Hi. Good afternoon everybody. Welcome to this month’s Antibiotic Stewardship program. I think it’s a pretty interesting topic today. So, If you have any questions first – before we get going. You got any questions about a patient you may have? – or issue. Can talk now or later. (inaudible) Well, let’s see just a second here Does anybody have any cases or questions or anything that they want to talk about real quick before we move on to the talk? Anything interesting going on out there? Maybe after the talk we’ll have a lot of questions. Okay. Alright so, Before we get to the more serious stuff I wanted to present this case. (inaudible) This was printed in this week’s New England Journal, It’s called: “Oropharyngeal Tularemia from Freshly Pressed Grape Must” So, Tularemia is an infection from exposure to rodents, rats stuff like that, and you can get it if you’re a hunter, and you’re skinning an animal, or if the rodents urinated in the water, or tick bites. Okay, so it’s mostly outdoor people – hunters. It can be various presentations. (inaudible) So this was a German winery and what they did was for one reason – and I don’t know why – They hand picked one bunch of grapes and they had another bunch of grapes that they used mechanical harvester for. Kinda just cuts it down – like a machine cuts it down So they had a great loss for hand picked ones and the mechanically harvest ones were separately pressed. And apparently for whatever reason the workers taste the – what’s called fresh must of the grape after it’s pressed. So 6 of the 8 workers who tasted the mechanically harvested, so it’s machine harvested grapes, Tasted only the mechanically harvest ones, they didn’t taste the hand pick ones, they all developed oral tularemia, they got very sick, oral complaints and fever and chills. And when they looked at the wine, which was mechanically harvested they found the DNA of (inaudible) which just was found in the mechanically harvested wine but in the other batch, which was handpicked, they found none of it. So then they looked at this wine, they found rodent DNA, in the mechanically harvested wine. So obviously the machine – when it was cutting the grape, also threw some mice in there. So – No rabbits? (laughs and chatter) Nothing beats a cool glass of freshly pressed wine rodent. I think you can get that at Trader Joe’s. Anyway so – (laughs) That’s a bad infection. Do they, what’s it called, pasteurized wine? I mean, I don’t know what happens to wine. I don’t know. I don’t know either. They just bottle it? I’ve never been concerned about wine before. (laughs) Does the alcohol not kill it? Anyway, so that was just something to think about next time you have a glass of wine. (laughs) Do you remember that case of Tularemia we had? When I first got hired 10 years ago. Yeah, oh yeah. And then I had one, I think first or second year I was here. (inaudible) Anyway, so let’s go on. That was just to quench your appetite. (laughs) So this is a really interesting article that Jason Gallagher, who’s a well-known clinical pharmacist he had tweeted about this, saying that he thought this was really interesting, he was a client. And this was an article that came out last week, and it’s called “Microbiology Comment Nudge Improves Pneumonia Prescribing” and this is from the Henry Ford hospital. What they were finding and what many of us find is that vancomycin and zosyn is often used or both community acquired and health care associated pneumonia when they get admitted. Obviously vanco zosyn is not probably indicated for community acquired pneumonia, but it is – if you look at the guidelines, a lot of people have said healthcare-associated pneumonia, anybody whose been exposed to the hospital since in the last three months should be started with vanco zosyns. So, because of those guidelines, up to 70 percent of people’s quote healthcare-associated pneumonia are often placed on vanco zosyn and about 20% of people of acquired pneumonia are put on vanco zosyn. And so they were very concerned that, you know, these drugs are being overused and they’re indicated. And so what they did was they wanted to see what happens once people – when they start the vanco zosyn, and then it comes back, you know, 2 days later 3 days later, that their – (inaudible) a normal flora, and so they got a baseline six-month period, and they I saw patients were on vanco zosyn, who then reported as normal flora. They wanted to see how long it took (inaudible) the hospitals and doctors taking care of them. What’s it called? Deescalate? Yes the deescalate of antibiotics are more appropriate. So then they did that, they had the baseline, they saw how often people did it, and what they changed it to, so then they talk to the microbiology lab, and they asked them do something very simple; instead of writing just normal flora only they said write normal flora only, no staff, no MRSA or Pseudomonas isolated. So all they did was, you know, normal flora, there’s no staff, no MRSA or Pseudomonas. Which if you read normal flora you’d normally just assume that, but they spelled it out, and they told the providers, yes, we’re doing this simple reporting (inaudible) showing it’s only normal flora and none of these pathogens were found. And so then they wanted to see what would happen in the next 6 months, Did this new way of reporting normal flora – did it change.. prescribing habits? And so what they found out was that with this – when they adjusted for the severity of the patient, so they basically had comparable patients, that if they put the statement in, the hospitals and the physician were 5.7 times more likely to deescalate. Not only did they deescalate, they deescalated about 2 days before – more quicker than before they started the study. Okay, so, and so what they found was that just… stating what what we assume – that there’s none of these pathogens and that they were able to increase the change of the deescalation and it was done quicker. And they looked at mortality difference and maybe this actually – it no mortality – they found no mortality difference, but they did find a significant decrease in acute kidney injury. So, Jason Gallagher said this was great, it’s a simple thing to do. And he highly recommended it, so, we’re hopefully looking at all the hospitals that are involved with Antibiotic Stewardship programs, but this seems like, you know everything else is always such a pain to do anything different, but this seems so simple. And I think it would reassure the hospitals or whoever that you could comfortably deescalate. So that was a really interesting and I think an important study. We saw this anecdotally with our C. diff. tests, (inaudible) We added in EIA toxin testing to our PCR testing about a year ago. And we’ve kind of gone through several variations of how it’s reported. First it was PCR positive, and then if the toxin was negative it would say toxin negative, but providers wanted to treat that PCR positive result. So then we changed it to so if it was a positive result it would just say C toxin, and the amount of PCR positive toxin negatives that were treated decreased at least anecdotally significantly. And then we saw the same thing with how the NAP1 result was reported as well with positive all caps people wanted to treat despite the toxin result now that the NAP1 result says C toxin. Again, we’ve seen a decrease anecdotally of the number of C. diff. colonizations that are treated with antibiotics. And don’t you always say that, you know, PCR positive toxin negative means patients most likely – colonized in treatment, yes. Treatment not indicated. So these simple simple interventions may make a big difference in your Antibiotic Stewardship program, so that was really interesting. You remember that study we did before I left, where we looked at HCAP patients and then, we treated them, well, we treated them as normal cap if they weren’t admitted to the ICU. And they would show that they were discharged one day earlier. It was a small study, but we had no problems. Yes so, (inaudible) you know, the vanco zosyn but, if you look at the patient they’re not that sick, I mean if you’ve got immersive pneumonia, Pseudomonas pneumonia, you’re gonna be sick as a dog. You’re gonna be on a respirator. If your temperatures 101 degrees, you’ve got lobar infiltrates, so clinically looking at the patient and not saying oh (inaudible) can be very helpful in terms of deescalating using pro-kinetic biotics. So this other study came out of the British Medical Journal (inaudible) and we all have trouble with is the risk, they look at the risk of MRSA and C. diff. developing in patients who have quote documented penicillin allergy and so what the Mass General Hospital asked is What was the risk of these two infections MRSA and C. diff. developing in patients given non-Beta lactam antibiotics due to reported penicillin allergy. Because a patient says, ‘I got a penicillin allergy’ okay, so instead of using a Beta lactam (inaudible) multiple times have to take alternative drugs and they commented that up to 16% of patients states they are penicillin allergic. But studies done by allergists however, showed that 95% of these patients are actually not allergic. Whether the allergy went away when there’s really a side effect, they got nauseated and they’re calling it an allergy, (inaudible) Identifying patients that are not kind of somewhat allergic could be very helpful. And because of this you say you’re penicillin allergic, oftentimes you use broad-spectrum antibiotics as a drug resistance to toxicity. So in this large study, they found that using alternative drugs (inaudible) the risk of somebody developing MRSA because they had a penicillin allergy to an alternative drug was 1.69 for MRSA and 1.26 for C. diff. So again, this takes a lot more effort, but addressing quote penicillin allergies may be an important public health strategy and in the hospital to reduce the risk for c diff other MRCA developments. But that’s usually the old headache, you know you have to go in and hopefully the pharmacist will go and say what is your – your allergy? So my mother told me, because Uncle John had a penicillin that we all should avoid. Alright so, those are some interesting articles. So, 2018 update on the fluoroquinolones and (inaudible) is not a joke. You will take your own risk. (inaudible) develops on a quinolone antibiotic, you are basically setting yourself up for being sued. All right so, (inaudible) in 2016 and now there’s a lot of updates a lot bigger warnings that have come out. And so just, remember the fluoroquinolone generations. If you’re old enough like me, I remember neuroxin. Which was the first one that came out and was for oral treatment for urinary tract infections but big ones that we use now are Ciprofloxacin, which gave you – it was orally absorbed – well absorbed, it gave you pseudomonas coverage Then you’ve got the respiratory quinolones – levofloxacin, which was a derivative of the old floxacin, now give you pneumococcal coverage. The third generation. And then a four generation – moxifloxacin. Add anaerobes to it, so basically it was similar to like a – (inaudible) or something like that, very – (inaudible) So really, the 3 that we talked about mostly are cipro and levo and moxifloxacin – sometimes you see but, cipro and levo are both generic. And so they’re the ones mostly prescribed. Okay so, if you remember about two years the FDA came out with warnings and you may be familiar with these potential fluoroquinolone side effects one as we’ve seen over and over again the quinolones increased risk for C. diff. colitis. They develop a resistance in the patranium and the drugs don’t work and leads to C. diff. very frequently. The other big one is acute tendinitis where you can get a rupture of your Achilles tendon particularly at any time early early (inaudible) There are QT prolongation issues in cost torsades. I usually don’t think about it. But then the pharmacist (inaudible) And they’re are central nervous systems and peripheral neuropathy. But most of us are aware of these – of these risk. So the FDA made a point back in May two years ago. They say serious side effects associated with fluoroquinolone antibiotics generally outweigh the benefits for 3 particular incidents; patients with acute sinusitis acute bronchitis and uncomplicated UTIs. If they have other treatment options. Fluoroquinolones should be reserved those who do not have alternative treatment options, okay. Basically, you should warn your patient if you’re giving out fluoroquinolones, so FDA is typically focused on sinusitis, bronchitis and uncomplicated UTI, that we have alternatives and you should not be using quionolones up front. So now this month, the FDA got – really, a crackdown even further they added additional fluoroquinolone warnings. And what they imported was the risk of hypoglycemia. And they said there’s been at least 67 cases of life threatening hypoglycemic coma. 13 deaths, 9 with permanent, oftentimes, comatose for extended period time. Permanent disabling injuries. These occurred more frequently in the elderly and those of diabetes taking an oral hypoglycemic medicine or insulin. And also, others who have renal insufficiency as a risk factor – didn’t say why maybe it was because the levels go higher, when you have renal insufficiency. And they said 4 of these antibiotics already have label drug interaction with sulfonylurea. And in their reports, the most commonly was seen with levofloxacin, cipro was second. Okay so this was a big warning going on. (inaudible) This could be reflected in maybe levofloxacin is prescribed more frequently. Okay. Yes And then a few other ones but these are not the ones we mostly use. They said not only, you have to watch for fatal hypoglycemia in these patients. And it’s only a risk clearly for those with diabetes. Was this is over a year or what was this all over? The time – This was – (inaudible) So, this is when the FDA went crazy on hypoglycemia. Particularly in diabetic patients and the risk of coma and death with these drugs. And then they, and then they did this, they updated the psychiatric side effects. And they wanted a new labeling, and they made, apparently the labeling was not consistent, some quinolones would be associated with CNS side effects and others and now they wanted these to be prominent and consistent across all fluoroquinolones. So, we knew about agitation, nervousness, and disorientation already listed but the other three new ones, disturbances in attention, memory impairment and delirium. And I think some of this is thought to be irreversible too. (inaudible) So they – You have C. diff., you have Achilles tendinitis, you have QT prolongation, you have potentially deadly hypoglycemia, and now you have severe neuropsychiatric problems and the FDA is making these big black box warnings. Alright, so, just to review, (inaudible) We talked about uncomplicated cystitis again, As Dr. Hooton talks, he is a urologist, sort of an expert in New England journal, wrote an article saying, Don’t treat asymptomatic bacteria, okay. There’s no reason to treat asymptomatic bacteria. Treating asymptomatic bacteria doesn’t reduce the risk of pylo or UTI developing, it doesn’t reduce the risk of almost anything. It doesn’t improve diabetic control, And he says when you when you diagnose cystitis, you want to go on the basis of symptoms only, and the only 2 symptoms or 3 symptoms are dysuria, frequency with no vaginal discharge or irritation. And there’s some evidence that as much as 95% chance that women who have these specific symptoms have cystitis, okay. A dipstick is gonna miss some of the cases because you can have cystitis with very few white cells, and culture will pick up greater than 100,000 but most – a lot of infections may have only a hundred to ten thousand colonies (inaudible) maybe it’s only 1 to 10 colonies by the micro lab because it’s 1 to thousands (inaudible) Again, Hooton just reinforces only treat patients who have symptoms, okay. Not because they’re confused, Not because you find it under admission your analysis or anything else like that. Don’t treat it. So really focus on when you treat treat uncomplicated cystitis, just treat patients with symptoms. Treatment could actually an increase the rate of infection because some of these bacteria are actually protective. Yeah, we’ve talked about that before. (inaudible) protective bacteria and you’re setting yourself up for pathogenic e.coli. and the other complications, so, The goal of treatment of Urinary Tract infection is to ameliorate symptoms. It’s not to do anything else. Obviously if you’re a pregnant woman or someone who’s to have a prostate biopsy that’s different. And so, What antibiotic should we pick? Okay. This is from Washoe County, and I also think Renown is very similar. Macrodantin which doesn’t cause C. diff., it’s urinary excreted, (inaudible) 98% of all e. coli (inaudible) are susceptible Macrodantin, so, That’s amazing susceptibility. Very well tirade for 5 days. If you look at Bactrim, For 3 days it’s about 75%, cipro was 78%. And cefdinir was about 90%, so, it doesn’t make sense to use a quinolone (inaudible) uncomplicated cystitis when you have better alternatives, okay, macrodantin or even bactrim. The other thing about this, maybe a woman comes in, and she responds to your antibiotic or a culture is not being done, so these may actually – you know, bactrim may be 75%, it maybe 75% of urine that’s actually culture. A lot of women may not be culture because they responded to bactrim, So you may actually have more efficacy than 75%, but again the recommendations at Renown are what? macrobid first line and then we use bactrim second, and then cephalosporin, either anywhere from (inaudible) as third line. Studies have shown that oral cephalosporin are not as effective bactrim and macrobid. So that’s our third line. I don’t hear cephoral on the list. That’s correct. Use these safer drugs And this was – I’ve mentioned the study before, but I have some more, This was a study looking at uncomplicated cystitis in a large private family-planing clinic. So these are well insured patients, they can pay for anything, or – (inaudible) Women coming in, they had 1546 visits, and they they didn’t look at patients with complicating factors like pregnancy, recurrent infection, antibiotic allergy or fever. And these providers, 52% of the prescriptions were fluoroquinolone – cipro or levoquin. (inaudible) Was it 3 days of cipro? 71% of these patients were given under 5 to 10 days of therapy, and only 29% were recommended for 3 days. The drug of choice in these family practice middle-class practices was cipro – wrong drug and too long of a time so you’re just setting yourself up for trouble. 36% use a macrodantin, you’re given for one week most of time instead of the 5 days and 12% use bactrim, which should be just 3 days. So primary care physicians strongly prefer fluoroquinolines, or prescribe longer courses of therapy than recommended in Guidelines. And with these side effects coming out, I wouldn’t recommend it. This came out this week. This was in Clinical Infectious Diseases. “Opportunities to improve Fluoroquinolone prescribing in the U.S. for Adult Ambulatory Care Visits”. and somehow this national Ambulatory Medical Care Survey was able to get all the prescription of antibiotics across the country and they – this was 2014. 31.5 million quinolons were prescribed. Approximately 25% of these were given either for viral URI or bronchitis, which as I mentioned are not indications the FDA recommends or not recommended for first line therapy such as uncomplicated UTI or sinusitis. Alright, so there’s a fantastic overuse of these quinolines. And this is what was interesting, This is coming out in JAMA Internal Medicine, They wanted to look at – this is not just about quinolones, but antibiotic usage depending on where the care is. So they looked at prescribing of millions of patient visits, in retail clinics, (inaudible) urgent care clinics, emergency departments and traditional ambulatory care settings, like in a physician’s office. The CDC funded the study and they wanted to look at prescribing patterns. So they want to know that prescription rates by care setting for business for antibiotics inappropriate respiratory diagnosis. (inaudible) bronchitis, asthma, (inaudible) So, they just looked at the same diagnosis in all these clinics, and it ranged from urgent care centers 45% were getting antibiotics. Emergency departments – 25%, medical office – 17%, and retail clinics – 14%. And so these were all probably on – most of time were unnecessary prescription, But with same diagnosis you can see how there’s such a variation in care. You don’t know, maybe people, you know, the provider figures that somebody’s paying $100, they’re gonna want a prescription or something. But the conclusion was that unnecessary prescribing practice in outpatient settings likely to exceed reported 30% of all dispensed antibiotics. (inaudible) While we’re really tight on controlling antibiotics in the hospital, the large majority of antibiotics are given in the outpatient setting and those are the patients, much of the time are coming in with C. diff. or at risk for C. diff. We can try to control the hospital, but it’s the outpatient settings that primary providers that are overusing antibiotics. Alright so, these were some of the guidelines for management of acute sinusitis, one of the indications that the FDA should not use the quinolones first. And they’re, you know, they should be symptomatic for more than 10 days, severe symptoms with purelent nasal drainage or fever and worsening symptoms. So, Recommendation is augmentin first, doxy, and levoquin only as an alternative, and no more than 5 days should be adequate. (inaudible) Ours are – it’s augmentin and doxy, and then levoquin is only – for current cases, where they can’t use the high-dose (inaudible) And they say do not use azithromycin given high incidence of resistant strep pneumoniae. So we looked at UTIs (inaudible) bactrim, (inaudible) acute sinusitis, augmentin and doxy, if these patients even need these kind of antibiotics. So, this was a patient we had, a few years ago, 56 year old female with asymptomatic bacteruria. She came in for a pre-op evaluation prior to elective hip replacement. She noted on urinalysis to have bacteriuria the positive culture but no symptoms. The surgeon prescribed one week of ciprofloxacin, completed day before surgery. First of all, there’s no check her urine. Second of all, she had no symptoms. And third of all, he used cipro, and if you’re supposed to use cipro which was not even on the list, it should’ve been for 3 days . And so she had a successful surgery, but she was readmitted the next day with fulminant C. diff colitis and dies. This was a 77 year old male with quote penicillin allergy and a dog bite. 4 days prior to emergency room visit bit in the part of his hand when separating 2 dogs. Came to the ER to find progressive onset redness swelling of his hand and arm. He was given oral levofloxacin, 750 (mg) a day for five days, and a week later developed severe unilateral Achilles tendonitis. Definitely you want to treat, find out what the allergy is, but definitely you want to treat pasteurella as a possibility, but you can use bactrim and other options. (inaudible) Again, these drugs are toxic. So, what’s online for patients to view? you got the hysterical family up top and you got the happy lawyer down. So this was – Can you play the link? Prescribed antibiotic. Doctors offer it for everything. From urinary tract infections to sinus infections. But a local mom is pushing to get levaquin off the shelves after she says she suffered devastating side effects. And a drug watch dog group is pushing the FDA for tougher warning labels. NBC Charlotte reporter Michelle Bowden has the story and it’s all new tonight. Shannon Meyers is trying to slyly wrap his Valentine’s Day gift for wife Adrienne. The two are a team no matter what. Everyday you just – you push through it. You push through it because you have to. Adrienne endures grueling physical-therapy several times a week. (inaudible) The 36 year old mother of 2 struggles to walk. It’s very painful for me, Just because my achilles hurt really bad. So in order for me to not lose strength in my legs I have to do this even – I just have to bear the pain. It started last summer. Adrienne was diagnosed with a sinus infection. Doctors prescribed levaquin, the brand name for a drug called Levofloxacin. A few days into the prescription… I started having issues with my legs. My legs hurt, they burned, they feel like I walked up hill all day. My feet hurt, I had problems with my eyes, my vision started becoming kind of blurred. It took 3 months and 4 doctors to come up with a diagnosis. Let’s put a timeline to this and see where we are and then see if we can kind of tease out any correlations. And that’s really where we were able to sort of get to the notion that hey, ‘this is a levaquin problem’. Doctor Ki Jong, Adrienne’s neurologist, says the levaquin caused tendinopathy and peripheral neuropathy. He said, unfortunately, you have nerve damage from taking levaquin. I’m not surprised. I’m thinking about this and working on this for years. This woman has a story that’s replicated in city after city, and case after case I’ve read. Doctor Charles Bennett chairs a drug watch dog agency at the University of South Carolina. He recently petitioned the FDA for new what’s called black box warnings for levaquin. Those are bold warnings meant to grab your attention. The FDA already required black box warnings in 2008, warning a possible tendon rupture and muscle weakness and in 2013, the FDA required a label change , warning of nerve damage. Bennett says the FDA’s own stats show 1200 people have died and nearly a hundred thousand have suffered side effects from levaquin or Levofloxacin. I’m a fortunate that it has not been a life-threatening thing for me, and so I just think about the positive. And hopefully my nerves will regenerate themselves and become healthy again. Makes you wish, just like anybody love, makes you wish you could go back, and do something about it, maybe. In Charlotte – Michelle Bowden, NBS Charlotte. Last slide. Alright so, Bottom line is growing medical and public awareness that the fluorquinolones are potentially toxic drugs. New serious toxicities are still being identified. Highest risk patients particularly from hypoglycemia and Neurological problems are elderly patients in treatment for diabetes, have renal insufficiency, and you know, PPI use, and hospitalized patients are in increased risk for C. diff. The greatest overuse of these drugs are in treatment of uncomplicated UTIs and asymptomatic bacteriuria, both in using them in the first place and then prescribing them for a longer course of treatment than indicated Should also not be first line treatment for sinusitis for acute bronchitis. And it would be difficult to defend the fluoroquinolone prescription in court if prescribed outside of guidelines and a serious complication develops. I would take this very seriously. So try to avoid them if you can. So, One of the conversations that I routinely have and I’m curious to get your opinion, is if the hospitals and the patient with say like E. coli bacterium being discharged, it’s either continue their IV cephalosporin as an outpatient in the infusion center where they have a pick line or go home on oral cipro. But I’m really scared that this cipro black-box warning – (inaudible) Absolutely. There’s risk of IV therapy and And so, I really think that’s reasonable choice, Does she want to be stuck in a nursery home for a week getting IV antibiotics and getting C. diff. And at risk for line infections, and that’s the conversation that – (inaudible) – address the conversation. It’s just, when you have alternative treatments (inaudible) UTI, sinusitis, bronchitis (inaudible) It’s a risk benefit. (inaudible) But I get the conversation fairly often. And so the other thing – look about – look at your antibiotic. Your microbiology labs, (inaudible) the idea of just simply adding (inaudible) will probably make the hospital’s executive patients much more comfortable (inaudible) because a lot of times, patients on vanco zosyn (inaudible) but the patient’s doing well. I don’t really want to rock the boat and particularly in intensive care units where the doctors don’t know them because they’re changing positions all the time. So I think if you help them and educate them, you can stop the antibiotics okay. And it’s been studied that all it does is have less toxicity. So I think that’s something people should look at too. Alright, I hope that’s helpful. Yeah, any questions or anything out there? – or comments? I didn’t know that some of the CNS problems were irreversible. All right, well, thank you very much. Thank you guys. Thank you. Thanks everyone, we’ll be back.. Have a glass of wine. With some doxy. We can only drink hand-picked wine though.