Treatment and Diagnosis of Community-Acquired Pneumonia
In this episode, Dr Rizzo interviews Hariharan Regunath, MD, about community-acquired pneumonia (CAP), including updates to the American Thoracic Society and Infectious Diseases Society of America guidelines on the diagnosis and treatment of adults with CAP, the use of the pneumonia severity index, the CURB-65 prediction tools to help decide the need for hospitalization, diagnostic tests, and more.
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Hariharan Regunath, MD, is an attending physician at University of Maryland Baltimore Washington Medical Center (Glen Burnie, MD).
Albert A. Rizzo, MD, is the Chief Medical Officer of the American Lung Association and Pulmonary Staff Physician for the Center for Virtual Health at ChristianaCare (Newark, DE).
TRANSCRIPTION:
Moderator: Hello, and welcome to Critical Observations in Pulmonary Medicine led by Chief Medical Officer of the American Lung Association, Dr Albert Rizzo. The views of the speakers are their own, and do not reflect the views of their respective institutions or Consultant360.
Dr Albert Rizzo: So, I believe the most recent guidelines put out by the American Thoracic Society and the Infectious Disease Society of America were in 2019. At that time, they updated several recommendations from the 2007 guidelines, and I hope we can highlight some of those changes during our discussion today.
Community-acquired pneumonia has been defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community, as distinguished from hospital-acquired or nosocomial pneumonia.
One of the terms that was dropped as a result of the guideline update is the Healthcare-Associated Pneumonia, or HCAP. Can you comment on why this term was dropped?
Dr Hariharan Regunath: Yes. Thanks for this question. HCAP was originally introduced in 2005 HAP/VAP guidelines, and it was a presumption to encompass patients who were thought to be at high risk for multidrug-resistant organisms, mainly via their contact with the healthcare system because that's where we commonly encountered multidrug-resistant organisms.
But over the subsequent decade, data has now shown that many who were labelled HCAP were not at high risk for multidrug-resistant pathogens. In other words, the studies revealed no association between the definition that made HCAP as a whole or any of its components to the presence of, or the isolation of, multidrug-resistant organisms.
So most patients who were labelled as HCAP were also from the community, harboring similar pathogens from those who had community-acquired pneumonia. So these were the considerations that they took into account and they voted for dropping the term HCAP.
Dr Albert Rizzo: Right. Well, that flows right into my next question which is, what is the current thinking regarding the primary etiologies of community-acquired pneumonia that the treating physician should keep in mind?
Dr Hariharan Regunath: Yes. Well, community-acquired pneumonia, I think it has stood the test of time. The most common pathogens...
Well, before I say that, I want to regroup the pathogens as bacterial pathogens and viral pathogens. Bacterial agents are by far still the most common. Now, the viral pathogens have been recently recognized, especially since the advent of molecular diagnostics. So I would say pneumococci is still the number one cause worldwide for community-acquired pneumonia, and in the United States, following pneumococci is gram-negatives, like Haemophilus influenzae, and then Staphylococcus aureus.
There's a little bit of overlap with the healthcare-associated settings. But I also want to clarify that while the CAP guidelines did say the reason for dropping the Healthcare-Associated Pneumonia is related to the observation that pathogens causing both are similar. But for those who qualified for those definition of Healthcare-Associated Pneumonia guidelines do acknowledge the fact that healthcare contact is, in fact, a potential risk factor for NDR pathogens.They just wanted to highlight that individual patient characteristics were better determinants of multidrug-resistant pathogens.
So cycling back to the current viral etiologies, I think the 2014/15 data from the CDC does say that among the vital etiologies, it used to be influenza in the winter season, rhinovirus throughout the year, and metapneumovirus. They were the most commonly seen cases in adults, but now with the advent of the pandemic, there's a little bit of a change in the epidemiology, depending on what we expose ourselves to and what risk factors.
Dr Albert Rizzo: And I think you almost predicted my next question here. Are there patient characteristics or comorbidities that make certain pathogens more likely to be suspected at the time of presentation?
Dr Hariharan Regunath: Yes. There are individual risk factors which have been identified to aid suspicion for specific pathogens, and the examples include structural lung disease,for example, where we often see Pseudomonas, Burkholderia, or S. aureus, including MRSA.
In patients who have alcohol dependence or alcohol use, we could see Klebisella or anaerobes, including Acinetobacter and then even pneumococci. In patients with HIV, it depends on whether they're early or late in the HIV disease, or that they're controlled or not. You can see the typical pathogens are opportunistic infections like PJP, Cryptococcus, or Histoplasma. And not to forget, the population where we can predict or suspect penicillin resistance, which includes elderly, aged than 65 years, and those who have been exposed to beta-lactam antibiotics within the past 90 days, and those who have children in day-care settings. Similarly, I can go on. This is an exhaustive list, where many factors can help us identify or suspect specific pathogens.
Dr Albert Rizzo: So it really points out the importance of the history. Especially the recent history as to where that patient's been, what they've been doing, along with their comorbidities and characteristics, right?
Dr Hariharan Regunath: Absolutely. Clinical teaching goes saying that if we miss something, the answer always lies in the history and physical exam.
Dr Albert Rizzo: Very good point. When confronted with community-acquired pneumonia in the clinical setting, let's say whether it's in a physician's office or the emergency room, determining whether a patient should be safely treated as an outpatient, or requires admission at least to observation or general medicine, or maybe a higher acuity is certainly an important first step. And I know there have been prediction tools developed to help a clinician decide the need for hospitalization. I'm referring to specifically the PSI or pneumonia severity index and the CURB-65. Can you describe them a bit and comment on their utility and your preference if there is one as to what tool should be used in certain settings?
Dr Hariharan Regunath: Yes. And this is a very important question for the learning providers, particularly. I want to emphasize a few important things when it comes to these tools. It is a conditional recommendation that is being given regarding the PSI or the CURB-65. Now it's also important to remember that they are never a standalone tool. They are always used as an adjunct or a supplement to clinical judgment. So there is no replacement of clinical judgment. But then why do the guidelines stress these tools? Because clinical judgment can be quite variable across the health care settings regarding admission rates, costs and risk for nosocomial complications. So that's why they emphasize the prediction tools as a guide. PSI has a better-discriminated power because it has lot more variables than the CURB-65. In other words, CURB-65 is a shorter version taking into account the most impactful factors, and PSI is a more elaborate portion.
So obviously it has a better discriminative power. It takes into account sex, age, comorbidities, exam, lab findings, and radiological findings, as opposed to CURB-65, where we have only four or five variables. So many clinicians, I believe, prefer to use CURB-65 because it's quick and easy, as opposed to PSI, but the new guidelines in their data, it is very clear that they prefer PSI compared to CURB-65. And to be honest, I do not think in terms of which score, but rather what components of them convinces me to decide whether a patient needs to be admitted or not. This is because clinical observation at a one-time point in time does not always provide an accurate estimate of the disease course.
Dr Albert Rizzo: Good point. Yes.
Dr Hariharan Regunath: And one last thing I want to emphasize is that it's really important to understand that they assist to determine the need for hospitalization, and not designed to select a level of care for an elderly hospitalized patient. So, the time point of admission is where these should typically be applied and not after.
Dr Albert Rizzo: Right. So, let's discuss some of the diagnostic tests after the history has been obtained. That really should be part of that evaluation of community-acquired pneumonia. For example, what is the role in the timing of obtaining sputum and blood cultures would you say?
Dr Hariharan Regunath: The diagnostic tests... Usual diagnostic tests help in assessing severity can be done with CBC, BMP. For comments about sputum and blood cultures, generally cultures from any tissue body fluids have the highest yield when we obtain them prior to antibiotic therapy. So having said that, we should consider the fact that most patients with non-severe community-acquired pneumonia are unable to provide a sputum sample that's considered microbiologically adequate. Hence, they have a poor yield, and it's not recommended as a test for outpatients. But in critically ill patients with severe community-acquired pneumonia who need mechanical ventilation, there is an easy access to the lower respiratory tract, so there is no excuse to not obtain a tracheal aspirate as soon as possible. Now we have to keep in mind that in an effort to obtain a sample, we should not delay antibiotic therapy. The first dose needs to get in as soon as possible. And you get the culture samples as soon as you can. You make every attempt to gather the sample before the antibiotic administration, so that you improve the yield, and thereby you subsequently deescalate antibiotics down the road.
Dr Albert Rizzo: Right. And I know you've also written about the importance of the turnaround time for antibiotic susceptibility testing or AST. Can you comment further on that?
Dr Hariharan Regunath: Yes. Well, the turnaround time has to be used in two different contexts when it comes to community-acquired pneumonia: blood cultures and sputum cultures. The blood cultures' turnaround time is pretty fast nowadays with the automated systems. The sputum cultures take their own sweet time because they are still done in the traditional way. So, while blood cultures are recommended in all patients with severe community-acquired pneumonia, they have a very low yield in outpatients. Blood cultures are also recommended for those who are being treated for MRSA or pseudomonas as a presumption. So in blood cultures, the turnaround time, typically (my answer is probably going to be a little long-winded here), from the time of collection, it takes about somewhere between two to five days for it to turn positive [The normal blood cultures are kept up to five days for processing and if no growth they’re discarded]. So let's say it turns positive on day two. Then it takes another 48 to 72 hours for it to be grown in cultures until we get the final susceptibility results. So it could take up to five days for us to narrow the antibiotic spectrum. In the past decade, this process has been intercepted by PCR soon after the bottles turn positive before you plate it. At that step when you do the PCR, it spits out a host of pathogens, including common gram positives, gram negatives, candida, and certain markers of genetic resistance. So in 48 hours, when the microbiologists calls you saying that, "I have a gram-positive pathogen." Within the next couple of hours, he does a PCR and it spits out a pathogen. At least he'll say, if what’s not included are pathogens such as the MRSA or pseudomonas, and thereby help you to quickly deescalate.
For sputum cultures, it's whole different ballgame. Because the sputum cultures... They follow the traditional path. We don't have a PCR to intercept the culture process. But we do now have what's called a non-culture based diagnostic test, which is a pneumonia panel or PCR done directly in the sputum sample. That, I am of a mixed opinion about it. They are upcoming as quick tests with a quick turnaround time. You'll get the results immediately if your lab does it in the same institution. But the problem is you detect a host of pathogens, which might be a colonizer, and you cannot differentiate between a pathogenic versus a non-pathogenic agent. What is most useful among such non-culture-based techniques/tests is the MRSA PCR, which has a good negative predictive value that helps you to deescalate when it is negative.
Dr Albert Rizzo: Very good. Yeah. I was going to ask more about PCR, but you covered that very well. And we heard a lot about PCR now as part of the evaluation, certainly to rule out COVID with the different viruses. And now we're looking at influenza, RSV. I guess there are multiplex PCRs that will help in the initial setting to define a pathogen. Is that correct?
Dr Hariharan Regunath: That is correct. We do in fact in our institution use the multiplex PCR, but then they come in a different variety of combinations. One that is combined with the regular respiratory pathogens panel and then that which has SARS-CoV-2 with it. And then there is a smaller version of it, which just has influenza/RSV and SARS-CoV-2, all three. And there's another one that also includes C. Diff with it. So I don't know why they include C. diff, but...
Dr Albert Rizzo: So, a lot of pick and choose from. Yep. Depending on your institution.
Dr Hariharan Regunath: Right.
Dr Albert Rizzo: As part of the initial evaluation, chest x-rays seem necessary. And can you comment on when you might consider going to a CT scan of the chest, and also comment on what the routine follow-up of a chest x-ray might be after someone's been treated for pneumonia?
Dr Hariharan Regunath: Absolutely. The chest x-ray is an important part of diagnoses. That is without question. CT chest on the other hand is generally considered,if there is a need to know the radiologic characterization, or for you to understand what else is going on in regards to complications, or host factors such as immunocompromised host. Or in patients who have recurrent pneumonia, then you may want to investigate why they are developing recurrent pneumonia for a better understanding of the pulmonary parenchyma. And certain pathogens have typical appearances in CT scans, for example,cavitary lesions for mycobacterium tuberculosis, the halo sign for aspergillus in solid-organ transplant patients, etc. And to further evaluate plural effusions, whether they are simple or complicated. Similarly, if patients don't follow the clinical course as you may expect, you probably want to have a CT scan of the chest to evaluate and see what else it may offer you in regards to clues towards diagnoses.
Follow-up imaging is generally not recommended for patients who are following the clinical course as expected, and they start recovering within five to seven days of treatment. But those who had a staggering response or who had atypical features, then those patients may require follow-up imaging. The current guidelines did evaluate about the role of follow-up imaging and what they found was that, in the studies that looked at follow-up imaging, the chances of really identifying the most worrisome diagnosis such as a malignancy or an underlying cancer, was very low. And for those patients where follow-up imaging studies did identify lung cancer, they were already qualifying for the lung cancer screening recommended by... You can name the association that's recommending it.
Dr Albert Rizzo: USPSTF.
Dr Hariharan Regunath: USPSTF. Yes. Thank you for clarifying that.
Dr Albert Rizzo: It's a mouthful. I've practiced it a number of times.
Dr Hariharan Regunath: Right. The USPSTF. So otherwise, right now follow up imaging is not routinely recommended for all patients.
Dr Albert Rizzo: Okay. Thank you. So if we begin to talk about antibiotic regimens for treating community-acquired pneumonia, is it still a useful framework to look at the site of treatment, outpatient versus inpatient, as well as immunocompromised versus non-immunocompromised? Does that help start delineating the regimen?
Dr Hariharan Regunath: Probably, yes. I would say because the guidelines are still using these in the context of treatment choices available in the United States. The choices for outpatient versus inpatient could vary based on the setting or other factors, of course. But when compared to the previous guidelines, the 2019 guidelines do emphasize the recognition of severe community-acquired pneumonia based on the 2007 IDSA/ATS criteria. Because they had, I believe the data from pooled meta-analysis... The meta-analysis pool sensitivity was around 84%, and specificity was around 78% for inpatients. And they recommend ICU admission for those in refractory shock or needing mechanical ventilation. So similarly, conditions or medications that cause immunocompromise and the duration and level of immunosuppression are important factors that would guide us in our empiric choices in regard to certain pathogens. [Autoimmune disease versus solid organ transplant versus bone marrow transplant patients, or what degree of immunosuppressant does,,, or HIV, for example... does give a guide to what pathogens should be considered for empiric choices]. So I do believe there is a role for it.
Dr Albert Rizzo: Okay. Thank you. Antibiotic stewardship is an important aspect. The appropriate use of antibiotics to avoid side effects, but also avoid the promotion of resistance. What are some best practices regarding duration of antibiotic therapy in community-acquired pneumonia?
Dr Hariharan Regunath: So minimum of five days of antibiotic therapy is essential, provided there is clinical recovery within a 72-hour period from the commencement of antibiotics. It can be prolonged if recovery is staggering, or if you have MRSA or pseudomonas. Then you could go up to seven days or eight days. Similarly, the complications such as empyema, lung abscess, or if they had complicating bacteremia, endocarditis, or metastatic focus of infection, they may require a longer duration of therapy depending on the clinical settings.
Dr Albert Rizzo: Great.
Dr Hariharan Regunath: So I would like to... In this setting, I think I also wanted to... Because you brought up antibiotic stewardship. I want to just mention that for severe community-acquired pneumonia, when we start broad-spectrum therapy, I think there's enough opportunity within the first 48 to 72 hours if they are clinically improving and when cultures are negative. And if cultures weren't obtained, then by using PCR or absence of risk factors in combination with the MRSA PCR, we can properly de-escalate therapy. So those are some other opportunities that we should also think about when it comes to stewardship.
Dr Albert Rizzo: Right. Especially in view of the fact that promoting resistance is a concern. And in that regard, do you see any significant changes coming up on the horizon with regarding newer therapies, newer antibiotics, because of some of the resistance it's developing?
Dr Hariharan Regunath: Yes. More and more antibiotics have become noticeable... I mean, for example, if you take ceftaroline as opposed to generation cephalosporins, it works on drug-resistant Gram positives, also the Gram negatives which may harbor a beta-lactamase or AMP-C resistance. [ MRSA, MSSA, drug-resistant strep, gram negatives, and pseudomonas]. There are upcoming antibiotics that the guidelines do talk about [a few of them], but there are others that are available outside the United States as well. The guidelines particularly talk about omadacycline, which is a tetracycline derivative, data compared to moxifloxacin, but it's only studied in inpatients and not on outpatients. And there are recent papers and meta-analysis and systematic reviews in the journal, the Clinical Infectious Diseases, that talk about doxycycline still having activity against pneumococci, hence justifying their role... And one of the commentaries does talk about how one of the guideline authors voted against it in the CAP guidelines, but wrote a commentary saying that doxycycline still holds good because of the data in-pooled analysis.
Dr Hariharan Regunath: Another antibiotic that is the first of its kind is lefamulin, which is a pleuromutilin antibiotic. And it inhibits bacterial protein synthesis in simple terms. It's active against gram positives and gram negatives. Most of the comparisons are to moxifloxacin, which is an oral agent and they have non-inferior results. And they did include comorbidities as a part of that study. So, they're looking at lefamulin as a potential alternative to fluoroquinolones because it [the latter] causes less QT prolongation and other adverse effects. So there might be a change within the next decade... as we know that it took about 10-plus years for new guideline to pop-up. So I am pretty sure there might be changes by the next time the guidelines will be revised.
Dr Albert Rizzo: A few years. Yep. Yep. Okay. Switching gears a little bit, an important role for healthcare providers to try to prevent disease when possible, and certainly pneumococcal pneumonia and influenza-related pneumonia are important. And we have vaccines that can play a role in this. Can you review the current recommendations from the ACIP regarding the pneumococcal vaccines, as well as the influenza vaccines that will likely be available this season?
Dr Hariharan Regunath: Sure. The 2021 ACIP iterations did introduce the PCV20, which is a conjugate vaccine, or a PCV15, which had two more strains, more than the prior PCV13. The PCV15, if we give, should be followed by the PPSV23 in series. These are the two options, either PCV20 alone, or PCV15 followed by PPSV23 after a year from PCV15.
Now, they try to simplify their recommendations as much as possible, but it is still quite complex when you try to interpret it. Cause we have a host of patients who has already received one or the other, and in such different age groups with different risk factors. So let me start with this. We had PCV13 and PPSV23 in the past, and now we have two more new vaccines. So how do we provide guidelines for all of them? So to simplify it, I would say the following
For those who have already received the PCV13, simply follow the previous recommendations with PSV23 [following the PCV13]. For those who only had the pneumococcal 23 valent vaccine in the past [the old one, the PSV23], they may receive either PCV20 alone, or a PCV 15 followed by another PSV23 after a year. Now we had to make sure that the first dose was based more than a year from the series, or the PCV20.
If you have not received any vaccine, you could just do PCV20 alone or PCV15 followed by 23. For immunocompromised patients, this duration [which is typically one year or more] that is between the other [newer] pneumococcal vaccines and the [old] PSV23, , can be shortened two months or more [More than or equal to eight weeks is what they say]. So this is the most simplified version I can give you.
Dr Albert Rizzo: I think the fact you said it's complex is an understatement, but I appreciate you trying to sort it out for us.
Dr Hariharan Regunath: Right. And the list of conditions that come under the comorbid conditions that qualify them to get vaccine from 19 to 64 years is a whole host of things, including chronic liver disease, chronic lung disease, chronic heart disease, HIV, asplenia, CSF leak, cochlear implant. And keeps going on, including hemoglobinopathies disease.
Dr Albert Rizzo: And switching gears to influenza. What do you think this year is going to be like? And what are you recommending to your patients?
Dr Hariharan Regunath: Well, the mask mandates have been fluctuating now. And the adherence by the public to mask requirements are quite variable. So it will not be surprising to see influenza cases. It was very clear during the COVID-19 pandemic with the mask mandates, we had almost no influenza activity, as opposed to this year. We probably will see some. We did see surges in flu B cases last year, much later when the mask mandates were relaxed in the influenza season. So it's important that we follow through the nationally recommended annual vaccination for influenza in all adults who do not have contraindications. And when it is available, get it prior to the onset of influenza activity in the community. There are intramuscular killed inactivated quadvalent vaccines, which can be egg-based or cell-culture based. And you have a recombinant vaccine and also a live vaccine. Particularly for adults more than 65 years who are most vulnerable, a higher dose inactivated vaccine is recommended as a single shot. Otherwise, for others, any inactivated vaccine can be used intramuscular .
Dr Albert Rizzo: And I guess as a last question, do you have any inside information on when the next COVID booster might be available?
Dr Hariharan Regunath: Well, there is talks among the infectious disease, critical care, and pulmonary groups that are more than likely we may have to get two doses. Hopefully there'll be a formulation that could cover the Delta, Omicron as well as the BA.5 or the BA.2. So it's going to be more than likely COVID-19 is going to be causing blips instead of a widespread pandemic in the future because herd immunity has picked up quite a bit. So SARS-CoV viruses... I think the main pandemic wave has gone away. And now we will probably just see the blips, particularly pertaining to host factors, i.e among those who will lose immunity in the long run related to their own host factors.
Dr Hariharan Regunath: I would say their immune phenotype or whatever undiscovered reasons, that might lead to discoveries. I cannot say anything for sure. But I would say a fourth booster is definitely in the pipeline. If you had natural infection, you might forgo it. But again, it may only last up to six months, which more and more studies have shown that. But after how many infections or after how many boosters are you considered immune for life? I don't think that's ever achievable because of the reassortment and the antigenic shift and drift that we see in influenza viruses. So mutations keep happening and new variants emerge... Yeah. You're going to see new versions of SARS-CoV too.
Dr Albert Rizzo: Well, this has been a very comprehensive discussion for our listeners. Any other points you wanted to make? I thank you for the topic you have covered very completely.
Dr Hariharan Regunath: Well, I think we covered most of it. I would like to emphasize that there is always a great opportunity to deescalate antibiotics in being an infectious disease and critical care physician myself. There's always scope for it in hospitalized patients.
Dr Albert Rizzo: Great. Great message. Thank you.
Dr Hariharan Regunath: All right. Thank you, Dr. Rizzo.
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