Correlation of the results of antibiotic synergy and susceptibility testing in vitro with results in experimental mouse infections.

Recent clinical isolates (approximately 150 strains) of the family Enterobacteriaceae were examined by agar diffusion, microdilution, and the Autobac automated system for their responses to beta-lactam antibiotics singly and in combination with amdinocillin (formerly called mecillinam). The ratio of ampicillin, carbenicillin, and cephalothin to amdinocillin was maintained at a 10:1 ratio in most of the evaluations. The same isolates were studied in mice challenged with 100 to 1000 LD50s and treated with graded doses of the antibiotics singly and in combination. Efficacy in vivo was based on the concentration of antibiotic in milligrams per kilograms (mg/kg) required to protect 50% of the animals (PD50). After a single administration of the antibiotics, plasma levels were determined in the critical time period (30 min to 4 hr) during which the acute, overwhelming systemic infections could be controlled by appropriate therapy. Regression curves comparing in vivo and in vitro results were used to establish cut-off points for categorizing bacterial susceptibility in each of the laboratory tests for the single agents and combinations. A high degree of synergism between amdinocillin and the beta-lactam agents was demonstrated in animals (54 to 78% of the strains examined) and to a lesser extent by laboratory methodologies. There was an excellent correlation of in vivo and in vitro responses to ampicillin, carbenicillin, and cephalothin alone and in combination with amdinocillin for those species for which the single antibiotics are generally indicated. The correlations validated the chosen cut-off points. The correlation of in vivo and in vitro responses to the single or combined antibiotics was generally poorer for those species not usually responsive to the single antibiotics. The greatest difficulty in predicting proper in vivo responses, based on the results of in vitro tests, was observed with amdinocillin.

Chemotherapeutic activity of 5-fluorocytosine and amphotericin B against Candida albicans in mice.

The effect of treatment with combinations of the two antifungal agents, 5-fluorocytosine (5-FC) and amphotericin B (AB), against systemic Candida albicans infections in mice was investigated. Graded doses of the single substances and of combinations of the drugs were administered daily for 21 days. The 50% curative dose (CD(50)) values were calculated on the basis of the presence or absence of C. albicans in cultures prepared from the kidneys of animals that succumbed during the experimental period or were sacrificed at the termination of the experiments. Overall, when graded doses of AB were administered in the presence of a constant, inactive dose of 5-FC (approximately one-half to one-fourth the CD(50) of 5-FC), the CD(50) values for AB were lower than those for amphotericin B alone. Similarly, the CD(50)s for 5-FC were reduced when AB was administered at a constant dose equal to one-half to one-fourth the CD(50) of AB alone. In no instance was there evidence of antagonism.

Effects of l-(2-nitro-l-imidazolyl)-3-methoxy-2-propanol and 2-methyl-5-nitroimidazole-l-ethanol against anaerobic and aerobic bacteria and protozoa.

1-(2-Nitro-1-imidazolyl)-3-methoxy-2-propanol (RO 7-0582) and 2-methyl-5-nitroimidazole-1-ethanol (Metronidazole), substances known to be potent trichomonacides, were shown to inhibit obligate anaerobic bacteria in vitro but were essentially without effect at the doses tested against bacteria capable of growing aerobically. A similar effect was noted in vivo in that both substances exhibited good chemotherapeutic activity against infections produced by three species of anaerobic protozoa but were essentially inactive at the doses tested against three species of aerobic protozoa.

Efficiency of a multitest system (Enterotube) for rapid identification of Enterobacteriaceae.

Enterotube, a multiple-test system which combines nine biochemical tests useful in the identification of members of the family Enterobacteriaceae, was tested and compared with the PathoTec test system in the identification of gram-negative bacilli isolated from clinical specimens. It was found that both the Enterotube and the PathoTec systems rapidly and accurately defined the position of the organisms in the major groups of the family Enterobacteriaceae. Discrepancies were noted between the results of citrate tests on Simmons' citrate-agar and in the Enterotube, as well as between Simmons' citrate-agar and the PathoTec citrate test. It was concluded that the Enterotube system provides a simple, reliable, and rapid method for the presumptive identification of Enterobacteriaceae. The major advantage of the Enterotube is that all tests are done simultaneously by inoculation from a single isolated colony.