Antimicrobial activity of metronidazole in anaerobic bacteria.

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 [14C]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 metronidazole's antimicrobial activity against anaerobic bacteria is bactericidal and independent of growth rate, and that it involves the uptake and metabolism of the compound.     

Susceptibility of anaerobic bacteria isolated from intra-abdominal infections to ofloxacin and interaction of ofloxacin with metronidazole.

The in vitro activities of ofloxacin alone and in combination with metronidazole against 177 anaerobic bacteria isolated from intra-abdominal infections, as determined by broth microdilution, showed that some Bacteroides fragilis strains were susceptible and that most other B. fragilis group species strains were resistant to ofloxacin. Isolates of other anaerobic species and genera, including those causing female genital tract disease, were generally susceptible to ofloxacin. Ofloxacin in combination with metronidazole usually showed an additive or indifferent interaction but no antagonism.     

Intravenous metronidazole therapy for Bacteroides fragilis meningitis.

A 69-year-old man developed meningitis due to Bacteroides fragilis and Streptococcus MG-intermedius, which progressed during chloramphenicol and nafcillin therapy to the extent that he seemed near death, with frank pus covering the spinal cord at surgery. Treatment with intravenous metronidazole and penicillin G was curative. After multiple trauma, a 20-year-old man developed meningitis due to Escherichia coli and B fragilis. He failed to respond to chloramphenicol alone, but responded to combined treatment with chloramphenicol and metronidazole. The right frontal sinus and epidural space abscesses were drained and a right frontal lobe abscess was excised. Metronidazole may be a uniquely effective agent for treatment of meningitis due to susceptible strains of Bacteroides fragilis.     

Comparative in vitro activities of niridazole and metronidazole against anaerobic and microaerophilic bacteria.

In vitro susceptibilities of anaerobic bacteria (Bacteroides spp., Fusobacterium spp., Clostridium spp., and Peptococcus sp.) and of Campylobacter jejuni and C. coli to niridazole and metronidazole were determined. The minimum inhibitory concentrations for niridazole ranged from 0.0037 to 1.0 microgram/ml and, for metronidazole, from 0.25 to 128 micrograms/ml.     

Activity of metronidazole and its hydroxy and acid metabolites against clinical isolates of anaerobic bacteria.

Susceptibility of clinical isolates of anaerobic bacteria to metronidazole and its two oxidation products, 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole (the "alcohol" metabolite) and 2-methyl-5-nitroimidazole-1-acetic acid (the "acid" metabolite), were determined by the agar dilution technique. Results disclosed that the alcohol metabolite, although less active than metronidazole, inhibited the organisms tested at levels considered susceptible for metronidazole. The acid metabolite was less active, not inhibiting the organisms at levels within the susceptible range. In other studies, mixtures of known concentrations of metronidazole and the metabolites were assayed in a bioassay system used to measure metronidazole levels. These studies showed that the bioassay will measure metronidazole or the alcohol metabolite; the acid metabolite is not measured at levels achieved in clinical specimens. Since the activity of the alcohol metabolite is comparable to that of metronidazole, we feel that microbiological assays can be used for therapeutic monitoring of metronidazole levels in clinical situations.     

Antimicrobial susceptibilities of anaerobic bacteria isolated from female genital tract infections.

Certain species or subspecies of anaerobic bacteria are isolated with higher frequency from female genital tract infections than from other anatomic sites. To gain susceptibility data more specific to the treatment of these infections, nine antimicrobial agents were tested by an agar dilution technique against 230 anaerobic bacteria isolated solely from obstetric and gynecological infections. These genital isolates were, in general, very susceptible to imipenem (most active, inhibiting all gram-negative rods at less than or equal to 1 microgram/ml), clindamycin (all isolates inhibited at less than or equal to 4 micrograms/ml), metronidazole (all gram-negative rods inhibited at less than or equal to 4 micrograms/ml), and chloramphenicol. Penicillin G had generally low activity against Bacteroides spp., not restricted to just the Bacteroides fragilis group, although it was very active against gram-positive species. Bacteroides bivius, a species uniquely common in female genital infections, was particularly resistant (90% MIC, 64 U/ml). Also, the Bacteroides melaninogenicus isolates were less susceptible than previously reported for isolates not exclusively from genital sites. Compared with moxalactam, cefotaxime, and cefoperazone, cefoxitin usually demonstrated equal or greater activity against most Bacteroides spp., with the exception of greater activity of moxalactam against B. fragilis (formerly subsp. fragilis). Resistance to moxalactam was observed among strains of Peptostreptococcus anaerobius, a common genital isolate. Overall, the activities of these four drugs were not as predictable as those observed for clindamycin, metronidazole, chloramphenicol, and imipenem.     

Moxalactam treatment of anaerobic infections in cancer patients

Of 30 patients with predominantly anaerobic localized infections superimposed on chronic tissue damage related to trauma, ischemia, or tumor, 22 (73%) responded satisfactorily to moxalactam therapy. Moxalactam-resistant anaerobic pathogens emerged in two patients and were responsible for treatment failure. In six patients, two of whom also acquired resistant anaerobic pathogens, isolation of moxalactam-resistant aerobic pathogens increased during therapy.     

PCR-based detection of resistance genes in anaerobic bacteria isolated from intra-abdominal infections

Little information is available on the distribution of antimicrobial resistance genes in anaerobes in Japan. To understand the background of antimicrobial resistance in anaerobes involved in intra-abdominal infections, we investigated the distribution of eight antimicrobial resistance genes (cepA, cfiA, cfxA, ermF, ermB, mefA, tetQ, and nim) and a mutation in the gyrA gene in a total of 152 organisms (Bacteroides spp., Prevotella spp., Fusobacterium spp., Porphyromonas spp., Bilophila wadsworthia, Desulfovibrio desulfuricans, Veillonella spp., gram-positive cocci, and non-spore-forming gram-positive bacilli) isolated between 2003 and 2004 in Japan. The cepA gene was distributed primarily in Bacteroides fragilis. Gene cfxA was detected in about 9 % of the Bacteroides isolates and 75 % of the Prevotella spp. isolates and did not appear to contribute to cephamycin resistance. Two strains of B. fragilis contained the metallo-β-lactamase gene cfiA, but they did not produce the protein product. Gene tetQ was detected in about 81, 44, and 63 % of B. fragilis isolates, other Bacteroides spp., and Prevotella spp. isolates, respectively. The ermF gene was detected in 25, 13, 56, 64, and 16 % of Bacteroides spp., Prevotella spp., Fusobacterium spp., B. wadsworthia, and anaerobic cocci, respectively. Gene mefA was found in only 10 % of the B. fragilis strains and 3 % of the non-B. fragilis strains. Genes nim and ermB were not detected in any isolate. Substitution at position 82 (Ser to Phe) in gyrA was detected in B. fragilis isolates that were less susceptible or resistant to moxifloxacin. This study is the first report on the distribution of resistance genes in anaerobes isolated from intra-abdominal infections in Japan. We expect that the results might help in understanding the resistance mechanisms of specific anaerobes.     

Activity of cefmetazole against anaerobic bacteria.

The in vitro activity of cefmetazole versus that of other antimicrobial drugs was assessed against 374 clinical isolates of Bacteroides spp., Clostridium spp., and anaerobic gram-positive cocci. Compared with cefoxitin, cefmetazole showed good activity against Bacteroides fragilis, other Bacteroides species, and anaerobic cocci. It was somewhat less active than cefoxitin against Bacteroides thetaiotaomicron, B. ovatus, B. distasonis, and B. vulgatus and somewhat more active against Clostridium spp.     

Interactions of ciprofloxacin with clindamycin, metronidazole, cefoxitin, cefotaxime, and mezlocillin against gram-positive and gram-negative anaerobic bacteria.

A total of 598 clinical isolates of anaerobic bacteria were tested against ciprofloxacin by the agar dilution technique with 10(5) CFU on Wilkins-Chalgren medium. Selected strains representative of the six major genera of anaerobes relatively resistant to the quinolones were tested for interactions with ciprofloxacin in combination with clindamycin, metronidazole, cefoxitin, cefotaxime, or mezlocillin by using a checkerboard agar dilution technique. Cefotaxime-ciprofloxacin and clindamycin-ciprofloxacin were the most effective combinations, with 16% of all isolates and 44% of the Bacteroides fragilis group isolates responding synergistically to the former combination and 9% of all isolates and 37% of Peptostreptococcus isolates responding synergistically to the latter. Occasional synergy was seen with all other antibiotic combinations except for metronidazole-ciprofloxacin. Likewise, synergism was seen with all groups of anaerobes except for Fusobacterium species. Antagonistic interactions were observed only with a Peptostreptococcus intermedius strain tested against clindamycin-ciprofloxacin. These data suggest that combinations of ciprofloxacin with these agents may be useful for certain resistant anaerobic infections.     

Aspiration pneumonia and anaerobic lung infections.

Anaerobic organisms and their role in pleuropulmonary infections have been recognized with increased frequency with advances in diagnostic techniques. Valuable clinical, microbiologic and radiologic clues exist and are extremely useful in the diagnosis and treatment of such infections.