Introduction - Uppsala Monitoring Centre

Facial parathesia = usually circumoral
Oral lesions = stomatitis, erosions, ulcers and leucokeratosis
Disturbed vision = included ambylopia, diminished accommodation, diplopia and optic neuritis
(Walker, 1961)
Renal dysfunction = raised blood urea nitrogen
Myocarditis = Fiedler’s myocarditis (Chatterjee & Thakre, 1958)
2 gm - Vertigo in 75% but no deafness
1 gm - Vertigo in about 15% (Ormerod, 1954).
Comment
Was the dosage of streptomycin used unduly high for too long? The Canadians
reduced their dosage from 2 G daily to 1G daily on November 1st 1947, but
McDermott in 1947 said that it was probable that 3G represented the upper limit of
the safe daily dose. Other papers published at this time did not suggest reducing the
dosage. The MRC study started recruiting patients in January 1947 and the dosage
of 2 G daily had been decided after speaking with Dr HC Henshaw, who had a wide
experience and in his paper of 17th January 1948 he suggested that in TB the
average daily dose be approximately 1G for a patient of average weight, but in
November 1946 he had recommended for adults 1 to 3G per twenty-four hours. The
difficulty in choosing a safe dose may have been due to:
1. The numerous forms of TB which demanded different doses, e.g. miliary TB,
TB meningitis, different sites of the TB infection and a wide range of severity.
2. Causal factors for vestibular dysfunction: patient aged over 45 years, size of
dose, duration of treatment, patient’s weight, a difference between complaints
of giddiness on a single daily dose compared with divided doses during the
day.
3. Varying purity and three different salts: Glaxo–S calcium chloride complex,
Merck–S hydrochloride and Pfizer - S sulphate.
Although the MRC study made little effort in exploring the adverse effects of
streptomycin most of the relevant facts had been established by the previous case
series.
Histamine release due to impurities suggests an anaphylactoid reaction due to
instant release of histamine without developing hypersensitivity whereas the
anaphylactic reactions only occurred after prior hypersensitzation. The injection site
reactions also seem to have been due to impurities and also do not occur after
1948, The fact that fever is not mentioned after 1948 suggests that too maybe due
to impurities but not connected with injection site reaction as its time to onset and
duration are rather too long and there is no mention of a relationship. Renal casts
and albuminuria are not mentioned after 1948 when purified streptomycin became
available so they too may have been due to impurities. Nausea and vomiting
developed about six weeks after the start of the trial and they were also thought to
be due to impurities as they ceased when the pure streptomycin became available