Clinical Characteristics of Metronidazole-induced Encephalopathy : A Report of Two Cases and a Review of 32 Japanese Cases in the Literature
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Metronidazole is an antibiotic classically used against most anaerobic bacteria and protozoa. Because an intravenous form of metronidazole has recently entered the market, the use of this antibiotic is attracting renewed interest in many clinical settings in Japan. However, neurotoxicity is a major adverse event: in the central nervous system metronidazole-induced encephalopathy is a rare but serious condition. We performed a literature review of 34 cases including 2 of our cases, 25 from domestic conference abstracts, and 7 cases presented in full research papers. The mean patient age was 64.7 years. The conditions most commonly treated with metronidazole were brain abscess (35.3%), liver abscess (17.6%), and Clostridium difficile infection (14.7%). The most common predisposing conditions were liver dysfunction (26.5%), diabetes and other metabolic disorders (20.6%), and hematologic or solid organ malignancy (14.7%). The mean period of administration before the onset of encephalopathy symptoms was 61.3 days, and the mean total dose was 95.9g. The initial chief complaints were dysarthria (in 70.6% of the cases) and ataxia (61.8%); 82.4% of the cases were diagnosed on the basis of MRI (T2-weighted or FLAIR imaging). The key imaging finding was high intensity in the dentate nucleus bilaterally (82.4%). Stopping the metronidazole led to symptom remission within 8.5 days, but the MRI changes remained longer than the clinical symptoms. Two patients (6.0%) developed irreversible disturbance of consciousness. Although the mechanisms of this type of encephalopathy have not yet been elucidated, localized nerve-cell edema is likely caused by decreased metronidazole metabolism associated with liver and metabolic dysfunction. Careful observation for neurologic signs should be conducted during the treatment of brain abscesses associated with metronidazole administration, because patients with brain abscesses are naturally at high risk of metronidazole-induced encephalopathy.Keywords:
Hepatic Encephalopathy
Abstract Metronidazole-induced encephalopathy is a rare toxic encephalopathy secondary to the common use to this antimicrobial drug. It has been reported mainly in adult patients but only rarely in children. Owing to possible devastating complication of this disease, clinicians should have a higher index of suspicion for encephalopathic patients on metronidazole therapy. Here, we report a 5-month-old infant with metronidazole-induced encephalopathy presenting with nonconvulsive status epilepticus. A review of the literature in pediatric, as well as adult metronidazole-induced encephalopathy, is also provided.
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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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Hepatic Encephalopathy
Portacaval shunt
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Objective To compare effects of the secnidazole and metronidazole tablets in treatment of anaerobic-induced chronic sinusitis,and to find new medicine for this disease.Methods 451 chronic sinusitis patients were chosen from October 2007 to July 2009 in our hospital,and were divided into secnidazole treatment group(test group) and metronidazole treatment group(control group).After 5 days' continual treatment,the type and quantity of anaerobic bacteria in the purulent secretion from two groups of patients were analyzed.Results After 5 days,the anaerobic bacteria in purulent secretions of two groups were significantly reduced in the types,the types of anaerobic bacteria in the test group were dropped from 40 to 6,while the control group from 39 to 11,the effective rates were 85.0%,71.8%,respectively.The difference was statistically significant(P0.05).Conclusion Both secnidazole tablets and metronidazole tablets were effective and safe in the treatment of chronic sinusitis;secnidazole tablets were better than metronidazole tablets.
Chronic sinusitis
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Hepatic Encephalopathy
Grading (engineering)
Pathogenesis
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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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Aim. To analyze the dynamics of hepatic encephalopathy after transjugular intrahepatic portosystemic shunting (TIPS). Material and Methods. It was analyzed the results of complex survey of 52 patients who underwent TIPS. Self-expanding stents 8–10 cm, diameter of 8–10 mm and stent-graft were applied for portosystemic shunt creation. Results. The two main complications of TIPS are hepatic encephalopathy progression and shunt’s malfunction. The increased degree of portosystemic encephalopathy in 18 months postoperatively was revealed in 3 (10%) patients. Symptoms of encephalopathy were eliminated and did not effect on the patients’ life quality after discharge. Conclusion. Assessment of encephalopathy’s degree and individual therapy in each patient significantly decrease the severity of encephalopathy postoperatively followed by improved life quality
Hepatic Encephalopathy
Shunting
Portosystemic shunt
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Abstract In the present report, five selected periodontal patients were treated for 1 week with metronidazole. Two of the patients had their teeth scaled and root‐planed the week they received metronidazole. Prior to treatment, B. asaccharolyticus accounted for 41 % of the cultivable isolates and the spirochetes averaged 29 % of the microscopic count in plaque removed from each of four pockets per patient. The presence of these elevated proportions of periodontopathic bacteria combined with the presence of periodontal pockets and attachment loss suggested that the patients were in a state of an active infectious process involving primarily anaerobic bacteria. If this be the case, then antimicrobial therapy directed against these anaerobes with metronidazole was indicated. The 1‐week treatment with metronidazole significantly reduced the proportions of these organisms for up to 6 months after treatment. Coincident with these findings was an improvement in the clinical parameters, especially in those sites that initially had greater than 5 mm pocket or attachment loss. These sites showed a 2 mm or more reduction in pocket depth and an almost 2 mm gain in apparent attachment that was evident 6 months after treatment. The results obtained were in only five patients. However, the magnitude of improvement suggests that antimicrobial therapy directed against anaerobic organisms may be a valuable adjunct to periodontal therapy.
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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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