Treatment with metronidazole of three patients with serious infections due to Bacteroides fragilis

The susceptibilities of 284 anaerobic bacteria, including 55 strains of the Bacteroides fragilis group, were determined by an agar dilution technique to metronidazole and two newer nitroimidazoles, ornidazole and SC-28538. All three agents showed marked in vitro activity against virtually all anaerobic bacteria tested. At concentrations c1 ,ig/ml, SC-28538 was significantly more active than either rnetronidazole or ornidazole. At concentrations of >1 ,ig/ml, the activities of all three agents were comparable. Propionibacterium and Actinomyces showed significant resistance to all three agents. Anaerobic and microaerophilic members of the genus Streptococcus were also often resistant, in contrast to Peptococcus and Peptostreptococcus strains. In addition, the bactericidal activities of ornidazole and SC-28538 were determined against 27 strains of the B. fragilis group by a broth dilution technique. The minimal inhibitory and minimal bactericidal concentrations of each agent were very close. At concentrations of c0.5 jg/ml, SC-28538 showed greater bactericidal activity; at concentrations of -2 jLg/ml, the activies of both agents were similar.

“…However, at 1-,ug/ml concentration, only 43. 6 and 61.8% of the strains were susceptible to metronidazole and ornidazole, respectively, whereas 94.5% were susceptible to SC-28538.…”

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confidence: 97%

“…It is presently available for therapy of anaerobic infections in Europe (6,7) and is undergoing clinical trials in the United States (8,15 (2). Subsequently, it was shown to be active in vitro (3,13,15,19,27) and in vivo (6)(7)(8)15) against a wide variety of anaerobic bacteria. Its pharmacokinetics have been well studied previously (9,11,16).…”

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confidence: 99%

Comparative Susceptibilities of Anaerobic Bacteria to Metronidazole, Ornidazole, and SC-28538

Goldstein¹,

Sutter²,

Finegold³

1978

“…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

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

“…When the strains were tested by the modified broth-disk method proposed by Metronidazole and related nitroimidazole derivatives, including ornidazole and tinidazole, are receiving increasing attention in the treatment of anaerobic infections. This interest rests on the results ofintensive in vitro susceptibility evaluations (2-4, 9, 10, 20, 24, 26, 28, 32) and limited but promising trials of these agents in patients infected with various anaerobic bacteria (14,19,31,39 Currently, there are several methods proposed for routine susceptibility testing ofanaerobic bacteria (5,8,21,25,29,36,37 Clostridium sporogenes, 1 Clostridium tertium, 1 Clostridium sp. The strains were maintained at room temperature in chopped-meat broth (13).…”

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confidence: 99%

Susceptibility of Anaerobic Bacteria to Metronidazole, Ornidazole, and Tinidazole and Routine Susceptibility Testing by Standardized Methods

Wüst

1977

A total of 114 strains ofanaerobic bacteria were examined for their susceptibility to metronidazole, ornidazole, and tinidazole by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration in different media. All strains, with the exception of the isolates ofPropionibacterium acnes, were inhibited by 3.1 ug each and killed by 6.3 ,ug each of all three nitroimidazole compounds per ml. No significant differences in MIC values were found among metronidazole, ornidazole, and tinidazole. Only minor differences were detected by comparing MIC values obtained in brain heart infusion agar with and without sheep blood, brucella agar, and Mueller-Hinton agar (both containing blood). When the strains were tested by the modified broth-disk method proposed by Metronidazole and related nitroimidazole derivatives, including ornidazole and tinidazole, are receiving increasing attention in the treatment of anaerobic infections. This interest rests on the results ofintensive in vitro susceptibility evaluations (2-4, 9, 10, 20, 24, 26, 28, 32) and limited but promising trials of these agents in patients infected with various anaerobic bacteria (14,19,31,39 Currently, there are several methods proposed for routine susceptibility testing ofanaerobic bacteria (5,8,21,25,29,36,37 Clostridium sporogenes, 1 Clostridium tertium, 1 Clostridium sp. The strains were maintained at room temperature in chopped-meat broth (13).Media. Throughout the experiments, prereduced, anaerobically sterilized media were used. These were prepared according to methods described by Holdeman and Moore (13). The basic media were supplemented brain heart infusion (BHI) broth and chopped-meat carbohydrate (CMC) broth. The basal peptone-yeast extract medium used for testing biochemical reactions contained 0.5% peptone (Difco) and 0.5% Trypticase (BBL) instead of 1% peptone (W. E. C. Moore, personal communication).The media used for MIC determinations were: BHI agar (Difco), supplemented with 0.5% yeast extract (Difco), with and without 5% citrated sheep blood (BHIA); brucella agar (kindly supplied by Pfizer Overseas, Inc., New York) with 5% sheep blood; Mueller-Hinton agar (BBL), supplemented with 0.5% yeast extract (Difco) and 5% sheep blood. All media for MIC determinations were supplemented with menadione (0.5 ,g/ml) and hemin (5 ,tg/ml).Antimicrobial agents. Metronidazole and ornidazole were kindly supplied by P. Angehrn, Hoffmann-La Roche & Co. AG, Basel, Switzerland, and tinidazole was supplied by E. Milek, Pfizer AG, Zurich, Switzerland.Stock solutions containing 1,000 ,ug of each antimicrobial agent per ml were prepared in distilled water, filter-sterilized (Millipore, 0.22 um), and kept frozen at -20°C.MIC determinations. MIC determinations were performed according to Blazevic (1). For the agar dilution technique, plates were prepared containing serial twofold dilutions of each antimicrobial agent from 100 to 0.1 ,ug/ml. The plates were held overnight at room temperature in GasPak jars (BBL) or prepared on the day of th...