883

SULPHATHIAZOLE

THE LANCET

.LONDON: : S9. T iTRD. Y, MAY 11, 1940

IT has been freely predicted that the successesof sulphanilamide and sulphapyridine in thetreatment of bacterial infections would lead to

therapeutic claims for other similar compoundswhich the chemists can readily prepare. Such a

compound is 2-(para-aminobenzene-sulphonamido)thiazole, a preparation in which sulphanilamideis linked to thiazole, a heterocyclic compound,in the same way as it is linked with pyridine insulphapyridine.

This preparation, provisionally called sulpha-thiazole, and its 4-methyl derivative (sulpha-methylthiazole) have been distributed in Americafor experimental and clinical trial, although notyet released in the open market. Early tests 1suggested that sulphathiazole and sulphamethyl-thiazole were more effective than sulphapyridinein staphylococcal infections, and HELMHOLTZ 2

has lately shown that in vitro the urine of patientsreceiving these drugs is bactericidal for bothStaphylococcus aureus and Streptococcus fcocalis.Another report 3 from the Mayo Clinic on theresults obtained with these two preparations inurinary infections caused by coliform bacilli (15cases), Strep. faecalis (7 cases) and Staph. aureus(5 cases) claims a 65 per cent. cure. These

findings naturally prompt us to ask how thesenew drugs compare in activity and toxicity withthose already in use for the treatment of bacterialinfections. PERRIN LONG 4 has presented a reportto the American Council on Pharmacy and Chem-istry which sum’marises the available Americandata on these two points. It seems, as Dr.BUTTLE points out on another page, that in experi-mental pneumococcal infections the new drugsare rather less effective than sulphapyridine, in

streptococcal infections they are about equal, andin staphylococcal infections (which are moredifficult to assess) they are somewhat superior tosulpha pyridine. Clinical data from America onthe treatment of infections due to these bacteriaare, with the possible exception of staphylococcalinfections, still too scanty to allow an opinion onthe usefulness of these preparations. However,

1. See Lancet, Jan. 20, 1940, p. 137.2. Helmholtz, H. F. Proc. Mayo Clin. Jan. 31, 1940, p. 65.3. Pool, T. L. and Cook, E. N. Ibid, Feb. 21, 1940, p. 113.4. Long, P. H. J. Amer. med. Ass. March 9, 1940, p. 870.

’a similar product called Ciba 3714, has been

clinically tested, in doses similar to those adoptedfor sulphapyridine, in a variety of bacterial infec-tions by GsELL.s Among 60 patients with pneu-monia, of whom 23 had lobar pneumonia and theothers bronchopneumonia and postinfluenzalpneumonia, there was in general a rapid ameliora-tion of symptoms and only 1 death, while 7 casesof acute cerebrospinal fever all recovered. Theconcentration of the drug in the cerebrospinalfluid was 4-6 mg. per cent., some 50-60 percent. 01 line Diooa level. uases ot gonorrnoea,erysipelas, and coliform pyelitis and cystitis werealso treated with success but 2 cases of general-ised staphylococcal infection failed to respond.Staphylococcal infections are indeed likely to bea stumbling-block for chemotherapy because oftheir great tendency to form localised abscesses.If it is to be effective the drug must be given veryearly, for without surgical drainage it has littlechance of success once pus has accumulated.As regards its pharmacology and toxicity,

sulphathiazole is readily absorbed from the boweland quickly excreted, while a smaller percentageof the drug becomes acetylated and inert than isthe case with sulphapyridine, although experiencewith the latter drug shows that the proportion ofconjugated drug varies greatly in different indi-viduals. With doses of 4 to 6 g. of sulphathiazoleper day the concentration in the blood seems torange between 3 and 5 mg. per cent.7 (the Swissworkers claim higher levels), and higher concen-trations are difficult to maintain despite increasesin the amount of drug prescribed. This is presum-ably due to the rapid excretion of the drug, andmay be a point of some practical importance,especially in severe infections. Experimentallyin mice the chronic toxicity of sulphathiazole is

greater than that of sulphapyridine, while thesodium salt of the methyl derivative is as acutelytoxic as the corresponding salt of sulphapyridine.In man, nausea and vomiting are less commonthan with sulphapyridine, and according to boththe Swiss and American investigators are neversevere enough to interfere with the use of the

drug, even with doses of 8-12 g. per day. Ifconfirmed, this is a point definitely in its favour.Drug rashes and drug fever are quite common,and some patients have shown an acute conges-tion of conjunctiva and sclera in association witha rash resembling that of erythema nodosum.Haematuria has been noted in several cases, andis more likely to occur with sulphamethylthiazolewhich is poorly soluble. In other words the toxiceffects are much the same as those produced bysulphapyridine except that the latter drug ismore liable to cause vomiting.

The position with regard to the new prepara-tions is admirably summed up by LONG: ’’ Theevaluation of these new chemotherapeutic com-pounds," he says,

" will necessitate extensive

5. Hartman, M. Schweiz. med. Wschr. April 20, 1940, p. 337;Meier, R., Allemann, O. and Merz, E. Ibid, p. 338.

6. Gsell, O. Ibid, p. 342.7. Reinhold, J. G., Harrison, F. F. and Schwartz, L. Amer. J.

med. Sci., March, 1940, p. 393.

884

experimental and clinical investigations in orderto determine their efficiency in the control ofinfections and their clinical toxic manifestations.Until the time when such data are in hand, it isto be hoped that enthusiasms do not outruncommon sense.

THE WOMAN WAR-WORKERTHE controversy over the rates of wages to be

paid to women who replace men in war-time jobsis a side-issue of the great national effort, whichrequires an equitable settlement if the machine isto run smoothly. The first round has been wonby the women bus and tram conductors who havebeen allotted by the Industrial Court the same" rate for the job " as the men they replace,provided they are over 21 and have given sixmonths’ service, while in the negotiations nowproceeding for the admission of women to theengineering industry the Amalgamated Engineer-ing Union are insisting on equal pay for equalwork. The argument between the transportworkers and the employers-in this case the muni-cipal authorities-followed traditional lines. Thefamiliar allegation that absenteeism for physicalreasons was commoner among women than amongmen was reviewed but not accepted by the court,and indeed it is more difficult to establish thisstatistically than would appear at first sight,though it is true that where comparable conditionsexist (which in peace-time is rarely the case) therate of absence for sickness among women isalmost invariably higher than among men.

Among London teachers for example the numberof days lost per head averages steadily about 8 perannum for women and 4 for men. Among indus-trial workers the rate for both sexes is usuallyhigher, but the differential rate between the sexesis variable and may be less than among teachers.The court may have considered that the differencedoes not justify a diminution in the standard ratesfor women. It must also be remembered thatsickness-rates vary far more with age than withsex. Sir HENRY BASHFORD has shown that inthe Post Office men between 40 and 60 incurred55 per cent. more sickness-absence than menunder 40, and women over 40 incurred 58 percent. more than women under that age. But inwar-time the average age of the women substi-tutes will be lower than that of the men left inthe transport services or in the factories, so thatthe sickness-rates should not be very different.

Once rates of pay are settled employers andunions would do well to get together withoutdelay and consider how to get the best out of thewomen engaged in arduous and unfamiliar tasks.The experiences of the last war showed that thepresence or absence of amenities has more influ-ence on the output of women than of men. Forwomen a skilled medical and lay welfare staff isnot so much a luxury as a necessity. A reportrecently issued by the Industrial Health ResearchBoard 2 points out that careful and accuraterecords of absences are the only means of check-

1. Proc. R. Soc. Med. 1938, 31, 185.2. Emergency Report, No. 1; see Lancet, April 13, 1940, p. 699.

ing the effects of new processes or changes in

working conditions. Where the causes of sicknessare collected and grouped it is found that much ofthe women’s excess rate is due to " nervous "

conditions-which can be greatly reduced by tact-ful welfare work. A small proportion of the excessis due to " ailments of women, " but disability dueto the menstrual function has shrunk to negligibleproportions, thanks to a recognition of the import-ance of cleanliness and exercise.In comparing the sickness-rate and working

capacity of men and women it is easy to forgethow unequally the pressure of domestic dutiesfalls on the two sexes. That great champion ofthe working woman, MARY MACARTHUR, used torelate the story of a friend who acted as fore-woman in a factory in the last war. Talking to aman engaged on an exactly similar job, she com-plained of the increasing difficulty and expense ofgetting her greasy overalls washed. " But howlazy of you not to do them yourself at home," heprotested,

"

my wife always does mine ! "

Leisuremust be really leisure if it is to restore theworker’s vigour unimpaired for the next day.Even when the workers are living at home sub-stantial canteen meals should be provided andpractical arrangements worked out for getting thelaundry done. Small day-nurseries for childrenproved invaluable in the last war and greatlyreduced short absences among married women.Today the introduction of a system of familyallowances in industry would bring military andcivilian conditions into line. The provision ofhostels for mobile labour is a real boon andenables a sympathetic watch to be kept over thegirls’ health. In the last war thousands of girlsat Gretna and Woolwich blossomed like the rosein spite of long hours and heavy work, and todaytheir daughters should prove as capable of quittingthemselves like men.

SCOPE OF INTERNAL PNEUMONOLYSISTHE popularity of internal pneumonolysis in

the collapse treatment of pulmonary tuberculosisshows no sign of waning. On the contrary,within the last few months there have been fourimportant contributions to the subject, two fromthis country and two from America. WOLIlASTON 1has reviewed 200 consecutive cases of adhesioncutting, and has compared them with pneumo-thorax cases discharged from the Royal NationalHospital, Ventnor, in 1934, in none of whichadhesiotomy was undertaken. He found thatwith internal pneumonolysis satisfactory collapsewas obtained in 58-8 per cent. of the patients,whereas in 1934 the figure was only 25-8 per cent.SMART,2 working in Chandler’s clinic at theLondon Chest Hospital, gives a detailed analysisof 52 operations on 42 patients who had beenfollowed up for two years; 27 of these now enjoygood health with a T.B. negative sputum, 7 arein fair health, 3 have relapsed or are very ill and5 have died. The material was not composed

1. Wollaston, F. L. Brit. J. Tuberc. 1940, 34, 13.2. Smart, J. Tubercle, 1940, 21, 81.