Intravenous metronidazole for treatment of infections involving anaerobic bacteria
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Intravenous metronidazole was administered, either by continuous or intermittent infusion, to 20 patients with infections involving anaerobic bacteria; 14 of the 20 patients were changed to oral administration of metronidazole for completion of therapy. Six of eight patients with infections derived from oropharyngeal bacterial flora were cured; the addition of ampicillin was required in one patient, however, because of an incomplete response to metronidazole. Eight of eleven evaluable patients with infections derived from bowel flora were also cured by metronidazole or metronidazole plus an aminoglycoside. Of 93 anaerobic bacteria isolated before therapy, 89 were susceptible to 16 micrograms or less of metronidazole per ml. Mean plasma levels of metronidazole were 27.6 +/- 11.4 micrograms/ml in patients receiving continuous infusions of drug and 19.9 +/- 10.7 micrograms/ml (trough) in patients receiving intermittent infusions. Two patients developed peripheral neuropathy during therapy. Metronidazole is an effective agent for the treatment of anaerobic infections. Because metronidazole is not active against facultative and aerobic bacteria, the addition of a second antimicrobial agent may be required for the treatment of mixed anaerobic-aerobic infections.Keywords:
Aerobic bacteria
Anaerobic infection
Bacteroides fragilis
Colorectal Surgery
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We practiced a preoperative prophylaxis with 1.5g metronidazole daily starting three days before operation because of the increasing knowledge about the importance of anaerobic microorganisms, causing nosocomial infections. By this regime we saw a significant decrease of postoperative morbidity, detected by means of postoperative febrile temperatures and laparotomy wound abscesses. Bacteriological examinations before and after prophylaxis revealed a relatively high elimination of anaerobic isolates without influence on the aerobic and physiologic flora. In 66% of the cases with infections we isolate anaerobic strains. In cases of pelvic inflammatory diseases metronidazole is to be recommended both prophylactically and therapeutically. There is no resistance against metronidazole.
Anaerobic infection
Flora
Wound infection
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Metronidazole is a 5‐nitroimidazole that has selective activity against anaerobic microorganisms, including bacteria and protozoa. Intravenous metronidazole has recently been approved by the U.S. Food and Drug Administration for the treatment of serious anaerobic bacterial infections. It is usually bactericidal at low concentrations, and its spectrum of activity encompasses almost all anaerobic bacteria and some capnophilic organisms. Anaerobic bacteria known to be resistant to metronidazole include occasional anaerobic cocci, some nonsporulating gram‐positive bacilli and propionibacterium. Metronidazole is the most active antimicrobial agent against Bacteroides fragilis , the most resistant of anaerobic bacteria. Kill‐curve studies demonstrate that there is a 2 to 5 log decrease in the number of colony forming units of S. fragilis and Clostridium perfringens within one hour. The only well documented metronidazole‐resistant strain is a B. fragilis isolated from the normal flora of a patient on long‐term metronidazole therapy for Crohn's Disease. Metronidazole resistance in Trichomonas vaginalis has recently been described in a few strains that are able to survive at increased oxygen tensions. Metronidazole has been shown to be efficacious in certain protozoal infections including trichomonal vaginitis, extraintestinal amebiasis, and giardiasis. Clinical studies have shown metronidazole to be efficacious in the therapy of a variety of anaerobic infections, including non‐traumatic brain abscesses, intraabdominal sepsis, pelvic suppuration and necrotizing soft tissue infections. There have been disappointing results in the therapy of anaerobic pleuropulmonary infections with a number of superinfections caused by aerobic bacteria. Since metronidazole lacks any activity against aerobic bacteria, it must be combined with other agents, usually aminoglycosides, in the treatment of mixed infections involving anaerobic and aerobic bacteria.
Bacteroides fragilis
Clostridium perfringens
Aerobic bacteria
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The activity of metronidazole was studied by the diffusion method using two discs on a model group of 40 anaerobic bacterial strains isolated recently from clinical specimens. The minimal inhibitory concentrations (MICs) were determined by the dilution method and regression curves by the method of minimum square errors. Some 82.5% of bacteria of the model group were susceptible to metronidazole. All the routinely isolated anaerobes (582 strains) were tested with metronidazole over a period of 20 months. Susceptibility was recorded in 469 strains (80.6%). The clinical study was carried out on two groups of inpatients with bacteriologically confirmed mixed aerobic and anaerobic infections. Subjects in Group 1 (25 patients) were given clindamycin and gentamicin and those in Group 2 (30 patients) metronidazole and gentamicin. The results showed that the two combinations of drugs had comparable effects.
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Anaerobic infection
Etiology
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Thirty patients with anaerobic sepsis were treated with intravenous and oral metronidazole. No other antimicrobial agents were given. Mixed growths of anaerobic and aerobic bacteria were isolated from 22 patients and anaerobes alone from 8 patients. Very satisfactory clinical results were seen in most patients, though in many surgical drainage was also essential. Only 2 of the 22 patients from whom both aerobic and anaerobic bacteria were cultured later required specific therapy for the aerobic organisms.
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Microscopic examination and cultural studies of subgingival dental plaque have indicated that a complex, predominantly anaerobic flora is associated with periodontal disease. About 10 to 15 bacterial species, all of them anaerobic with the exception of A actinomycetemcomitans, have been suggested to be periodontal pathogens. These data indicate that most forms of periodontal disease are chronic anaerobic infections. This possibility has been evaluated by the systemic use of metronidazole, an antimicrobial whose spectrum of activity is limited to anaerobes. These six metronidazole double-blind studies demonstrate that metronidazole, given for periods of time as short as 1 week, can lead to a significant improvement in periodontal health. Maximal benefits are obtained when the metronidazole is given after the tooth surfaces are debrided of plaque and calculus. The best response is often noted in the more advanced cases, in which an anaerobic flora including spirochetes and black-pigmented Bacteroides usually predominates in the subgingival plaque. The success of short-term metronidazole treatment in these investigations indicates that the overgrowth of certain anaerobes in the plaque is responsible for most forms of periodontal disease.
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Dental plaque
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In a study carried out with 565 patients undergoing gynaecological and general surgical procedures, metronidazole ('Flagyl') was used pre- and postoperatively and the incidence of post-operative infection, particularly that due to anaerobic organisms, was recorded. This was not a controlled study but, by comparison with other series, it would appear that the use of oral metronidazole had substantially reduced the likelihood of supervention of anaerobic sepsis. It is probable that the use of intravenous metronidazole therapy would have reduced the incidence of anaerobic sepsis still further had this preparation been available at the time.
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Intravenous metronidazole was administered, either by continuous or intermittent infusion, to 20 patients with infections involving anaerobic bacteria; 14 of the 20 patients were changed to oral administration of metronidazole for completion of therapy. Six of eight patients with infections derived from oropharyngeal bacterial flora were cured; the addition of ampicillin was required in one patient, however, because of an incomplete response to metronidazole. Eight of eleven evaluable patients with infections derived from bowel flora were also cured by metronidazole or metronidazole plus an aminoglycoside. Of 93 anaerobic bacteria isolated before therapy, 89 were susceptible to 16 micrograms or less of metronidazole per ml. Mean plasma levels of metronidazole were 27.6 +/- 11.4 micrograms/ml in patients receiving continuous infusions of drug and 19.9 +/- 10.7 micrograms/ml (trough) in patients receiving intermittent infusions. Two patients developed peripheral neuropathy during therapy. Metronidazole is an effective agent for the treatment of anaerobic infections. Because metronidazole is not active against facultative and aerobic bacteria, the addition of a second antimicrobial agent may be required for the treatment of mixed anaerobic-aerobic infections.
Aerobic bacteria
Anaerobic infection
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