Phage Therapy Case Study from 1936

Stephen T. Abedon

Department of Microbiology – The Ohio State University

phage.org – phage-therapy.org – biologyaspoetry.org


 

This article can’t be found via a PubMed search but can be found here: jama.jamanetwork.com/article.aspx?articleid=1156439. It is not free, but most of it can be found on that page. The reference is Morrison, S., Gardner, R.E. (1936). The Treatment of a Lung Abscess due to Bacillus coli with a Lytic Filtrate. JAMA 107(1):33-34. It is a fascinating account because it walks you through the case in some detail plus presents both efficacy and side effects, neither of which can be unquestionably attributed to the phage itself since the formulation used was not purified. Still, pretty amazing stuff, and I quote:

N, S., a woman, aged 22, who had previously been in excellent health, suddenly experienced a severe diffuse abdominal pain, Aug. 5, 1934… On the third day the patient’s condition became critical and she was rushed to the Chambersburg (Pa.) Hospital, where an emergency operation was performed by Dr. L. H. Seaton. When the abdomen was opened a gangrenous appendix with generalized peritonitis was disclosed. The remainder of the appendix was removed and drains were inserted…

[Approximately one month later,] after an excruciating pain, examination disclosed massive collapse of the left lung. During the subsequent few days slight signs of partial return of pulmonary function were observed, but relapse followed. Clinical and x-ray signs of effusion developed. Aspiration was performed September 12 and 500 cc. of very heavy purulent material with a foul and typical colon odor was obtained. A culture of the pus at this time yielded only Bacillus coli. Three days later, because the material was too thick to be aspirated, rib resection was done with a virtual gush of pus. A bronchial fistula developed shortly after the rib resection and the patient was expectorat¬ ing the same kind of material as that which drained from the resection wound. The appearance of the area around the resection opening was necrotic and “mossy” and failed to show any improvement on local irrigations with 1,000 cc. of saline solution twice a day. Digital examination through the resection wound disclosed many walled off abscesses surrounded by necrotic tissue. In view of the hectic fever and the general condition, which indicated toxic absorption, an especially resistant abscess which failed to open was incised by an approach between the ribs just above the rib resection. A drain was inserted and in a few days healing took place.

A second sample of pus was collected at this time (September 16) and another pure culture of colon bacillus isolated which was fairly readily lysed by a bacteriophage that was active against various strains of B. coli isolated from other sources.

After a cutaneous test September 20 of 0.1 cc. of the lytic filtrate twelve hours previously had given little or no reaction, and after irrigating the chest with 1 liter of physiologic solution of sodium chloride, 1 ounce (30 cc.) of the phage was instilled and allowed to remain for two hours. This was followed saline irrigation and the wound covered by a dressing saturated with the bacteriophage. The following day the observation was made that the discharge had become thin and watery and had lost its offensive character for the first time since the resection was done five days before, even though saline irrigations had been administered twice daily during this five day period. A second and equally remarkable change had occurred at the resection wound itself, where the mossy, necrotic character was entirely changed to a clean, fresh, healthy appearing incision.

Since the first use of bacteriophage had given such excellent results, a second application seemed indicated, and therefore the procedure was repeated. However, within ten minutes a violent generalized rose-colored urticaria appeared and the patient complained of nausea and vomited. The bacteriophage was drained immediately and the chest irrigated with large quantities of saline solution. Epinephrine was administered…

After such a marked allergic reaction to the bacteriophage had occurred it was decided to discontinue bacteriophage instillations and continue only with saline irrigations and external dressings saturated with bacteriophage. The dressings of bacteriophage were continued for a week along with irrigations of physiologic solution of sodium chloride. Throughout this period the resection wound maintained its healthy normal appearance and the discharge remained clear, watery and nonodorous. The temperature reached 102.2 F. each day for the thirteen days prior to the urticarial reaction. On that day the reading was 103.2 F. after the reaction. After this reaction the temperature did not go above 102.2 F.

The patient’s general condition was remarkably improved and within six weeks she was able to leave the hospital. The appendiceal wound had healed but the fever, less hectic in type, continued as well as the thin nonodorous drainage. At home the fever gradually subsided as well as the drainage, and heal¬ ing was practically complete toward the end of December.

Whether the bacteriophage acted as a specific or indirectly as a Synergist to antibody formation cannot be stated.

Thus, no proof of explicitly phage-mediated efficacy, no proof that the condition would not have spontaneously reversed on its own, and no controls, but instead a remarkable result, with an indication as well of reason for caution regarding potential immunological reactions perhaps associated with the lack of formulation purification. Interesting indeed!

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