Unique Bactericidal Action of Metronidazole Against Bacteroides fragilis and Clostridium perfringens

The relative efficacy of single doses of antibiotics in modifying the development of Bacteroides fragilis subsp. fragilis endocarditis was studied in an experimental model. Antibiotics were administered 0.5 -h before intravenous injection of B. fragilis subsp. fragilis into rabbits prepared by insertion of a polyethylene catheter into the left side of the heart; 48 h later, intracardiac vegetations were excised and cultured anaerobically. B. fragilis was recovered from 92% of untreated animals. After a single dose of procaine penicillin G (250 mg/kg intramuscularly), 80% of the animals remained infected. Chloramphenicol (30 mg/kg), carbenicillin (50 mg/kg), and metronidazole (10 mg/kg) were also ineffective (76, 80, and 75% infected, respectively). Cefamandole (30 mg/kg), cefoxitin (30 mg/kg), and erythromycin (30 mg/kg) were significantly more active (50, 55, and 45% infected, respectively), as were higher doses of carbenicillin. Clindamycin (50 mg/kg) was the most effective regimen (11% infected). At present, the relevance of these results to the therapy of serious B. fragilis infections is not known, but this model may prove useful in the evaluation of the prevention of B. fragilis subsp. fragilis bacteremia.

Section: Resultscontrasting

confidence: 39%

Effect of Antibiotics on the Prevention of Experimental Bacteroides fragilis Endocarditis

Goldman

Durack

Petersdorf

1978

“…On B. fragilis species, Clostridium species, and anaerobic gram-positive cocci its activity was poor. Tinidazole has a unique bactericidal action against B. fragilis and C. perfringens (10). In our studies, the drug appeared effective against all types of anaerobic microorganisms tested, with the exception of the anaerobic gram-positive cocci.…”

Section: Resultsmentioning

confidence: 63%

Anaerobic Wound Infections in Cancer Patients: Comparative Trial of Clindamycin, Tinidazole, and Doxycycline

Klastersky

Husson

Weerts-Ruhl

et al. 1977

Clindamycin, tinidazole (a parent compound to metronidazole), and doxycycline were compared in vitro against 376 anaerobic bacteria isolated from clinical specimens. Bacteriostatic tests indicated that clindamycin was the most active drug, on a weight basis, against these strains except for Clostridium species. The three drugs were compared as therapies for anaerobic wound infections in cancer patients. In a randomized double-blind study, no statistically significant differences between clindamycin and tinidazole could be documented. Doxycycline was less active presumably because of the lack of clinical response in three out of four patients infected with doxycycline-resistant strains. No major untoward effects were observed. The bactericidal dilution of the serum was predictive of the clinical outcome.

“…Ralph and Kirby suggested that metronidazole has a marked bactericidal effect which occurs after a prolonged lag phase (16). There remains the possibility, however, that this prolonged lag period was an artifact ofmethodology.…”

mentioning

confidence: 90%

Antimicrobial activity of metronidazole in anaerobic bacteria

Tally¹,

Goldin²,

Sullivan³

et al. 1978

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.