The antibacterial activity of metronidazole

Ingham, H. R.; Selkon, J. B.; Hale, J. H.

doi:10.1093/jac/1.4.355

Cited by 65 publications

(22 citation statements)

References 21 publications

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“…The (Ingham, Selkon and Hale, 1975;Coxon and Pallis, 1976); the type of neuropathy is similar to that which we have encountered with Ro 07-0582. The mechanism of neurotoxicity is at present unknown.…”

Section: Methodssupporting

confidence: 64%

Clinical testing of the radiosensitizer Ro 07-0582: Experience with multiple doses

Dische¹,

Saunders²,

Lee³

et al. 1977

Br J Cancer

229

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The hypoxic cell radiosensitizer, Ro 07-0582, has now been given in multiple doses to 16 patients. They have received a total of 15-51 g in 3-20 doses. Immediate tolerance was good, and satisfactory plasma levels of the drug were consistently obtained. Neurotoxicity was, however, troublesome: convulsions occurred in the patient given the highest dose, and there was peripheral neuropathy in 11 cases. Tumour concentrations similar to those in plasma were obtained in human tumours, in contrast to the findings in mouse tumours where concentrations are usually below 40% of plasma levels. In the treatment of human tumours, a lower dose of Ro 07-0582 should give useful hypoxic cell sensitization. Although the total dose of Ro 07-0582 must be limited, there is a real prospect that it will give benefit in clinical radiotherapy. Images Fig. 4

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Section: Methodssupporting

confidence: 64%

Clinical testing of the radiosensitizer Ro 07-0582: Experience with multiple doses

Dische¹,

Saunders²,

Lee³

et al. 1977

Br J Cancer

229

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“…Metronidazole has a wide spectrum of bactericidal action against obligate anaerobes [Ingham et al, 1975;Sundquvist, 1976]. In fact, metronidazole decreases bacterial populations of human periodontal pockets [Loesche et al, 1981;Lekovic et al, 1983;Yeung et al, 1983], especially certain speciesofanaerobes [Loescheetal., 1981[Loescheetal., ,1984.Theaim of this paper is to clarify bactericidal efficacy of metro nidazole against bacteria of human carious dentin.…”

mentioning

confidence: 99%

Bactericidal Efficacy of Metronidazole against Bacteria of Human Carious Dentin in vitro

Hoshino

Iwaku²,

Sato³

et al. 1988

Caries Res

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The bactericidal efficacy of metronidazole against bacteria in carious dentin was clarified by measuring (1) the difference between bacterial recovery from suspensions of carious dentin on metronidazole-containing BHI-Blood agar plates (10 μg/ml) and control plates and (2) the difference between bacterial recovery from carious lesions of freshly extracted teeth, covered by α-tricalcium phosphate (TCP) cement containing metronidazole (5%) for 1–3 days and that covered by TCP only. More than 10³ bacteria per milligram sample were recovered from carious dentin. More than 99% of the bacteria were, however, not recovered when samples were inoculated on metronidazole-containing BHI-Blood agar plates or when the lesions were covered by TCP cement containing metronidazole, indicating that metronidazole effectively disinfected the carious dentin.

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“…Against aerobic organisms, however, metronidazole is relatively inactive (2), and, moreover, earlier studies have shown that it is inactivated by certain aerobic bacteria (6,8).…”

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Inactivation of Metronidazole by Anaerobic and Aerobic Bacteria

Ralph

Clarke

1978

Antimicrob Agents Chemother

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The rate of inactivation of metronidazole in vitro was determined during the course of time-kill curves against anaerobic and aerobic bacteria in the stationary phase of growth. Metronidazole at a concentration of 10 jig/ml, as measured by bioassay, was rapidly inactivated in broth culture by susceptible anaerobic bacteria (miniimum bactericidal concentration c 3 ,ug/ml), and this correlated closely with its bactericidal activity. In contrast, the drug was neither inactivated nor had any bactericidal activity against a resistant strain of Propionibacterium acnes (minimum bactericidal concentration > 1,500 ,ug/ml). Three of four aerobic bacteria also inactivated metronidazole, although at generally slower rates than the anaerobes, but this was not associated with a bactericidal effect against these organisms. The presence of aerobic bacteria in mixed cultures with Bacteroides fragilis did not, moreover, inhibit the bactericidal activity of metronidazole against the latter organism. However, the possibility still remains that, in vivo, aerobic bacteria capable of inactivating metronidazole could inhibit the action of the drug against anaerobes in mixed infections.It has been well established that metronidazole is consistently bactericidal in vitro against many anaerobic bacteria (2, 13) and appears to be effective clinically in the treatment of anaerobic infections (1,14). Against aerobic organisms, however, metronidazole is relatively inactive (2), and, moreover, earlier studies have shown that it is inactivated by certain aerobic bacteria (6,8).A study was devised to examine the rate of inactivation of metronidazole by both anaerobic and aerobic bacteria and the potential inhibitory effect of aerobic organisms on its activity against anaerobes.MATERIALS AND METHODS Bacterial organisms. Six clinical anaerobic isolates (Bacteroides fragilis, Fusobacterium nucleatum, Eubacterium lentum, Peptostreptococcus anaerobius, Clostridium perfringens, and Propionibacterium acnes) and four aerobic strains (Staphylococcus aureus, Escherichia coli, Proteus morganii, and Streptococcus faecalis) were used as the test organisms. AU were maintained on blood agar in an anaerobic glove box (Coy Manufacturing, Ann Arbor, Mich.). The gas mixture within the anaerobic glove box consisted of 85% nitrogen, 10% hydrogen, and 5% carbon dioxide. The bacteria were subcultured in brucella broth (Difco) containing 5 ug per ml of hemin(BB+H) 18 to 48 h before each experiment.The minimum inhibitory concentrations (MICs) of metronidazole for these organisms were determined by the tube dilution method in BB+H in the anaerobic glove box at an inoculum size of approximately 105 colony-forming units per ml (CFU/ml). The minimum bactericidal concentrations (MBCs) were determined after subculture of tubes showing no growth above to brucella agar (Difco) containing hemin (BA+H) and defined as the lowest concentration at which no growth occurred.Time-kill curves. All procedures were performed within the anaerobic glove box (AGB) except the pouring of plate...

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The antibacterial activity of metronidazole

Cited by 65 publications

References 21 publications

Clinical testing of the radiosensitizer Ro 07-0582: Experience with multiple doses

Clinical testing of the radiosensitizer Ro 07-0582: Experience with multiple doses

Bactericidal Efficacy of Metronidazole against Bacteria of Human Carious Dentin in vitro

Inactivation of Metronidazole by Anaerobic and Aerobic Bacteria

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