Dr. Taylor was not kept in suspense for long. One of his fears was confirmed that afternoon by a call from the resident then on duty in the nursery. He called to report that the new sick baby the three-pound nine-day-old—was dead. His illness had lasted a scant eight hours. The next morning brought another confirmation. There was a final laboratory report on the first sick baby: the cause of his death was definitely a Pseudomonas infection. There was a forty-eight-hour report on the second sick baby: the gram- negative bacteria grown from his blood had all the important characteristics of Pseudomonas aeruginosa. There was a twenty four-hour report on the third sick baby: cultures grown from his blood had been identified as gram-negative bacteria. And that was too much for coincidence. It meant—it could almost certainly only mean—that a Pseudomonas epidemic had struck the premature nursery.
Pseudomonas aeruginosa is one of a group of gram-negative pathogens that have only recently come to be seriously pathogenic. Other members of this group include Escherichia coli and the several species of the Proteus and the Enterobacter-Klebsiella genera. Their rise to eminent virulence is a curious phenomenon. These micro-organisms regularly reside in soil and water, and in the gastro-intestinal tracts of most (if not all) human beings. Their presence in that part of the body is normally innocuous. Healthy adults are impervious to the thrust of such bacteria. The victims of Pseudomonas (and E. coli and Proteus and Enterobacter) infections are the very old, the very young, and the very debilitated (the badly burned, the postoperative, the cancerous), and in almost every case they have been receiving vigorous sulfonamide or antibiotic or adrenal-steroid therapy. Most antimicrobial drugs have little destructive effect on bacteria of the Pseudomonas group. Just the reverse, in fact. Their action, in essence, is tonic. In people rendered susceptible to the gram-negative pathogens by age or illness, the result of chemotherapy is the elimination not only of the immediately threatening pathogens but also of the natural resident bacteria that normally hold further incursions of Pseudomonas (or E. coli or Proteus or Enterobacter) in check. The virulence of Pseudomonas and its kind is thus a wry expression of perhaps the most beneficent accomplishment of twentieth- century medicine.
It is also cause for some alarm. "One of the great changes wrought by the widespread use of antibacterial agents has been the radical shift in the ecologic relations among the pathogenic bacteria that are responsible for the most serious and fatal infections," the New England Journal of Medicine noted editorially in July of 1967. "Whereas John Bunyan could properly refer to consumption as 'Captain of the Men of Death,' this title, according to Osier, was taken over by pneumonia in the first quarter of this century. During the last two decades, it has again shifted, at least in hospital populations, first to the staphylococcal diseases and more recently to infections caused by gram-negative bacilli. Most of the gram-negative organisms that have given rise to these serious and highly fatal infections are among the normal flora of the bowel and have sometimes been referred to as 'opportunistic pathogens.' . . . Before the present antibiotic era, some of them, like Escherichia coli, although they frequently caused simple urinary- tract infections, only occasionally gave rise to serious sepsis. . . . Strains of Proteus or Pseudomonas did so very rarely, and those of Enterobacter were not even known to produce infections in human beings before the introduction of sulfonamide drugs. Of great importance are the facts that most of these opportunistic pathogens are resistant to the antibiotics that have been most widely used, and that the infections they produce are associated with a high mortality." This mortality is anachronistically high. It is roughly that resulting from the common run of pathogenic bacteria some thirty years ago—in the days when the best defense against the many Men of Death was a strong constitution.
The most conspicuously troublesome of these ordinarily unaggressive pathogens is E. coli. It has been implicated in some ninety per cent of the urinary-tract infections caused by members of this group, and it is responsible for many of the more serious cases of bacteremia, gastroenteritis, and pneumonia. It is not, however, the most opportunistic. The organism best equipped to take advantage of almost any chemotherapeutic opportunity is the Pseudomon;is bacillus. Pseudomonas aeruginosa is all but invulnerable to the present pharmacopoeia. Only two antibiotics—polymyxin B and colistin—are generally effective against most Pseudomonas strains. Moreover, both must be used with great discretion to prevent severe kidney side reactions. Ps. aeruginosa is also distinctively lethal. Its mortality rate, as numerous recent outbreaks (including that in Pittsburgh in 1965) have shown, may run as high as seventy-five per cent.
An investigation into the source of the Pseudomonas infections in the premature nursery at Magee-Womens Hospital was started by Dr. Taylor on Friday morning, July 16. A forty-eight-hour report from the laboratory had by then established as Ps. aeruginosa the gram-negative bacteria that had been cultured from the blood of the third sick baby, and the presence of an epidemic was now beyond dispute. The investigation began with a survey to determine the scope of the trouble. There were at that time, in addition to the surviving (or diarrheal) sick baby, twenty-eight babies in the nursery. Samples of nose, throat, and stool material were taken from each, to be dispatched to the laboratory for culture and analysis. Dr. Taylor saw this work well under way, and then walked down to his office and put in a call to a colleague named Horace M. Gezon, at the Graduate School of Public Health. Dr. Gezon (at the time professor of epidemiology and microbiology at the University of Pittsburgh Graduate School of Public Health and now chairman of the Department of Pediatrics at the Boston University School of Medicine) is an authority on hospital infections, and Dr. Taylor wanted his help. Dr. Gezon had two immediate suggestions. One was that the investigators meet at the hospital the following morning for an exchange of information and ideas. The other was that Joshua Fierer, of the Allegheny County Health Department, be invited to join the investigation. Dr. Fierer (now a postdoctoral fellow in infectious diseases at the University of Pittsburgh Department of Medicine) was an Epidemic Intelligence Service officer assigned to Allegheny County by the National Communicable Disease Center, in Atlanta.
"Dr. Taylor called me on Friday afternoon," Dr. Fierer says. "I know it was Friday, because that's when all investigations seem to begin—at the start of the weekend. I knew Dr. Taylor. I had met him with Dr. Gezon back in March—on a Friday in March. There had been an outbreak of diarrhea in the premature nursery that they thought might be a viral disease, and they called the county because we had the only virus-diagnostic laboratory in the area. That case turned out to be nothing to worry about. It got the three of us together, though, and I guess that was what brought me to mind when this new problem came up. I was delighted to be asked to participate. Pseudomonas is a very interesting organism these days. But I had to tell Dr. Taylor that I couldn't make the Saturday-morning meeting. Or, if I could, I'd be late. I had a firm commitment at the Pittsburgh Children's Zoo on Saturday morning. They had a chimpanzee out there with hepatitis.
"I got to the hospital, but I was more than late. It was after lunch, and the meeting was over and everybody had gone. I looked around the nursery, feeling kind of foolish, and said hello to the nurses, and they told me who had been at the meeting. There were six in the group, including Dr. Taylor and Dr. Gezon. The others were the two residents, a study nurse of Dr. Gezon's, and an assistant professor of epidemiology at the School of Public Health named Russell Rycheck. Dr. Rycheck was a particular friend of mine. I went over to the school and looked him up, and he gave me a good report. The meeting had naturally concentrated on the nursery. The big question, of course, was: Where had the infection come from? How had Pseudomonas been introduced into the nursery? Well, Pseudomonas is a water-dwelling organism. It can live on practically nothing in the merest drop of water. That suggested water as the probable source of the trouble, and the nursery had plenty of such sources. There were thirty incubator bassinets equipped with humidifiers drawing on water reservoirs. and there were fourteen si
nks—one in each of the ten baby rooms, three in the central nursing station, and one in the gown room And then there were the usual jugs of sterile water for washing the babies' eyes and for other medicative purposes. Dr. Gezon at ranged for water samples from every possible source. That in eluded two samples from each sink—one from the drain and our from the aerator on the faucet. The screens that diffuse the water in an aerator can provide a water bug like Pseudomonas with an excellent breeding place. For good measure, he took a swab of the respirator used in the ward. Also, Dr. Rycheck said, Dr. Gezon arranged for throat and stool samples from the two residents and from all the nurses working in the premature nursery. And he had called another meeting for Monday morning. The laboratory findings would be ready for evaluation by then.
"I made the Monday meeting. The laboratory reports were presented, and then we tried to decide what they meant. The human studies made pretty plain reading. There were two sets— the nurses and residents, and the twenty-eight seemingly well babies in the nursery. The laboratory eliminated the nurses and residents as possible carriers. Their cultured specimens were all negative for Pseudomonas. The reports on the babies confirmed what I think most of us had already suspected. This was a real epidemic. Twenty-two of the babies were negative for Pseudomonas, but six were positive. They weren't clinically sick. They didn't show any symptoms. They were, however, infected with Ps. aeruginosa. Why they weren't sick is hard to say. There were several possible explanations. The best one was that their exposure was relatively slight and their natural defenses were strong—they hadn't been weakened by antibiotics. The results of the environmental studies were very interesting. But they were also rather confusing. They showed five sink drains and three of the bassinet reservoirs to be contaminated. Everything else was negative for Pseudomonas—the water jugs, the respirator, the faucet aerators, and the other drains and bassinets. The contaminated drains were in Room 207, Room 209, Room 227, an unoccupied room, and the gown room. The contaminated bassinets were in 224, 227, and 229. All the infected babies were associated with just two rooms. I hey were, or had been, in either Room 227—the room where the first baby took sick—or Room 229, where he died and where the two other babies became sick. There was a contaminated sink in Room 227, but the sink in 229 was clean. There was a contaminated bassinet reservoir in each room, but only one of the bassinets was, or had been, occupied by an infected baby. There were no infected babies in two rooms—Room 209 and Room 207 that had contaminated sinks, and none in Room 224, which had a contaminated bassinet. It was all very peculiar. We had a lot of contamination and we had a lot of infected babies, but there didn't seem to be any connection between the two. The only link we could think of was the nurses. The babies had no contact with each other. The bassinets were self-contained, and none of the babies shared any equipment or medication. The nurses might have carried the infection on their hands. They could do that without becoming infected themselves. Healthy adults don't succumb to Pseudomonas. But why did they carry it only to the babies in 227 and 229?
"The meeting ended on that unsatisfactory note. Dr. Gezon was as puzzled as the rest of us. But, of course, this puzzling point was only part of the investigation. We still had an epidemic to contain. We didn't understand the mechanics of its spread, but we did know what it was, and we thought we had enough information to bring it under control. We knew who was sick and we knew that the nursery was contaminated at eight specific sites. By Monday night, the nursery was as clean as Dr. Gezon and the nursery staff knew how to make it. All the sinks were scrubbed with sodium-hypochlorite disinfectant. The bassinet reservoirs were emptied and disinfected with an iodophor, and only those in use were refilled. As a further precaution, that water was to be changed every day. Certain nurses were assigned to take exclusive care of the infected babies. Also, in the hope of dislodging their infection, all the infected babies were placed on a five-day course of colistimethate given intramuscularly, and colistin sulphate by mouth It wasn't necessary to isolate the infected babies. They were already isolated. And it was arranged that specimens be taken every day from all the babies in the nursery, and from all the sinks and bassinets and so on. That would give us a constant focus on the course of the epidemic.
"I didn't participate in the sanitation program. They didn't need me. I would have been an extra thumb. I went back to my office and back to the regular Health Department routine, but part of my mind was still out there at the nursery, and I got to thinking about something I'd read a few months before. It was a report in the Lancet about an outbreak of Pseudomonas in an English nursery that was traced to a catheter used to relieve throat congestion in the babies. The source of the trouble eluded detection for almost a year. What I particularly remembered about the report was a description of a new system of microbial identification. There are several different types of Ps. aeruginosa, and this report told how they could be differentiated by a laboratory procedure called pyocine typing. Pyocine typing makes use of the fact that certain strains of Pseudomonas will kill or inhibit the growth of other Pseudomonas strains, and it's a complicated procedure. Well, it occurred to me that pyocine typing might help to clarify our problem. It could at least tell us if all the sinks and all the bassinets and all the infected babies were infected with the same strain of Pseudomonas. I thought about it, and finally I called up Dr. Gezon. He saw the point at once. But, as I say, pyocine typing was then very new, and we didn't know where to turn for help. It could be that the system was being used only in England. We talked it over and decided that the best place to begin was at the Communicable Disease Center, in Atlanta. If anybody was doing pyocine typing in this country, the people there would certainly know. That was Monday evening. On Tuesday morning, I got on the phone to Atlanta and talked to one of my friends at C.D.C. and asked him what he knew about something called pyocine typing. 'Pyocine typing?' he said. 'Why, Shulman is working on that right now. I'll switch you over to him.' Shulman was Dr. Jonas A. Shulman, and a fellow Epidemic Intelligence Service officer. He's now assistant professor of preventive medicine at Emory University. I described the case to him and asked him if he could help us out, and he was more than willing. He was eager. He wanted all the work he could get. So as soon as we finished talking I arranged for specimens of all our isolates to be airmailed down to Atlanta. Pyocine typing takes about two days. Shulman might have something for us by Thursday.
"Before I left the hospital, I went around to the premature nursery. That Lancet paper was still on my mind. Not pyocine typing. What interested me now was the source of the outbreak it described—that contaminated catheter. I looked up one of the pediatric residents and asked him what went on in the delivery rooms. I was thinking about contaminated equipment that the babies might have shared. For example, did they use a regular aspirator? The resident said no. The aspirators they used were all disposable and were discarded after each use. What about the resuscitators? Did they have humidifying attachments? A humidifier would mean water, and a possible breeding place for Pseudomonas. Another no. The resuscitators used in the delivery rooms were simply bags and masks attached to an oxygen line from the wall. I asked a few more questions along those lines and got the same kind of answers, and gave up. This wasn't a case like the Lancet case. So I was back in the nursery again. But the more I thought about those contaminated sinks and bassinets the less convinced I was that they were the source of our trouble. I just couldn't see any plausible link between those particular sites and those nine particular babies. But if the answer wasn't a piece of contaminated equipment, what else could it be? A contaminated person? And then I got a thought—maybe a contaminated mother. It sounded only too possible. A contaminated mother could very easily transmit an infection to her baby in the course of its birth. Childbirth is not a very tidy process.
"The next question was: Which mother? I thought I could answer that. It had to be the mother of the second sick baby. Not the baby in whom the infection was first diagnosed. The significant case was the second Pse
udomonas baby—the term baby who came into the nursery with pneumonia and then developed diarrhea The first sick baby had been healthy until the day before his death He had been healthy for over three weeks. So he was actually No 2. It wasn't hard to reconstruct the possible course of events. The infection was introduced into the nursery by the term baby and then spread to the other babies by the nurses. Pseudomonas is a difficult organism. You can't wash it off your hands with a little soap and water, the way you can the staphylococcus bug. To get Pseudomonas off, you have to scrub and scrub and scrub. And it's also extremely resistant to most disinfectants. But what made the infected-mother theory really attractive was that it seemed to explain what the environmental theory left unexplained. It explained why the infected babies were concentrated in Room 227 and Room 229. Both of those rooms were intensive-care rooms, and there was very little traffic between them and the other rooms. However, it was just a theory. It was based on the supposition that the diarrheal baby's mother was a Pseudomonas carrier. So the next thing to do was find out. The first thing I found was that the baby had been discharged on Saturday, and that he and his mother were now at home. I got the address, and Dr. Taylor and the baby's pediatrician gave me the necessary permission. I went out to the house and introduced myself, and the mother was nice and cooperative, and I got the specimens I needed and took them back to the Health Department lab.
The Medical Detectives Volume I Page 23
