200 their viral gut flora, and we should be wary of jumping to conclusions about causation. One baby (case 5) changed her E.M.-detectable viruses four times in one month (13 stool spe’
cimens).
Full details, including viral and bacterial cultures, of the stools from babies in this study will be published later. We thank Dr J. P. Stanfield, Dr I. W. Pinkerton, Dr W. C. Love, Dr 1. D. Riley, and Dr E. G. Fox for allowing us to study patients under their care.
Regional Virus Laboratory and University of Glasgow Department of Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB.
C. R. MADELEY B. P. COSGROVE
clinical applications should be approached cautiously, the public is today being offered many commercial products, such as deodorant soaps, whose medical rationale is the alteration of normal flora. Cosmetics, topical and systemic drugs, and occlusive dressings are other common assaults which may affect resident flora and their environment. It is unfortunate that little regard is apparently being given to environmental monitoring. Dermatoses and their therapy are particular candidates for examination. We should like to add our confirmation2of in-vivo production of a penicillin-like substance by dermatophytes and an increase in penicillin-resistant flora in experimental human dermatophytoses. There was also an increase in total flora, especially in numbers of Staphylococcus epidermidis, but there was no drift toward gram-negative microorganisms.
AMPICILLIN RESISTANCE IN STAPHYLOCOCCI
SIR,—Mr Pollock and Miss Evans (Dec. 20, p. 1251) found that 100% of Staphylococcus aureus isolated from urine speciof hospital
sensitive to ampicillin. Since ampicillin is inactivated by penicillinase this means that all Staph. aureus strains from hospital urine specimens in Scarborough in that year were non-penicillinase producers and thus would have been sensitive to penicillin. This is a very surprising, if not amazing, result, until one realises that a 25 µg strength ampicillin disc was used to test the sensitivity. In my experience it is not possible to show penicillinase production by staphylococci (and hence ampicillin resistance) with any degree of reliability, using a 25 jig ampicillin disc. Many staphylococci which appeared sensitive to ampicillin were proved to be penicillinase-producers when tested with a penicillin G disc (1 µg or 2 [µg strength). For this reason I would suggest that the accuracy of the findings which refer to staphylococci in Pollock and Evans’ report may be
mens
patients
in 1971
Army Institute of Research, Presidio of San Francisco, California 94129, U.S.A. Letterman
J. BIBEL JOSEPH H. GREENBERG DAVID
ROBERT D. KING
were
LEG ABSCESSES CAUSED BY SALMONELLA HEIDELBERG
SIR,—Salmonellæ commonly
cause acute gastroenteritis. frequently they may cause more serious illnesses (i.e., enteric, septicaemia and focal).3 The following case illustrates the latent period between ingestion and illness, and also the host factor responsible for determining the site of infection. A 41-year-old woman was admitted to hospital with abscesses in her right leg, along the course of the long saphenous vein (see figure)--one had broken down, leaving a discharging
Less
questionable. Department of Bacteriology, Royal Infirmary, Glasgow C4.
*t*This letter has been shown whose reply follows.—ED. L.
J. S. CARGILL to
Mr Pollock and Miss Evans
SIR,—taphylococcus aureus accounted for only 7.7% of all inpatient urinary organisms in 1971 and 4.4% in 1974. The use of the 25 µg ampicillin disc for testing sensitivity of bacterial isolates from urine has been standard in this, as in many other hospitals for several years. It is true-as Dr Cargill points out-that a disc of this strength can often overcome the penicillinase produced by Staph. aureus. The use of the higher strength of ampicillin disc is justified by the high concentration of ampicillin (and other antibiotics) found in urine compared with other tissue fluids when the antibiotic is administered in therapeutic doses.
Scarborough Hospital, North Yorkshire.
A. V. POLLOCK MARY EVANS
ANTIBIOSIS IN SKIN FLORA
SIR,-We are encouraged by your editorial,’ for therapeutic of antibiotic skin flora is a long-term goal of our research programme. However, we are concerned that the medical community may drift to superficiality in approaching the concept of bacteriotherapy. One of the reasons why the theory continues to pop in and out of vogue is the lack of appreciation of the ecological complexities involved. Furthermore, antibiosis is merely one ecological interaction of skin microoruse
ganisms. The role of normal flora in natural resistance or predisposition to disease is far from clear. Yet, while you justly warn that 1. Lancet,
1975, ii,
1080.
Medial aspect of right second operation).
thigh showing sites of three
abscesses
(1 week after
ulcer of 2.5 cm diameter; above the knee there was a poinung abscess of 2.5cm diameter, and higher up a larger subcutaneous lump. She had not been well for some time. 9 weeks earlier she had had gastroenteritis during which she had passed some blood per rectum. This settled without treatment. Shortly afterwards she developed thrombophlebitis in the right long saphenous vein. Tetracycline tablets were prescribed but a rash developed so treatment was changed to ampicillin, but this also made her unwell. The phlebitis resolved after 2 weeks, but a few days later three tender, red lumps were noticed. The day after admission the pointing abscess was incised and drained, the ulcer curetted, and the right long saphenous vein was ligated high up in the groin. Material from vein, abscess, and ulcer yielded a pure growth of Salmonella heidelberg sensitive to tetracycline, ampicillin, and co-trimoxazole. Tratment with co-trimoxazole was started immediately. No organisms were isolated from blood cultures taken before 2. 3.
Bibel, D. J., Lebrun, J. R. J. invest. Derm. 1975, 64, 119. Christie, A. B. Infectious Diseases; p. 38. Edinburgh, 1974.
201 the antibiotic was given, but faeces were not cultured at that time. A week later the third abscess was drained. No further infection developed. The ulcers began to heal, and 23 days after admission the patient was discharged. Chemotherapy was given for 4 weeks. The most likely sequence of events is that during a gastroenteritis caused by S. heidelberg a bacteraemic phase occurred. A thrombophlebitis was developing at that time, and the bacteria were trapped in the saphenous vein giving rise to the abscesses.
I thank Mr J. E.
Trapnell for his permission to
report this
case.
Public Health Laboratory, Church Lane,
Heavitree,
J. B. KURTZ
Exeter EX2 5AD.
ESCHERICHIA COLI K1
StR,-Bacon and his colleagues’ noted that agglutination tests on
strains of Escherichia coli indicated the presence of K 1
antigen, but this finding was not confirmed by immunoelectrophoresis. In a study which we have been carrying out on the relationship between E. coli Kl antigen and the group-B polysaccharide of Neisseria meningitidis, we have found that it may be difficult to demonstrate antigens in conventional systems. Other workers2 3 have shown that group-B N. meningitidis and E. coli 07:Kl(L):NM share a heat-labile antigen, and in immunodiffusion experiments Grados and Ewing2 showed a line of precipitation between the E. coli OK antiserum and an extract of group-B N. meningitidis. Kasper et al. showed that
molarity of electrolyte in the gel, the reaction became more pronounced, until finally, in agarose gel made with distilled water, not only was there a strong reaction between Kl antigen and Kl antiserum but there was also a reaction of identify between Kl antiserum and pure-group-B meningococcal polysaccharide (see figure). These results not only confirm the immunochemical identity of group-B meningococcal polysaccharide with the Klantigen of E. coli but also explain why the reaction between rabbit antiserum to the KI antigen and Kl and group-B polysaccharides may not have been seen previously in gels because of their electrolyte content. It might also be significant that Kl antisera produced in rabbits are very variable: the serum used in these studies is the most reactive that we have seen. Preliminary experiments show that by using dilute buffer the reaction between pure group-B meningococcal polysaccharide and Kl or group-B meningococcal antiserum in counterimmunoelectrophoresis is enhanced to a degree similar to that seen in ordinary immunodiffusion. This finding has obvious implications for those working with "difficult" antigen/antibody systems.
Group-B meningococcal polysaccharide and goat antiserum group-B N. meningitidis were provided by Dr E. Gotschlich. Department of Laboratory Medicine, Ruchill Hospital,
Glasgow G20
to
R. J. FALLON
9NB.
Research Department, Wellcome Reagents Limited, Wellcome Research Laboratories,
Beckenham,
M. B. MCILLMURRAY
Kent BR3 3BS.
HEREDITARY RECURRENT HÆMATURIA
SIR,-We have seen three
cases
similar
to
the
one
described
by Dr Argianas and others (Oct. 11, p. 715), in which persons of the same family had relapsing painless haematuria. Nothing was found on detailed laboratory and X-ray examinations (including angiography). Nevertheless, follow-up was suggested and one year later epithelioma of the left kidney was detected in
one
of them. Before haematuria is characterised
as
idio-
pathic investigations must be repeated so that other causes which might be missed in the first instance can be definitely excluded.
immunodiffusion using 1% agarose gel in distilled
water.
1. Group-B meningococcal polysaccharide. 2. K1 antigen. 3. Goat antiserum to group-B N. meningitidis. 4. Antiserum to E. coli 07:K1(L)NM.
the
group-specific polysaccharide of group-B N. meningitidis polymer of N-acetyl neuraminic acid immunochemically similar to the polysaccharide K antigen of E. coli 07:K1(L):NM. In diffusion experiments using rabbit antiserum to N. meningitidis groulrB antigen these workers showed that E. coli K1(L) antigen gave a reaction of identity with all of four different lots of N. meningitidis group-B polysaccharide. In view of these findings one of us (M.B.M.) prepared a rabbit antiserum to E. coli Kl antigen. This serum agglutinated both E. coli 07:Kl(L):NM and group-B N. meningitidis. In conventional immunodiffusion tests using 1% agarose in saline (39 g/1), only a weak line developed between Kl antiserum and crudely purified Kl antigen. However, if immunodiffusion tests were modified by decreasing the
was a
1
Bacon, C. J , Kenna, A. P., Ingham, H. R., Gross, R. J., Rowe, B. Lancet, 1975, ii, 1091. 2. Grades, O., Ewing, W. H. J. infect. Dis. 1970, 122, 100. 3 Kasper, D. L., Winkelhake, J. L., Zollinger, W. D., Brandt, B. L., Artenstein, M. S. J. Immun. 1973, 110, 262.
Department of Urology, State General Hospital, of Athens, Greece
C. DIMOPOULOS N. PANAYOTIDES
ŒDEMA IN COR PULMONALE
SIR,-It is twenty years and
more
since I first
wrote
about
pulmonary hypertension in patients with congenital and acquired heart-disease and chronic lung disease: you might reasonably assume that senility has made me foolish enough to comment critically about your comprehensive editorial (Dec. 27, p. 1289). However, I would like to take you to task over the statement that "Despite a raised pulmonary arterial pressure the cardiac output is usually normal, so that the pulmonary vascular resistance is very high". The pulmonary vascular resistance and the pulmonary arterial blood-pressure are raised in anoxic cor pulmonale! but usually not very high when compared with levels seen in patients with congenital septal defects2 and shunt reversal with idiopathic3 or thromboembolic4 pulmonary hypertension, or quite commonly with mitral stenosis. 1 also think that you have put the cart before the horse, and I would suggest that what you were trying to say was: "Despite an increased pulmonary vascular resistance, priWhitaker, W. Q. Jl Med. 1954, 23, 57. Heath, D., Whitaker, W. Br. Heart J. 1957, 19, 327. 3. Thadani, U., Burrow, C., Whitaker, W., Heath, D. Q. Jl
1. 2.
133. 4.
Olley, P. M., Whitaker, W. Br. Heart J. 1967, 29, 369.
Med.
1975, 44,
cimens).
Full details, including viral and bacterial cultures, of the stools from babies in this study will be published later. We thank Dr J. P. Stanfield, Dr I. W. Pinkerton, Dr W. C. Love, Dr 1. D. Riley, and Dr E. G. Fox for allowing us to study patients under their care.
Regional Virus Laboratory and University of Glasgow Department of Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB.
C. R. MADELEY B. P. COSGROVE
clinical applications should be approached cautiously, the public is today being offered many commercial products, such as deodorant soaps, whose medical rationale is the alteration of normal flora. Cosmetics, topical and systemic drugs, and occlusive dressings are other common assaults which may affect resident flora and their environment. It is unfortunate that little regard is apparently being given to environmental monitoring. Dermatoses and their therapy are particular candidates for examination. We should like to add our confirmation2of in-vivo production of a penicillin-like substance by dermatophytes and an increase in penicillin-resistant flora in experimental human dermatophytoses. There was also an increase in total flora, especially in numbers of Staphylococcus epidermidis, but there was no drift toward gram-negative microorganisms.
AMPICILLIN RESISTANCE IN STAPHYLOCOCCI
SIR,—Mr Pollock and Miss Evans (Dec. 20, p. 1251) found that 100% of Staphylococcus aureus isolated from urine speciof hospital
sensitive to ampicillin. Since ampicillin is inactivated by penicillinase this means that all Staph. aureus strains from hospital urine specimens in Scarborough in that year were non-penicillinase producers and thus would have been sensitive to penicillin. This is a very surprising, if not amazing, result, until one realises that a 25 µg strength ampicillin disc was used to test the sensitivity. In my experience it is not possible to show penicillinase production by staphylococci (and hence ampicillin resistance) with any degree of reliability, using a 25 jig ampicillin disc. Many staphylococci which appeared sensitive to ampicillin were proved to be penicillinase-producers when tested with a penicillin G disc (1 µg or 2 [µg strength). For this reason I would suggest that the accuracy of the findings which refer to staphylococci in Pollock and Evans’ report may be
mens
patients
in 1971
Army Institute of Research, Presidio of San Francisco, California 94129, U.S.A. Letterman
J. BIBEL JOSEPH H. GREENBERG DAVID
ROBERT D. KING
were
LEG ABSCESSES CAUSED BY SALMONELLA HEIDELBERG
SIR,—Salmonellæ commonly
cause acute gastroenteritis. frequently they may cause more serious illnesses (i.e., enteric, septicaemia and focal).3 The following case illustrates the latent period between ingestion and illness, and also the host factor responsible for determining the site of infection. A 41-year-old woman was admitted to hospital with abscesses in her right leg, along the course of the long saphenous vein (see figure)--one had broken down, leaving a discharging
Less
questionable. Department of Bacteriology, Royal Infirmary, Glasgow C4.
*t*This letter has been shown whose reply follows.—ED. L.
J. S. CARGILL to
Mr Pollock and Miss Evans
SIR,—taphylococcus aureus accounted for only 7.7% of all inpatient urinary organisms in 1971 and 4.4% in 1974. The use of the 25 µg ampicillin disc for testing sensitivity of bacterial isolates from urine has been standard in this, as in many other hospitals for several years. It is true-as Dr Cargill points out-that a disc of this strength can often overcome the penicillinase produced by Staph. aureus. The use of the higher strength of ampicillin disc is justified by the high concentration of ampicillin (and other antibiotics) found in urine compared with other tissue fluids when the antibiotic is administered in therapeutic doses.
Scarborough Hospital, North Yorkshire.
A. V. POLLOCK MARY EVANS
ANTIBIOSIS IN SKIN FLORA
SIR,-We are encouraged by your editorial,’ for therapeutic of antibiotic skin flora is a long-term goal of our research programme. However, we are concerned that the medical community may drift to superficiality in approaching the concept of bacteriotherapy. One of the reasons why the theory continues to pop in and out of vogue is the lack of appreciation of the ecological complexities involved. Furthermore, antibiosis is merely one ecological interaction of skin microoruse
ganisms. The role of normal flora in natural resistance or predisposition to disease is far from clear. Yet, while you justly warn that 1. Lancet,
1975, ii,
1080.
Medial aspect of right second operation).
thigh showing sites of three
abscesses
(1 week after
ulcer of 2.5 cm diameter; above the knee there was a poinung abscess of 2.5cm diameter, and higher up a larger subcutaneous lump. She had not been well for some time. 9 weeks earlier she had had gastroenteritis during which she had passed some blood per rectum. This settled without treatment. Shortly afterwards she developed thrombophlebitis in the right long saphenous vein. Tetracycline tablets were prescribed but a rash developed so treatment was changed to ampicillin, but this also made her unwell. The phlebitis resolved after 2 weeks, but a few days later three tender, red lumps were noticed. The day after admission the pointing abscess was incised and drained, the ulcer curetted, and the right long saphenous vein was ligated high up in the groin. Material from vein, abscess, and ulcer yielded a pure growth of Salmonella heidelberg sensitive to tetracycline, ampicillin, and co-trimoxazole. Tratment with co-trimoxazole was started immediately. No organisms were isolated from blood cultures taken before 2. 3.
Bibel, D. J., Lebrun, J. R. J. invest. Derm. 1975, 64, 119. Christie, A. B. Infectious Diseases; p. 38. Edinburgh, 1974.
201 the antibiotic was given, but faeces were not cultured at that time. A week later the third abscess was drained. No further infection developed. The ulcers began to heal, and 23 days after admission the patient was discharged. Chemotherapy was given for 4 weeks. The most likely sequence of events is that during a gastroenteritis caused by S. heidelberg a bacteraemic phase occurred. A thrombophlebitis was developing at that time, and the bacteria were trapped in the saphenous vein giving rise to the abscesses.
I thank Mr J. E.
Trapnell for his permission to
report this
case.
Public Health Laboratory, Church Lane,
Heavitree,
J. B. KURTZ
Exeter EX2 5AD.
ESCHERICHIA COLI K1
StR,-Bacon and his colleagues’ noted that agglutination tests on
strains of Escherichia coli indicated the presence of K 1
antigen, but this finding was not confirmed by immunoelectrophoresis. In a study which we have been carrying out on the relationship between E. coli Kl antigen and the group-B polysaccharide of Neisseria meningitidis, we have found that it may be difficult to demonstrate antigens in conventional systems. Other workers2 3 have shown that group-B N. meningitidis and E. coli 07:Kl(L):NM share a heat-labile antigen, and in immunodiffusion experiments Grados and Ewing2 showed a line of precipitation between the E. coli OK antiserum and an extract of group-B N. meningitidis. Kasper et al. showed that
molarity of electrolyte in the gel, the reaction became more pronounced, until finally, in agarose gel made with distilled water, not only was there a strong reaction between Kl antigen and Kl antiserum but there was also a reaction of identify between Kl antiserum and pure-group-B meningococcal polysaccharide (see figure). These results not only confirm the immunochemical identity of group-B meningococcal polysaccharide with the Klantigen of E. coli but also explain why the reaction between rabbit antiserum to the KI antigen and Kl and group-B polysaccharides may not have been seen previously in gels because of their electrolyte content. It might also be significant that Kl antisera produced in rabbits are very variable: the serum used in these studies is the most reactive that we have seen. Preliminary experiments show that by using dilute buffer the reaction between pure group-B meningococcal polysaccharide and Kl or group-B meningococcal antiserum in counterimmunoelectrophoresis is enhanced to a degree similar to that seen in ordinary immunodiffusion. This finding has obvious implications for those working with "difficult" antigen/antibody systems.
Group-B meningococcal polysaccharide and goat antiserum group-B N. meningitidis were provided by Dr E. Gotschlich. Department of Laboratory Medicine, Ruchill Hospital,
Glasgow G20
to
R. J. FALLON
9NB.
Research Department, Wellcome Reagents Limited, Wellcome Research Laboratories,
Beckenham,
M. B. MCILLMURRAY
Kent BR3 3BS.
HEREDITARY RECURRENT HÆMATURIA
SIR,-We have seen three
cases
similar
to
the
one
described
by Dr Argianas and others (Oct. 11, p. 715), in which persons of the same family had relapsing painless haematuria. Nothing was found on detailed laboratory and X-ray examinations (including angiography). Nevertheless, follow-up was suggested and one year later epithelioma of the left kidney was detected in
one
of them. Before haematuria is characterised
as
idio-
pathic investigations must be repeated so that other causes which might be missed in the first instance can be definitely excluded.
immunodiffusion using 1% agarose gel in distilled
water.
1. Group-B meningococcal polysaccharide. 2. K1 antigen. 3. Goat antiserum to group-B N. meningitidis. 4. Antiserum to E. coli 07:K1(L)NM.
the
group-specific polysaccharide of group-B N. meningitidis polymer of N-acetyl neuraminic acid immunochemically similar to the polysaccharide K antigen of E. coli 07:K1(L):NM. In diffusion experiments using rabbit antiserum to N. meningitidis groulrB antigen these workers showed that E. coli K1(L) antigen gave a reaction of identity with all of four different lots of N. meningitidis group-B polysaccharide. In view of these findings one of us (M.B.M.) prepared a rabbit antiserum to E. coli Kl antigen. This serum agglutinated both E. coli 07:Kl(L):NM and group-B N. meningitidis. In conventional immunodiffusion tests using 1% agarose in saline (39 g/1), only a weak line developed between Kl antiserum and crudely purified Kl antigen. However, if immunodiffusion tests were modified by decreasing the
was a
1
Bacon, C. J , Kenna, A. P., Ingham, H. R., Gross, R. J., Rowe, B. Lancet, 1975, ii, 1091. 2. Grades, O., Ewing, W. H. J. infect. Dis. 1970, 122, 100. 3 Kasper, D. L., Winkelhake, J. L., Zollinger, W. D., Brandt, B. L., Artenstein, M. S. J. Immun. 1973, 110, 262.
Department of Urology, State General Hospital, of Athens, Greece
C. DIMOPOULOS N. PANAYOTIDES
ŒDEMA IN COR PULMONALE
SIR,-It is twenty years and
more
since I first
wrote
about
pulmonary hypertension in patients with congenital and acquired heart-disease and chronic lung disease: you might reasonably assume that senility has made me foolish enough to comment critically about your comprehensive editorial (Dec. 27, p. 1289). However, I would like to take you to task over the statement that "Despite a raised pulmonary arterial pressure the cardiac output is usually normal, so that the pulmonary vascular resistance is very high". The pulmonary vascular resistance and the pulmonary arterial blood-pressure are raised in anoxic cor pulmonale! but usually not very high when compared with levels seen in patients with congenital septal defects2 and shunt reversal with idiopathic3 or thromboembolic4 pulmonary hypertension, or quite commonly with mitral stenosis. 1 also think that you have put the cart before the horse, and I would suggest that what you were trying to say was: "Despite an increased pulmonary vascular resistance, priWhitaker, W. Q. Jl Med. 1954, 23, 57. Heath, D., Whitaker, W. Br. Heart J. 1957, 19, 327. 3. Thadani, U., Burrow, C., Whitaker, W., Heath, D. Q. Jl
1. 2.
133. 4.
Olley, P. M., Whitaker, W. Br. Heart J. 1967, 29, 369.
Med.
1975, 44,
