Scandinavian journal of infectious diseases. Supplementum

Comparative antimicrobial activity of metronidazole and the hydroxy metabolite against Gardnerella vaginalis.

PMID 6607518


Metronidazole (M) (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) undergoes oxidative metabolism with the formation of several metabolites, the most important quantitatively in serum and urine being the "hydroxy" metabolite (HM) (1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole). The antimicrobial activity of HM was compared with M against strains of G. vaginalis using minimal inhibitory (MIC) and bactericidal (MBC) concentration determinations and time-kill curve studies. At an inoculum of 10(6) colony forming units per ml (cfu/ml), and anaerobic incubation for 48 hours, the median MIC and MBC of HM were 1 and 2 micrograms/ml, respectively, compared to 4 and 16 micrograms/ml for M. HM also demonstrated a more rapid bactericidal effect than M in time-kill curves against exponential (10(6) cfu/ml) and stationary phase (10(10-13) cfu/ml) organisms. However, the cidal effect of HM against G. vaginalis was slower than that previously shown for M against obligate anaerobes such as B. fragilis. The degree of inactivation of both HM and M, determined by high pressure liquid chromatography, was similar during the time-kill studies and averaged less than 10% with exponential phase organisms and approximately 40% against stationary phase organisms after 48 hours' incubation. Pharmacokinetic studies have shown that on usual dosage regimens of M used for non-specific vaginitis the serum levels of HM would likely exceed the MIC/MBC for most strains of G. vaginalis. Therefore, HM likely contributes a significant antimicrobial effect against this organism.

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Metronidazole-OH, VETRANAL, analytical standard