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CARBENICILLIN-RESISTANT PSEUDOMONAS
1141 When the R-wave voltage falls, prolonged intracoronary infusions of dipyridamole in no way restore the voltage to normal levels, as is usually the case-in the early stages at least-after injections of hydrocortisone.7 And when the R-wave voltage falls there is no evidence that coronary flow has declined. When there is evidence from arteriograms 10 that the distribution of coronary flow is reduced, dipyridamole is valueless in reversing this state. This, no doubt, is because the coronary vasoconstriction prevents adequate perfusion, and myocardial damage is already irreversible. All my observations lead me to believe that platelet aggregation is a consequence, and not the cause, of a hmmodynamic vascular upset involving vasoconstriction and disturbWhen this happens, intravenous ance of laminar flow. steroids appear to have the double function (in humans but not in dogs) of restoring the integrity of the host-transplant frontier and dispersing platelets. These drugs, however, have severe practical limitations for long-term use, hence my interest in testing non-steroidal anti-inflammatory agents in organ transplants. How does the therapeutic value of dipyridamole correlate with lymphocyte typing ? With so many anti-rejection regimens being employed in kidney transplantation, the lymphocyte typers are going to be hard pressed to get their message through the mists of clinical empiricism. Department of Surgery, Roval Postgraduate Medical School, London W.12.
I am grateful to the Beecham Research Laboratories for supplies of carbenicillin, and to the Boots Pure Drug Co. for the ethidium bromide. This work is supported by a grant from The East Anglian Regional Hospital Board. Papworth Hospital, S. W. B. NEWSOM. Cambridge.
OPHTHALMIC INFECTION IN INFANCY SIR,-Dr. J. A. Smith (Nov. 1, p. 954) uses figures for " bacteria associated with infections of the eye in infancy " to support his statement that " It is clear that Staph. aureus is the commonest cause of ophthalmic infection in infancy ". There is, in fact, no proof that the frequent association of Staphylococcus aureus with conjunctivitis of the newborn is always causative. There is some evidence to the contrary.l.2 Public Health Laboratory, Royal Hampshire County Hospital,
Winchester.
W. J. DEMPSTER.
CARBENICILLIN-RESISTANT PSEUDOMONAS
SIR,-Ishould like to report the isolation of a highly carbenicillin-resistant strain of Pseudomonas ceruginosa, which, like those of Dr. Lowbury and his colleagues (Aug. 30, p. 448), inactivates the antibiotic. This organism came from the sputum of a patient three days after the insertion of a Celestin tube to relieve a malignant oesophageal obstruction. The patient’s sputum had previously been free from pathogens; he had received penicillin G and streptomycin for 3 days before the isolation of the pseudomonas, but had never been given any carbenicillin. further
The organism had the typical appearance of Ps. oeruginosa; it was not typable by the pyocine method, but reacted with antiserum to Habs group 5 (presumptively 5c). This type has not been found before in the hospital. Growth of the organism was not inhibited by a 100 ug. carbenicillin sensitivity disc, and a 250-fold dilution of an overnight broth culture of it grew unchanged on nutrient agar containing 20 mg. carbenicillin per ml. A small inoculum of the organism (approximately 12 cells) was inhibited by 12-5 mg. of the antibiotic per ml., but grew as small colonies on agar containing 10 mg. per ml. The destruction of an antibiotic was tested for by adding 1 mg. of antibiotic to 9 ml. of an overnight broth-culture of the organism, and incubating for 1 hour at 37°C. The mixture was then passed through a Millipore filter, and the filtrate was assayed for remaining antibiotic on an agar plate using the Oxford staphylococcus as an indicator organism. Carbenicillin, and penicillin G were completely destroyed, ampicillin was partially destroyed, but methicillin appeared unaffected. Reversion of the antibiotic resistance was not noted in a preliminary experiment, in which the organism was incubated in sublethal concentrations of ethidium bromide; this is said by Bouanchaud et al.ll to be the most efficient method for eliminating transferable resistance.
The high level of carbenicillin resistance of this organism is similar to that described by Dr. Lowbury and his colleagues, and is much greater than that described by Darrell and Waterworth 12 and Bell and Smith.13 The organism differs from those described bv Dr. Lowburv and his 10. 11.
colleagues by having an even higher resistance to carbenicillin, by destroying ampicillin as well; and by not (so far) reverting to a sensitive type. It presumably owes its resistance principally to the production of carbenicillindestroying enzymes, and it will be of great interest to see whether any other penicillin can block these enzymes, and also to see how the organism will behave when exposed to cx-sulphoaminobenzy lpenicillin.
Dempster, W. J. Br. med. J. 1968, i, 695. Bouanchaud, D. H., Scavizzi, M. R., Chabbert, Y. A. J. Microbiol. 1968, 54, 417. 12. Darrell, J. H., Waterworth, P. M. Br. med. J. 1969, iii, 141. 13. Bell, S. M., Smith, D. D. Lancet, 1969, i, 753.
gen.
M. H. HUGHES.
INDUCTION OF TOLERANCE IN MAN TO HORSE-IgG SIR,-Following the remarkable report by Dr. Taub and his colleagues (Sept. 6, p. 521) of induction of tolerance to equine anti-human-thymocyte gamma-globulin in man, we should like to record that we in Munich have obtained similar results. Reactions such as urticaria, anaphylaxis, and serum nephritis in patients treated with horse antilymphocyte globulin (A.L.G.) led to criticism of its use in clinical practice-we have observed these in nearly 10% of over 100 patients treated intravenously with the " Munich A.L.G." to date.3 After devising a method of inducing tolerance to horse-IgG in adult dogs 4-7 we started, several months ago, a trial in which we attempted to induce a tolerant state to horse-IgG, in patients who were to receive A.L.G., by pretreating them with small doses of ultracentrifuged normal horse-IgG. (The A.L.G. and horse-IgG were prepared by the Behring-
Werke, Germany.) For this treatment we selected patients with autoimmune diseases, for whom our present schedule of immunosuppressive therapy consists of one week of thoracic-duct drainage followed by combined treatment with A.L.G., steroids, and azathioprine (’ Imuran’). 5 patients received two intravenous injections of ultranormal horse-IgG (centrifuged at 30,000r.p.m. for 90-120 minutes), the first (10 mg. per kg. body-weight) 6 days, and the second (30 mg. per kg.) 3 days before commencement of A.L.G. administration. Then, A.L.G. was given in doses of 10 ml. (500 mg. protein) daily intravenously for a period of 4-5 weeks, in addition to 100 mg. azathioprine, and 50 mg. prednisolone. In
centrifuged 60,000
1. 2. 3. 4.
5. 6. 7.
Hutchison, J. G. P., Bowman, W. D. Acta. pœdiat., Stockh. 1957, 46, 125. Hughes, M. H. J. Hyg., Camb. 1961, 59, 419. Brendel, W., Land, W. Dt. med. Wschr. 1969, 110, 893. Pichlmayr, R., Land, W., Wagner, E., Seifert, J., Fateth-Moghadam, A., Eulitz, W., Brendel, W. Klin. Wschr. 1969, 47, 628. Land, W., Brendel, W., Seifert, J., Fateh-Moghadam, A. International Symposium on Pharmacology, 1968. Mailand (in the press). Hopf, U., Land, W., Seifert, J., Fateh-Moghadam, A., Brendel, W. Joint Meeting of the Surgical Research Society, London, 1969. Land, W., Seifert, J., Fateh-Moghadam, A., Hopf, U., Brendel, W. Z. ges. exp. Med. (in the press).
I am grateful to the Beecham Research Laboratories for supplies of carbenicillin, and to the Boots Pure Drug Co. for the ethidium bromide. This work is supported by a grant from The East Anglian Regional Hospital Board. Papworth Hospital, S. W. B. NEWSOM. Cambridge.
OPHTHALMIC INFECTION IN INFANCY SIR,-Dr. J. A. Smith (Nov. 1, p. 954) uses figures for " bacteria associated with infections of the eye in infancy " to support his statement that " It is clear that Staph. aureus is the commonest cause of ophthalmic infection in infancy ". There is, in fact, no proof that the frequent association of Staphylococcus aureus with conjunctivitis of the newborn is always causative. There is some evidence to the contrary.l.2 Public Health Laboratory, Royal Hampshire County Hospital,
Winchester.
W. J. DEMPSTER.
CARBENICILLIN-RESISTANT PSEUDOMONAS
SIR,-Ishould like to report the isolation of a highly carbenicillin-resistant strain of Pseudomonas ceruginosa, which, like those of Dr. Lowbury and his colleagues (Aug. 30, p. 448), inactivates the antibiotic. This organism came from the sputum of a patient three days after the insertion of a Celestin tube to relieve a malignant oesophageal obstruction. The patient’s sputum had previously been free from pathogens; he had received penicillin G and streptomycin for 3 days before the isolation of the pseudomonas, but had never been given any carbenicillin. further
The organism had the typical appearance of Ps. oeruginosa; it was not typable by the pyocine method, but reacted with antiserum to Habs group 5 (presumptively 5c). This type has not been found before in the hospital. Growth of the organism was not inhibited by a 100 ug. carbenicillin sensitivity disc, and a 250-fold dilution of an overnight broth culture of it grew unchanged on nutrient agar containing 20 mg. carbenicillin per ml. A small inoculum of the organism (approximately 12 cells) was inhibited by 12-5 mg. of the antibiotic per ml., but grew as small colonies on agar containing 10 mg. per ml. The destruction of an antibiotic was tested for by adding 1 mg. of antibiotic to 9 ml. of an overnight broth-culture of the organism, and incubating for 1 hour at 37°C. The mixture was then passed through a Millipore filter, and the filtrate was assayed for remaining antibiotic on an agar plate using the Oxford staphylococcus as an indicator organism. Carbenicillin, and penicillin G were completely destroyed, ampicillin was partially destroyed, but methicillin appeared unaffected. Reversion of the antibiotic resistance was not noted in a preliminary experiment, in which the organism was incubated in sublethal concentrations of ethidium bromide; this is said by Bouanchaud et al.ll to be the most efficient method for eliminating transferable resistance.
The high level of carbenicillin resistance of this organism is similar to that described by Dr. Lowbury and his colleagues, and is much greater than that described by Darrell and Waterworth 12 and Bell and Smith.13 The organism differs from those described bv Dr. Lowburv and his 10. 11.
colleagues by having an even higher resistance to carbenicillin, by destroying ampicillin as well; and by not (so far) reverting to a sensitive type. It presumably owes its resistance principally to the production of carbenicillindestroying enzymes, and it will be of great interest to see whether any other penicillin can block these enzymes, and also to see how the organism will behave when exposed to cx-sulphoaminobenzy lpenicillin.
Dempster, W. J. Br. med. J. 1968, i, 695. Bouanchaud, D. H., Scavizzi, M. R., Chabbert, Y. A. J. Microbiol. 1968, 54, 417. 12. Darrell, J. H., Waterworth, P. M. Br. med. J. 1969, iii, 141. 13. Bell, S. M., Smith, D. D. Lancet, 1969, i, 753.
gen.
M. H. HUGHES.
INDUCTION OF TOLERANCE IN MAN TO HORSE-IgG SIR,-Following the remarkable report by Dr. Taub and his colleagues (Sept. 6, p. 521) of induction of tolerance to equine anti-human-thymocyte gamma-globulin in man, we should like to record that we in Munich have obtained similar results. Reactions such as urticaria, anaphylaxis, and serum nephritis in patients treated with horse antilymphocyte globulin (A.L.G.) led to criticism of its use in clinical practice-we have observed these in nearly 10% of over 100 patients treated intravenously with the " Munich A.L.G." to date.3 After devising a method of inducing tolerance to horse-IgG in adult dogs 4-7 we started, several months ago, a trial in which we attempted to induce a tolerant state to horse-IgG, in patients who were to receive A.L.G., by pretreating them with small doses of ultracentrifuged normal horse-IgG. (The A.L.G. and horse-IgG were prepared by the Behring-
Werke, Germany.) For this treatment we selected patients with autoimmune diseases, for whom our present schedule of immunosuppressive therapy consists of one week of thoracic-duct drainage followed by combined treatment with A.L.G., steroids, and azathioprine (’ Imuran’). 5 patients received two intravenous injections of ultranormal horse-IgG (centrifuged at 30,000r.p.m. for 90-120 minutes), the first (10 mg. per kg. body-weight) 6 days, and the second (30 mg. per kg.) 3 days before commencement of A.L.G. administration. Then, A.L.G. was given in doses of 10 ml. (500 mg. protein) daily intravenously for a period of 4-5 weeks, in addition to 100 mg. azathioprine, and 50 mg. prednisolone. In
centrifuged 60,000
1. 2. 3. 4.
5. 6. 7.
Hutchison, J. G. P., Bowman, W. D. Acta. pœdiat., Stockh. 1957, 46, 125. Hughes, M. H. J. Hyg., Camb. 1961, 59, 419. Brendel, W., Land, W. Dt. med. Wschr. 1969, 110, 893. Pichlmayr, R., Land, W., Wagner, E., Seifert, J., Fateth-Moghadam, A., Eulitz, W., Brendel, W. Klin. Wschr. 1969, 47, 628. Land, W., Brendel, W., Seifert, J., Fateh-Moghadam, A. International Symposium on Pharmacology, 1968. Mailand (in the press). Hopf, U., Land, W., Seifert, J., Fateh-Moghadam, A., Brendel, W. Joint Meeting of the Surgical Research Society, London, 1969. Land, W., Seifert, J., Fateh-Moghadam, A., Hopf, U., Brendel, W. Z. ges. exp. Med. (in the press).