Scandinavian Journal of Infectious Diseases
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Treatment of Anaerobic Infections with Metronidazole Bertil Christensson, Sven Årke Hedström & Bo Ursing To cite this article: Bertil Christensson, Sven Årke Hedström & Bo Ursing (1979) Treatment of Anaerobic Infections with Metronidazole, Scandinavian Journal of Infectious Diseases, 11:1, 69-72, DOI: 10.3109/inf.1979.11.issue-1.11 To link to this article: http://dx.doi.org/10.3109/inf.1979.11.issue-1.11
Published online: 02 Jan 2015.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd19 Download by: [RMIT University Library]
Date: 17 March 2016, At: 01:58
Scand J Infect Dis 11: 69-72, 1979
Treatment of Anaerobic Infections with Metronidazole BERTIL CHRISTENSSON, S V E N A K E HEDSTROM a n d BO URSING From the Department of Infectioirs Diseases, University Hospital, Lund, Sweden
Downloaded by [RMIT University Library] at 01:58 17 March 2016
ABSTRACT. Metronidazole (Flagyl@),a compound widely used in man with minimal side-effects, has been used in the treatment of anaerobic infections caused by Bacteroides fragilis and other Bacteroides species. Seven patients were treated and all were restored to full health. Four of them did not respond to lincomycin or clindamycin which so far have been the drugs of choice against anaerobic infections. The reasons for the good results during metronidazole therapy such as the good penetration through the blood/brain barrier and into abscess cavities are discussed.
INTRODUCTION Metronidazole has been used for several years for the treatment of various parasitic infestations (1, 2, 6) a n d Vincent’s stomatitis (10). It has also proved to have a bactericidal effect on most anaerobic organisms (7, 11, 12) a n d has been reported t o b e useful in anaerobic infections (5, 9, 14). Furthermore an effect in Crohn’s disease has been suggested (15). P A T I E N T S A N D METHODS During the last 2 years we have successfully treated 12 patients suffering from suspected anaerobic infections with metronidazole (FlagyP). The drug has been given orally. In 5 of these cases the result of treatment could not be surely evaluated because of lack of bacteriological diagnosis or insufficient and additional chemotherapy. Thus, the study group reported here consists of 7 patients, 6 women and 1 man. Anaerobic cultures were performed according to the routine at the Medical Microbiological Laboratory, University Hospital, Lund. Sensitivity tests for anaerobic bacteria were not done. C A S E REPORTS Case I A 62-year-old man with a perforated diverticulitis of colon was treated with chloramphenicol, gentamicin and ampicillin. Five months later a resection of the sigmoideum was done and 2 months later a cholecystectomy. The last operation was complicated by a bile fistula and sepsis. Blood cultures were negative, but culture from the fistula showed Bacteroides fragilis, Proteus vulgaris, Escherichia coli,. Klebsiella pneumoniae and enterococci. The ESR was 91 mmlh and hemoglobin 89 gll. Electrophoretic acute phase reactants were very high. Before the result of culture was obtained, he was treated with cephalothin and ampicillin for 13 days without effect.
The therapy was changed to gentamicin and lincomycin which he received for 24 days without effect on the clinical state. He was then given chloramphenicol for 10 days without improvement, still having symptoms as high septic fever and discharge from several abdominal fistulas. The treatment was finally changed to metronidazole 400 mg 3 times a day for 1 week and thereafter 200 mg 3 times a day for 2 months. During treatment with metronidazole the patient became afebrile, the pus secretion from the fistulas diminished and cultures were negative. During 3 weeks he received gentamicin in dextran solution locally in the fistula. Two months after instituting metronidazole the fistula was completely healed and the drug could be discontinued. The patient was afebrile, ESR was 27 mmlh and hemoglobin 123 g/l. At a check-up 1 month later he showed no signs of infection. Case 2 A 34-year-old woman fell ill with abdominal pain and fever. Laparascopy revealed a right-sided pyosalpinx and she was treated with phenoxymethylpenicillin for 5 days and thereafter with doxycycline for another 5 days. ESR was 114 mmlh and hemoglobin 117 g/l. The temperature was still elevated and an abscess developed. A drainage of an appendico-tubo-ovarial abscess was done. Cultures from the cavity grew B. fragilis and E. coli. She received successful gentamicin and clindamycin therapy for 8 days and then cephalexin and clindamycin for one month. One week after terminating antibiotic treatment she had a relapse. The body temperature rose and in the right pelvis a tender mass developed corresponding to the previous abscess. ESR was 15 mmlh and hemoglobin 130 gll. Blood culture was not performed. Treatment with metronidazole was instituted, 400 mg 3 times a day for 5 days, thereafter 200 mg 3 times a day for 5 weeks. In 24 h the patient was afebrile, her clinical state improved and the mass gradually diminished. At a check-up 1 month after the end of metronidazole therapy no resistance was palpable. ESR was 11 mmlh. Case 3 A 25-year-old woman developed a suspected intrauterine ‘infection during the last month of pregnancy. A caesarean
Downloaded by [RMIT University Library] at 01:58 17 March 2016
70
B . Christensson et (11.
section was performed. Because of fever and suspected infection she was treated with clindamycin for 1 week postoperatively. Due to diarrhea the treatment was changed to trimethoprim-sulphamethoxazole for 2 weeks. One month after the operation she had a relapse with high fever, abdominal pains and putrid discharge from the cervix. The examination showed a tender uterus and the clinical picture was considered an endometritis. The body temperature was 39.6"C, ESR 109 mmlh and hemoglobin I12 g/l. In 4 blood cultures there was growth of B. fragilis. Initially she was treated with doxycycline and lincomycin for 6 days. No effect was seen and the treatment was changed to metronidazole 400 mg 3 times a day for 1 week and then 200 mg 3 times a day for 16 days. After 4 days of treatment she was afebrile. The abdominal symptoms subsided in a week after institution of therapy. One month later she was well and the metronidazole was discontinued. The ESR was 16 mmlh and hemoglobin 124 gll. Case 4
A 49-year-old woman had abdominal pains and dysuria for 2 weeks and later on fever. ESR was 108 mmlh and hemoglobin 122 g/l. A laparascopy showed a pelviperitonitis, acute salpingitis and bilateral sactosalpinx. No culture was performed. There was a temporary improvement during 13 days of treatment with doxycycline and a simultaneous treatment with tinidazole (Fasigyn@)2 g daily for 4 days which was given for trichomonas infection. However, 1 week later her condition deteriorated with high fever and abdominal pains. A bilateral salpingo-oophorectomy was performed. Cultures from the Douglas cavity showed growth of B. fragilis and E. coli. The temperature was still elevated. The ESR was 115 mmlh and hemoglobin 108 gll. Blood culture was not performed. Treatment with lincomycin and gentamicin for 1 week and thereafter doxycycline for 1 week had no effect on the fever. She then received cephalexin in low doses for another week without effect. Metronidazole was added to the treatment in a dose of 400 mg 3 times a day for I week. The temperature normalized in 2 days. The ESR was then 100 mmlh and hemoglobin 110 g/l. At a check-up 5 months later she was in a very good condition. No further culture was performed. Cusp 5
A 45-year-old woman with tetraplegia and chronic bacteriuria developed a suspected urosepsis. However, cultures from urine and blood were negative. On admission she had a sacral decubital wound with a diameter of 3 cm, from which cultures showed B. fragilis, Peptococcus anaerobicus, Fusobacterium and Staphylococcus aureus. ESR was 95 mmlh and hemoglobin 115 g/l. She was initially treated with gentamicin and carbenicillin for about a week without effect. Chloramphenicol in dextran solution was instituted locally but she still had fever. Therefore metronidazole 200 mg 3 times a day was added. She improved rapidly and became afebrile. The discharge diminished and cultures from the wound were negative 2 weeks later. The metronidazole treatment was given for 1 month. After an excision of the decubital wound a primary suture was done without postoperative complications. She
was checked 14 months later and was still in good condition. Case 6
A 19-year-old woman provoked an abortion in 7th month of pregnancy by thumping herself in the hypogastrium daily for 2 weeks. The abortion was complicated by a symphyseolysis, septic fever and signs of endometritis. The blood cultures showed Staph, epidermidis in repeated samples, probably a contamination. Cultures from urine showed growth of E. coli. The patient was treated with ampicillin, benzylpenicillin, tetracycline and cloxacillin in varying combinations during 2 weeks. No obvious improvement was seen and the fever continued. She developed a septic thrombosis and a local suprapubic abscess. The abscess was punctured and the cultures showed growth of B. melaninogenicus and gamma-streptococci. Before the result of culture was known she was treated with lincomycin and trimethoprim-sulphamethoxazolefor 5 days without effect. The fever continued. The ESR was 105 mmlh and the hemoglobin was I l l g/l. Then metronidazole 400 mg 3 times a day was given for I week followed by 200 mg 3 times a day for 6 weeks. Metronidazole showed an effect on the fever in 24 h and the abcess diminished in size. At a check up 1 month later she was completely restored. The ESR was 25 mm/h and hemoglobin 132 g/l. X-ray showed no signs of osteitis and the symphyseolysis was reduced. Case 7
A 6-month-old girl developed bacterial meningitis. The entrance of the infection was a fistula under a sacral naevus and an occult spina bifida. She was initially treated with chloramphenicol, sulphonamide and benzylpenicillin without effect on the fever or the clinical state. Cultures from CSF showed, however, a mixed flora with bacteroides species, anaerobic streptococci, Enterobacter cloacae and Staph. aureus and the treatment was changed to metronidazole in combination with lincomycin. During the 1st month the child received 100 mg of metronidazole 3 times a day and then 50 mg 3 times a day for another 6 weeks. During this treatment the body temperature gradually normalized and her general condition improved The culture from CSF became negative and ESR fell to 7 mmlh. During the antibiotic therapy an excision of the sacral epidural fistula was done without postoperative complications and all antibiotics could be discontinued. The child has been restored to full health.
RESULTS Of the 7 patients treated with metronidazole all were cured and restored to full health. In case 1, gentamicin given locally against the aerobic flora in the fistula might have contributed to the healing in spite of the failure with gentamicin given generally. In case 2 the gentamicin and cephalexin therapy against E. coli and clindamycin therapy against B. fragilis at first seemed to be
Downloaded by [RMIT University Library] at 01:58 17 March 2016
Metroniduzole treatment of anaerobic infections
efficient. But although the therapy continued for 6 weeks, there was a relapse only 1 week later which metronidazole cured. In case 3 there was a relapse after what was thought to be an efficient therapy with clindamycin and trimethoprim-sulphamethoxazole. At the relapse B . fragilis was isolated. The lincomycin treatment was a failure whereas the metronidazole treatment was successful. The same thing happened with lincomycin in case 4. Cephalexin which was given against the E. coli probably did not contribute to the good result in a decisive way, since it was given in a small dose. In case 5 there was a partially simultaneous local treatment with chloramphenicol which might have contributed to the effect. In case 6 it was the metronidazole that promptly made the patient afebrile which lincomycin had failed to do. In case 7 the improvement was slower than in the others. One reason might be that the intracerebral infection was caused by a mixed flora where the main bacteria were supposed to be bacteroides and staphylococci. The treatment against staphylococci was limited to lincomycin which penetrates badly into the cerebrospinal fluid. The patient, however, regained full health. Side-effects None of the 7 patients showed any adverse effects of the metronidazole therapy: neither short treatment side-effects as nausea, nor longterm effects as paresthesia (4, 8, 15).
DISCUSSION In 5 of the cases the bacterial findings showed both aerobic and anaerobic bacteria but even though fully adequate therapy against the aerobic bacteria was given, the patients did not improve until metronidazole was instituted. This suggests that the anaerobic infections in these cases were responsible for the patients’ symptoms. It is remarkable that in almost all cases a rapid improvement occurred in 24 h. All patients had received treatment with various antibiotics before institution of metronidazole therapy, but the antibiotics failed to influence the clinical condition. In no case was a surgical drainage which could explain the rapid improvement performed at the time of metronidazole treatment. Metronidazole has previously been reported to be highly effective against anaerobic bacteria (3, 13). However, in most clinics clindamycin and lincomy-
71
cin are still the drugs of choice in these cases. It is noteworthy that in 4 of our patients these antibiotics showed no effect at all though they were given together with other antibiotics effective on the aerobic flora. As no sensitivity tests for anaerobic bacteria have been performed it is not known if resistance developed against lincomycin and or clindamycin. The reason for the extremely good results in metronidazole therapy is probably the high tissue levels obtainable, including a good penetration through the blood/brain barrier and into abscess cavities (1 1). Since the drug, at least in short term treatment, seems to be virtually nontoxic and free of severe side-effects in man, metronidazole may .in the future be the drug of choice for anaerobic infections.
ACKNOWLEDGEMENT This study was supported by AB Leo Research Foundation.
REFERENCES I . Bassilly, S., Farid, Z., Mikhail, J. W., Kent, D. C. & Lehman, J. S., Jr: Treatment of Giardia lamblia with mepacrine, metronidazole and furazolidone. J Trop Med Hyg 73: 15, 1970. 2. Cosar, C. & Julou, L.: Activitt de I’(hydroxy2’tthyl)-l methyl-2 nitro-5 imidazole (8.823 R.P.) vis-ti-vis des infections exptrimentales ?I Trichomonas vaginalis. Ann Inst Pasteur (Paris) 96: 238, 1959. 3. Eykyn, S. J. & Phillips, I.: Metronidazole and anaerobic sepsis. Br Med J 2: 1418, 1976. 4. Ingham, H. R., Rich, G. E., Selton, J. B., Hale, J. H., Rosby, C. M., Botley, M. J., Johnson, P. W. G. & Uldall, P. R:: Treatment of metronidazole of three patients with serious infections due to Bacteroides fragilis. J Antimicrob Chemother 1: 235, 1975. 5. Mitre, R. J. & Rotheram, E. B.: Anaerobic septicemia from thrombophlebitis of the internal jugular vein. JAMA 230: 1168, 1974. 6. Powell, S. J., MacLeod, I., Wilmot, A. J. & ElsdonDew, R.: Metronidazole in amoebic dysentery and amoebic liver abscess. Lancet 2: 1329, 1966. 7. Ralph, E. D. & Kirby, W. M. M.: Unique bactericidal action of metronidazole against Bacteroides fragilis and Clostridium perfringens. Antimicrob Agents Chemother 8:409, 1975. 8. Ramsey, I. D.: Endocrine ophthalmology. Br Med J 4:706, 1%8. 9. Sharp, D. J., Coningham, R. E. T., Nye, E. B., Sagor, G. R. & Noone, P.: Successful treatment of Bacteroides bacteraemia with metronidazole, after failure with clindamycin and lincomycin. J Antimicrob Chemother 3: 233, 1977.
12
B . Christensson et al.
10. Shinn, D. L. S.: Metronidazole in acute ulcerative gingivitis. Lancet 1 : 1191, 1962. 1 1 . Tally, F. P., Sutter, V. L. & Finegold, S. M.:
12.
Downloaded by [RMIT University Library] at 01:58 17 March 2016
13.
14.
15.
Metronidazole versus anaerobes-in vitro data and initial clinical observations. Calif Med 117: 22, 1972. Whelan, J. P. F. & Hale, J. H.: Bactericidal activity of metronidazole against Bacteroides fragilis. J Clin Pathol26: 393, 1973, Willis, A. T., Ferguson, I. R., Jones, P. H., Phillips, K. D., Tearle, P. V., Berry, R. B., Fiddian, R. V., Graham, D. F., Harland, D. H. C., Innes, D. B., Mee, W. M., Rothwell-Jackson, R. L., Sutch, I., Kilbey,C. & Edwards, D.: Metronidazole in prevention and treatment of bacteroides infections after appendicectomy. Br Med J 1 : 318, 1976. Willis, A. T.: Metronidazole in anaerobic infections. Scott Med J 22: 155, 1977. Ursing, B. & Kamme, C.: Metronidazole for Crohn's disease. Lancet 1: 1775, 1975.
Address f o r reprints:
B . Christensson, M.D., Dept. of Infect. Dis., University Hospital, S-221%5 Limd, Sweden
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Treatment of Anaerobic Infections with Metronidazole Bertil Christensson, Sven Årke Hedström & Bo Ursing To cite this article: Bertil Christensson, Sven Årke Hedström & Bo Ursing (1979) Treatment of Anaerobic Infections with Metronidazole, Scandinavian Journal of Infectious Diseases, 11:1, 69-72, DOI: 10.3109/inf.1979.11.issue-1.11 To link to this article: http://dx.doi.org/10.3109/inf.1979.11.issue-1.11
Published online: 02 Jan 2015.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd19 Download by: [RMIT University Library]
Date: 17 March 2016, At: 01:58
Scand J Infect Dis 11: 69-72, 1979
Treatment of Anaerobic Infections with Metronidazole BERTIL CHRISTENSSON, S V E N A K E HEDSTROM a n d BO URSING From the Department of Infectioirs Diseases, University Hospital, Lund, Sweden
Downloaded by [RMIT University Library] at 01:58 17 March 2016
ABSTRACT. Metronidazole (Flagyl@),a compound widely used in man with minimal side-effects, has been used in the treatment of anaerobic infections caused by Bacteroides fragilis and other Bacteroides species. Seven patients were treated and all were restored to full health. Four of them did not respond to lincomycin or clindamycin which so far have been the drugs of choice against anaerobic infections. The reasons for the good results during metronidazole therapy such as the good penetration through the blood/brain barrier and into abscess cavities are discussed.
INTRODUCTION Metronidazole has been used for several years for the treatment of various parasitic infestations (1, 2, 6) a n d Vincent’s stomatitis (10). It has also proved to have a bactericidal effect on most anaerobic organisms (7, 11, 12) a n d has been reported t o b e useful in anaerobic infections (5, 9, 14). Furthermore an effect in Crohn’s disease has been suggested (15). P A T I E N T S A N D METHODS During the last 2 years we have successfully treated 12 patients suffering from suspected anaerobic infections with metronidazole (FlagyP). The drug has been given orally. In 5 of these cases the result of treatment could not be surely evaluated because of lack of bacteriological diagnosis or insufficient and additional chemotherapy. Thus, the study group reported here consists of 7 patients, 6 women and 1 man. Anaerobic cultures were performed according to the routine at the Medical Microbiological Laboratory, University Hospital, Lund. Sensitivity tests for anaerobic bacteria were not done. C A S E REPORTS Case I A 62-year-old man with a perforated diverticulitis of colon was treated with chloramphenicol, gentamicin and ampicillin. Five months later a resection of the sigmoideum was done and 2 months later a cholecystectomy. The last operation was complicated by a bile fistula and sepsis. Blood cultures were negative, but culture from the fistula showed Bacteroides fragilis, Proteus vulgaris, Escherichia coli,. Klebsiella pneumoniae and enterococci. The ESR was 91 mmlh and hemoglobin 89 gll. Electrophoretic acute phase reactants were very high. Before the result of culture was obtained, he was treated with cephalothin and ampicillin for 13 days without effect.
The therapy was changed to gentamicin and lincomycin which he received for 24 days without effect on the clinical state. He was then given chloramphenicol for 10 days without improvement, still having symptoms as high septic fever and discharge from several abdominal fistulas. The treatment was finally changed to metronidazole 400 mg 3 times a day for 1 week and thereafter 200 mg 3 times a day for 2 months. During treatment with metronidazole the patient became afebrile, the pus secretion from the fistulas diminished and cultures were negative. During 3 weeks he received gentamicin in dextran solution locally in the fistula. Two months after instituting metronidazole the fistula was completely healed and the drug could be discontinued. The patient was afebrile, ESR was 27 mmlh and hemoglobin 123 g/l. At a check-up 1 month later he showed no signs of infection. Case 2 A 34-year-old woman fell ill with abdominal pain and fever. Laparascopy revealed a right-sided pyosalpinx and she was treated with phenoxymethylpenicillin for 5 days and thereafter with doxycycline for another 5 days. ESR was 114 mmlh and hemoglobin 117 g/l. The temperature was still elevated and an abscess developed. A drainage of an appendico-tubo-ovarial abscess was done. Cultures from the cavity grew B. fragilis and E. coli. She received successful gentamicin and clindamycin therapy for 8 days and then cephalexin and clindamycin for one month. One week after terminating antibiotic treatment she had a relapse. The body temperature rose and in the right pelvis a tender mass developed corresponding to the previous abscess. ESR was 15 mmlh and hemoglobin 130 gll. Blood culture was not performed. Treatment with metronidazole was instituted, 400 mg 3 times a day for 5 days, thereafter 200 mg 3 times a day for 5 weeks. In 24 h the patient was afebrile, her clinical state improved and the mass gradually diminished. At a check-up 1 month after the end of metronidazole therapy no resistance was palpable. ESR was 11 mmlh. Case 3 A 25-year-old woman developed a suspected intrauterine ‘infection during the last month of pregnancy. A caesarean
Downloaded by [RMIT University Library] at 01:58 17 March 2016
70
B . Christensson et (11.
section was performed. Because of fever and suspected infection she was treated with clindamycin for 1 week postoperatively. Due to diarrhea the treatment was changed to trimethoprim-sulphamethoxazole for 2 weeks. One month after the operation she had a relapse with high fever, abdominal pains and putrid discharge from the cervix. The examination showed a tender uterus and the clinical picture was considered an endometritis. The body temperature was 39.6"C, ESR 109 mmlh and hemoglobin I12 g/l. In 4 blood cultures there was growth of B. fragilis. Initially she was treated with doxycycline and lincomycin for 6 days. No effect was seen and the treatment was changed to metronidazole 400 mg 3 times a day for 1 week and then 200 mg 3 times a day for 16 days. After 4 days of treatment she was afebrile. The abdominal symptoms subsided in a week after institution of therapy. One month later she was well and the metronidazole was discontinued. The ESR was 16 mmlh and hemoglobin 124 gll. Case 4
A 49-year-old woman had abdominal pains and dysuria for 2 weeks and later on fever. ESR was 108 mmlh and hemoglobin 122 g/l. A laparascopy showed a pelviperitonitis, acute salpingitis and bilateral sactosalpinx. No culture was performed. There was a temporary improvement during 13 days of treatment with doxycycline and a simultaneous treatment with tinidazole (Fasigyn@)2 g daily for 4 days which was given for trichomonas infection. However, 1 week later her condition deteriorated with high fever and abdominal pains. A bilateral salpingo-oophorectomy was performed. Cultures from the Douglas cavity showed growth of B. fragilis and E. coli. The temperature was still elevated. The ESR was 115 mmlh and hemoglobin 108 gll. Blood culture was not performed. Treatment with lincomycin and gentamicin for 1 week and thereafter doxycycline for 1 week had no effect on the fever. She then received cephalexin in low doses for another week without effect. Metronidazole was added to the treatment in a dose of 400 mg 3 times a day for I week. The temperature normalized in 2 days. The ESR was then 100 mmlh and hemoglobin 110 g/l. At a check-up 5 months later she was in a very good condition. No further culture was performed. Cusp 5
A 45-year-old woman with tetraplegia and chronic bacteriuria developed a suspected urosepsis. However, cultures from urine and blood were negative. On admission she had a sacral decubital wound with a diameter of 3 cm, from which cultures showed B. fragilis, Peptococcus anaerobicus, Fusobacterium and Staphylococcus aureus. ESR was 95 mmlh and hemoglobin 115 g/l. She was initially treated with gentamicin and carbenicillin for about a week without effect. Chloramphenicol in dextran solution was instituted locally but she still had fever. Therefore metronidazole 200 mg 3 times a day was added. She improved rapidly and became afebrile. The discharge diminished and cultures from the wound were negative 2 weeks later. The metronidazole treatment was given for 1 month. After an excision of the decubital wound a primary suture was done without postoperative complications. She
was checked 14 months later and was still in good condition. Case 6
A 19-year-old woman provoked an abortion in 7th month of pregnancy by thumping herself in the hypogastrium daily for 2 weeks. The abortion was complicated by a symphyseolysis, septic fever and signs of endometritis. The blood cultures showed Staph, epidermidis in repeated samples, probably a contamination. Cultures from urine showed growth of E. coli. The patient was treated with ampicillin, benzylpenicillin, tetracycline and cloxacillin in varying combinations during 2 weeks. No obvious improvement was seen and the fever continued. She developed a septic thrombosis and a local suprapubic abscess. The abscess was punctured and the cultures showed growth of B. melaninogenicus and gamma-streptococci. Before the result of culture was known she was treated with lincomycin and trimethoprim-sulphamethoxazolefor 5 days without effect. The fever continued. The ESR was 105 mmlh and the hemoglobin was I l l g/l. Then metronidazole 400 mg 3 times a day was given for I week followed by 200 mg 3 times a day for 6 weeks. Metronidazole showed an effect on the fever in 24 h and the abcess diminished in size. At a check up 1 month later she was completely restored. The ESR was 25 mm/h and hemoglobin 132 g/l. X-ray showed no signs of osteitis and the symphyseolysis was reduced. Case 7
A 6-month-old girl developed bacterial meningitis. The entrance of the infection was a fistula under a sacral naevus and an occult spina bifida. She was initially treated with chloramphenicol, sulphonamide and benzylpenicillin without effect on the fever or the clinical state. Cultures from CSF showed, however, a mixed flora with bacteroides species, anaerobic streptococci, Enterobacter cloacae and Staph. aureus and the treatment was changed to metronidazole in combination with lincomycin. During the 1st month the child received 100 mg of metronidazole 3 times a day and then 50 mg 3 times a day for another 6 weeks. During this treatment the body temperature gradually normalized and her general condition improved The culture from CSF became negative and ESR fell to 7 mmlh. During the antibiotic therapy an excision of the sacral epidural fistula was done without postoperative complications and all antibiotics could be discontinued. The child has been restored to full health.
RESULTS Of the 7 patients treated with metronidazole all were cured and restored to full health. In case 1, gentamicin given locally against the aerobic flora in the fistula might have contributed to the healing in spite of the failure with gentamicin given generally. In case 2 the gentamicin and cephalexin therapy against E. coli and clindamycin therapy against B. fragilis at first seemed to be
Downloaded by [RMIT University Library] at 01:58 17 March 2016
Metroniduzole treatment of anaerobic infections
efficient. But although the therapy continued for 6 weeks, there was a relapse only 1 week later which metronidazole cured. In case 3 there was a relapse after what was thought to be an efficient therapy with clindamycin and trimethoprim-sulphamethoxazole. At the relapse B . fragilis was isolated. The lincomycin treatment was a failure whereas the metronidazole treatment was successful. The same thing happened with lincomycin in case 4. Cephalexin which was given against the E. coli probably did not contribute to the good result in a decisive way, since it was given in a small dose. In case 5 there was a partially simultaneous local treatment with chloramphenicol which might have contributed to the effect. In case 6 it was the metronidazole that promptly made the patient afebrile which lincomycin had failed to do. In case 7 the improvement was slower than in the others. One reason might be that the intracerebral infection was caused by a mixed flora where the main bacteria were supposed to be bacteroides and staphylococci. The treatment against staphylococci was limited to lincomycin which penetrates badly into the cerebrospinal fluid. The patient, however, regained full health. Side-effects None of the 7 patients showed any adverse effects of the metronidazole therapy: neither short treatment side-effects as nausea, nor longterm effects as paresthesia (4, 8, 15).
DISCUSSION In 5 of the cases the bacterial findings showed both aerobic and anaerobic bacteria but even though fully adequate therapy against the aerobic bacteria was given, the patients did not improve until metronidazole was instituted. This suggests that the anaerobic infections in these cases were responsible for the patients’ symptoms. It is remarkable that in almost all cases a rapid improvement occurred in 24 h. All patients had received treatment with various antibiotics before institution of metronidazole therapy, but the antibiotics failed to influence the clinical condition. In no case was a surgical drainage which could explain the rapid improvement performed at the time of metronidazole treatment. Metronidazole has previously been reported to be highly effective against anaerobic bacteria (3, 13). However, in most clinics clindamycin and lincomy-
71
cin are still the drugs of choice in these cases. It is noteworthy that in 4 of our patients these antibiotics showed no effect at all though they were given together with other antibiotics effective on the aerobic flora. As no sensitivity tests for anaerobic bacteria have been performed it is not known if resistance developed against lincomycin and or clindamycin. The reason for the extremely good results in metronidazole therapy is probably the high tissue levels obtainable, including a good penetration through the blood/brain barrier and into abscess cavities (1 1). Since the drug, at least in short term treatment, seems to be virtually nontoxic and free of severe side-effects in man, metronidazole may .in the future be the drug of choice for anaerobic infections.
ACKNOWLEDGEMENT This study was supported by AB Leo Research Foundation.
REFERENCES I . Bassilly, S., Farid, Z., Mikhail, J. W., Kent, D. C. & Lehman, J. S., Jr: Treatment of Giardia lamblia with mepacrine, metronidazole and furazolidone. J Trop Med Hyg 73: 15, 1970. 2. Cosar, C. & Julou, L.: Activitt de I’(hydroxy2’tthyl)-l methyl-2 nitro-5 imidazole (8.823 R.P.) vis-ti-vis des infections exptrimentales ?I Trichomonas vaginalis. Ann Inst Pasteur (Paris) 96: 238, 1959. 3. Eykyn, S. J. & Phillips, I.: Metronidazole and anaerobic sepsis. Br Med J 2: 1418, 1976. 4. Ingham, H. R., Rich, G. E., Selton, J. B., Hale, J. H., Rosby, C. M., Botley, M. J., Johnson, P. W. G. & Uldall, P. R:: Treatment of metronidazole of three patients with serious infections due to Bacteroides fragilis. J Antimicrob Chemother 1: 235, 1975. 5. Mitre, R. J. & Rotheram, E. B.: Anaerobic septicemia from thrombophlebitis of the internal jugular vein. JAMA 230: 1168, 1974. 6. Powell, S. J., MacLeod, I., Wilmot, A. J. & ElsdonDew, R.: Metronidazole in amoebic dysentery and amoebic liver abscess. Lancet 2: 1329, 1966. 7. Ralph, E. D. & Kirby, W. M. M.: Unique bactericidal action of metronidazole against Bacteroides fragilis and Clostridium perfringens. Antimicrob Agents Chemother 8:409, 1975. 8. Ramsey, I. D.: Endocrine ophthalmology. Br Med J 4:706, 1%8. 9. Sharp, D. J., Coningham, R. E. T., Nye, E. B., Sagor, G. R. & Noone, P.: Successful treatment of Bacteroides bacteraemia with metronidazole, after failure with clindamycin and lincomycin. J Antimicrob Chemother 3: 233, 1977.
12
B . Christensson et al.
10. Shinn, D. L. S.: Metronidazole in acute ulcerative gingivitis. Lancet 1 : 1191, 1962. 1 1 . Tally, F. P., Sutter, V. L. & Finegold, S. M.:
12.
Downloaded by [RMIT University Library] at 01:58 17 March 2016
13.
14.
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Address f o r reprints:
B . Christensson, M.D., Dept. of Infect. Dis., University Hospital, S-221%5 Limd, Sweden
