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Resistant Pseudomonas
473
toxic for man was bactericidal in both tissues and urine. Because the antibiotics act in quite different ways they suggest that the development of resistance is improbable, but LowBURY’s demonstration of infectious resistance makes this forecast seem optimistic. A rather different approach is that of PRICE and his co-workers,3 who have been investigating the action of a variety of new semisynthetic penicillins on Ps. aeruginosa. The best seem to be the sulphoamino-penicillins, which are 8-16 times more lethal than benzylpenicillin. There have been no reports as yet on the toxicity of these compounds. We should like to commend the final paragraph in LowBURY’s paper to all who have to treat these infections. The mere presence of Ps. aeruginosa in the urine or a wound swab is not a good reason by itself for treating the patient with carbenicillin. Its use must be limited to those patients in whom this organism seems to be an immediate danger to life or limb. Using a suitable selective medium the bacteriologist can isolate it from many specimens where its presence is a matter of little concern. Ps. aeruginosa is not an organism like the anthrax bacillus, to be exterminated as soon as it is recognised. In those liable to infection it is an ever-present danger. The decision when to use carbenicillin is a difficult one, to be made by the surgeon and the bacteriologist in consultation. There seems no immediate hope of specific prophylaxis. Some benefit might result if other antibiotics were not used so often and with so little thought to their possible consequences. After all, it is the patient who is to be treated, not his infections. not
THE LANCET LONDON
30
AUGUST
1969
Resistant Pseudomonas WE have to learn to live with Pseudomonas aeruginosa, because this bacterium occurs naturally in a good many human bowels and it (or closely related organisms) are common enough in water and soil. Infection in man causing obvious disease is confined almost entirely to those whose defensive mechanisms are below par-the old, the very young, and the severely wounded or burned. To these must be added those who have been treated (or overtreated) with corticosteroids or wide-spectrum antibiotics. Because this organism is resistant to the action of many antibiotics, their use is likely to encourage its growth if the competition of more sensitive bacteria is removed. Now that such organisms as streptococci seldom complicate surgical treatment, Ps. ceruginosa has become a pest in almost every hospital. It is liable to cause severe and sometimes lethal infections not only of wounds but also of the urinary tract. For some years the only antibiotics which had much effect on this organism were some of the polymixins and gentamycin, and all of these are more or less toxic to man. More recently the semisynthetic penicillin, carbenicillin, gave promise of its usefulness, but strains resistant to this drug made their appearance fairly soon.1 On p. 448 this week Dr. Low BURY and his colleagues in Birmingham examine this problem in some detail. Between 1966 and 1969 all strains of Ps. aeruginosa which they isolated were tested for sensitivity to polymixin, gentamycin, and carbenicillin. The number resistant to the first two increased slightly, but resistance to carbenicillin multiplied steadily throughout until, suddenly and simultaneously, two unrelated strains became highly resistant because they were producing a carbenicillinase. The same effect could be produced in vitro by growing the organisms in sublethal concentrations of carbenicillin, but not when they were grown in ampicillin or cloxacillin. Because resistance appeared almost simultaneously in the two " wild " strains and could be abolished by exposure to acriflavine, Dr. LowBURY and his associates were inclined to attribute the phenomenon to an infectious extrachromosomal factor. From the introduction of carbenicillin it was an obvious gambit to use this drug and gentamycin at the same time. SONNE and JAWETZ2 found that a combination of the two drugs at levels which were 1. Smith, C. B., Finland, M. 2. ibid. 1969, 17, 893.
Appl. Microbiol. 1968, 16, 1753.
and Fatty Infiltration of Viscera in Children
Encephalopathy IN toxic
encephalopathy (also called acute encephalopathy and acute non-suppurative encephalitis) the brain is swollen and neurons degenerate, but there is no inflammatory reaction.4 acute
The condition, which is commoner in children in adults, may follow certain acute exanthems as chickenpox, and smallpox vaccination; or it be associated with hypertension, liver failure,
than such may
lead
intoxication, hypernatraemia, or poisoning, epilepsy. Often, however, there is no clue to the aetiology and pathogenesis; and this type of obscure water
constituted 6% of all infants and children on whom necropsies were performed during ten years at the Massachusetts General Hospital.5 The clinical onset is abrupt. After an apparently minor illness, high fever, change in level of consciousness, and intractable seizures ensue, and most patients die. At necropsy brain swelling is severe, but microscopical case
3. ibid. p. 881. 4. Scott, T. F. McN. Med. Clins N. Am. 1967, 51, 701. 5. Lyon, G., Dodge, P. R., Admas, R. D. Brain, 1961, 84, 680.
toxic for man was bactericidal in both tissues and urine. Because the antibiotics act in quite different ways they suggest that the development of resistance is improbable, but LowBURY’s demonstration of infectious resistance makes this forecast seem optimistic. A rather different approach is that of PRICE and his co-workers,3 who have been investigating the action of a variety of new semisynthetic penicillins on Ps. aeruginosa. The best seem to be the sulphoamino-penicillins, which are 8-16 times more lethal than benzylpenicillin. There have been no reports as yet on the toxicity of these compounds. We should like to commend the final paragraph in LowBURY’s paper to all who have to treat these infections. The mere presence of Ps. aeruginosa in the urine or a wound swab is not a good reason by itself for treating the patient with carbenicillin. Its use must be limited to those patients in whom this organism seems to be an immediate danger to life or limb. Using a suitable selective medium the bacteriologist can isolate it from many specimens where its presence is a matter of little concern. Ps. aeruginosa is not an organism like the anthrax bacillus, to be exterminated as soon as it is recognised. In those liable to infection it is an ever-present danger. The decision when to use carbenicillin is a difficult one, to be made by the surgeon and the bacteriologist in consultation. There seems no immediate hope of specific prophylaxis. Some benefit might result if other antibiotics were not used so often and with so little thought to their possible consequences. After all, it is the patient who is to be treated, not his infections. not
THE LANCET LONDON
30
AUGUST
1969
Resistant Pseudomonas WE have to learn to live with Pseudomonas aeruginosa, because this bacterium occurs naturally in a good many human bowels and it (or closely related organisms) are common enough in water and soil. Infection in man causing obvious disease is confined almost entirely to those whose defensive mechanisms are below par-the old, the very young, and the severely wounded or burned. To these must be added those who have been treated (or overtreated) with corticosteroids or wide-spectrum antibiotics. Because this organism is resistant to the action of many antibiotics, their use is likely to encourage its growth if the competition of more sensitive bacteria is removed. Now that such organisms as streptococci seldom complicate surgical treatment, Ps. ceruginosa has become a pest in almost every hospital. It is liable to cause severe and sometimes lethal infections not only of wounds but also of the urinary tract. For some years the only antibiotics which had much effect on this organism were some of the polymixins and gentamycin, and all of these are more or less toxic to man. More recently the semisynthetic penicillin, carbenicillin, gave promise of its usefulness, but strains resistant to this drug made their appearance fairly soon.1 On p. 448 this week Dr. Low BURY and his colleagues in Birmingham examine this problem in some detail. Between 1966 and 1969 all strains of Ps. aeruginosa which they isolated were tested for sensitivity to polymixin, gentamycin, and carbenicillin. The number resistant to the first two increased slightly, but resistance to carbenicillin multiplied steadily throughout until, suddenly and simultaneously, two unrelated strains became highly resistant because they were producing a carbenicillinase. The same effect could be produced in vitro by growing the organisms in sublethal concentrations of carbenicillin, but not when they were grown in ampicillin or cloxacillin. Because resistance appeared almost simultaneously in the two " wild " strains and could be abolished by exposure to acriflavine, Dr. LowBURY and his associates were inclined to attribute the phenomenon to an infectious extrachromosomal factor. From the introduction of carbenicillin it was an obvious gambit to use this drug and gentamycin at the same time. SONNE and JAWETZ2 found that a combination of the two drugs at levels which were 1. Smith, C. B., Finland, M. 2. ibid. 1969, 17, 893.
Appl. Microbiol. 1968, 16, 1753.
and Fatty Infiltration of Viscera in Children
Encephalopathy IN toxic
encephalopathy (also called acute encephalopathy and acute non-suppurative encephalitis) the brain is swollen and neurons degenerate, but there is no inflammatory reaction.4 acute
The condition, which is commoner in children in adults, may follow certain acute exanthems as chickenpox, and smallpox vaccination; or it be associated with hypertension, liver failure,
than such may
lead
intoxication, hypernatraemia, or poisoning, epilepsy. Often, however, there is no clue to the aetiology and pathogenesis; and this type of obscure water
constituted 6% of all infants and children on whom necropsies were performed during ten years at the Massachusetts General Hospital.5 The clinical onset is abrupt. After an apparently minor illness, high fever, change in level of consciousness, and intractable seizures ensue, and most patients die. At necropsy brain swelling is severe, but microscopical case
3. ibid. p. 881. 4. Scott, T. F. McN. Med. Clins N. Am. 1967, 51, 701. 5. Lyon, G., Dodge, P. R., Admas, R. D. Brain, 1961, 84, 680.