214
position of one patient in the rank order and is thus less impressive than the difference between mean hospital stays of 16 and 30 days that Walesby et al. report, the size of this difference being heavily dependent upon one patient who was in hospital for 59 days. Surgical Unit, St. Mary’s Hospital, London W2
H. A. F. DUDLEY
TREATMENT OF ANAEROBICALLY INFECTED PRESSURE SORES WITH TOPICAL
METRONIDAZOLE
SIR,-Non-sporing anaerobes are commonly present as significant pathogens in infected pressure sores. This is always true for sacral and other decubitus ulcers that develop in close proximity to the anus, but pressure sores at more peripheral sites such as the wrists, elbows, and heels are also frequently subject to anaerobic sepsis. As with other suppurative non-clostridial anaerobic infections these lesions are characterised by their putrid odour. In view of the notable successes achieved with systemic metronidazole in the management of postoperative and other anaerobic sepsis,1-5 we were encouraged to formulate the drug for the topical treatment of these superficial, but often refractory, infections. There do not seem to be any commercial preparations of metronidazole for topical use. Metronidazole (pure powder kindly supplied by May & Baker) was prepared in our hospital pharmacy as a 1% solution (w/v) in 0.6% saline and sterilised by autoclaving at 121 °C for 20 min. The lotion was applied to infected ulcers as a wet dressing. Lesions we have treated in this way include pressure sores in elderly and in chronically ill patients, diabetic ulcers of the feet, and varicose ulcers. We have also used metronidazole irrigation or packs in the management of ischiorectal abscesses, other large abscesses, and of the extensive undermining subcutaneous cavitation that may complicate simple sacral pressure sores. Topical treatment is rapidly effective. Within a few hours patients are no longer malodorous, a condition that eusol and other antimicrobial dressings do little to alleviate. Within 24 h ulcer floors are usually clean and free of cultivable anaerobes, and any surrounding marginal cellulitis is resolving. P. H. JONES A. T. WILLIS I. R. FERGUSON
Public Health Laboratory, Luton and Dunstable Hospital, Luton LU4 0DZ
The patient was a 24-year-old male who had first presented with an ileovesical fistula due to Crohn’s disease of the terminal ileum. This was treated by ileocaecal resection but a few months later he developed fsecal fistulae in the left iliac fossa and left buttock area which on culture grew Klebsiella aerogenes, anaerobic streptococci, and B. fragilis. He was treated by ileocolic bypass but in April, 1974, his fistulae recurred and he was started on metronidazole (800 mg, 6-hourly) with rapid improvement in discharge and health. In August, 1975, the dose was reduced to 400 mg 12-hourly and he remained well with only occasional discharge until November, 1977, when the amount of discharge and fxcal loss from the nstulse suddenly increased. Culture of the pus revealed B. fragilis resistant to metronidazole. He was admitted and a surgical resection of the ascending colon and bypassed distal ileum was performed under antibiotic cover with clindamycin (300 mg 8-hourly). Histology of the resected specimen showed no evidence of residual Crohn’s disease and his recovery was uneventful. This case shows that resistance to metronidazole can develop during long-term therapy. The organism grew on blood agar incubated anaerobically at 370C but not when incubated for 7 days in 10% carbon dioxide plus air, confirming that it was an obligate anaerobe. It was identified as B. fragilis ss fragilis by the criteria of Duerden et al .7 When tested with a 5 fLg metronidazole disc, no zone of inhibition was apparent and the minimum inhibitory concentration, which was determined by inoculating the organism onto blood agar plates containing doubling dilutions of metronidazole, was found to be 70 g/ml. After 16 serial passages on metronidazole-free blood agar the minimum inhibitory concentration was unchanged. While present evidence suggests that short-term metronidazole chemotherapy does not generate anaerobes with significant resistance, long-term therapy may do so. Patients receiving metronidazole for long periods must therefore be monitored. H. R. INGHAM SHEILA EATON C. W. VENABLES Newcastle General Hospital, P. C. ADAMS Newcastle upon Tyne NE4 6BE
IN-VITRO SENSITIVITY TO MECILLINAM OF MULTIRESISTANT GRAM-NEGATIVE RODS
SiR,-Mecillinam is a penicillamic-acid derivative differing significantly from conventional -lactam antibiotics.1,2 To find out its role in hospitals where multiresistant organisms have done routine mecillinam disc diffusion sensitall gram-negative isolates, mainly from midstream or catheter specimens of urines with 20-100 or more pus cells per high-power field, after centrifugation, which showed resistance to any three of five antibiotics commonly used to treat urinary-tract infections. 65 strains (62 from urines and 3 from wound swabs) were examined by the disc diffusion test (25 fLg and 10 g discs of mecillinam for urine and wound swabs, respectively) on DST agar (Oxoid) containing 5% lysed blood using Escherichia coli (NCTC 10418) as the control organism. 25 strains grew up to or within 2 mm of the disc margin (i.e., they were resistant). The organisms were identified by the biochemical reactions using the API system. The minimum inhibitory concentrations (M.LC.S) were determined by the agar incorporation technique using the same medium as above. Pure mecillinam powder was dissolved in sterile water and then further diluted in phosphatebuffered solution (pH 7-2) before incorporation into the agar.
abound,
BACTEROIDES FRAGILIS RESISTANT TO METRONIDAZOLE AFTER LONG-TERM THERAPY
SIR,-Metronidazole is effective in the
treatment
of infec-
tions with
gram-negative, non-sporing, obligate anaerobes, particularly Bacteroides fragilis. Despite the increased clinical of metronidazole, there is little evidence that such bacteria becoming resistant to it. Chardon et a1.6 isolated a strain of B. fragilis resistant to metronidazole from a patient treated with the agent but did not report the minimum inhibitory concentration. Resistance was quickly lost when the strain was subcultured in the absence of metronidazole. We have lately encountered a case in which metronidazole-resistant B. fragilis use
are
appeared during long-term therapy. 1. Study Group J. antimicrob. Chemother. 1975, 2. Study Group Br. med. J. 1977, i, 607. 3. Eykyn, S. J., Phillips, I. ibid. 1976, ii, 1418. 4. Ingham, H. R., Hood, F. J. C., Bradnum, P., 5. 6.
1, 393.
Tharagonnet, D., Selkon, J. B. Br. J. oral Surg. 1977, 14, 264. Ingham, H. R., Selkon, J. B., Roxby, C. M. Br. med. J. 1977, ii, 991. Chardon, H., Ratignier, A., Luneau, R., Garrigues, B. Nouv. Presse méd. 1977, 6, 2165.
ivity
we
tests on
Duerden, B. I., Holbrook, W. P., Collee, J. G., Watt, B. J. appl. Bact. 1976, 40, 163. 1. Greenwood, D., O’Grady, F. J. clin. Path. 1973, 26, 1. 2. Neu, H. C. Antimicrob. Ag. Chemother. 1976, 9, 793.
7.
position of one patient in the rank order and is thus less impressive than the difference between mean hospital stays of 16 and 30 days that Walesby et al. report, the size of this difference being heavily dependent upon one patient who was in hospital for 59 days. Surgical Unit, St. Mary’s Hospital, London W2
H. A. F. DUDLEY
TREATMENT OF ANAEROBICALLY INFECTED PRESSURE SORES WITH TOPICAL
METRONIDAZOLE
SIR,-Non-sporing anaerobes are commonly present as significant pathogens in infected pressure sores. This is always true for sacral and other decubitus ulcers that develop in close proximity to the anus, but pressure sores at more peripheral sites such as the wrists, elbows, and heels are also frequently subject to anaerobic sepsis. As with other suppurative non-clostridial anaerobic infections these lesions are characterised by their putrid odour. In view of the notable successes achieved with systemic metronidazole in the management of postoperative and other anaerobic sepsis,1-5 we were encouraged to formulate the drug for the topical treatment of these superficial, but often refractory, infections. There do not seem to be any commercial preparations of metronidazole for topical use. Metronidazole (pure powder kindly supplied by May & Baker) was prepared in our hospital pharmacy as a 1% solution (w/v) in 0.6% saline and sterilised by autoclaving at 121 °C for 20 min. The lotion was applied to infected ulcers as a wet dressing. Lesions we have treated in this way include pressure sores in elderly and in chronically ill patients, diabetic ulcers of the feet, and varicose ulcers. We have also used metronidazole irrigation or packs in the management of ischiorectal abscesses, other large abscesses, and of the extensive undermining subcutaneous cavitation that may complicate simple sacral pressure sores. Topical treatment is rapidly effective. Within a few hours patients are no longer malodorous, a condition that eusol and other antimicrobial dressings do little to alleviate. Within 24 h ulcer floors are usually clean and free of cultivable anaerobes, and any surrounding marginal cellulitis is resolving. P. H. JONES A. T. WILLIS I. R. FERGUSON
Public Health Laboratory, Luton and Dunstable Hospital, Luton LU4 0DZ
The patient was a 24-year-old male who had first presented with an ileovesical fistula due to Crohn’s disease of the terminal ileum. This was treated by ileocaecal resection but a few months later he developed fsecal fistulae in the left iliac fossa and left buttock area which on culture grew Klebsiella aerogenes, anaerobic streptococci, and B. fragilis. He was treated by ileocolic bypass but in April, 1974, his fistulae recurred and he was started on metronidazole (800 mg, 6-hourly) with rapid improvement in discharge and health. In August, 1975, the dose was reduced to 400 mg 12-hourly and he remained well with only occasional discharge until November, 1977, when the amount of discharge and fxcal loss from the nstulse suddenly increased. Culture of the pus revealed B. fragilis resistant to metronidazole. He was admitted and a surgical resection of the ascending colon and bypassed distal ileum was performed under antibiotic cover with clindamycin (300 mg 8-hourly). Histology of the resected specimen showed no evidence of residual Crohn’s disease and his recovery was uneventful. This case shows that resistance to metronidazole can develop during long-term therapy. The organism grew on blood agar incubated anaerobically at 370C but not when incubated for 7 days in 10% carbon dioxide plus air, confirming that it was an obligate anaerobe. It was identified as B. fragilis ss fragilis by the criteria of Duerden et al .7 When tested with a 5 fLg metronidazole disc, no zone of inhibition was apparent and the minimum inhibitory concentration, which was determined by inoculating the organism onto blood agar plates containing doubling dilutions of metronidazole, was found to be 70 g/ml. After 16 serial passages on metronidazole-free blood agar the minimum inhibitory concentration was unchanged. While present evidence suggests that short-term metronidazole chemotherapy does not generate anaerobes with significant resistance, long-term therapy may do so. Patients receiving metronidazole for long periods must therefore be monitored. H. R. INGHAM SHEILA EATON C. W. VENABLES Newcastle General Hospital, P. C. ADAMS Newcastle upon Tyne NE4 6BE
IN-VITRO SENSITIVITY TO MECILLINAM OF MULTIRESISTANT GRAM-NEGATIVE RODS
SiR,-Mecillinam is a penicillamic-acid derivative differing significantly from conventional -lactam antibiotics.1,2 To find out its role in hospitals where multiresistant organisms have done routine mecillinam disc diffusion sensitall gram-negative isolates, mainly from midstream or catheter specimens of urines with 20-100 or more pus cells per high-power field, after centrifugation, which showed resistance to any three of five antibiotics commonly used to treat urinary-tract infections. 65 strains (62 from urines and 3 from wound swabs) were examined by the disc diffusion test (25 fLg and 10 g discs of mecillinam for urine and wound swabs, respectively) on DST agar (Oxoid) containing 5% lysed blood using Escherichia coli (NCTC 10418) as the control organism. 25 strains grew up to or within 2 mm of the disc margin (i.e., they were resistant). The organisms were identified by the biochemical reactions using the API system. The minimum inhibitory concentrations (M.LC.S) were determined by the agar incorporation technique using the same medium as above. Pure mecillinam powder was dissolved in sterile water and then further diluted in phosphatebuffered solution (pH 7-2) before incorporation into the agar.
abound,
BACTEROIDES FRAGILIS RESISTANT TO METRONIDAZOLE AFTER LONG-TERM THERAPY
SIR,-Metronidazole is effective in the
treatment
of infec-
tions with
gram-negative, non-sporing, obligate anaerobes, particularly Bacteroides fragilis. Despite the increased clinical of metronidazole, there is little evidence that such bacteria becoming resistant to it. Chardon et a1.6 isolated a strain of B. fragilis resistant to metronidazole from a patient treated with the agent but did not report the minimum inhibitory concentration. Resistance was quickly lost when the strain was subcultured in the absence of metronidazole. We have lately encountered a case in which metronidazole-resistant B. fragilis use
are
appeared during long-term therapy. 1. Study Group J. antimicrob. Chemother. 1975, 2. Study Group Br. med. J. 1977, i, 607. 3. Eykyn, S. J., Phillips, I. ibid. 1976, ii, 1418. 4. Ingham, H. R., Hood, F. J. C., Bradnum, P., 5. 6.
1, 393.
Tharagonnet, D., Selkon, J. B. Br. J. oral Surg. 1977, 14, 264. Ingham, H. R., Selkon, J. B., Roxby, C. M. Br. med. J. 1977, ii, 991. Chardon, H., Ratignier, A., Luneau, R., Garrigues, B. Nouv. Presse méd. 1977, 6, 2165.
ivity
we
tests on
Duerden, B. I., Holbrook, W. P., Collee, J. G., Watt, B. J. appl. Bact. 1976, 40, 163. 1. Greenwood, D., O’Grady, F. J. clin. Path. 1973, 26, 1. 2. Neu, H. C. Antimicrob. Ag. Chemother. 1976, 9, 793.
7.
