70 In normal subjects plasma-renin activity is related to the prevailing state of sodium balance 16 ’9 and ranges between 0.5 and 2.0 ng/ml/h in samples collected at noon and when they are receiving a sodium intake of 80-120 mmol/day.2O Higher levels occur after dietary sodium restriction.19 Although both patients studied were receiving low-sodium diets, normal or only moderately raised levels of plasma-renin might have been anticipated since exchangeable sodium and blood-volume were normal. However, plasma-renin levels were enormously increased to 25-50 times those found in normal subjects. There is little doubt therefore that the hypertension in both patients was solely renin-dependent. Buhler et al. 21 showed in a group of patients with hypertension of mixed aetiology that those whose plasma-renin activity was raised responded well to propranolol, whereas those with low levels responded poorly. The response of the blood-pressure was related to the reduction in plasma-renin activity, a finding which was not confirmed by Birkenhager et al. 22 who studied a group of patients with essential hypertension and failed to find such a relationship. Differences such as these may be due in part to different patient selection and the probability remains that certain groups of hypertensive patients with raised plasma-renin levels, such as those described here, may respond particularly well to p-blocking drugs with dramatic falls in both plasma-renin and blood-pressure. The highly significant correlation between mean arterial pressure and plasmarenin in patient 1 suggests that the fall in blood-pressure induced by propranolol was mediated via its effect upon renin release. Most patients with malignant hypertension and hypertension associated with chronic renal failure have angiotensin n levels above the normal range when related to exchangeable odium. 16 In these cases p-blocking drugs may lower blood-pressure by inhibiting renal renin release rather than by central inhibition of sympathetic outflow.23 It would be of interest to study in patients with chronic renal failure the effect of other -blocking drugs such as pindolol, which has been shown to lower the blood-pressure of patients with normal or only slightly impaired renal function without lowering plasma-renin.24 If pindolol failed to lower blood-pressure in patients with chronic renal failure one might conclude that in this situation only those -blocking drugs which interfered with renin release would be effective
hypotensive agents. In both patients the administration of propranolol radically changed the course of their progress. Bloodpressure remained under good control, severe postural hypotension during dialysis ceased, weight-gain occurred (patient 1, 15 kg; patient 2, 6 kg) and a feeling of wellbeing returned. Finally, the use of this drug obviated the need for either patient to undergo bilateral nephrectomy. It is suggested therefore that patients receiving dialysis treatment and whose blood-pressure remains refractory despite the removal of sodium and water should be given a trial of propranolol before bilateral nephrectomy is considered. Requests for reprints should
be addressed
to
F.
J. G.
BACTEROIDES: AN UNUSUAL CAUSE OF BREAST ABSCESS
J. E. HALE
R. M. PERINPANAYAGAM G. SMITH
Departments of Surgery and Bacteriology, Westminster and Queen Mary’s Hospitals, London Three cases of breast abscess from which the non-sporing anaerobe Bacteroides was isolated are described. This organism has apparently not previously been reported as a cause of abscess in a breast without underlying malignancy.
Summary
Case-reports FIRST CASE
45-year old nulliparous woman complained of a painful left breast. Examination revealed an irregular lobulated swelling beneath the nipple, and mammography showed an ill-defined density but no evidence of malignancy. A giant fibroadenoma was diagnosed, but at operation an abscess containing foul-smelling pus was found. Culture yielded a pure growth of Bacteroidesfragilis, sensitive to clindamycin and erythromycin, resistant to penicillin and tetracycline. During the ensuing weeks a foul discharge persisted, so clindamycin 300 mg was given four times daily for ten days. This had little effect, and B. fragilis with sensitivities similar to the original isolate was cultured on numerous occasions. Metronidazole 200 mg thrice daily was substituted for the clindamycin. This resulted in rapid improvement with loss of tenderness, but an inA
Dathan, J. R. E., Johnson, D. B., Goodwin, F. J. Clin. Sci. molec. Med. 1973, 45, 77. 2. Goodwin, F. J., Dathan, J. R. E., Greenwood, R. H., Ledingham, J. M. Proc. Int. Congr. Nephrol. 1972, 3, 81. 3. Blumberg, A., Nelp, W. B., Hegstrom, R. M., Scribner, B. H. Lancet, 1967, ii, 69. 4. Vertes, V., Cangiano, J. L., Berman, L. B., Gould, A. New Engl. J. Med. 1969, 280, 978. 5. Wilkinson, R., Scott, D. F., Uldhall, P. R., Kerr, D. N. S., Swinney, J. Q. Jl Med. 1970, 39, 377. 6. Onesti, G., Swartz, C., Ramirez, O., Brest, A. N. Trans. Am. Soc. artif. intern. Organs, 1968, 14, 361. 7. Kolff, W. J., Nakamoto, S., Poutasse, E. F., Straffon, R. A., Figueroa, J. E. Circulation, 1964, 30, suppl. n, 23. 8. Schupak, E., Sullivan, J. F., Lee, D. Y. Ann. intern. Med. 1967, 67, 708. 9. Medina, A., Bell, P. R. F., Briggs, J. D., Brown, J. J., Fine, A., Lever, A. F., Morton, J. J., Paton, A. M., Robertson, J. I. S., Tree, M., Waite, M. A., Weir, R., Winchester, J. Br. med. J. 1972, iv, 694. 10. Ledingham, J. M. J. R. Coll. Physns, 1971, 5, 103. 11. Brown, J. J., Dusterdieck, G., Fraser, R., Lever, A. F., Robertson, J. I. S., Tree, M., Weir, R. J. Br. med. Bull. 1971, 27, 128. 12. Rao, T. K. S., Manis, T., Delano, G., Friedman, E. A. Trans. Am. Soc. artif. intern. Organs, 1973, 19, 340. 13. Winer, N., Chokshi, D. S., Yoon, M. S., Freedman, A. D. J. clin. Endocr. Metab. 1969, 29, 1168. 14. Michelakis, A. M., McAllister, R. G. ibid. 1972, 34, 386. 15. Assaykeen, T. A., Clayton, P. L., Goldfien, A., Ganong, W. F. Endocrinology, 1970, 87, 1318. 16. Davies, D. L., Beevers, D. G., Briggs, J. D., Medina, A. M., Robertson, J. I. S., Schalekamp, M. A., Brown, J. J., Lever, A. F., Morton, J. J., Tree, M. Lancet, 1973, i, 683. 17. Nadler, S. B., Hidalgo, J. U., Bloch, T. Surgery, 1962, 51, 224. 18. Nicholson, J. P., Zilva, J. F. Clin. Sci. 1964, 27, 97. 19. Ledingham, J. G. G., Bull, M. B., Laragh, J. H. Circulation Res. 1967, 21, 1.
suppl. ii, 177. 20. Newton, M. A., Laragh, J. K. J. clin. Endocr. Metab. 1968, 28, 1006. 21. Bühler, F. R., Laragh, J. H., Baer, L., Vaughan, E. D., Brunner, H. R. New Engl. J. Med. 1972, 287, 1209. 22. Birkenhäger, W. H., Krauss, X. H., Schalekamp, M. A. D. H., Kolsters, G., Kroon, B. J. M. Folia med. neerl. 1971, 14, 67. 23. Lewis, P. J., Myers, M. G., Reid, J. L., Dollery, C. T. New Engl. J. Med 1973, 288, 689. 24. Stokes, G. S., Weber, M. A., Thornell, I. R. Br. med. J. 1974, i, 60.
71
termittent serous discharge persisted. The sinus was therefore excised, and the wound healed by granulation. The excised tissue, like the serous discharge, produced no bacterial growth. SECOND CASE
21-year-old nulliparous woman was admitted with right breast abscess. There was a past history of recurrent abscesses of the same breast discharging sterile pus, the last occasion being two years previously. Foul-smelling pus was obtained following incision on this occasion, and, the significance of this being realised, the specimen was sent to the laboratory with minimum delay. Culture yielded a pure growth of a Bacteroides species which because of its colonial and microscopic morphology and its sensitivity pattern was almost certainly B. fragilis. No antibiotics were given, but, after an infected nipple fistula was excised, the wound healed; and the patient A
a
remains well six months later. THIRD CASE
A 22-year-old nulliparous woman had had breast abscess drained, from which no bacterial
a
left
growth
obtained. The breast remained painful, and, on reexploration two months later, a large volume of foulsmelling pus, yielding a pure growth of B. melaninogenicus, sensitive to penicillin, tetracycline,
was
erythromycin, and clindamycin, was released. No antibiotics were given, and the patient has remained well. Discussion
Bacteroides spp. were first recognised as pathogens in 1897. Since then isolation of this group of organisms has been reported in various types of inflammation,l-3 but it is only recently that its importance as a significant cause of postoperative wound sepsis has been widely appreciated. Improved methods for the isolation of this fastidious group of anaerobic organisms and better care in collection and transfer of specimens to the laboratory 4 account for this increased recognition. Leigh et awl. reported that Bacteroides was a major cause of wound infection following intestinal surgery, and Chow et al.5 reported similar results after surgery in the genitourinary tract. Clarke et al. reviewing 174 cases of wound infection due to B. fragilis, found that three-quarters of the isolates came from the abdominal and perineal areas. In only 1 patient in their series was B. fragilis responsible for a breast abscess, which occurred in association with an underlying breast carcinoma. The isolation of this organism from a breast abscess in 3 patients without any underlying disease or history of recent operation emphasises that it may also be the cause of sepsis in less well recognised sites. Anaerobic organisms have been found to be responsible for 10% of bacteraemia in a general hospital. The colon, vagina, and oropharynx are sites where B. fragilis is present in large numbers and a transient B. fragilis bacterxmia without symptoms has been reported after sigmoidoscopy.8 Our second patient had a sigmoidoscopy nine months before her most recent admission, but the long interval between the examination and development of the last abscess makes any association unlikely. Possibly the oropharynx of a sexual partner might have been the source of the organism, and it is note-
worthy that all our patients were engaged to be married. A survey of aspiration pneumonia incriminated B./ra7!
in 17% of cases,9 and there is now an increased awareness of the numerical dominance of anaerobes among the indigenous bacterial inhabitants of mucosal surfaces. The presence of foul-smelling pus’° in a wound infection suggests the presence of non-sporing anaerobes, and, provided a good liaison exists between the clinician and microbiologist, B. fragilis and indeed other Bacteroides species should now be isolated more often by modern anaerobic methods of isolation.9 Specimens of pus rather than swabs should be obtained and examined with a minimum of delay. Treatment of wound infections due to B. fragilis involves drainage of pus, and appropriate antibiotics, but the anaerobe is rarely sensitive to the commonly prescribed agents such as penicillin or the aminoglycoside groups of drugs. Tetracycline has been used with success in the past, but recent reports indicate a substantial degree of resistance.l 12 Tetracycline has since been superseded by lincomycin and clindamycin which have been considered the drugs of choice in the treatment of infections with Bacteroides species. It was therefore somewhat surprising that clindamycin produced no apparent improvement in our first patient, though it was .given in adequate dosage and with surgical drainage. The patient was then given oral metronidazole, which is now recognised to be effective in non-clostridial anaerobic infections.’3 But, although the organism was eliminated, further surgical drainage was necessary. Nobles14 has emphasised the importance of concurrent
drainage. Recently metronidazole has been used prophylactically in gynaecological surgery15 and appendicectomiesl6 with a significant reduction in postoperative infections. A preliminary study has shown that it may be administered safely by the intravenous17 and rectal routesl6 Once a large number of patients has been studied and the drug is widely available for systemic use, metronidazole will probably supersede lincomycin and clindamycin in the treatment of infections with non-sporing anaerobes because of the now well-recognised complication of pseudomembranous colitisl8 associated with these latter drugs. to
We thank Prof. Harold Ellis and Mr A. G. Rutter for publish these cases.
Requests for reprints should be addressed to J. Hospital, Roehampton, London SW15 5PN.
E.
permission
H., Queen Mary’s
REFERENCES
1. Gillespie, W. A., Guy, J. Lancet, 1956, i, 1039. 2. Gunn, A. A. Jl R. Coll. Surg. Edinb. 1956. 2, 41. 3. Stokes, E. J. Lancet, 1958, i, 668. 4. Leigh, D. A., Simmons, K., Norman, E. J. clin. Path. 1974, 27, 997. 5. Chow, A. W., Marshall, J. R., Guze, L. B. Obstetl. gynec. Surv. 1975, 30, 477. 6. Clarke, L. P., Marshall, H. A., Ackerman, N. B. Surgery Gynec. Obstet. 1974, 138, 562. 7. Wilson, W. R., Martin, W. J., Wilkowski, C. J., Washington, J. A. Mayo Clin. Proc. 1972, 47, 639. 8. Lefrock, J. L., Ellis, C. A., Turchik, J. B., Weinstein, L. New Engl. J. Med. 1973, 289, 467. 9 Bartlett, J. G., Gorbach, S. L., Thadepall, H., Finegold, S. M., Lancet,
1974, i, 338. Altemeier, W. A. Ann. Surg. 1938, 107, 634. Kislak, J. W. J. infect. Dis. 1972, 125, 295. Okubadejo, O. A , Green, P. J., Payne, D. J. H. Br. med. J. 1973, ii, 2, 212. Nastro, L. J., Finegold, S. M. J. infect. Dis. 1972, 126, 103. 14. Nobles, E. R. Ann. Surg. 1973, 177, 601. 15. Report by a Study Group. Lancet, 1974, ii, 1540. 16. Willis, A. T., Ferguson, J. R., Jones, P. H., et al. Br. med. J. 1976, i, 318. 17. Ingham, H. R., Rich, G. E., Selkon, J. B., et al. J. antimicr. Chemother. 1975, 1, 235. 18. Smart, R. F, Ramsden, D. A, Gear, M. W. L., Nicol, A, Lennox, W. M. Br. J. Surg. 1976, 63, 25 10. 11. 12. 13.
hypotensive agents. In both patients the administration of propranolol radically changed the course of their progress. Bloodpressure remained under good control, severe postural hypotension during dialysis ceased, weight-gain occurred (patient 1, 15 kg; patient 2, 6 kg) and a feeling of wellbeing returned. Finally, the use of this drug obviated the need for either patient to undergo bilateral nephrectomy. It is suggested therefore that patients receiving dialysis treatment and whose blood-pressure remains refractory despite the removal of sodium and water should be given a trial of propranolol before bilateral nephrectomy is considered. Requests for reprints should
be addressed
to
F.
J. G.
BACTEROIDES: AN UNUSUAL CAUSE OF BREAST ABSCESS
J. E. HALE
R. M. PERINPANAYAGAM G. SMITH
Departments of Surgery and Bacteriology, Westminster and Queen Mary’s Hospitals, London Three cases of breast abscess from which the non-sporing anaerobe Bacteroides was isolated are described. This organism has apparently not previously been reported as a cause of abscess in a breast without underlying malignancy.
Summary
Case-reports FIRST CASE
45-year old nulliparous woman complained of a painful left breast. Examination revealed an irregular lobulated swelling beneath the nipple, and mammography showed an ill-defined density but no evidence of malignancy. A giant fibroadenoma was diagnosed, but at operation an abscess containing foul-smelling pus was found. Culture yielded a pure growth of Bacteroidesfragilis, sensitive to clindamycin and erythromycin, resistant to penicillin and tetracycline. During the ensuing weeks a foul discharge persisted, so clindamycin 300 mg was given four times daily for ten days. This had little effect, and B. fragilis with sensitivities similar to the original isolate was cultured on numerous occasions. Metronidazole 200 mg thrice daily was substituted for the clindamycin. This resulted in rapid improvement with loss of tenderness, but an inA
Dathan, J. R. E., Johnson, D. B., Goodwin, F. J. Clin. Sci. molec. Med. 1973, 45, 77. 2. Goodwin, F. J., Dathan, J. R. E., Greenwood, R. H., Ledingham, J. M. Proc. Int. Congr. Nephrol. 1972, 3, 81. 3. Blumberg, A., Nelp, W. B., Hegstrom, R. M., Scribner, B. H. Lancet, 1967, ii, 69. 4. Vertes, V., Cangiano, J. L., Berman, L. B., Gould, A. New Engl. J. Med. 1969, 280, 978. 5. Wilkinson, R., Scott, D. F., Uldhall, P. R., Kerr, D. N. S., Swinney, J. Q. Jl Med. 1970, 39, 377. 6. Onesti, G., Swartz, C., Ramirez, O., Brest, A. N. Trans. Am. Soc. artif. intern. Organs, 1968, 14, 361. 7. Kolff, W. J., Nakamoto, S., Poutasse, E. F., Straffon, R. A., Figueroa, J. E. Circulation, 1964, 30, suppl. n, 23. 8. Schupak, E., Sullivan, J. F., Lee, D. Y. Ann. intern. Med. 1967, 67, 708. 9. Medina, A., Bell, P. R. F., Briggs, J. D., Brown, J. J., Fine, A., Lever, A. F., Morton, J. J., Paton, A. M., Robertson, J. I. S., Tree, M., Waite, M. A., Weir, R., Winchester, J. Br. med. J. 1972, iv, 694. 10. Ledingham, J. M. J. R. Coll. Physns, 1971, 5, 103. 11. Brown, J. J., Dusterdieck, G., Fraser, R., Lever, A. F., Robertson, J. I. S., Tree, M., Weir, R. J. Br. med. Bull. 1971, 27, 128. 12. Rao, T. K. S., Manis, T., Delano, G., Friedman, E. A. Trans. Am. Soc. artif. intern. Organs, 1973, 19, 340. 13. Winer, N., Chokshi, D. S., Yoon, M. S., Freedman, A. D. J. clin. Endocr. Metab. 1969, 29, 1168. 14. Michelakis, A. M., McAllister, R. G. ibid. 1972, 34, 386. 15. Assaykeen, T. A., Clayton, P. L., Goldfien, A., Ganong, W. F. Endocrinology, 1970, 87, 1318. 16. Davies, D. L., Beevers, D. G., Briggs, J. D., Medina, A. M., Robertson, J. I. S., Schalekamp, M. A., Brown, J. J., Lever, A. F., Morton, J. J., Tree, M. Lancet, 1973, i, 683. 17. Nadler, S. B., Hidalgo, J. U., Bloch, T. Surgery, 1962, 51, 224. 18. Nicholson, J. P., Zilva, J. F. Clin. Sci. 1964, 27, 97. 19. Ledingham, J. G. G., Bull, M. B., Laragh, J. H. Circulation Res. 1967, 21, 1.
suppl. ii, 177. 20. Newton, M. A., Laragh, J. K. J. clin. Endocr. Metab. 1968, 28, 1006. 21. Bühler, F. R., Laragh, J. H., Baer, L., Vaughan, E. D., Brunner, H. R. New Engl. J. Med. 1972, 287, 1209. 22. Birkenhäger, W. H., Krauss, X. H., Schalekamp, M. A. D. H., Kolsters, G., Kroon, B. J. M. Folia med. neerl. 1971, 14, 67. 23. Lewis, P. J., Myers, M. G., Reid, J. L., Dollery, C. T. New Engl. J. Med 1973, 288, 689. 24. Stokes, G. S., Weber, M. A., Thornell, I. R. Br. med. J. 1974, i, 60.
71
termittent serous discharge persisted. The sinus was therefore excised, and the wound healed by granulation. The excised tissue, like the serous discharge, produced no bacterial growth. SECOND CASE
21-year-old nulliparous woman was admitted with right breast abscess. There was a past history of recurrent abscesses of the same breast discharging sterile pus, the last occasion being two years previously. Foul-smelling pus was obtained following incision on this occasion, and, the significance of this being realised, the specimen was sent to the laboratory with minimum delay. Culture yielded a pure growth of a Bacteroides species which because of its colonial and microscopic morphology and its sensitivity pattern was almost certainly B. fragilis. No antibiotics were given, but, after an infected nipple fistula was excised, the wound healed; and the patient A
a
remains well six months later. THIRD CASE
A 22-year-old nulliparous woman had had breast abscess drained, from which no bacterial
a
left
growth
obtained. The breast remained painful, and, on reexploration two months later, a large volume of foulsmelling pus, yielding a pure growth of B. melaninogenicus, sensitive to penicillin, tetracycline,
was
erythromycin, and clindamycin, was released. No antibiotics were given, and the patient has remained well. Discussion
Bacteroides spp. were first recognised as pathogens in 1897. Since then isolation of this group of organisms has been reported in various types of inflammation,l-3 but it is only recently that its importance as a significant cause of postoperative wound sepsis has been widely appreciated. Improved methods for the isolation of this fastidious group of anaerobic organisms and better care in collection and transfer of specimens to the laboratory 4 account for this increased recognition. Leigh et awl. reported that Bacteroides was a major cause of wound infection following intestinal surgery, and Chow et al.5 reported similar results after surgery in the genitourinary tract. Clarke et al. reviewing 174 cases of wound infection due to B. fragilis, found that three-quarters of the isolates came from the abdominal and perineal areas. In only 1 patient in their series was B. fragilis responsible for a breast abscess, which occurred in association with an underlying breast carcinoma. The isolation of this organism from a breast abscess in 3 patients without any underlying disease or history of recent operation emphasises that it may also be the cause of sepsis in less well recognised sites. Anaerobic organisms have been found to be responsible for 10% of bacteraemia in a general hospital. The colon, vagina, and oropharynx are sites where B. fragilis is present in large numbers and a transient B. fragilis bacterxmia without symptoms has been reported after sigmoidoscopy.8 Our second patient had a sigmoidoscopy nine months before her most recent admission, but the long interval between the examination and development of the last abscess makes any association unlikely. Possibly the oropharynx of a sexual partner might have been the source of the organism, and it is note-
worthy that all our patients were engaged to be married. A survey of aspiration pneumonia incriminated B./ra7!
in 17% of cases,9 and there is now an increased awareness of the numerical dominance of anaerobes among the indigenous bacterial inhabitants of mucosal surfaces. The presence of foul-smelling pus’° in a wound infection suggests the presence of non-sporing anaerobes, and, provided a good liaison exists between the clinician and microbiologist, B. fragilis and indeed other Bacteroides species should now be isolated more often by modern anaerobic methods of isolation.9 Specimens of pus rather than swabs should be obtained and examined with a minimum of delay. Treatment of wound infections due to B. fragilis involves drainage of pus, and appropriate antibiotics, but the anaerobe is rarely sensitive to the commonly prescribed agents such as penicillin or the aminoglycoside groups of drugs. Tetracycline has been used with success in the past, but recent reports indicate a substantial degree of resistance.l 12 Tetracycline has since been superseded by lincomycin and clindamycin which have been considered the drugs of choice in the treatment of infections with Bacteroides species. It was therefore somewhat surprising that clindamycin produced no apparent improvement in our first patient, though it was .given in adequate dosage and with surgical drainage. The patient was then given oral metronidazole, which is now recognised to be effective in non-clostridial anaerobic infections.’3 But, although the organism was eliminated, further surgical drainage was necessary. Nobles14 has emphasised the importance of concurrent
drainage. Recently metronidazole has been used prophylactically in gynaecological surgery15 and appendicectomiesl6 with a significant reduction in postoperative infections. A preliminary study has shown that it may be administered safely by the intravenous17 and rectal routesl6 Once a large number of patients has been studied and the drug is widely available for systemic use, metronidazole will probably supersede lincomycin and clindamycin in the treatment of infections with non-sporing anaerobes because of the now well-recognised complication of pseudomembranous colitisl8 associated with these latter drugs. to
We thank Prof. Harold Ellis and Mr A. G. Rutter for publish these cases.
Requests for reprints should be addressed to J. Hospital, Roehampton, London SW15 5PN.
E.
permission
H., Queen Mary’s
REFERENCES
1. Gillespie, W. A., Guy, J. Lancet, 1956, i, 1039. 2. Gunn, A. A. Jl R. Coll. Surg. Edinb. 1956. 2, 41. 3. Stokes, E. J. Lancet, 1958, i, 668. 4. Leigh, D. A., Simmons, K., Norman, E. J. clin. Path. 1974, 27, 997. 5. Chow, A. W., Marshall, J. R., Guze, L. B. Obstetl. gynec. Surv. 1975, 30, 477. 6. Clarke, L. P., Marshall, H. A., Ackerman, N. B. Surgery Gynec. Obstet. 1974, 138, 562. 7. Wilson, W. R., Martin, W. J., Wilkowski, C. J., Washington, J. A. Mayo Clin. Proc. 1972, 47, 639. 8. Lefrock, J. L., Ellis, C. A., Turchik, J. B., Weinstein, L. New Engl. J. Med. 1973, 289, 467. 9 Bartlett, J. G., Gorbach, S. L., Thadepall, H., Finegold, S. M., Lancet,
1974, i, 338. Altemeier, W. A. Ann. Surg. 1938, 107, 634. Kislak, J. W. J. infect. Dis. 1972, 125, 295. Okubadejo, O. A , Green, P. J., Payne, D. J. H. Br. med. J. 1973, ii, 2, 212. Nastro, L. J., Finegold, S. M. J. infect. Dis. 1972, 126, 103. 14. Nobles, E. R. Ann. Surg. 1973, 177, 601. 15. Report by a Study Group. Lancet, 1974, ii, 1540. 16. Willis, A. T., Ferguson, J. R., Jones, P. H., et al. Br. med. J. 1976, i, 318. 17. Ingham, H. R., Rich, G. E., Selkon, J. B., et al. J. antimicr. Chemother. 1975, 1, 235. 18. Smart, R. F, Ramsden, D. A, Gear, M. W. L., Nicol, A, Lennox, W. M. Br. J. Surg. 1976, 63, 25 10. 11. 12. 13.
