Chapter: 06 Research on Bacterial and Fungal Infections
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In this segment, Dr. Bodey discusses papers of importance that he produced during his career. He begins with “Hypersplenism Due to Disseminated Candidiasis in a Patient with Acute Leukemia,” indicating how this work helped identify a sequence of treatments for this patient. He then talks about an NCI-funded study of causes of death in leukemia patients that helped to establish different types of antibiotic treatments. Next Dr. Bodey discusses a key paper, “Quantitative Relationships Between Circulating Leukocytes and Infection in Patients with Acute Leukemia” (1966), the first paper to quantify the white cell count levels at which leukemia patients would be extremely vulnerable to infection. Next, he talks about his work on carbenicillin and its significant role in combating pseudomonas. He sketches what an infection can do to a cancer patient, then talks about an article in the Houston Post that reported the carbenicillin results.
Next Dr. Bodey talks about the results of the first paper studying the use of anti-biotics in patients treated in Life Islands. He notes the psychological effects of the life islands on patients and how carefully they screened patients for their studies. Dr. Bodey then notes that he provided support for Dr. Emil J Freireich and others who studied chemotherapy treatments. He explains the “semi-quantitative total body skin culture” studies, in which he measured the populations of bacteria and fungus growing on different parts of patients’ bodies when they were in the protected environments. He notes another paper on carbenicillin that resulted in a 90% reduction of pseudomonas in leukemia patients.
Identifier
BodeyGP_02_20130626_C06
Publication Date
6-26-2013
City
Houston, Texas
Interview Session
Gerald P. Bodey Sr., MD, Oral History Interview, June 26, 2013
Topics Covered
The Interview Subject's Story - The ResearcherThe Researcher Discovery and Success Overview Definitions, Explanations, Translations Patients Patients, Treatment, and Survivors Character, Values, Beliefs, Talents
Transcript
Tacey Ann Rosolowski, PhD:
So, what’s the title of this paper?
Gerald P. Bodey Sr., MD:
This is a very interesting paper and of some importance because it reported a patient who had acute myelogenous leukemia and went into bone marrow remission. But his blood counts failed to recover, and he was still febrile and not doing well. It was finally determined that he had hypersplenism due to disseminated candidiasis, and had Candida in his spleen and liver and all that stuff. They did a splenectomy on him, and when they took his spleen out his blood counts all returned to normal and his candidiasis responded to amphotericin B therapy, and he went into remission and did well. That was a somewhat unusual case that made us alert to that as a possibility in the future.
Tacey Ann Rosolowski, PhD:
Did that actually become part of the treatment with individuals who had this very acute fungal infection?
Gerald P. Bodey Sr., MD:
Well, we were very aggressive about treating fungal infections when we knew they were present. I don’t know how many cases like this we saw. This is really a very unusual case.
Tacey Ann Rosolowski, PhD:
How did this particular case help you understand cases that were less acute?
Gerald P. Bodey Sr., MD:
I think I was somewhat alert—well, really the most important point in this paper was the fact that he had persistent low blood count.
Tacey Ann Rosolowski, PhD:
Oh, okay.
Gerald P. Bodey Sr., MD:
And so it was not possible to treat his fungal infection adequately until his blood counts recovered. So they took his spleen out, his blood counts came up, and then amphotericin B therapy worked for him. He remained in remission then for six months after the splenectomy, but then his leukemia recurred again. There’s a photograph of the spleen. These are Candida lesions.
Tacey Ann Rosolowski, PhD:
Oh my gosh. So that really shows what the fungal infection can do. It actually attacks—
Gerald P. Bodey Sr., MD:
Yeah, what was a little extraordinary is the fact that there weren’t any obvious signs of the fungal infection. I’m not quite sure anymore why I was smart enough to figure out that he had a problem with his spleen and needed a—
Tacey Ann Rosolowski, PhD:
What do you think helped you identify that?
Gerald P. Bodey Sr., MD:
Probably my experiences at the National Cancer Institute, where I did clinical studies such as this one on the causes of death in acute leukemia.
Tacey Ann Rosolowski, PhD:
If you would hang on just one moment, Dr. Bodey, I would like to read for the record the title of this paper that we were just discussing, which is “Hypersplenism Due to Disseminated Candidiasis in a Patient with Acute Leukemia,” and the co-authors with Dr. Bodey are David Dejongh, Adolfo Isassi, and Emil Freireich. Okay, thank you. So now, that next paper you were going to be talking about?
Gerald P. Bodey Sr., MD:
The next one is the causes-of-death paper. This was actually done at the National Cancer Institute. We reviewed the cause of death in 414 patients with acute leukemia, and 70% of the patients the cause of death was infection, 52% of them had hemorrhage, and then in 38% of the patients there was more than one cause leading to their death.
Tacey Ann Rosolowski, PhD:
And what was the research question of this particular study?
Gerald P. Bodey Sr., MD:
Really to define the frequency of infections causing death in the patient population, and then they did lead to some approaches to treatment that improved the outcome.
Tacey Ann Rosolowski, PhD:
So this was done at the NCI when you were working with—
Gerald P. Bodey Sr., MD:
Dr. Freireich. For example, hemorrhage as a cause of death decreased during the course of the study because they were beginning to give platelet transfusions to patients who had inadequate platelets. Of course, then also it gave us some information on the kind of infections that were most likely to be causing these patients—so that we would know what kind of antibiotics to administer, even before we actually had the definite diagnosis.
Tacey Ann Rosolowski, PhD:
Oh, okay. Now I’d like, too, to talk about that key 1966 study. Is that the one, the quantitative relationships?
Gerald P. Bodey Sr., MD:
That’s this one, yeah.
Tacey Ann Rosolowski, PhD:
Yeah, if you could just tell the title of that paper, and then talk a little bit about what was so significant about that?
Gerald P. Bodey Sr., MD:
See, the problem that we’re getting into is that everything we’re talking about is stuff that was done before I came to MD Anderson.
Tacey Ann Rosolowski, PhD:
Right, but I think that’s really important because it was really the foundation of the work that both you and Dr. Freireich did later too, isn’t it?
Gerald P. Bodey Sr., MD:
Well, it is, but I’m not sure that it meets the objectives of a book that’s supposed to be about MD Anderson. Isn’t that right?
Tacey Ann Rosolowski, PhD:
No. I mean, because it’s also about your career too. This was so foundational; I think it’s really significant. It’s also really important how many times it’s been cited. It’s really a foundational kind of study.
Gerald P. Bodey Sr., MD:
Okay, well then—let’s see what we have. Well, this one was a study in which we looked at fifty-two patients from the time of their admission to their death. And we looked at the relationship between the white blood cell counts and infection. These were all patients with acute leukemia. We were able to show that—here it is—the chart that shows the relationship between infection and the white blood count.
Tacey Ann Rosolowski, PhD:
Wow, so it really—
Gerald P. Bodey Sr., MD:
Actually, this is the neutrophil count, which is one element.
Tacey Ann Rosolowski, PhD:
Right.
Gerald P. Bodey Sr., MD:
It’s the one that fights infection.
Tacey Ann Rosolowski, PhD:
Right. So it really drops amazingly with that. So what was so unusual and landmark about this particular study?
Gerald P. Bodey Sr., MD:
Well, I don’t know. I mean, we all knew that the patients who didn’t have any neutrophils (granulocytes) were at higher risk of infections. But this gave us quantitative figures and gave us ideas of at what level a patient is less likely to get into troubles with infection. The cutoff point was around 1000. This then helped us also if a patient had some fever and he had a neutrophil count of less than 100, then we needed to really get busy and treat him intensively with antibiotics, because otherwise he’s going to die.
Tacey Ann Rosolowski, PhD:
And when Javier at the archives printed out the citations in a list that showed how often this paper had been cited—it’s been cited over 1400 times.
Gerald P. Bodey Sr., MD:
Oh, really?
Tacey Ann Rosolowski, PhD:
Yeah. It’s a very cited paper.
Gerald P. Bodey Sr., MD:
Because to my knowledge, it’s the only paper that really gave quantitative values. People knew some of this. The information wasn’t all that earth shaking, but this actually gave quantified data of what the results were and also the outcomes. This side actually looks at the duration of low counts. You know, the longer you had a low count the greater your chances of getting an infection. Again, not any earth-shaking information, but it does quantify it.
Tacey Ann Rosolowski, PhD:
Which gives you some real guidelines.
Gerald P. Bodey Sr., MD:
Yes. And I think there is—
Tacey Ann Rosolowski, PhD:
So that paper was published in 1966, and just let me read the title for the record. This is “Quantitative Relationships Between Circulating Leukocytes and Infection in Patients with Acute Leukemia,” and the co-authors with Dr. Bodey—who is first author on this paper—are Monica Buckley, Y.S. Sathe, and Emil J Freireich. And this was published while all of these authors were at the NIH.
Gerald P. Bodey Sr., MD:
And that’s an important point, too, because it would have been difficult to do these studies almost anywhere else at that time.
Tacey Ann Rosolowski, PhD:
Why?
Gerald P. Bodey Sr., MD:
Because we had an acute leukemia service at the National Cancer Institute, so we had patients who had been referred from all over the United States that came. I don’t think there was any other institution that had as high a concentration of patients with acute leukemia as did the National Cancer Institute, at least at that particular time.
Tacey Ann Rosolowski, PhD:
Right, because then MD Anderson started.
Gerald P. Bodey Sr., MD:
MD Anderson became—had a large service too, later on, but not at that time, or at least not as well organized as this was.
Tacey Ann Rosolowski, PhD:
And did that start when Tom Frei and J Freireich came to it and established—?
Gerald P. Bodey Sr., MD:
Well, they began establishing it and getting it moving.
Tacey Ann Rosolowski, PhD:
Right, okay. What’s the next paper? Actually, here’s the press release.
Gerald P. Bodey Sr., MD:
Well, that was after—
Tacey Ann Rosolowski, PhD:
This is the carbenicillin. Can you tell me about this one? We talked about carbenicillin the last time.
Gerald P. Bodey Sr., MD:
Carbenicillin was really a very important advance because the antibiotics that we had available that were active against Pseudomonas prior to that were not very effective in the neutropenic patients in particular. Carbenicillin had activity even in neutropenic patients. For drugs like polymyxin, which had activity against Pseudomonas—but if they didn’t have an adequate number of neutrophils, then it wasn’t very effective. Whereas with carbenicillin, even if you didn’t have very many neutrophils, carbenicillin would still be effective if the organism was sensitive to that antibiotic. So it really had a major impact because Pseudomonas was one of the most common infections—maybe the most common infection—at that time. Originally Staphylococcus was, but after methicillin became available and some of the other anti-staph medications, then there was a major drop in staph infections. Then Pseudomonas began to emerge as the most dangerous organism to leukemic patients. It became fairly common, and it was not responding to antibiotics until carbenicillin came along.
Tacey Ann Rosolowski, PhD:
Now, let me ask you—because it kind of surprised me to see that photograph of the spleen that had that kind of encrustation with the fungus—did the bacteria also attack organs in that same way?
Gerald P. Bodey Sr., MD:
Typically you wouldn’t have those large lesions; they would just be little pinpoints. Some of them would have localized abscesses in an organ like the spleen or liver.
Tacey Ann Rosolowski, PhD:
Because I actually had no idea of exactly what these kinds of bacteria or fungi would do inside the body. I mean, when I hear, “You have an infection,” I think of a patient having a serious fever, but I don’t think of the organs being attacked.
Gerald P. Bodey Sr., MD:
They could be—not only the liver and spleen but the lungs. It could be really any organ in the body. Some of them get infections in the brain—meninges. So it was possible for a variety of organs to be involved. Of course, the chances of responding depended somewhat on what organs were a major source of infection, as well as the organisms itself and its susceptibility to antibiotics. Tacey Ann Rosolowski Now, you showed me that graph that showed that the longer a patient had an infection or the longer the patient had low neutrophils the greater the risk—
Gerald P. Bodey Sr., MD:
—the greater the risk of them getting an infection.
Tacey Ann Rosolowski, PhD:
And I assume that would also mean greater the risk of getting a very serious one that would attack these organ systems, or was that not necessarily the case?
Gerald P. Bodey Sr., MD:
Not necessarily true. That would depend on things like the organism’s susceptibility to antibiotics and that sort of thing. It could be—it often was a very serious infection, but it didn’t always have to be.
Tacey Ann Rosolowski, PhD:
Now, you had given me a photocopy of an article that appeared in the Houston Chronicle, and maybe you can tell me about that. It was related—
Gerald P. Bodey Sr., MD:
That’s from the Houston Post.
Tacey Ann Rosolowski, PhD:
Oh, the Houston Post.
Gerald P. Bodey Sr., MD:
This goes way back to the days when we had the Houston Post. (End of Audio 1 Session 2)
Gerald P. Bodey Sr., MD:
But Mary Jane Schier was—I don’t know if you know her or not.
Tacey Ann Rosolowski, PhD:
I do.
Gerald P. Bodey Sr., MD:
She was a Post reporter at that time. I knew her for her associations with MD Anderson and all. She interviewed me about this use of carbenicillin and its impact on leukemic patients. However, she got a little mixed up in what she reported. I won’t go into that, but it was published on a Sunday morning in the paper, and it was a front page headline. I got up and got the newspaper and almost had a stroke when I saw this. I was embarrassed going to church that morning, because it was a headline in the newspaper. And actually, it got circulated around. I started getting letters and all from all over the world—
Tacey Ann Rosolowski, PhD:
I bet.
Gerald P. Bodey Sr., MD:
—that had become aware of this article.
Tacey Ann Rosolowski, PhD:
And the headline is “Leukemia Victims Get New Hope,” and then the subtitle is, “A drug is revolutionizing treatment of leukemia.”
Gerald P. Bodey Sr., MD:
That’s the problem. It wasn’t treating leukemia; it was treating the infection.
Tacey Ann Rosolowski, PhD:
It’s treating the infections, yes. Right. So what kind of letters did you get from people? What were they asking?
Gerald P. Bodey Sr., MD:
Some of them—there weren’t a lot of letters, but there were some. They would be asking me for advice or could they get the drug—those kinds of things. There was one aspect of it that really upset me. I had the original copy of the paper and the letters that came and all that sort of thing, and there were some letters, I think, to the editor and all that. I had them in a box in my secretary’s office, and they were there for years. Then we got a new, young secretary—junior secretary—and one day, without consulting anyone else, she took the box and threw it out. I almost had a stroke.
Tacey Ann Rosolowski, PhD:
I don’t believe it.
Gerald P. Bodey Sr., MD:
And my—and two of my secretaries actually went down into the trash bin at Anderson to see if they could find this box. They spent over an hour going through the trash trying to find this box, and they could never find it.
Tacey Ann Rosolowski, PhD:
Gosh.
Gerald P. Bodey Sr., MD:
That just really, really upset me, because this was something special. I could not get another copy of the paper. Fortunately, some years later—and unfortunately, I don’t remember her name—but there was somebody doing some work at MD Anderson, sort of like you’re doing, and they went into the archives of the newspaper and came across this article and was able to make a copy of it. That’s how I have that. But I was really—they thought I was going to kill this girl. I mean, I was really upset, because we had kept it for—at that time, at least five or six years. I couldn’t duplicate it, and that was the most important thing I ever had happen to me—the front page headline.
Tacey Ann Rosolowski, PhD:
Right. Wow. Well, I’m glad you were able to eventually get a copy.
Gerald P. Bodey Sr., MD:
Now, I don’t know what all you want to do with this big pile, but here’s a paper on the first protected environment, so-called “life islands.”
Tacey Ann Rosolowski, PhD:
Sure.
Gerald P. Bodey Sr., MD:
And there’s reporting on the results of the—
Tacey Ann Rosolowski, PhD:
What date is that paper?
Gerald P. Bodey Sr., MD:
This was on July 1968. And this reported the first eleven patients who were in these so-called “life islands,” on oral antibiotics to try to limit any infections from occurring. I think we talked about how that operated and so on.
Tacey Ann Rosolowski, PhD:
We did, yes.
Gerald P. Bodey Sr., MD:
And this paper reports that the effects of the antibiotic regimens on the strains of organisms in the patients and that sort of thing. For example, that suppressed 92% of the organisms in the GI tract, and 88% from nose cultures, so that’s the most important things—66% of throat cultures. But the patients had to stay on the antibiotics the entire time. If you stopped them, then some of the organisms would grow back again. They really didn’t have—they tolerated the antibiotics well, and as I said, the effect of them—I don’t know that this paper actually looked at anything else, like infections or anything. I don’t see anything here. So it was mainly just the impact on the patient’s organisms when they went into the unit.
Tacey Ann Rosolowski, PhD:
Let me just read the title of this for the record, “Protected Environment for Cancer Patients: Effect of a Prophylactic Antibiotic Regimen on the Microbial Fleura of Patients Undergoing Cancer Chemotherapy.” Dr. Body is the first author, and then the second and third authors are John Loftus, MD, and Eleanor Bowen, MS.
Gerald P. Bodey Sr., MD:
Now, while you’re on that, we had one patient that stayed in this life island—a patient with acute leukemia—for 216 days. I think I’ve mentioned to you the last time around—216 days. I don’t know how on earth he ever tolerated being in for that long.
Tacey Ann Rosolowski, PhD:
Tell me, what was the effect—the psychological effect—on patients? What did they—?
Gerald P. Bodey Sr., MD:
Most of them tolerated. We did have a rare patient who just couldn’t tolerate that isolation. Of course, we screened them pretty carefully before we selected them.
Tacey Ann Rosolowski, PhD:
How did you do that?
Gerald P. Bodey Sr., MD:
Because they could see things—there was at least one area of the room which they could look out and see what was going on, and they had nurses coming in and talking to them, and the doctors and so on, so they weren’t totally isolated that they didn’t see anybody. Obviously, their lives were very restricted, but during the—I don’t know—maybe we had to remove one or two patients prematurely, but the vast majority of them tolerated it quite well.
Tacey Ann Rosolowski, PhD:
Now, you said you screened the patients. How did you do that?
Gerald P. Bodey Sr., MD:
Well, the biggest question was their disease and what is the remission rate in this form of leukemia and things like their age. Elderly patients were less likely to respond than young ones. And did they already have an infection or not? The biggest factor to whether they got to go in a room or not was whether there was a room available. That played a role. But then later on, as we had different antileukemic regimens, then we would tend to put the patients in the unit if they were getting their first course of leukemia therapy, where they had the greatest chance of going into remission. So we didn’t usually put in patients who had relapsed and were going to get treated again. That was primarily reserved for first-time treatments. Then we got into some other cancers—lymphoma—we started doing some studies on, too.
Tacey Ann Rosolowski, PhD:
The one thing we didn’t talk about last time was the work on chemotherapy that you did. Do you have any articles in that stack on your chemotherapy work?
Gerald P. Bodey Sr., MD:
Possibly so, but you’ll have to give me a couple of minutes here.
Tacey Ann Rosolowski, PhD:
Yeah, let me pause it, and then we can look through. I’m just pausing the recorder at 2:20. (End of Audio 2 Session 2)
Gerald P. Bodey Sr., MD:
—heavily involved in taking care of the patients who were getting the treatment. The regimens were generally things that were developed by Dr. Freireich. He was the one who did that, but I was—spent a good bit of my time taking care of those patients. This is an interesting one. I don’t know that you want to go into any detail, but we developed a method—a semi-quantitative culture of patient’s total body skin. We divided the body up into different sections, and then we would take forceps, put a piece of cotton on it, and then moisten it and rub it over that area of the body, then put it in a liquid culture.
Tacey Ann Rosolowski, PhD:
So the name of this study is “A Semi-Quantitative Total Body Skin Culture Technique for Patients in a Protected Environment.” Now, what was the aim of this? I don’t understand semi-quantitative total body skin culture.
Gerald P. Bodey Sr., MD:
Well, it was semi-quantitative, meaning it wasn’t totally accurate. It was a good estimate, but it couldn’t say, “Well, this is exactly how many they have.”
Tacey Ann Rosolowski, PhD:
So how many would somebody have on their entire skin surface? Was that the idea, approximately?
Gerald P. Bodey Sr., MD:
Approximately, because that was then a way of measuring the efficacy of our antibiotic therapy, particularly the cleansing therapy of the skin. A lot of this—I must say, looking back on it, it wasn’t terribly earth shaking, but it was of interest at that time, because nobody had done any of this before. And it was quite a bit of work.
Tacey Ann Rosolowski, PhD:
Well, it’s—I mean, it’s kind of interesting, because now there’s so much information on the Internet and in the news about how we’re not really individual organisms, we’re actually multiple organisms because of all the creatures living on our skin. So this was kind of the preliminary work in quantifying that.
Gerald P. Bodey Sr., MD:
Now, here is a paper that talks about the outcome of therapy with carbenicillin.
Tacey Ann Rosolowski, PhD:
Okay.
Gerald P. Bodey Sr., MD:
We treated fifty-six episodes, and the response rate was 91% in the twenty-three episodes of Pseudomonas infections.
Tacey Ann Rosolowski, PhD:
Wow. So it was really effective.
Gerald P. Bodey Sr., MD:
Then 58% in twelve episodes of E. coli. But the big thing—and it wasn’t effective in Klebsiella and a couple other organisms. The big thing was the results on Pseudomonas. That was dramatic, because prior to carbenicillin, almost every patient who got a significant Pseudomonas infection died.
Tacey Ann Rosolowski, PhD:
Let me just read the title of that paper, “Carbenicillin Therapy, A Gram-Negative Bacilli Infections.” And the authors are Dr. Bodey, V. Rodriguez, and J. K. Luce. This paper was published in 1969 in the American Journal of the Medical Sciences.
Gerald P. Bodey Sr., MD:
And we did all kinds of studies. I don’t think you want to spend too much time on these microbiological studies. This was one on our patients, and—
Tacey Ann Rosolowski, PhD:
Okay, well, let’s—I’ll pause the recorder, and then we can look through for some chemo—
Gerald P. Bodey Sr., MD:
There’s an awful lot in here. (End of Audio 3)
Recommended Citation
Bodey, Gerald P. MD and Rosolowski, Tacey A. PhD, "Chapter: 06 Research on Bacterial and Fungal Infections" (2013). Interview Chapters. 990.
https://openworks.mdanderson.org/mchv_interviewchapters/990
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