Treatment of Anaerobic Infections with Metronidazole

Tally, Francis P.; Sutter, Vera L.; Finegold, Sydney M.

doi:10.1128/aac.7.5.672

Cited by 122 publications

(46 citation statements)

References 18 publications

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“…These compounds also possess excellent inhibitory activity against anaerobic bacteria (4,5,9,21,24) and are used increasingly for treatment of infections caused by these microorganisms.…”

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confidence: 99%

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Nilsson-Ehle¹,

Ursing²,

Nilsson‐Ehle³

1981

Antimicrob Agents Chemother

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We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase highpressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected.The two nitroimidazoles metronidazole and tinidazole have been used as antiprotozoal agents for many years. These compounds also possess excellent inhibitory activity against anaerobic bacteria (4, 5, 9, 21, 24) and are used increasingly for treatment of infections caused by these microorganisms.Metronidazole is metabolized in the liver mainly by oxidative processes; the two major metabolites excreted in urine are 1-(2-hydroxyethyl) -2 -hydroxy -methyl -5-nitroimidazole(hydroxy metabolite) and 2-methyl-5-nitroimidazole-1-acetic acid (acetic acid metabolite) (20). High-pressure liquid chromatography methods have been developed to measure the parent compound metronidazole and its two major metabolites (6, 12, 25). Measurements of tinidazole by using high-pressure liquid chromatography have also been reported (12,16).We report here a rapid and simple assay involving high-pressure liquid chromatography for quantitation of metronidazole and its two main metabolites in serum and urine; with a slight alteration in the composition of the mobile phase, this assay was also used for quantitation of tinidazole. The

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“…These compounds also possess excellent inhibitory activity against anaerobic bacteria (4,5,9,21,24) and are used increasingly for treatment of infections caused by these microorganisms.…”

mentioning

confidence: 99%

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Nilsson-Ehle¹,

Ursing²,

Nilsson‐Ehle³

1981

Antimicrob Agents Chemother

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“…Metronidazole is a bacteriocidal agent which is effective against anaerobes (Tally et al, 1975) and may be of value in proctitis. We first treated 14 patients in an open trial in which all patients were given 800 mg imetronidazole orally, while some also had 200 mg twice daily by enema; six responded well, one improved a little, and seven were unchanged.…”

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confidence: 99%

“…Metronidazole is a bacteriocidal agent which is effective against anaerobes (Tally et al, 1975) A clinical assessment was made initially and at the end of each treatment period; this included sigmoidoscopic examination with a rectal biopsy. The sigmoidoscopic changes were recorded using similar criteria to those described by Baron et al (1964).…”

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confidence: 99%

Metronidazole in the treatment of chronic proctitis: a controlled trial.

Davies¹,

Rhodes²,

Heatley³

et al. 1977

Gut

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SUMMARY Twenty-two patients with chronic proctitis were treated with metronidazole for 28 days in a double-blind controlled trial, but they did not appear to benefit from the drug.Although the cause of proctitis and ulcerative colitis remains unknown, anaerobic bacteria may play a part in the pathogenesis by provoking an immune response (Monteiro et al., 1971), or by secondary invasion of inflamed mucosa. Metronidazole is a bacteriocidal agent which is effective against anaerobes (Tally et al., 1975) and may be of value in proctitis. We first treated 14 patients in an open trial in which all patients were given 800 mg imetronidazole orally, while some also had 200 mg twice daily by enema; six responded well, one improved a little, and seven were unchanged.We then treated 22 patients in a double-blind controlled study. The patients had relatively mild symptoms of increased bowel frequency with loose stools and loss of blood and mucus; the rectal mucosa was abnormal on sigmoidoscopic examination and a previous barium enema was normal. The study was of crossover design in which patients were given metronidazole suppositories (500 mg three times daily) and a placebo in randomised order during two consecutive 28 day periods. During each period patients recorded daily on a diary card the frequency of bowel actions and the occurrence of rectal bleeding. At the end of each period they indicated their clinical progress as excellent, good, fair, bad, or terrible.A clinical assessment was made initially and at the end of each treatment period; this included sigmoidoscopic examination with a rectal biopsy. The sigmoidoscopic changes were recorded using similar criteria to those described by Baron et al. (1964). Grade I was normal; grade II showed hyperaemic mucosa; grade III included spontaneous bleeding and haemorrhages on light contact, and grade IV Received for publication 25 January 1977 referred to severe changes. Rectal biopsies were examined by one pathologist without knowledge of the order of treatments given. The acute inflammatory reaction was graded as normal, moderate, or severe using sections stained with haematoxylin and eosin. This was based on the degree of acute inflammatory infiltrate in the lamina propria, the presence of crypt abscesses, and polymorphs adjacent to epithelial tubules. In addition, sections were stained for eosinophils with carbol chromatrobe and the eosinophil counts were made over five high-power fields.

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“…Recent studies have documented its in vitro bactericidal activity against anaerobic bacteria (14). Metronidazole appears to be efficacious in clinical anaerobic infections (18), and two groups have reported its use prophylactically in gynecological and colonic surgery (6,21). The common denominator in these diverse indications is this antimicrobial agent's exclusive activity against anaerobic microorganisms.…”

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confidence: 99%

Antimicrobial activity of metronidazole in anaerobic bacteria

Tally¹,

Goldin²,

Sullivan³

et al. 1978

Antimicrob Agents Chemother

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The antimicrobial activity of metronidazole was investigated in anaerobic bacteria by use of time-viability studies. This antimicrobial agent has a rapid onset of bactericidal activity under proper reducing conditions. The bactericidal rates were not affected by inoculum size or nutritional requirements, nor by inhibition of growth and protein synthesis by chloramphenicol. Using supernatant fractions of actively growing cultures of susceptible organisms, we observed a disappearance of metronidazole and a loss of biological activity, but there was no significant change in preparations from resistant bacteria. The decrease in drug concentration with susceptible cells occurred during the time that its bactericidal action was being exerted. Extracts from susceptible organisms rapidly reduced the concentration of metronidazole, confirming previous observations which suggest that the drug acts as a terminal electron acceptor. Radioisotope experiments with ['4C]metronidazole revealed that the compound was taken up by both resistant and susceptible bacteria, although there was a difference in rate and extent of accumulation. These studies demonstrate that mentronidazole's antimicrobial activity against anaerobic bacteria is bactericidal and independent of growth rate, and that it involves the uptake and metabolism of the compound.

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Treatment of Anaerobic Infections with Metronidazole

Cited by 122 publications

References 18 publications

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Metronidazole in the treatment of chronic proctitis: a controlled trial.

Antimicrobial activity of metronidazole in anaerobic bacteria

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