Controversies in the management of community-acquired pneumonia in adults

[Music] Welcome to the Australian Prescriber Podcast. An independent, no-nonsense podcast for busy health professionals.

I'm Dhineli Perera, your host for this episode, and I'm super excited to be talking to Dr Emily Tucker today about the juicy controversies that exist around management of community-acquired pneumonia, also known as CAP in adults. Emily is an infectious disease physician at the Royal Adelaide Hospital. She, together with her co-authors, Maeve O'Sullivan and Lisa Waddell, have extracted some of the key areas around CAP management that seem to continue to draw debate. Emily, a warm welcome to you.

Thank you so much for having me.

Emily, CAP, it's probably one of those clinical areas of infectious diseases that's taught to all of us health professionals really early in our degree and we see it frequently in our clinical practise. Why is it then that it just continues to be controversial and have uncertainty around its management?

Yeah. I think that there are a number of reasons for this. Community-acquired pneumonia is a very common infectious disease and a leading cause globally of mortality and morbidity, but it is a really tricky infection to diagnose in many cases, and that's because it often presents in a quite nonspecific way. A lot of our diagnostic approaches do not always clearly give us the answer about what's going on, and so therefore if you have difficulty with a diagnosis, then that obviously then leads to challenges with how you assess severity and select appropriate treatment.

Yes. And I can imagine with what you're saying with diagnostics, like in the community sector, we don't have quick access to a chest X-ray, for example, that can help to illustrate that further on the spot, right?

Yeah, exactly. And also even if you do have access, there are differentials, including non-infectious causes like heart failure, for example. It cannot always be particularly easy to delineate even when you do have access to imaging.

So then let's talk about the severity scoring tools. There are so many. How do health professionals know which one to use and when?

I think delving into pneumonia severity scoring tools quickly gets us into some of the controversies around pneumonia. There are a number of different severity scoring tools that have been developed, largely for use in clinical trials. But then as we go to that idea of how hard it is to initially diagnose but then stratify how we treat our patients with pneumonia, there's been many attempts when we write guidelines to really come up with some sort of clear structure to help prescribers and clinicians actually work out what to do next. And so a lot of these different scoring tools have been developed and validated in different populations. And through the guidelines and internationally different scoring tools have been favoured. For example, in the American guidelines, they use Pneumonia Severity Index, which has really been validated to look at mortality and whether a patient can be managed inpatient or outpatient setting.

It's a challenging tool to use because it has, I think, more than 20 different points to collect, and so it is really quite impractical in the clinical setting. There are other scoring tools that are used in the British guidelines like CURB-65, which is a simpler tool that's also been validated for a similar purpose of inpatient versus outpatient management. In Australia, previous editions of our national guidelines have recommended the use of SMART-COP, which is actually designed to tell us instead more about severity and whether a patient may deteriorate and require mechanical ventilation.

The challenge with all of these is that they can't be used on their own without clinical judgement . They only give you a single time point of how a patient is going in a dynamic situation and they also can under or over estimate disease severity depending on the tool and the patient. So in the Australian guidelines, they don't recommend the use of a severity scoring tool, but instead have a list of features that suggest a patient might need hospital admission and then some red flags for patients that you need to be concerned about deterioration instead of actually using a particular tool.

So moving on to antimicrobials, let's talk about spectrum. What has been shown to be the most important organism to cover for CAP?

In general and particularly when we start with low severity pneumonia, the focus is on the most common bacterial cause of community-acquired pneumonia, which is Streptococcus pneumoniae. The key antibiotic to cover that organism is amoxicillin, or benzylpenicillin if it's being prescribed intravenously. Really, in patients where we're less concerned about deterioration, then our focus is very much on that organism.

Okay. So when you talk about amoxicillin, is there a particular dose that you'd recommend for adults? Because I think it's safe to say that all doses have existed out there from BD, TDS, QID and all the different numbers. What would be your recommendation?

Yeah. It's tricky because we use amoxicillin to treat lots of different infections, so there's going to be different dosing recommendations to target different infections and pathogens. And so for community-acquired pneumonia, the oral dose for amoxicillin is 1 gram TDS, and the usual recommendation is for 5 days of therapy.

I noticed that doxycycline is mentioned in both your article and the guidelines as an alternative. Will it cover Strep as well as amoxicillin well?

Doxycycline is a really important antibiotic that can be used for treatment of community-acquired pneumonia. The challenge with using it as monotherapy is that there are higher rates of resistance compared to amoxicillin, which still makes amoxicillin our first choice if possible.

So I guess there's an element of caution to be considered if you are going down the route of monotherapy for doxycycline, especially in a patient that doesn't have an allergy to amoxicillin. Your preference would still be to cover that Streptococcus really well.

Exactly. But also you do need to think about the side effect profile, and particularly in some patients, older patients, for example, there are some challenges with doxycycline with regards to risks of esophagitis, the fact that you need to take it with a big drink of water, etc. And some of those considerations, particularly in patients that might have issues sitting upright, etc, really need to be taken into account as well.

Absolutely. So the administration of it is nowhere near as straightforward. Your article, Emily, mentions the other organisms that can be involved with CAP. What are these organisms and when are they an important consideration?

Even before we talk about other bacterial causes, obviously, one of the key causes of community-acquired pneumonia are viruses, so that's really important to consider. If it's clear that the patient has a viral cause of their pneumonia, then, obviously, there is not a role for antibiotics necessarily. Influenza A and B and COVID are key causes of community-acquired pneumonia that need to be considered, obviously taking into account local epidemiology for the patient.

And then there are other organisms classically called the atypical pathogens and these are organisms that are not covered by oral amoxicillin and need to be considered in patients particularly with particular exposure risks or maybe a presentation that may fit with one of these organisms, because sometimes they'll present with a less common presentation with diarrhoea or headache or things like that. Those are organisms like Mycoplasma pneumoniae and Legionella, which are key other considerations in both low, moderate, and high severity pneumonia, particularly Legionella in higher severity pneumonia.

And then there are other less frequent causes as well. You really need to think a lot about the patient in front of you. Have they travelled? Have they been to a tropical area? Are they at risk of other organisms like tuberculosis and their clinical picture has actually got some features that suggest things have been going on for a little bit longer? The considerations really need to be individualised to the patient.

Yes, especially if they're not responding to that initial course the way that you would expect, right?

Exactly. Often, there's only so much that you can work out on your initial review with a patient, and it's really important with pneumonia that this is a condition that's at high risk of deterioration and has a significant burden of morbidity and mortality associated with it. And so, it's really important that patients are followed up for progress so that we can see are they responding to treatment. And if they're not, then thinking about whether that treatment is appropriate, and also the consideration of other organisms.

What role, if any, do macrolides and fluoroquinolones play in the management of CAP?

They have a key role, but I think there are challenges because we do see overuse of these agents, particularly in lower severity pneumonia.

Macrolides are options in the community setting for patients particularly with drug allergy. And in the current version of the Australian Therapeutic Guidelines, clarithromycin is the recommended oral antibiotic. In patients with severe community-acquired pneumonia, then it's recommended that patients receive dual therapy with ceftriaxone to give you that streptococcal and other broader spectrum bacterial cover and then also azithromycin, so a macrolide antibiotic, and that's particularly in place to cover for Legionella. It has a key role in covering some of those pathogens such as Legionella and Mycoplasma as well.

Fluoroquinolones, in the Australian context, are not a first-line recommendation for community-acquired pneumonia outside of targeted therapy, and that's really when you know what you're treating. There are particular indications where a fluoroquinolone might be of use. The other setting is in patients, particularly in the inpatient setting. When they have anaphylaxis to penicillin and so they can't have a penicillin or a cephalosporin, then there is a role for moxifloxacin in that particular setting but it's a very specific recommendation. You'll see when you look at international guidelines, there's a lot broader use of respiratory fluoroquinolones, but that is not something that we use or recommend in Australia currently, and we'd like to keep it that way.

Yes, I was going to say and thankfully. Finally, to amoxicillin clavulanate, let's dispel some myths about this one. I've heard prescribers tell me that they don't think it's broader, it's just stronger, and that it can and should be used for CAP. Does the evidence that you've recently looked into show that this medicine has a role? And if so, where?

I think there's certainly antibiotic prescribing data to support the fact that it's significantly overused in community-acquired pneumonia. And so I think there are some important considerations to have about amoxicillin clavulanic acid and the idea that it's a stronger or a better antibiotic than amoxicillin when it's dosed at its 875-125 BD dosing, you are actually giving the patient a lower dose of amoxicillin than you would be if we're giving that gramme TDS dose. That is the recommended dose for oral therapy for community-acquired pneumonia.

The first thing is that you're actually giving a lower dose of the antibiotic that we will be using, particularly targeting Streptococcus pneumoniae. And so also then we have to think about the collateral issues that we have when we give an antibiotic that has a broader spectrum of activity, which amoxicillin clavulanate has compared to amoxicillin. That impact is the risk of C. diff infection, the risk of antibiotic resistance, the collateral issues with the gut microbiome, as well as the fact that oral amoxiclav [amoxicillin-clavulanate] does have a higher risk of adverse drug reactions like hepatotoxicity than amoxicillin.

There are potentially settings where amoxicillin/clavulanic has a role in community-acquired pneumonia, but it's a narrower setting and, in particular patient cohorts, some patients with significant medical comorbidities who have pneumonia with an organism that is resistant to amoxicillin, there is potentially a role there, but it's more nuanced and it's not usually part of first-line therapy.

Now coming back to one of the topics in your article, you've talked about the IV and oral debate. And I wanted to know your stance on the argument that some prescribers might think that their patient is sick enough to be in hospital, therefore they must need IV antibiotics.

This is an ongoing discussion. I think, it's a hotter topic in infectious diseases research for a lot of reasons, because there's a lot of benefits in not giving somebody intravenous antibiotic therapy. You're avoiding an IV cannula. There's good data to suggest you don't stay in hospital as long if you're on oral therapy and there are reduced healthcare costs as well as risks to the patient.

The other thing is that in community-acquired pneumonia, a lot of the agents that we are recommending for treatment, including amoxicillin, doxycycline, and the macrolide antibiotics all have excellent oral bioavailability. So, depending on how severe the pneumonia is in a patient who's able to tolerate oral therapy, then there is a select group of patients when they're admitted to hospital, even with moderate pneumonia, that would do just fine with oral therapy and that then saved that patient needing an IV cannula and the associated risks and costs.

So moving onto the duration of therapy, which is another contentious debate, there seems to be a constantly evolving duration. And we've gone in my short time of practising 14 days, 7 days, 5 days, and now talking 3 days. What would be your best advice for prescribers when they are trying to optimise the duration of therapy for the patient in front of them?

We're getting some really great evidence in this area, but it's a space that continues to evolve. What we read in the evidence and how you actually approach it in clinical practise can be two quite separate things when you've got the patient in front of you. So I think we do have data that really clearly supports a shortening duration of antibiotic therapy for pneumonia. The dogma that you needed these more prolonged courses of therapy for treatment of pneumonia has really been well dispelled now. And internationally, the recommendation for patients who are clinically improving is 5 days of therapy.

There was a more recently published paper a couple of years ago now that actually looked at a select group of patients that potentially can even shorten that duration to 3 days of therapy in carefully selected patients. The crux of it is that the patient needs to be clinically improving, and so the key step is rapid and regular ongoing review of patients. And those patients that are clinically improving, then potentially some of them may be able to have therapy truncated to a shortest 3 days, many will be 5 days.

We do know that if a patient isn't improving at 5 days, then they're at higher risk of complications or issues associated with their pneumonia. Really, part of that is do they have a complication of pneumonia or are we going down the right pathway with regards to diagnostics? Is there something else going on, or are we treating the correct pathogen? Really, one of the keys to selecting duration of therapy is safety netting the patient with regular review. Now, that's easier to do in the inpatient setting than the outpatient setting, where bringing a patient back for review is a little bit trickier to do. And so some of that safety netting needs to be education of the patient as well to represent if they're not improving.

If you were calling a patient to do that rapid follow-up and you weren't able to see them in front of you, is there specific questions you like to ask them to see how they're progressing?

Patients do take time to improve. One of them is really just asking them how they're feeling compared to their initial presentation. Patient's symptoms should steadily improve. You would expect that, within about 48 hours, their fever should have subsided. Things like appetite and other markers of systemic health can be useful to ask as well, but symptoms like cough, breathlessness, etc, they can take longer to improve. And that doesn't necessarily mean that the patient still needs antibiotics, but we expect that they may take weeks to resolve and, obviously, depends on what their other medical comorbidities, their underlying lung function, etc. is. And then if they're a patient that's in hospital, then you've got other parameters such as oxygenation, respiratory rate, heart rate, etc. Other parameters that you can follow on the phone, those would be the sorts of things I'd be thinking.

Your article also mentions corticosteroids. I was wondering if you could tell us a little bit about the evidence for their use in CAP. Who should receive them and what dose form would you recommend?

This is an area of developing data and there's been a number of different studies published looking at the use of corticosteroids in pneumonia. Predominantly, this is in patients in the intensive care setting with high severity pneumonia and there's been a couple of key publications over the last few years that has helped evolve our thinking about the role of steroids and pneumonia. I think this has coincided with our understanding about steroids in other respiratory settings and in sepsis and, really, where do corticosteroids fit in pneumonia. And I don't think we have the complete answer yet, but there has been some publications that suggested with a correctly selected patient with higher severity pneumonia, if you give steroids early, then there's a mortality benefit.

The challenge is that we are still learning about what the correct steroid, the correct dose, the correct duration is, and really making sure that we select the correct patient. There are some other ongoing pneumonia studies which are going to add further evidence to this, including a really pivotal large multicenter study called the REMAP-CAP study where I suspect we'll get even more information. I think one of the challenges in pneumonia is making sure we have good data to support our recommendations, and the great thing is we are starting to get more and more of this data now.

Really, despite CAP being as common as it is, it's just a moving target for us all.

It is. But I hope in my career that we'll get to a point where we're able to take a much more precise approach to the individual patient in front of us.

Thank you so much, Emily, but that's unfortunately all the time we've got for this episode. Really appreciate you taking the time for today.

Thanks. It was great to chat to you.

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Emily's article, Controversies in the management of community-acquired pneumonia in adults, is available at the Australian Prescriber website. The views of the hosts and guests on the podcasts are their own and may not represent Australian Prescriber or Therapeutic Guidelines. Emily and her co-authors, Maeve and Lisa, are members of the expert group for the upcoming Therapeutic Guidelines Antibiotic Version 17. I'm Dhineli Perera and thanks for joining us on the Australian Prescriber Podcast.