Antibiotics in Chronic Respiratory Infections

LEADING ARTICLES

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likely to be any better in patients with congestive cardiac failure, and the figures given by BERLIN et al. for total blood volume and for plasma volume, obtained by difference, must be accepted with some reserve. that patients in congestive failure secondThey claim " to arteriosclerotic or ary hypertensive cardiovascular disease " have a blood volume which is low, normal, or at most slightly elevated." In rheumatic heart-disease with congestive failure, however, the " blood volume was almost uniformly elevated." Some of the patients with a normal blood volume did have an increased plasma volume ; and these workers express surprise that some patients with normal blood volume had " engorged vessels and tissues full of blood." Other studies on the blood volume in congestive heart-failure, by means of the labelled red-cell and hæmatocrit method, are similarly conflicting 9 lo ; and until closer agreement is reached physicians will be tempted to accept the witness of their unaided senses that these patients are plethoric. One possible further method, which has already been applied in congenital cyanotic heart-disease,". is to measure red-cell volume and plasma volume simultaneously by a dye method. This evades the use of the hæmatocrit percentage, but is open to the criticism 12 that in congestive heart-failure dye may leave the vessels with abnormal facility, so giving an exaggerated "estimate" of the plasma volume. Comparison of direct determinations of the plasma volume with " indirect " determinations involving the h2ematocrit might help to decide whether loss of dye in congestive heart-failure is in fact excessive. Our sympathy goes out to investigators of congestive heart-failure, which cannot be induced in animals, has a guilty liaison with that mysterious organ the kidney, and complicates the interpretation of the methods used for its study. not

THE LANCET LONDON :SATURDAY, MARCH 14,1953

Determination of Blood Volume MEASUREMENT of the plasma volume by means of dyes,!2 or of the total red blood-cell volume by labelling with radioactive phosphorus,3 causes the patientvery little discomfort, is quickly completed, and is

reasonably accurate;

yet neither of these methods has into general clinical use. BERLIN et awl.4 now claim that " the determination of the blood volume turns out to be of great importance in the been

brought

of major medical and surgical problems," doubt whether this need be added to the load of " routine investigations borne by the longthe hand patients are other On suffering patient. from such estimations in research benefiting every day - as may perhaps best be illustrated by reference to the of hsematemesis. Nowadays in for orit is transfusion assumed that deciding against the haemoglobin level and red blood-cell count soon after haematemesis are misleadingly high, giving little indication of the amount of blood lost. This assumption is made without subjecting the patient to determination of the plasma volume ; but it is based on many blood-volume determinations in patients with haematemesis by the late IzoD BENNETT and his

handling but

we

"

management

colleagues,5 Similarly,

the demonstration by BERLIN large amounts of blood are lost during thoracic operations is not a reason for extending their research procedure to all such cases, though it is a good ground for liberal transfusion-a measure which they take by giving routinely a litre of blood. Measuring total red-cell volume with radioactive phosphorus, BERLIN et al. have shown that in cancer, ursemia, pulmonary tuberculosis, and hepatic cirrhosis there is a true reduction in red-cell mass and not merely a reduction in the red-cell count due to hydræmic plethora. Unfortunately, extension of this method to measure total blood volume, by dividing the red-cell volume by the hæmatocrit percentage and multiplying by 100, involves an additional source of error in the hsematocrit percentage. It is almost certainly wrong to suppose that the venous hsematocrit represents the proportion of red-cell volume to total blood volume throughout the circulation; BARNES et al. found that the red-cell volume, calculated from haematocrit and plasma volume, was 13% greater than the red-cell volume measured directly by the Ashby technique ; and from a further analysis8 they concluded that the chief cause of this- discrepancy was unequal distribution of plasma and red cells through the circulating blood. Mixing of the blood is et al.themselves that

Keith, N. M., Rowntree, L. G., Geraghty, J. T. Arch. intern. Med., 1915, 16, 547. 2. Gibson, J. G., Evans, W. A. J. clin. Invest. 1937, 16, 301. 3. Nylin, G. Brit. Heart J. 1945, 7, 81. 4. Berlin, N. I., Hyde, G. M., Parsons, R. J., Lawrence, J. H. New Engl. J. Med. 1952, 247, 675. 5. Bennett, T. I., Dow, J., Lander, F. P. L., Wright, S. Lancet, 1938, ii, 651. 6. Berlin, N. I., Rowles, D. F., Hyde, G. M., Parsons, R. J., Samson, P. C., Port, S. Surg. Gynec. Obstet. 1951, 92, 712. 7. Barnes, D. W. H., Loutit, J. F., Reeve, E. B. Clin. Sci. 1948, 7, 135. 8. Barnes, D. W. H., Loutit, J. F., Reeve, E. B. Ibid, p. 155.

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Antibiotics in Chronic Respiratory Infections CLINICIANS are alive to the dangers of administering In such diseases as antibiotics indiscriminately. chronic bronchitis and bronchiectasis, however, it is often difficult to be sure which organisms are pathogens and which are harmless saprophytes ; and this uncertainty is increased by the risk that orthodox methods of culture may fail to reveal the true bacterial flora of the sputum.13 In these chronic diseases, therefore, antibiotics cannot be administered as rationally as in, for example, acute pneumococcal pneumonia or streptococcal sore throat : the chemotherapy of chronic bronchitis and bronchiectasis is to some extent " blind." BARACH et al.14 have investigated in some detail the response of these two conditions to penicillin, " given mainly by inhalation, and to " broad-spectrum antibiotics-chloramphenicol, aureomycin, and terramycin. They name the indications for penicillin therapy in cases of chronic productive cough as the demonstration of pus cells in the sputum as well as "

9. Nylin, G., Hedlund, S. Amer. Heart J. 1947, 33, 770. J. clin. Incest. 1950, 10. Ross, J. F., Baker, W. H., Freis, E. D. 29, 842. 11. Scott, H. W., Elliott, S. R., Clay, R. C. Bull. Johns Hopk. Hosp. 1951, 89, 121. 12. Peters, J. P. New Engl. J. Med. 1948, 239, 353. 13. May, J. R. Lancet, 1952, ii, 1206. 14. Barach, A. L., Bickerman, H. A., Beck, G. I. Arch. intern. Med. 1952, 90, 808.

530 the presence of Gram positive organisms on culture "’. In these cases, the organisms are not specified. however, cultures of sputum rarely contain no grampositive organisms at all; and thus penicillin therapy would be indicated almost always in chronic bronchitis Yet or bronchiectasis where the sputum is purulent. are that some cases has shown experience only benefited by penicillin, administered either by inhalation or by intramuscular injection. BARACH and his colleagues report that penicillin by inhalation caused " marked or moderate " improvement in 58 out of 70 cases of bronchiectasis, 46 out of 50 cases of chronic bronchitis without clinical evidence of bronchospasm, and 97 out of 200 cases of chronic bronchitis associated with bronchial asthma. At first sight these figures may seem encouraging, but unfortunately in 20% of patients with bronchitis and asthma the inhalations increased wheezing so much that the It appears treatment had to be discontinued. that penicillin administered intramuscularly to these patients gave less benefit than inhalations. One reason for this was that with inhalations the concentrations of the antibiotic in the sputum ranged from 50 to 2000 units per ml.-a range high enough to swamp many organisms not normally regarded as sensitive to penicillin. BARACH et al. remark that this applied to many apparently penicillin-resistant staphylococci. It may also have applied to Hœmophilus influenzœ—a gram-negative organism which MULDER et al.15 believe to be the most significant pathogen in all types of respiratory infection. The studies by BARACH et al. of the effects of the broad-spectrum antibiotics on chronic bronchitis and bronchiectasis shed little new light on the role of different organisms in these diseases. As with penicillin inhalations the clinical responses were encouraging. " Marked or moderate improvement, as judged by cough, expectoration and clinical well-being," was observed in 26 out of 31 cases of bronchiectasis and in 37 out of 45 cases of chronic bronchitis. But the changes in the bacterial flora of the sputum in cases improved by this therapy do not seem to have followed BARACH et al. apparently any consistent pattern. attach great importance to Staphylococcus aureus. This was present in the sputum of 11 patients after therapy ; yet the condition of 9 of these had been improved considerably. Similarly each of 7 patients in whose sputum Friedlander’s bacillus was found after therapy had been greatly improved by treatment. With regard to the pneumococcus, however, there was closer correlation between clinical improvement and eradication of the organism : pneumococci were present in the sputum of only 2 patients after therapy ; in neither of these had definite improvement been observed, but the eradication of pneumococci from the sputum of 15 other patients was in each case associated with improvement. The pneumococcus has been found to be distributed intermittently in the sputum 13 - and this organism may have been present, but not detected, in the sputum of some of BARACH’S cases where clinical improvement could not be correlated clearly with changes in the bacterial flora. This is important, since the antibiotic of choice in such cases would always be penicillin, intramuscular injection of which would be adequate 15. Mulder, J., Goslings, W. R. O., van der Plas, M. C., Lopes Cardozo, P. Acta med. Scand. 1952, 143, 32.

and free from the side-effects that may accompany the The need for use of the broad-spectrum antibiotics. of the use broad-spectrum antiavoiding unnecessary biotics is once again evident from the fact that in the 76 cases of respiratory infection treated with these by BARACH et al. there were no fewer than 7 deaths, all of which were ascribed to the development of infection by organisms highly resistant to all anti. biotics.

Mealtimes EATING, besides satisfying a physiological need, reflects a psychological state, as in the overeating of the emotionally deprived and the anorexia nervosa of the despairing. It has also a religious symbolism; while communal meals and ceremonial feasts make for sociability. The body likes a- rhythm of recurring mealtimes but is less particular about the tune. The traditional Englishman starts his day with a good breakfast of porridge and bacon and eggs, and later has a light lunch. The Frenchman living in a similar climate goes to work after a cup of coffee and a roll, but lunches substantially. Kaffirs prefer to wait for their big meal till evening, when the heavy labour is Babies fed whenever they cry for food finished.1 establish their own timetable of feeds every usually 3-4 hours.2 Hunger probably reflects internal metabolic rhythms,3 about which little is known 4 ; and, like other biological rhythms such as sleep, it can be modified by training. There are said to be and starvation centres in the hyposeparate hunger at least in rats and cats 5: destroy one white thalamus, centre and the animal overeats to extreme obesity, destroy the other and henceforth it refuses all food. Under more or less natural conditions the healthy man need not bother about all this : his stomach will tell him when to eat. Modern industrial life, however, is far from natural, and the relation between working performance and frequency of meals is of interest to factory managers, and also to athletes, schools, and the Services. If the worker’s blood-sugar level begins to drop towards the end of a shift, perhaps an interim snack would stay this decrease and maintain his output ? Unfortunately, HUTCHINSON,6 from his review of published work, mainly American, concludes that with the possible exception of breakfast the ingestion of food is not followed by an increase in industrial productivity or improvement in athletic performance : indeed, a large meal may impair both, since it causes drowsiness and lack of coordination. Yet we know that long periods between meals may give rise to restlessness, irritability, and diminished concentration ; and HUTCHINSON goes so far as to suggest that efficiency may be greatest with small but frequent meals, numbering as many as six a day. In research of this kind it is very difficult to disentangle the physiological effects of meals from the psychological value of the accompanying rest pauses. particularly when these break the monotony of repetitive work. (BERGIN7 advises meals every two V. H., Graham, G. Hutchison’s Food and the Principles of Dietetics. London, 1948 ; p. 255. 2. Illingworth, R. S., Stone, D. G. H., Jowett, G. H., Scott, J. F. Lancet, 1952, i, 683. 3. Kleitman, N. Physiol. Rev. 1949, 29, 1. Proc. roy. Soc. B. 1953, 140, 578. 4. Kennedy, G. C. 5. Anand, B. K., Brobeck, J. R. Proc. Soc. exp. Biol., N.Y. 1. Mottram,

1951, 77, 323. Nutr. Abstr. Rev. 1952, 22, 283. 6. Hutchinson, R. C. Aviation Medicine. 7. Bergin, K. G. Bristol, 1949;

p. 79.