Arnold Markowitz, MD, on His Suggestion to Revisit CAP Treatment Guidelines

After analyzing data from his own community teaching hospital, Arnold Markowitz, MD, suggests that the recently updated guideline for the treatment of community-acquired pneumonia be revisited from a local community hospital standpoint. In this podcast, Dr Markowitz explains his findings, the reasoning behind his treatment suggestion, and why the research is especially timely amid the COVID-19 pandemic. 

Additional Resource:

• Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. 2019;200(7)e45-e67. doi:10.1164/rccm.201908-1581ST

Arnold Markowitz, MD, is the chairman of Infection Prevention at St. Joseph’s Mercy Hospital, Oakland, and chairman of Infection Control at Pontiac General in Pontiac, Michigan.

TRANSCRIPT:

Colleen Murphy: Hello everyone, and welcome to another installment of Podcasts360 your go-to resource for Medical News and clinical updates on your moderator Colleen Murphy with Consultant360 Specialty Network.

Researchers recently conducted a study to determine whether the Infectious Diseases Society of America and American Thoracic Society recommendations for the treatment of community-acquired pneumonia with ceftriaxone and azithromycin are optimal. Based on their findings, the researchers made the suggestion that the guidelines be altered.

Today I am joined by one of the study's authors, Dr. Arnold Markowitz. Dr. Markowitz is the chairman of Infection Prevention at St. Joseph's Mercy Hospital, Oakland, and the chairman of Infection Control at Pontiac General in Michigan. He will be explaining his research, highlighting why he thinks it is of particular importance especially amid the COVID-19 pandemic. Thank you for talking with me today, Dr Markowitz.

Arnold Markowitz: My pleasure.

CM: Let’s first begin with why you conducted your study. 

AM: The fundamental reason was because the guidelines had been quite outdated. I think they were like about 13 years out of date; I thought it was time to take another look to see whether or not those recommendations were still appropriate. And I work in a community teaching hospital, and we see you know community-acquired pneumonia fairly frequently and what I was wondering was whether the guidelines were appropriate to our community, because a lot of times the guidelines come out of national centers. All of us tend to have a little different spectrum of bacteria, bacteriology, infectious disease, ad I just wanted to see if those recommendations are appropriate.

The other thing is I'm a primary infectious disease practitioner, and I often find that after antibiotics have been in use for a number of years, the bacteria tend to be a little bit resistant. So I started this particular study to see how our Strep pneumoniae sensitivity patterns were vs the rest of the world, pretty much.

I did have some students and a writer that worked with me on it. The students were part of something called AW Research—and they're both college students—they just basically did the statistics for me. And Lydia Lohrer was a writer for the Detroit Free Press in the past. She’s an excellent resource, she’s a wonderful editor, wonderful writer and was very helpful in doing the analysis with me. But fundamentally, it was just a very simple study; we just looked at microbiology and sensitivities. 

CM: Can you briefly explain your study and its results?

AM: Sure, so what I did was kind of a very simple review of sensitivity studies on all of the strip pneumonia isolates that we saw over a 33-month period of time starting in 2017 and ending in 2019. So what we did then was, we just looked at the sensitivities of all the Strep pneumoniae isolates that we had in the hospital, most of which were related to pneumonia, some of which were related to other sources, but all of the Strep pneumoniaes. And I think over that period of time, there were 157 step pneumonia isolates, and what we did then was we just looked at the sensitivity pattern. And what we saw was that ceftriaxone, which is the primary agent that was recommended for the treatment of community-acquired pneumonia was effective 147 of those 157 isolates. But when we looked at Zithromax, we found that only 74 were sensitive to Zithromax and that 107 were sensitive to doxycycline. So that was the primary part of the study that I was really looking at was whether doxycycline was as good as Zithromax in these patients and perhaps even better. And because community-acquired pneumonia makes up—or at least prior to COVID most of community-acquired pneumonia was either Strep pneumoniae, or atypical pneumonias, or aspiration pneumonia—I thought that doxycycline would be an interesting drug for use in any of those settings. 

So Zithromax works pretty good in atypical pneumonias; it’s not so good for aspiration pneumonia. Doxy is apparently as good in aspiration pneumonia and may even be better in atypical pneumonias, and in our study, it turned out that it was even more effective against Strep pneumoniae isolates.

CM: Based on these findings, you suggest that the current guidelines for community-acquired pneumonia be altered. In what ways do you say that they should be changed?

AM: Well, when you can use primary cephalosporin. And I think that that's appropriate. And if you need a secondary agent because you have not established whether it's Strep pneumoniae or one of the atypicals or aspirations that the second antibiotic that you should add should be doxycycline rather than azithromycin, again, based on the fact that the atypicals have a very similar pattern but Strep pneumo has a better response to Pneumococcus. The second recommendation was that if you can't use a cephalosporin because of allergies or adverse reactions or access that actually doxycycline might be a better primary drug to use all by itself. And by the way, that doxycycline or Vibramycin

fundamentally the same—one is a brand name the other generic—but that was the drug that we were comparing it to was doxycycline. So our recommendations, after looking at this, were that if you could use a cephalosporin, that the second agent that might be helpful is doxycycline rather than Zithromax and in that setting where you could not use a cephalosporin, doxycycline might be preferential as the primary single drug

So interestingly, after we did all this, the American Thoracic Society and Infectious Diseases Society did come up with newer recommendations, probably the end of 2019, but I think that this information should be looked at from a local community hospital standpoint and look at our own sensitivities, rather than dependent on the sensitivities collected at major medical centers because we see the pneumonia through maybe some different bacteriology

CM: You just said that the guidelines have been updated since your study. Did the updates highlight any of what you looked into?

AM: Not so much actually. They do list doxycycline or Vibramycin as an agent that can be used when you can't use anything else. Our thought was that it might even be a better drug to use than some of the others. And I think the other recommendation was a group of drugs called quinolones was added to the primary recommendations, and they're fairly decent from a treatment standpoint for pneumococcus but not so great for the atypical pneumonias or aspiration pneumonias. The other thought that came out of our study was that if you look at the various toxicities of azithormax or the arithromycins vs the tetracycline that tertacyclines are a lot safer. They don't seem to cause any cardiac toxicity. So that was not real important when we were looking at that study. And we really didn't look to see if patients had any adverse outcomes, we were just looking at the microbiology insensitivity. But as you get to the current issue—the COVID issue–that may be much more important.

CM: That brings me to my next question. We’re obviously talking right now in the midst of the COVID-19 pandemic. How does the current pandemic highlight this need for updated recommendations that you are suggesting? 

AM: Well there are a number of aspects to it. I think we need to remember that that still community-acquired pneumonia may exist side-by-side with COVID, that maybe sometimes seen with it, or maybe independent of it. And when our diagnosis is kind of weak because we don't have appropriate nasal pharyngeal cultures or testing or bloodwork to define the agent, we still need to be concerned about community-acquired pneumonia from the pattern of previous history which is Pneumococcus, atypicals, and aspiration. We need to add to the list, but we shouldn't exclude those. And if you keep those in mind, then doxy might be an equally effective agent in the treatment of those because with COVID, one of the initial recommendations was that Zithromax should be used. So the other part of it is that if now we are treating COVID with Zithromax—which I think is less frequent these last couple weeks—with plaquenil, we see additive cardiac toxicity. So maybe when we're adding plaquenil because of the suspicion of COVID, maybe we ought to avoid the azithromycins altogether and use a tetracycline as a supplemental agent. Again related to cardiac toxicity. And then the third aspect is that when you have everybody using Zithromax, you might run out of the stuff and may be starting to create a pattern of community resistance for the organism which often happens when only one drug is used; it tends to select out mutations and resistance patterns. So those are the, I think the major aspects of why I thought it was important to bring this study to the floor because if Zithromax becomes one of our primary agents in treating community-acquired pneumonia, I think we're going to miss a lot of them. And I think we’re going to undertreat a lot that might have done better with the tetracycline, particularly doxycycline.

CM: For your peers who are listening, is there anything they can do now—listening to your results and suggestions–to implement into their practice?

AM: That’s an excellent question. I think what we all ought to do is talk to our microbiology lab and take a look at the sensitivities and pay attention to what's going on. So most hospitals, once a year so have something called an antibiogram; I think we need to take another look at it and see how our sensitivities are doing. As far as the COVID issue, again I think that unless there's an overwhelming reason to use Zithromax, they might want to consider using doxycycline as the supplemental agent to ceftriaxone for the treatment of community-acquired pneumonia. And if you can't use ceftriaxone, doxycycline might be a better drug to use all by itself for community-acquired pneumonia and may not have any different effects on COVID—that data is not out yet, so I guess we need to pay attention to that over the next few weeks as data start to come out from these large outbreaks of newly acquired community-acquired pneumonia due to COVID.

CM: Yes, that is something we’ll definitely have to keep an eye out for. It’s obvious how timely your research is right now, so Dr Markowitz, I want to thank you for your time. And I hope your peers who are listening find what you presented today to be thought-provoking. 

AM: Well thank you so much for the opportunity to present it to my community. Thanks again. I appreciate it.