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Paul de Kruif, "Conquest of a Killer," Reader’s Digest March 1945, pp. 27-31
Bacterial endocarditis, an infection of the heart, has until now been the most surely deadly of all microbic maladies. It has killed 97 out of every 100 persons it attacked, and the few who survived have seemed saved only by some freakish whim of nature. It is estimated that endocarditis murders at least 10,000 Americans annually. In the past year certain men of medicine have thrown this death march into reverse; they bring hope of recovery to 80 out of every 100 victims. And this death-fighting victory means a better chance for life for nearly 1,000,000 Americans in various stages of rheumatic heart disease, for it is chiefly these people who are threatened by endocarditis. Their rheumatic condition doesn't have to be active; bacterial endocarditis may aim its murderous blow at the scarred valves of hearts that have long ago recovered from rheumatic trouble. While a variety of germs may cause endocarditis, by far the most frequent murderer is the green streptococcus, one of the strangest creatures in the rogues' gallery of the microbe hunters. The green streptococcus is ordinarily a gentle creature. It lives innocently in the mouths of nearly all human beings, harmlessly minding its own obscure microbe business. Even when it gets into the blood circulation, as it sometimes does after the pulling of a tooth, or from infected tonsils or sinuses, it does not harm at all--if the person's heart is healthy. But let this gentle germ light on the damaged or scarred valves of a rheumatic heart, and it becomes an implacable assassin. The microbe guards itself cleverly from medical attack by burrowing into those valves and covering itself with a cauliflowerlike vegetation of clotted blood. In this evil nest it grows and swarms, seemingly out of reach of any curative serum or chemical. Then it sallies out into the blood. It not only wrecks the heart by attacking the delicate valves but it causes deadly mischief all over the human body. Bits of blood clot from the heart valves detach themselves, swirl through the circulating blood, and lodge in arteries of the brain, the kidneys, the eyes, the skin, the lungs and the heart itself. This blocking of the arteries, called embolism, devitalizes one part of the body after another. In the early stages of this inexorable murder the sufferers may simply feel very tired and strangely sleepy. They have low fevers and feel grippy, and their doctors may think they’re suffering early tuberculosis, or typhoid, or malaria, or rheumatic fever, or any of a dozen different diseases. Then little red spots come out on their bodies; and little hemorrhages, looking like splinters, appear under the nails of toes and fingers. Doctors can diagnose the ailment early by testing the blood for the presence of the green streptococcus. But—until now—when they have found it, they have been faced with the tragic task of telling the patient's family that the situation is desperate, almost hopeless. More than 30 years ago Dr. Emanuel Libman of New York wrote the classic description of this dread sickness. After that, death fighters tried every weapon in their medical arsenal—serums, arsenicals, transfusions, fever treatment—all in vain. In the late 1930's came a hint of hope from the new sulfas. A few cures were registered, but not enough to dent the endocarditis death rate. Then in 1943 penicillin entered the battle. High hopes were held because this new wonder drug was not only powerful but marvelously safe. Yet, after what seemed to be thorough testing, a committee of the National Research Council published gloomy news. Of 17 cases of bacterial endocarditis treated with penicillin four were dead, ten showed no appreciable improvement, and two of the three who had seemed to get a bit better relapsed soon after the treatment was discontinued. It was officially decided to break off the battle for the time being, because penicillin was still so scarce and so badly needed for saving the wounded of our armed forces. This negative report was published in The Journal of the American Medical Association on August 28, 1943, and this is a date to be particularly remembered. On August 27, the day before, Dr. Leo Loewe and his associates in the Jewish Hospital in Brooklyn stood by the bedside of a 34-year-old man far gone with bacterial endocarditis. For more than six months they had fought a losing battle to save his life. They'd tried huge doses of sulfas, and added artificial fever, but in vain. Then to the sulfa treatments they'd added the drug, heparin, which acts to slow the clotting of the blood. They'd hoped that heparin might act upon those blood clot vegetations on the man's heart valves, exposing the green streptococcus to the sulfa-magic. Then in June they'd combined moderate doses of penicillin with heparin; and still they were baffled. As death-fighters the Brooklyn doctors stood with their backs to the wall. And so Dr. Loewe took drastic action. He had been using what was considered an orthodox daily dose of penicillin, little more than 40,000 units. Now, since the patient was so far along the road to death, he decided to risk enormous doses. The Brooklyn physicians began giving the dying man five times the orthodox dose of penicillin—200,000 units daily, combined with heparin injections every other day. From a large flask above the man's bed a continuous flow of penicillin dripped for 14 days and nights into a vein in the region of his wrist. The needle inserted in his vein was held in place by a strip of adhesive tape. The man could move his hand freely, and it was remarkable how this continuous injection was no bother to him, waking or sleeping. The green streptococcus vanished from the patient's blood during this treatment. But after the treatment was stopped, the man relapsed. Then, after a second course of 200,000 unites daily, the evil microbe disappeared for good. This man, who'd been marked for death, is alive and in excellent health today. On August 28, 1943, the very day the Government thumbs-down on penicillin for endocarditis was published, a 52-year-old woman was brought to the Jewish Hospital in Brooklyn. She was in coma, paralyzed from blood clots blocking blood. vessels of her brain. She was at the brink of death--moribund is the medical word for her condition. Dr. Loewe and his co-workers at once began the massive penicillin-plus-heparin treatment, and kept it up for 13 days. The second day this woman sat up in bed. Within two weeks she was free of her infections. I've just talked to this historic woman. A year and a half after she was brought to the hospital, so sure to die, she is alive, strong and working. She told me she had read a newspaper statement by a high Government authority that, while penicillin is a remarkable medicine, it couldn't be expected to raise people from the dead. "But penicillin made me as good as sit up in my coffin, and I'm resurrected," she said. And I wish you could have seen her smile. By the end of 1943, Leo Loewe and his co-workers, Drs. Philip Rosenblatt and Harry J. Greene and their technical assistant, Mortimer Russell, were ready to make their scientific report of seven consecutive, unselected cases of bacterial endocarditis who had recovred after the new treatment. This was published in The Journal of the American Medical Association in January 1944. The National Research Council decided to restudy the effect of penicillin upon disease. Now to the Jewish Hospital in Brooklyn came a parade, in ambulances, on stretchers, of victims of endocarditis. Many of them were in pitiful condition. Some were already suffering,congestive heart failure, so that it was risking immediate death even to begin to treat them. Dr. Loewe and his co-workers turned none of them away. They knew that the inevitable deaths of some of the far gone might tend to discredit their work, but they tried their new method anyway. In his report in The Canadian Medical Association Journal, in January 1945, Dr. Loewe thus defended his boldness: "Despite the precarious manifestations of many of the afflicted, we had no choice…since refusal was tantamount to the imposition of a death sentence." To put it bluntly, he didn't care about a fine show of statistics, he just wanted to save lives. From the very start of this life-saving adventure the Brooklyn doctors had a nonmedical co-worker without whom they would have been helpless. This was John L. Smith, vice-president of the Charles Pfizer company of Brooklyn. This firm was one of the first to engage in penicillin research in America and to pioneer large-scale production in fermentation vats. Smith furnished the penicillin for the new treatment After the report of the recovery of those seven cases, the National Research Council added a certain amount of penicillin to the quantities the Pfizer Company was giving—free—to Dr. Loewe and his co-workers, as well as to other doctors who were now beginning to join the hopeful battle. Mr. Smith stood at the bedside of virtually every one of these victims whose lives had been saved by the new treatment. Day after day he went back and told the Pfizer scientists, engineers and workmen of the lives their skill and devotion had saved. "They were all thrilled; and their knowing they were saving those lives has been a major factor in our tremendous increase in penicillin production," reports Mr. Smith. When you remember the large proportion of the far-gone forlorn who came to the Jewish Hospital, grasping at a straw for life, it's no wonder that Dr. Loewe and his associates had to record failures among their growing number of fantastic penicillin-heparin successes. In their second report, totaling 54 cases, the Brooklyn death-fighters recorded 13 fatal treatment failures, one reinfection, and three deaths from heart failure after the victims had been absolutely sterilized of all trace of the green streptococcus, as proved by autopsy. Of the 13 people who died in spite of the treatment, ten could not be saved because their hearts were too far gone; or the blood vessels of their brains were blocked by embolisms; or there was a profound wasting of their tissues, or terminal pneumonia. Only three deaths were due to infection with a green streptococcus resistant to penicillin. Dr. Loewe and his associates found that the longer the evil green streptococcus had been gnawing at the heart valves of the victims, the longer they had to treat them, and the larger they had to make the doses. As of today, when the recovery rate for unselected cases (from early to far-gone desperate) is exceeding 80 out of every 100, most patients are treated continuously for at least five weeks, with as much as 1,000,000 or more units of penicillin daily, plus heparin. Heparin, unlike penicillin, is a two-edged sword; if it's given in excessive doses, hemorrhages and even death may occur. However Drs. Loewe and Rosenblatt, with the cooperation of E. H. Bobst and Dr. R. D. Shaner, of Roche-Organon, Inc., another pharmaceutical concern, have developed a safe way of administering the drug. They dissolve it in gelatin, acetic acid and dextrose, a medium invented by Dr. George Pitkin. Injected in this form it is absorbed very slowly and safely. Dr. Walter S. Priest and his associates at Wesley Hospital, Chicago; Dr. M. H. Dawson and his co-workers at Presbyterian Hospital, New York; and Dr. Ward J. MacNeal and his co-workers at Post-Graduate Hospital, New York, have all confirmed penicillin's power against this most dread of all infections of the heart. Tests of massive doses of penicillin, with and without heparin, are being conducted in a growing number in hospitals. On December 1, 1944, the National Research Council included subacute bacterial endocarditis in the list of diseases to be treated by penicillin when the infection is due to susceptible microbes—which includes the vast majority of all endocarditis cases. And now our death-fighters have the weapons with which to work. Nearly a score of chemical and pharmaceutical manufacturers have succeeded in increasing production of penicillin so sharply that the price to the Government per 100,000 units has tumbled in the past year from $20 to 85 cents. Now that the power of the new treatment for bacterial endocarditis has been established, physicians will be more alert to detect the affliction, by taking blood cultures when it first hits. They can feel confident that when bacterial endocarditis is detected within three months of its onset and before the heart valves are too grievously damaged, and if the microbes are sensitive to penicillin, as the great majority of them are, then recovery may be expected in virtually every case. Two years ago victims of this disease had only three chances out of 100 to remain alive!
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