ANNEXURE D.
Chloromycetin in Typhoid Fever,
As typhoid fever had assumed epidemic proportions in the Colony by the middle of 1950, and as many of the cases reaching the hospitals were seriously ill, a large scale experiment with chloromycetin was decided on, and begun in June 1950.
Cases of the disease have been treated as far as possible in two hospitals in the Colony; one at Lai Chi Kok on the Kowloon side, the other at Sai Ying Pun on the island of Hong Kong. A small group of cases has also been treated at the Queen Mary Hospital. This segregation of cases made the application of systematic treatment very much easier.
A proforma was drawn up to facilitate the collection of clinical and bacteriological data in all cases and to show the dosage of chloro- mycetin employed. A tentative dosage scheme consisting of 3 grammes of C. as a loading dose, followed by 2.75 gm. of C. on subsequent days up to a total of 25 gm. was used for all adult cases. Previous experience with chloromycetin had shown that the results obtained with a schedule of this sort were quite as good as those obtained by giving the drug in smaller doses at more frequent intervals. This scheme had to be modified in the light of later experience.
On admission to one of the receiving hospitals blood and marrow were taken from each patient for culture wherever possible. Few if any patient were admitted to the typhoid centres without a positive Widal reaction having already been obtained, but a positive Widal in an urban population such as Hong Kong's cannot be interpreted as proof positive of the existence of typhoid fever. Many of the victims of the disease, however, were refugees or country people who had recently arrived in Hong Kong and in such cases a Widal reaction showing a titre of 1/200 to H and O could safely be accepted as proof of typhoid fever. Wherever possible an attempt was also made to have at least a total white cell count done. Stool and urine culture were also made in cases where other investigations had proved negative. The ideal patient, of course, was one admitted with a +ve Widal reaction which was subsequently con- firmed by +ve blood and marrow cultures. As the series is not yet complete the % of such cases cannot yet be given accurately.
When these investigations had been completed treatment was begun on the lines already described, with dosage modifications where necessary for age. Although the data obtained have not yet been fully analysed certain points emerge clearly from an experience of the drug in approximately 200 cases of the disease. First, the dosage originally
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suggested was probably too smali in amount and too concentrated in time. Relapses, usually in the sixth week of the disease, became so common in September and October that the total dosage was raised to 30 gm. for the full course and this was spread over 14 days. This increase appears to have been effective in helping to reduce the relapse rate. Second, it has been made abundantly clear that the seriously ill patient admitted profoundly toxæmic in the third or fourth week of the disease does not stand a loading doer of 3 gm. In two of our early cases of this type an initial loading dose of that order was followed by a rapid Herxheimer-like reaction and death. The schedule was accordingly modified and all patients severely ill on admission were given either 0.25 gm. at hourly intervals up to a total of 3 gm, after which a total daily dose of 2.75 gm. in three divided doses could safely be given, or they were given 1 gm. at 4 hourly intervals to a total of 3 gm. on the day of admission and then 2.75 daily in three divided doses. No further Herxheimer reactions have been noted since these modifications were adopted. It has been noted that seriously ill patients of this type respond more rapidly to chloromycetin if intravenous fluid is given by drip (glucose saline 5%) during the first 24 hours of treatment. Third, chloromycetin resistance appears to exist and has been noted in at least two bacteriologically proved cases in this series. Fourth, the majority of cases respond rapidly and uneventfully to the drug. Within four days of beginning treatment the temperature becomes normal in most cases, but more striking and earlier thau the decline in temperature is the disappearance of delirium and mental confusion. Not infrequently a patient who on admission was restless, semi-conscious and in need of tube feeding, has become quiet and rational within 48 hours of beginning treatment although his fever may still be high.
General treatment followed the normally accepted lines; parti- cular stress is laid on small frequent feeds of a high caloric, high vitamine tow residue diet, and the maintenance of adequate hydration. In a few cases in this series it has been necessary to employ penicillin for respira- tion or other complications. A certain number of our patients on admission were incapable of swallowing. Such cases have been succesa- fully treated by passing a nasal tube and administering chloromycetin through it in a watery suspension. One such case, a young woman who developed a toxi-infective psychosis early in her attack of typhoid, was given both chloromycetin and fluids in this way throughout the whole course of her disease and was finally transferred to the Mental Hospital, where she slowly made a complete recovery. All cases bave been kept in bed for at least 14 days from the beginning of treatment and the majority of patients were clamouring to be up and about before this period had expired. Great difficulty has also been experienced in keeping the ravenous appetite of the average convalescent within reasonable bounds.
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