability after oral administration. And moxifloxacin has very good bioavailability as well. So this is from the last incarnation – I think the current incarnation of the IDSA Diabetic Foot Infection Guidelines, suggested empiric antibiotic therapy for mild, moderate and severe diabetic foot infections and they list levofloxacin as being one of the suggested regiments of – for mild and moderate infections, sensibly because of its spectrum of activity and its bioavailability.

    And then we look down here, levofloxacin or ciprofloxacin with clindamycin for moderate and severe infections. Essentially what they're saying is, clindamycin has a gap in the gram-negative spectrum and now you can plug that gap with either levofloxacin or ciprofloxacin, which tend to be good gram-negative killers.

    This is a table from UpToDate, so you can go back and look at this online if you want to know – I don't know that if you need sort of a log in or something for UpToDate. You may – this may be public information. We get this stuff at the college, so I really don't know.

    This is the range of mean bone to serum concentration ratios of various antibiotics, in other words, a bone penetration for selected antibiotics. And right at the top are levofloxacin, ciprofloxacin and moxifloxacin. And – which puts me in the mind of a – of a quote from Eric Senneville who said, "It seems logical that preference should be given to antibiotics that exhibit high diffusion into bone, i.e., a bone-blood ratio of greater than 0.3 and have a good oral bioavailability, i.e., greater than 90%."

    [10:03]

    Which sort of – which sort of, you know, identifies drugs like levofloxacin, which has good bioavailability and really good bone to serum concentration ratios.

    And I've used levofloxacin to treat osteomyelitis. I don't know now as much as I'm learning about quinolones and I'm learning it every week with the FDA warnings that are coming out, if I'm going to continue to do that or not.

    This is the OVIVA study. Everybody should be familiar with the OVIVA study. It was published in the journal – I'm sorry, published in New England Journal of Medicine earlier this year. It's a trial which looked at oral versus intravenous antibiotics for bone and joint infections. And the choice for a PO antibiotics in treating bone and joint infections went to the – went to the quinolone class of antibiotics.

    Let's look at the bad. And first off, you know, every antibiotic has an adverse event profile. Every antibiotic has its good points and its bad points and its adverse events. But it's up to us as physicians to choose an antibiotic that's active against the presumed or proven pathogen and is the safest.

    So let's look at some of the drug-drug interactions that we see with respect to quinolones. This should be – so you've decided to prescribe quinolones. So here's some quinolone caveats. And one of the biggest caveats is a chelation when – of divalent and trivalent cat ion containing compounds. In other words, if you've chosen your quinolone, essentially because it gives you good bioavailability, and good serum concentration after oral administration, you don't want to screw that up by chelating your antibiotic, by giving aluminum, or magnesium, or zinc, iron, or calcium containing compounds at the same time, I mean, the same time. You don't take the quinolone at the same time you take your antacid. It's going to tie up the quinolone and that high bioavailability that you're counting on, that you prescribe the quinolone for, is going to be negated.

    [12:02]

    And you can – you can have up to a 45% decrease in peak plasma concentration if you give those two compounds within two hours. So give yourself a wide margin, four or five, six hours between giving those two medications, or you're going to tie up your quinolones, and you're going to negate that high serum concentration that you were looking for.

    And we know this, you know, everybody knows that it decreases the clearance of caffeine, quinolones do. And by the way, when I say quinolones for the point – for the purposes of this lecture, I mean, fluoroquinolones. It decreases the clearance of theophylline, it decreases serum concentration of dilantin. But more importantly, and I think, in a more practical aspect for us, it increases the anticoagulant effect of warfarin.

    So many – quinolones aren't the only antibiotics that do this, right? Citrine sulfur, metronidazole, and I think we'd ever use erythromycin or terconazole orally, and the tetracyclines, metacyline, or doxycycline. So think what happens if you want to treat a CA-MRSA infection with an oral antibiotic, and they're on Coumadin. Now, you have to worry about increasing the ion or potentially getting the anticoagulant effect of warfarin. Well, some quinolones do this more efficiently than others, ciprofloxacin interferes with the metabolism and elimination of the warfarin. Levofloxacin and moxifloxacin decrease gut flora and decrease production of vitamin K. Delafloxacin seems to have no effect on the coagulation pathway from the data that we have available to us.

    Nausea, vomiting, diarrhea are all frequent adverse events in not only quinolones, or pretty much any antibiotic or probably any drug, period, you look at the adverse event profile and nausea and vomiting, and diarrhea probably way up there. Quinolones are also associated with C. difficile colitis. And most students will tell you the one antibiotic that's almost strongly associated with the C. diff colitis is clindamycin, but that's not true. Pretty much, any antibiotic enclose C. diff colitis and quinolones are among them.

    [14:04]

    You can have transient elevations in amino transferase level, so you might bump up your liver enzymes a bit, give you transaminitis, but it's an uncommon side effect. I'm putting this slide up just to show you, and to illustrate the fact that not all quinolones are created equal.

    How many people in here, show of hands, remember trovafloxacin? So anybody remember Trovan? When I did my ID fellowship in 1999 at Saint Michaels, we would put patients in the hospital on oral Trovan, not parenteral Trovan. That was an acute infection, we want a rapid effect, maybe we'd start with an IV. But we wean him off to PO Trovan in the hospital, not IV. It was a great drug, it had very high bioavailability after oral administration, great activity against anaerobes and B. frag activity. It was a great drug. There was 300,000 prescriptions a month worldwide, $160 million the first year of trovafloxacin. Unfortunately, there are a hundred reports of liver toxicity and liver deaths, and Trovan was pulled from the market.

    Not all quinolones are created equal. Fluoroquinolones, some of them, have the potential to prolong the QT interval. So if you take a patient who has underlying risk factors for QT interval prolongation, hypokalemia, bradycardia, CHF, and you layer on two or more medications through themselves, can prolong the QT interval, you've got a problem.

    Now, fluoroquinolones, moxifloxacin and ciprofloxacin can have this effect, moxifloxacin does it a little bit more robustly than cipro. There's been no QTc-interval or other cardiac events with delafloxacin reported so far. In fact, there is no QTc warning in the delofloxacin label. But look at all the other QTc interval prolongers, right? Amitriptyline, suppose you're treating a diabetic patient whose taking Elavil for diabetic neuropathy, or Haldol, or methadone.

    [16:06]

    And we see plenty of patients in our patient population in Metropolitan Hospital who are on methadone, and many of them are on Haldol.

    There are so many drug-drug interactions. You know, people think that antibiotics are a safe class of drug, prescribe them with impunity, they can only do good, and that's not true. Antibiotics can kill you if you use them incorrectly, and if you have the wrong drug-drug interaction. I always use a drug interaction checker, and so should you. Use a drug interaction checker, take a good drug history, a good medication history from your patient. I use Medscape Drug Interaction Checker, it's free, it's online, it's constantly update. Whatever interaction checker you want to use but I would suggest that every time you prescribe not only an antibiotic but any medication.

    Now, we're going to look at class effects. I can thank my wife for putting in horses, no zebras, I said, what do you think about this slide? "Oh, you mean horses and no zebras." I said, that's what I'm going to write down, so I thank her for that. I have meant this slide to show, I'm just going to look at the most common adverse events and adverse, whether a class effect of quinolones, and not every single one. We can't, it's only half an hour.

    This is the black box warning from all the four big – the big fluoroquinolones that we use. And I put this up here just – and you're going to have to just take my word for it because you can't see it from the back. They all show tendinitis and tendon rupture, peripheral neuropathy, and CNS effects, and I put this up ostensibly to show that those warnings apply to every one of the currently available quinolones.

    It turns out that the mechanism of action of quinolones might actually be responsible in many cases for their adverse events. And essentially, quinolones kill bacteria by inhibiting DNA gyrase and topoisomerase, and both are present in host mitochondria.

    [18:08]

    So it's thought that the idiosyncratic damage to host mitochondria might play a role. So not only the quinolone's affecting the DNA of the bacteria, they might also be affecting the DNA and the mitochondrial DNA of the patient. Is it predictable or is it unpredictable? Well, so far, it's unpredictable. I suspect that pharmacogenetics are going to play a huge role in how we prescribe our drugs in the future. Does that patient have a gene that's responsible for them developing an adverse event? They're already doing that with aminoglycocides and all the toxicity.

    Every school child knows that tendinopathy is one of the most well-known adverse events of quinolones, right? There's a clinician at the college who developed bilateral Achilles tendon ruptures, or at least Achilles tendon tears, partial tear, as a result of using ciprofloxacin.

    The interesting thing about tendinopathy and quinolones is that it can occur as early as the first couple of doses or as late as six months after the last dose, which is really important to remember because not only do we have the ability to cause an Achilles tendon rupture by prescribing a quinolone, but we also have the potential to treat an Achilles tendonitis or tendon rupture caused by another doctor who prescribed the quinolone, maybe three or four, five months ago for UTI, or an upper respiratory tract infection. So that all feeds in to the patient's medication history. Not only what they're taking now, but what they have been taken for the last several months.

    Do quinolones cause retinal detachment? Well, we have a close family friend who developed a retinal detachment and his only risk factor was that he was taking levofloxacin.

    [20:03]

    The FDA, on the other hand would disagree, and the fact that in this FDA safety announcement, fluoroquinolones don't appear to cause retinal – this is 2017, fluoroquinolones don't appear to cause retinal detachment, or aneurysm or dissection, the FDA set on Thursday as part of its ongoing safety review of the antibiotic class, 2017. 2018 – so 2017, no problem. 2018, problem. And everybody knows this latest safety warning. Increased risk or ruptures or tears in the aorta, blood vessels on certain patients.

    Well, maybe in a couple years, they will have enough patients to draw the link between the retinal detachment and quinolones. And who are those patients? Well, patients who really fit the demographic of a lot of the patients that we see. Patients with peripheral arterial disease, hypertension, elderly patients, and the advice is to stop the fluoroquinolone treatment immediately if a patient report side effects suggestive of a Triple A or dissection. And what's one of the symptoms of a Triple A? Back pain. What elderly patient doesn't have back pain? So you have to wonder whether this is underrecognized, and an underreported adverse event. Well, we'll be seeing more of this.

    How about fluorouquinolone used in peripheral neuropathy? Now, I'm just going to read this. This is – this is 08/15/2013 from the FDA Drug Safety Communication. The result to the FDA's recent review of the Adverse Event Reporting System, AERS, now it's called FAERS. I'll show you the access of that at the end of the talk. Indicated – although the risk of peripheral neuropathy is described in the drug labels of each marketed systemic fluoroquinolone, the potential rapid onset and risk of permanents was not adequately described. The review showed the continued association between fluoroquinolone use and disabling peripheral neuropathy. The onset, after starting quinolone therapy was often rapid, and often within a few days. And in some patients, the symptoms were ongoing for more than a year, despite discontinuation of the quinolone and the best, the FDA has not identified any specific risk factors.

    [22:10]

    So here, we have an adverse event of the peripheral nervous system which has a rapid onset may resolve or persist and may last greater than a year, and maybe permanent despite discontinuance of the fluoroquinolone. Now, the question is, is this underreported? Suppose this happens in a patient with diabetes, suppose a patient with diabetes reports symptoms of neuropathy, how many people are going to link this to fluoroquinolones? And how many people are going say, well, this is just part and parcel of diabetes and maybe a diabetic neuropathy, and not linked to the drug. It's permanent.

    Take a look at the CNS report. Now, this is coag negative staph and take a look at the drugs that they ran against the coag negative staph. And look at the quinolones, you could tell the fluoroquinolones because they have the Floxin. So we're looking at ciprofloxacin, enrofloxacin, orbifloxacin, I took off the trade names because I don't want trade names.

    But look at enrofloxacin and orbifloxacin, these two drugs you never heard of before. Well, that's because the patient is not a human, it's a lizard, right? It's an animal. It's a lizard, right? One of my wife's patients, she's a veterinarian. So she shared me with this a couple – shared this – the CNS report with me a couple years ago, and I want to pass it along to you because it always reminded me that quinolones have CNS effect. So why don't we use – that was the patient by the way, I think that's a Uromastyx lizard, yeah.

    So one of the big drugs, one of the go-to drugs in the veterinary community is enrofloxacin, right. And enrofloxacin is a fluoroquinolone. Why don't we see that available for human use? And the reason is because it's a very efficient crosser of the blood-brain barrier. Crossing the blood-brain barrier isn't necessarily a bad thing, especially if you want to treat a brain infection, or brain aptis or meningitis.

    [24:01]

    But it shows such an increased seizure risk and hallucinations in humans that it was never approved for use in human beings, only in animals. Now, I tell you an anecdote, apparently, one of her coworkers, decides to treat themselves for an upper respiratory tract infection with the medication that they have in the closet, and it was enrofloxacin. And they developed hallucinations. And I'll tell you, apparently, it wasn't pleasant either. But again, it always remind me, I'll never forget that quinolones have the potential, again, they're not all created equal, can cause CNS effects. So I always wondered how do we know that they are not causing hallucinations in animals, right? So if this lizard got hallucinations from it, how would we even know and how would he even know that it wasn't supposed to happen, right, because he's a lizard?

    So, you know, CNS effects are one of the more common adverse events for fluoroquinolone used occurring in a little under 1% to 11% of patients. And it turns out that fluoroquinolones, as we said, cross the blood-brain barriers, some quinolones do it more efficiently than others. Apparently, because of the structure delafloxacin, there's a lower CNS – incidence of CNS adverse events. And apparently they – a displaced GABA from receptors, which gives you a caveat because apparently, NSAIDs and theophylline can also augment the fluoroquinolone displacement of GABA from the receptors. So if you're going to prescribe quinolones, here's you caveat to look for CNS effects in patients who are taking NSAIDs or theophylline.

    And neuropsychiatric effects can be easily missed, headache or drowsiness and the patient might not even put in two in two together, people get headaches all the time. Or it can become very severe and debilitating as we saw in the enrofloxacin, delirium and hallucinations. Here's my delafloxacin slide, and a lot of people are wondering about delafloxacin and its place for use in practice, in general.

    [26:03]

    And I'm going to say this, I'm going to quote from an article by Tom Lodise, on the safety of delafloxacin and its called Focus on Adverse Event of Special Interest, and it's sort of a copout slide, to quote Lodise, "Due to what's unique structure, dela has the potential to minimize some of the known safety concerns of fluoroquinolones, particularly CNS events and phototoxicity." But remember, and here's the caveat, here's the editorial, remember that the data, it's a new antibiotic, the database is currently very small relative to the size required to see some of the less frequently occurring adverse events continue to monitor and educate – in the words of SYMS, an educated consumer is your best customer. You can, yourself, monitor the FDA reporting systems.

    So when patients present with various adverse events and they report it to the FDA, you can access this via the FAERS public dashboard. So you go to Google, you put in FAERS public dashboard and you can access on any drug at all, not just antibiotics, all the adverse events that have been reported, and you keep up the data on all your favorite drugs.

    So I promised you weird, and again, I say this respectfully, but there is a weird component to what I'm going to show you. Part of your homework now is going to go, tonight, and Google the following terms, you're going to Google floxi, and you're going to Google floxxed. And you can search Facebook for something called "The Wall of Pain" and you're going to go to YouTube, and you're going to look up flox documentary. And what you're going to learn about is something called the Flox Network, which is a social network of individuals with strong concerns over fluoroquinolone toxicity, and many of these patients have sustained severe disabling and so far, permanent disability from the toxic effects of quinolones.

    [28:01]

    It does go from the amusing to the weird. And they were all types of people and yes, there's probably some hypochondriacal component to some of the people on these sites. But then some are decidedly sad. So the fluoroquinolone, all the pain, fluoroquinolones I took out the – I took out the trade names, I don't want trade names. The fluoroquinolones are hurting people, these are their stories of pain.

    This is the Facebook Fluoroquinolone Wall of Pain, Floxie Hope, saferpills.org. It's me, I ran the marathon – ran the New York City marathon over the Quinolone Vigilance Foundation. Here's a World Fluoroquinolone Toxicity Syndrome Awareness day. There are companies now who have marketed themselves to help patients with the disabling effects of fluoroquinolones. And for some reason, my movie didn't play, but that's okay. And of course, down at the bottom of the pool are the lawyers. Now, I can only imagine that this law firm putting quinolone lawyer, and fluoroquinolone attorney, so that no matter what search term you put into Google, it would lead him to this site.

    No, can we have sound? Sound?

    [Video Playing]

    Female Speaker: – in Oroville, California. Helping husband Rob raise his son Cole from a previous marriage. But all that changed suddenly after she took a prescription drug called Levaquin to prevent infection, following routine sinus surgery. Wilcox developed severe pain in her joints and muscles and even when she stopped taking the medication, the symptoms grew worse, until she could no longer walk.

    [30:00]

    Willcox: I couldn't even hold my head up. And I was bedridden for over a year. And when I say that, I mean, I couldn't even get myself out of bed to get into my wheelchair to go use the restroom. I had to be picked up out of bed.

    Female Speaker: Today, with the help of her husband, Wilcox struggles to at least three therapy sessions a week. Her neurologist continues to treat her for Levaquin toxicity.

    The medical problems have also taken their toll on her quality of life. She became so disabled she had to give up her teaching job. And without her income, the Willcox family lost their home. Just a few years ago Jen –

    Mark Kosinksi: There we go. That was, I recognized Judy Woodruff as the reporter and it's probably from and ABC or NBC news show. So what's the verdict? Are quinolones friends or are they foes, or are they friendly foes? Well, I'll give you this. I'll end with this slide. This New England Journal in Medicine Journal Watch, sort of like a Barry Black question of the week. So the questions where that they post to the readership, true or false, quinolones are more dangerous than other antibiotics? So you could either vote true, they should only be used when safer alternatives are contraindicated. Or false, all antibiotics have risks, and fluoroquinolones are getting attention because they are so widely used.

    How many people say A for true? All right. And how many people say B for false? All right, and some non-committal there, okay. Here's how it came out, 54% versus 46% true that they should be used only when safer alternatives are contraindicated, and I would tend to go along with that. This is in 2012, I wonder if they repost this question now with all the FDA warning since then, whether we would have a different distribution, and it's interesting, maybe I'll ask Barry Black if he'll post this as his question of the week.

    [32:04]

    Thank you very much. Two things before I end, to report an adverse drug reaction of quinolones or any other drug, you can go to FDA MedWatch. Just Google FDA MedWatch, you could do it online, and you can access any adverse events report that's been turned into the FDA, by looking at the FDA Adverse Event Reporting System or FAERS.

    Thank you very much.

    TAPE ENDS - [32:26]