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

Abstract

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...

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

“…Metronidazole has significant in vitro activity against virtually all obligate anaerobes at readily achievable blood levels (13,20). Previously the microaerophilic and anaerobic streptococci, Actinomyces and Propionibacterium have been reported to be resistant (13); our data are in agreement with those observations.…”

“…Wurst (20) reported the susceptibilities of 114 strains of anaerobes to ornidazole and metronidazole. All of his strains, except seven isolates of P. acnes, were inhibited by c3.1 jig of both agents.…”

“…1) is a recently synthesized nitroimidazole derivative with antitrichomonad activity (12). It has been previously tested and found to be active against several strains of anaerobic bacteria (20). The pharmacokinetics (pKa, protein binding, volume of distribution, and peak serum levels) and metabolism of ornidazole are similar to those of metronidazole (11).…”

Bile and serum levels of tinidazole after a single oral dose.

“…In the bile, tinidazole levels initially rose more slowly but from about 12 h after the dose, the bile levels were similar to those in the serum sample taken at the same time. Reynolds et al (1975) and Wust (1977) found minimal inhibitory concentrations of tinidazole for common anaerobic pathogenic bacteria not greater than 3.1 ug/ml. This suggests that in our cases antibacterial levels were reached in the blood within 2 h of a 2 g oral dose and persisted for at least 24 h.…”

Stereoselective Glucuronidation of Ornidazole in Humans: Predominant Contribution of UDP-Glucuronosyltransferases 1A9 and 2B7

“…The antimicrobial mechanism of ornidazole involves the formation of a hydroxylamine intermediate in the microbe, which damages microbial DNA, disrupts transcription, and ultimately causes cell death (Edwards, 1979;Muller, 1983;Kedderis et al, 1989). Ornidazole, which is similar in activity to metronidazole, shows a longer half-life (14.4 hours) than metronidazole (8.4 hours) and has reduced dosage frequency and duration of therapy in many relevant clinical infections (Schwartz and Jeunet, 1976;Wust, 1977;Goldstein et al, 1978). Ornidazole is usually administered orally, intravenously, intravaginally, or rectally as racemates in clinical practice.…”