Speaker 1  00:05
Lange, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University College of Pharmacy.

Narrator - Dr. Abel  00:11
This podcast is produced by pharmacy faculty to supplement study material and provide relevant drug and professional topics.

Speaker 1  00:19
We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge.

Narrator - Dr. Abel  00:27
This is an educational production copyright Rosalind Franklin University of Medicine and Science.

Speaker 1  00:32
This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider.

Narrator - Dr. Abel  00:47
And now on to the show.

Dr. Sean Kane  00:51
Welcome to episode seven of HelixTalk. I'm your co host, Dr. Kane. I'm Dr. Patel, and I'm Dr. Schuman, and today we're talking about community acquired pneumonia, specifically the 2007 guidelines from the Infectious Disease Society of America and the American Thoracic Society.

Speaker 2  01:08
So I noticed that, yeah, guidelines published in 2007 may not necessarily be as applicable today as they were. Then any thoughts for if they're going to be updated anytime soon?

Dr. Sean Kane  01:17
So theoretically, they're supposed to be updated or due to be updated in the fall of 2015 but as we know from many other guideline publishers, sometimes that can be pushed back depending on kind of how much red tape is involved in new studies that come out that need to be incorporated in the guidelines.

Speaker 3  01:34
So first of all, when the patient presents with pneumonia, how do we decide whether we need to treat the patient as an outpatient, or treat the patient as an inpatient. So what are the diagnostic measures?

Speaker 2  01:46
I think there are a couple of them that can be used. There's the curb 65 and then the pneumonia severity index. So the curb 65 they're looking at confusion, uremia, respiratory rate, blood pressure, and then age greater than 65 and taking those factors into account. And then with the psi, it's primarily age and sex, but then it also looks at past medical history, physical exam, and, of course,

Dr. Sean Kane  02:08
some labs with it. So this is one way for providers, let's say, in the emergency department, to ascertain whether or not a patient needs to go home, if they're stable enough to go home for treatment, or if they need to be treated inpatient because of the risk for mortality because of the pneumonia. Obviously, these are clinical tools, not absolute. Yes, no, black and white. So clinical Gestalt is important in terms of understanding the number in combination with what you see with the patient.

Speaker 3  02:33
And then once they decide the patient to keep it or go ahead with the treatment option, the diagnosis is usually made, just like we mentioned, looking at the clinical symptoms, how severe they are. Sometimes, we will also throw in a chest X ray to see what the infiltrates look like, and then microbiology information, such as doing a culture.

Speaker 2  02:53
And I know, with most patients, you know blood and sputum culture should be should be taken. Hopefully you can get them before you start an antibiotic. But certainly most patients requiring hospital admission. That's especially with those who have a higher severity of illness or higher risk, to really get to know what kind of bugs you're dealing

Dr. Sean Kane  03:07
with here. Then, in addition to those two cultures, sputum and blood, we can also get what are called urine antigen tests, and we'll talk about the microbiology or the pathogens associated with community acquired pneumonia, but we actually have a test where we can check for specific antigen Streptococcus pneumoniae, which is the most common bug that we're worried about with community acquired pneumonia. We can also check a urine antigen for something called Legionella, which is much less common, but it can form very severe community acquired pneumonia.

Speaker 3  03:39
And correct me if I'm wrong when it comes to starting antibiotics early versus late, most of the clinicians will throw in the empiric regimen when they're waiting for the culture reports correct Absolutely.

Dr. Sean Kane  03:52
So we know that delay in antibiotics is not a good thing. It worsens patient outcomes. So while the diagnostic process is being undertaken, it's absolutely important to get the antibiotics on if there is a clinical suspicion of pneumonia.

Speaker 2  04:05
And I think with some of those blood tests we were talking about, the advantage of them, as we said, is sometimes cultures aren't always drawn beforehand, so you want to still start an antibiotic empirically. But one of the nice things about some of these, these newer tests, is that they can work even after the antibiotics are given.

Dr. Sean Kane  04:20
Yeah, and I think it's important to know the sensitivity and specificity of these urine antigen testing. So instead of trying to grow the bacteria on an agar plate, we're actually testing for the antigen in the urine. So if that test is negative, depending on the patient population and the study you look at, it's somewhere between 50 to 90% sensitive, meaning that 50 to 90% of the time you're able to detect the antigen if it truly is present, but that means that anywhere from 10 to 50% of the time you have a false negative. So the patient does have either strep pneumo or they do have Legionella, but your test wasn't positive. Conversely, though, if your test is positive, meaning. And that you have either a positive antigen for Legionella or strep pneumo it means that they probably do have that. So the specificity is very, very high, meaning that it's easy to rule in these infections, but it's more difficult to rule them out with a negative test.

Speaker 2  05:15
The other thing with it is that this also does not give you the sensitivity you can you still want to, want to run and see what kind of antibiotics this bug is susceptible to.

Dr. Sean Kane  05:23
As we'll talk about, strep pneumo is one of those bugs that, over time, has kind of become an angry bug, where it's developed a lot of resistance patterns. So having that sensitivity is very important.

Speaker 3  05:33
And talking about being it being an angry bug, let's talk about the most common organisms that are involved. We already mentioned strep pneumo. It's a gram positive commonly seen in patients who are older or patients with comorbidity, and like Dr. Kane mentioned, there is this angry strep pneumo. It's called drug resistant strep pneumo, you'll see the acronym drsp. When we are looking at the drug resistant we're testing it against the penicillin and macro lines to see if it's resistant or not.

Dr. Sean Kane  06:04
It's important to note that strep pneumo also has another nickname, called pneumococcus, to kind of confuse things further. So we may call it strep pneumo Streptococcus pneumoniae or pneumococcus, and all three terms mean the same thing. It's the same bug, secondary to Streptococcus pneumoniae or pneumococcus. The two most common gram negatives that we'll see in the community acquired pneumonia setting are Haemophilus influenzae and also Moraxella catarrhalis. And both of these are less common, but we do see them, so it is important that we have some gram negative coverage with our community acquired pneumonia patients.

Speaker 2  06:37
And then there's a few more that I always thought were pretty interesting in micro is you have your atypicals, and these, because of some of the waxy coating they have on, they just don't stain as well. And so we can't come up with a gram positive or negative, and they're also pretty difficult to culture in the labs. And some of the more common ones are gonna be the Mycoplasma pneumoniae and the Chlamydophila pneumoniae. And they're generally mild and self-limiting.

Dr. Sean Kane  07:00
so if you've heard of the term walking pneumonia, this is either mycoplasma or chlamydophilia, but we do have an atypical that is not walking pneumonia,

Speaker 3  07:08
and that is Legionella. And whenever there is a Legionella pneumonia infection, it is usually a severe disease.

Dr. Sean Kane  07:14
And this really speaks to the point of why that urine Legionella test is important. It's a fairly rare thing that happens, but when patients do have Legionella, it can be severe community acquired pneumonia; they're usually very, very sick, and we need to know that, because that really dictates our antibiotic therapy. So thinking about the antibiotics that we should give, it gets pretty complicated if we don't have a couple rules up front to help summarize some of the antibiotic recommendations.

Speaker 3  07:38
So first and foremost, you heard macrolide already. The two agents that we are using in this category is azithromycin and clarithromycin. What about erythromycin? Yes, it is available. It is a macrolide, but we are not using it for CAP.

Dr. Sean Kane  07:52
The reason for that is its adverse effect profile, primarily things like diarrhea. We have better data for communicator pneumonia with things like azithromycin or Z Pak or Clarithromycin, the by accident, and then

Speaker 2  08:03
another class we can look at. It's fairly commonly used. It's gonna be respiratory fluoroquinolones, and these can be medications like moxifloxacin or the brand name Avelox; levofloxacin, also known as Levaquin; and then gemifloxacin, Factive. And that latter one's not as commonly used. And we say respiratory here, meaning refers actually to its better strep pneumo coverage, and not to any kind of penetration. Sometimes we say it's urinary versus respiratory based on how well a drug is absorbed into the body. Here, it's not about absorption, just about what microbes it covers.

Speaker 3  08:34
So I did not notice ciprofloxacin here. Does that mean that it is not a respiratory fluoroquinolone?

Speaker 2  08:40
in that it does not cover the strep pneumo as well as those other bugs. I guess

Unknown Speaker  08:45
that's an important distinction to make that. I think that's

Dr. Sean Kane  08:47
again important to re emphasize is respiratory fluoroquinolone does not mean it doesn't get in the lung. This is something that I see from many pharmacy students that just don't understand the difference between lung penetration and coverage of strep pneuma, which is the most common pathogen for cap.

Speaker 3  09:04
And then there are some patients who might not be able to tolerate macrolide just because they have some sort of drug allergy, had drug interactions such as QTC prolongation if they're taking other medications. So in those patient we do go along with doxycycline. It's a reasonable alternative. However, the data is not as strong as we have with macrolide or respiratory Chloroquine loans,

Speaker 2  09:26
but at the very least, again, it does have that some of the atypical covers. So that might make it if you're if you're limited, that could be an attractive option.

Speaker 3  09:33
So if your patient cannot take the respiratory fluorophenolone, the alternative is using the azithromycin plus one of the high dose beta lactam and we'll go over what high dose we're talking about in detail a little later.

Dr. Sean Kane  09:46
Then finally, for those who are severe enough to require inpatient administration of let's say, IV antibiotics, one of the drug classes that we recommend are third generation cephalosporins, traditionally and typically, this is going to be. Drug called rocephin, which is ceftriaxone. However, there's kind of a cousin drug to ceftriaxone, which is cefotaxime, not commonly used, at least on the adult side. But it's important to know that cefotaxime and ceftriaxone are very, very similar with similar recommendations. But for the purposes of this podcast, to keep it simple, we're only going to be recommending ceftriaxone or rocep,

Speaker 3  10:21
and to just make a distinction, it is a parenterally used product.

Dr. Sean Kane  10:25
Once we have the rules out of the way, what are some of the medications that we would recommend in terms of antibiotics for someone who comes to an outpatient clinic who's otherwise healthy that has what we suspect is community acquired pneumonia?

Speaker 2  10:38
All right? Well, I guess right off the bat, if it's outpatient, and if we're, if we're not concerned about some of the drug resistance, rep, pneumo then, and they don't have any kind of other comorbidities, what we can do is we can just stick with with a macro line. So that goes with, as we said, the popular Z pack, something like the six of those 250 milligram tablets, where you take two and it even has it in the packs, that kind of has it handy, lined up in the foil to the first day one each of the next four days, so a total of a five day course,

Dr. Sean Kane  11:05
as Dr. Schuman had said, for those who are at risk for drug resistant strep pneumo or drsp, this could either be because they've had recent antibiotics in the past, or it could be that you're in some area of the country that has a high drsp rate. A Z pack probably isn't a good option, and we need to give something that is in a different drug class so that we can ensure coverage of

Speaker 3  11:26
strep pneumo so that alternate drug class that Dr. Kane's mentioning will be your respiratory fluoroquinolone. And for some reason, if your patient cannot tolerate the fluoroquinolone, here comes back to high dose beta lactam and macrolide. So those two high dose beta lactam you're talking about is your amoxicillin, you're going to use it about two gram dose, and Augmentin, whose generic is amoxicillin-clavulanate. There are several other cephalosporin alternatives, as we mentioned, cefuroxime, that's a second generation, or cefpodoxime, which is a third generation. However, again, the data with these cephalosporins is not as strong as amoxicillin or the amoxicillin-clavulanate combination, so we go ahead with those two.

Speaker 2  12:09
And one thing I think I want to like to point out is just that when we look at the reason why, if we say we can't use just a macro and why we don't just use, you know, a single beta lactam is, again, we want to cut make sure we're covering both some of those gram positives as well as the gram negatives and the atypicals. And so when you use either a four quinolone, you can get a lot of kind of that one stop shopping, whereas if you use a macrolide, we're going to still want that that extra coverage from the beta lactam.

Speaker 3  12:33
And if you are using the macrolide with beta lactam, make sure you not use the Z pap dose. That's a common mistake that some of the clinicians make, according to the guidelines that macrolide dose if you're using azochromyos, and it's 500 milligrams every day, not the Z pack kind.

Dr. Sean Kane  12:48
So using either these regimens, either the respiratory fluoroquinolone or the beta lactam plus macrolide, this is appropriate for two different patient populations. So one is the one that we already mentioned, the patients who are at risk for drsp, the drug resistant strep, pneumo but this is also appropriate for outpatients where the patient has comorbidities or chronic conditions of the heart, lung, kidneys, any diabetics, alcoholics, cancer, those who don't have spleens, so asplenia, and anyone who's immunosuppressed, which also goes along with lacking the spleen. So essentially, we have for outpatient therapy. We have two camps that patients will fall into. Either they have almost no comorbidities and they're otherwise healthy, they get either a Z pack or some alternative that we've already talked about. Or the other camp is anyone who has a risk of resistance with drsp, or pretty much any comorbidity that would put them at risk for mortality if we don't cover their pneumonia very well.

Speaker 3  13:43
So that was for the patients who are seen in the clinic, meaning they're ambulatory, they're outpatient. What about so let's say patient is in the inpatient but not really admitted to the ICU. What are the options we

Speaker 2  13:55
have for those? We have the respiratory for a clinical loans, and these are preferred. The patient is penicillin allergic, there's sometimes some issues with penicillin cross reactivity that I think Dr. kamer would love to speak to. So I'm

Dr. Sean Kane  14:06
actually pretty passionate about the penicillin allergy problem, because I am penicillin allergic. And the reason that this is important is that all too often it's easy for a provider to say, what are you allergic to? And someone says, penicillin, and no one asks the follow up question of, well, what happens when you take penicillin? So if we look at the data, when we look and see if a patient says that they're penicillin allergic, and we skin test them, about 80 to 90% of the time, they skin test negative, meaning that they think they have a penicillin allergy, but when given a penicillin, they don't have a reaction. And of that, if we were to give a cephalosporin to the patients who truly do have a skin test positive penicillin allergy, anywhere from low threes to maybe 10% of the time, will we have cross reactivity to a cephalosporin? And of that, it's about less than 1% of the time that we'll have an anaphylaxis reaction. So if you do all the statistics there, we'll look. At 80 to 90% of the time is not a true penicillin allergy. Less than 10% of the time it is cross reactive to a cephalosporin. And then less than 1% of the time, will we cause a reaction so significant, like anaphylaxis, that we have kind of an emergent medical situation on our hands.

Speaker 3  15:17
So what you're trying to say, if I had a patient who said, Well, I just had a rash with penicillin. I can go ahead and use ceftriaxone in this patient without having to worry about anaphylactic reaction.

Dr. Sean Kane  15:29
Not that you would never have to worry about it, but the risk would be extremely low. And I think it's beneficial to think about things like cephalosporins in those penicillin allergic patients, so that we're not, let's say, reutilizing a fluoroquinolone every time they have a new pneumonia, but we're offering other antibiotic options that may be more appropriate.

Speaker 3  15:47
And what if a patient said that they did have angioedema or an anaphylactic reaction with penicillin, then obviously we want to avoid the cephalosporins

Dr. Sean Kane  15:56
correct Exactly. And I really wish that the new guidelines that come out, hopefully in a year, we'll make that discrimination that not all penicillin allergic patients should never be given a cephalosporin.

Speaker 2  16:07
And I think there's, it's important, like you said, to dig a little bit into what the nature gives. A lot of times, I've had individuals come up to me and say, I have a penicillin allergy. I get an upset stomach, or I get some nausea when I when I take it, and then something as simple as just a little bit of counseling about, you know, taking it, you know, with a little bit of food, making sure it's a little easy on your stomach, something that little bit you can delineate between a serious allergen. So now we have a medication class that we can still stay fresh with and still use it in that individual, instead of just completely eliminating it all just based upon, again, a little bit of miscommunication.

Dr. Sean Kane  16:38
So in patients who can't take a beta lactam, a third generation cephalosporin like ceftriaxone or Rocephin, in combination with the macrolide for atypical coverage, like azithromycin, would be appropriate as well.

Speaker 2  16:49
So we were ready to move on and talk about how we would treat an individual who is inpatient, but specifically in an ICU population. So we're maybe dealing with a little bit of a more serious situation, maybe some more comorbidities involved here.

Dr. Sean Kane  17:01
So really, the only difference between ICU versus non ICU is that we're going to try to avoid the respiratory fluoroquinolone, if we can. So that would mean that we're using our third generation cephalosporin, like ceftriaxone, or Rocephin is the brand name again, plus the macrolide like azithromycin. But for the patients who can't take ceftriaxone, if we do choose to use that respiratory fluoroquinolone, we're going to add an agent called aztreonam.

Speaker 3  17:26
And the reason for adding aztreonam is because it's a monobactam with only gram negative coverage, so we don't see any cross reactivity with beta-lactams. So we don't have to worry about penicillin allergy there. And another reason we add aztreonam on top of the fluoroquinolone, because these are ICU patients, and we've seen increased risk of resistant fluoroquinolone. That's why we want to offer a broader spectrum.

Speaker 2  17:51
And what about those patients who are maybe concerned about a little bit of community acquired MRSA or methicillin resistant staph aureus?

Dr. Sean Kane  17:58
So the guidelines do discuss Pseudomonas and community-acquired MRSA. But oftentimes patients won't receive empiric coverage for MRSA or Pseudomonas. Oftentimes they actually have risk factors that would classify them in not the community-acquired pneumonia camp, but a completely different guidelines called the healthcare-associated pneumonia guidelines, which we'll talk about in our next episode.

Speaker 2  18:20
So one thing we want to do is just kind of go over a quick overview of what the what covers, what? So what do those three kind of main classes of antibiotic Exactly, exactly cover? So with our cephalosporins, what we're primarily getting is we're getting a decent degree of gram positive coverage. So we're getting that, that strep pneumo, then we're also getting some of these, the gram negatives. Again, we're not getting the we're not getting this, the pseudomonal coverage. But again, unless we're really, really, really concerned, we have a positive culture that's not necessarily something we're going to empirically treat. And then what we're also getting with our macrolide, one thing that we can bring to the table with that one is some of that atypical coverage as well. And so then we have that combination, whereas what we can do with the fluoroquinolone, again, especially with the respiratory fluoroquinol, is get some of that gram positive coverage with that strep pneumo But then we're also providing that atypical coverage from the macrolide, so you can kind of blend into both areas with that fluoroquinolone. Again, making sure it's respiratory fluoroquinolone.

Dr. Sean Kane  19:18
So in the patients who are hospitalized, oftentimes, we'll give them IV therapy until, you know they get better. So at what point can we do an IV to PO conversion, save some money, get them teed up to go outpatient? When is that appropriate to do for these community acquired pneumonia patients?

Speaker 2  19:35
And I think a lot of times it's going to maybe be on a case by case basis. Would you agree? Dr. Patel, definitely.

Speaker 3  19:40
So a few things that we want to look at is how patients doing it overall, okay? Is patient hemodynamically stable? Are the vitals? Okay? It's patient improving its patient has po access. If patient is taking food by mouth or has a PO access, we can go ahead and definitely switch that. Or if the patient have normally functioning GI tract, we also want to look at that as well. I think

Dr. Sean Kane  20:04
it's important to think about things like quinolones have excellent bioavailability. It's not like the drug doesn't work as well when you give it Po. It's just that we would prefer to give IV therapy to ensure, you know, 100% bioavailability in that patient who is really sick, who can't take po or we're concerned they may have hypoperfusion to their GI tract, where their bioavailability would be lower. Once a patient is healthy and stable, they're good to go to get an oral fluoroquinolones, for example,

Speaker 3  20:31
and not to forget that po therapy would be much cheaper to their counterpart of the IV version.

Dr. Sean Kane  20:36
So regardless of IV or PO, how long should we be treating these patients with community-acquired pneumonia,

Speaker 2  20:42
I believe it's generally understood that there's going to be a minimum of five days. You can generally do five to seven days, again, at the discretion of the clinician, based upon some of the severity and some of those individualized factors. You also want to make sure that the patient has been a fever off for two to three days. So if you know, if they've still got a fever, then again, what we're concerned is we want to make sure that, you know, we are actually covering what we need to, and that there, you know, something else isn't growing, or there's some, not some sort of resistance pattern. So you know, you may want to reevaluate at that time. But if they've been a fever off for two to three days, then we should be starting to think about if we need to go ahead and discontinue that antibiotic. You can also look at just some other things, you know, do the do the vitals look good? How are their other Oh, two SATs on room air. You know, if they're again, if they're still on oxygen, it may not be the best time, but if they're starting to look better, take all these things into account.

Speaker 3  21:30
I believe so. Again, summarizing the whole pack cards today, a few things that we want to make sure is we know that what kind of bugs are involved from which then you can derive your therapy. So we mentioned that strep pneuma, aka pneumococcus, and got other names too, which is the gram positive it's most common. And then some of the atypicals, like mycoplasma, Chlamydia, is also very common. Legionella is also an atypical. However, it's very rarely seen.

Dr. Sean Kane  21:59
So in terms of the regimens that we should be thinking about for outpatients, if it's an otherwise healthy patient who's appropriate for outpatient antibiotics, azithromycin or other macrolide is appropriate; if they have any comorbidities, so any lung, heart, kidney comorbidities, if they're a diabetic, they're an alcoholic, if they have cancer, any immunosuppression at all, pretty much any comorbidity, we should be thinking about adding high dose beta-lactam like amoxicillin or amoxicillin-clavulanate (Augmentin). And the reason for that is that we want to have better strep pneumo coverage than what our macrolide offers on its own. But by maintaining the macrolide, we still have that atypical coverage that we need.

Speaker 2  22:39
And then for patients that are those who end up going inpatient, but aren't in the ICU setting. We have the option of the respiratory fluoroquinolones. Again, that's in somebody who is a true anaphylactic penicillin allergy. We can use that respiratory fluoroquinolone otherwise, we can do a combination of a beta lactam and a macrolide. And that's again, thinking with beta lactam, where you know something like a ceftriaxone or a rosefin, and plus that macrolide, such as that azithromycin, again, kind of still is our workhorse there. And then, the other thing we want to emphasize too, with that is that the azithromycin dose, it's a high dose. It's a 500 milligrams daily, not that Z pack dose.

Speaker 3  23:14
So then let's say the patient doesn't improve and gets transferred to an ICU, the first line therapy we try to go to is beta-lactam plus macrolide, so like just summarized, it should be ceftriaxone plus 500 milligrams azithromycin. In cases where patients are allergic to penicillin, we can go ahead and use respiratory fluoroquinolone, but to avoid resistance we should add aztreonam as well. This is also a monobactam which does not have penicillin cross-reactivity. And another point, on the pharmacy side and cost side we want to consider is, whenever possible, switch the patients from IV therapy to PO therapy, and again keep duration of therapy in mind. Obviously you want to look at the patient as a whole, but the minimum duration is five to seven days. Great.

Dr. Sean Kane  24:04
So that concludes today's podcast. If you haven't done so already, we'd really appreciate a five star review in iTunes. You can find us at HelixTalk.com and with that, I'm your co host, Dr. King,

Speaker 3  24:15
and I'm Dr. Schuman, and I'm Dr. Patel, and as always, study hard.

Narrator - Dr. Abel  24:21
Thank you for listening to this episode of HelixTalk. For more information about the show, please visit us at HelixTalk.com you.