David Greenwood

Factors influencing the activity of the trometamol salt of fosfomycin

The antibacterial activity of trometamol fosfomycin and its potentiation by glucose-6-phosphate were found to vary considerably in different culture media, although not all bacteria tested were equally affected. In general, the lowest MICs were obtained in the presence of glucose-6-phosphate in nutrient broth and Eugonbroth. The influence of inoculum size, pH and potentiation by glucose-6-phosphate were investigated by agar incorporation MIC titrations on nutrient agar. The activity of trometamol fosfomycin against many strains increased as the pH was lowered from 7.9 to 5.5. Only 9% of the strains showed an inoculum effect when tested at pH 5.5 in the presence of glucose-6-phosphate compared with 37% of the strains tested at pH 7.1 and 22% of the strains tested at pH 7.9. In the absence of glucose-6-phosphate, about 10% of the strains showed an inoculum effect at all three pH levels. The addition of glucose-6-phosphate to culture media seems reasonable for the testing of fosfomycin susceptibility.

Comparison of the response ofEscherichia coli to fosfomycin and fosmidomycin

The responses ofEscherichia coli to fosfomycin and fosmidomycin were investigated by continuous turbidimetric monitoring of cultures exposed to the drugs and by microscopy. The activity of both agents was potentiated by glucose-6-phosphate, suggesting that they share the inducible hexose phosphate transport system inEscherichia coli, but several differences of response were also detected: the inoculum effect was much smaller with fosfomycin than with fosmidomycin; inhibition of bacterial growth occurred much more rapidly with fosfomycin than with fosmidomycin; and fosfomycin was able to induce the formation of spheroplasts much more rapidly than fosmidomycin. Stable resistance to fosfomycin and fosmidomycin was readily induced in cultures ofEscherichia coli, and some resistant variants retained susceptibility (or partial suceptibility) to the other compound. These observations suggest that although fosfomycin and fosmidomycin may be transported intoEscherichia coli by a similar mechanism, the intracellular target site may be different.

Turbidimetric response ofStaphylococcus aureus andEnterococcus faecalis to daptomycin

The response to daptomycin of three strains ofStaphylococcus aureus (one of which was methicillin-resistant) and a strain ofEnterococcus faecalis was investigated by continuous turbidimetric monitoring. Daptomycin caused partial inhibition of bacterial growth at concentrations well below those suppressing growth overnight. The activity of the drug was more than 200-fold greater in the presence of a physiological concentration of calcium (2.5 mmol/l) than in its absence. Variants present in cultures inhibited by daptomycin were shown to exhibit decreased susceptibility to the drug and the susceptibility declined further on repeat exposure; however, there was a slow but incomplete reversion to susceptibility on sequential subculture in drug-free broth. Resistance was difficult to induce when the concentration of calcium in the broth exceeded 2.5 mmol/l.

Relationship of beta-lactamase production to growth phase inBacteroides species

1. Kunin, C. M., Brandt, D.: Comparative studies ofampicillin, cephalothin and a new cephalosporin derivative,cephaloglycin. American Journal of the Medical Sciences 1968, 255 : 196-201. 2. Yourassowsky, E., Van der Linden, M. P., Lismont, M. J., Crokaert, F.: Growth curve patterns and regrowth in post antibiotic period of Escherichia coli exposed to ampicillin and amoxicillin. Journal of Antimicrobial Chemotherapy 1983, 11: 333-338. 3. Goodell, E. W., Lopez, IL, Thomasz, A.: Suppression of lytic effect of beta-lactams on Escherichia coli and other bacteria. Proceedings of the National Academy of Sciences of the United States of America 1976, 73: 3293-3297. 4. Lopez, R., Ronda-Lain, C., Tapia, A., Waks, S. B., Thomasz, A.: Suppression of the lyric and bactericidal effects of cell wall-inhibitory antibiotics. Anrimicrobial Agents of Chemotherapy 1976, 10: 697-706. 5. Tallgren, L. G., Von Bonsdoref, C. H.: The effect of varying the pH level upon the sensitivity of urinary bacteria to antibiotics. Acta Medica Scandinavica 1965, 178: 543-551.

Studies on the emergence of resistance to lomefloxacin in vitro

The emergence of resistance to lomefloxacin, norfloxacin and ciprofloxacin was investigated in nalidixic acid sensitive and resistant urinary isolates by continuous turbidimetry. A decline in susceptibility was observed after a single exposure to each of the drugs, and further increments of resistance occurred during three sequential passages. Variants resistant to one quinolone were cross-resistant to the others. The level of resistance selected by norfloxacin in three of the five test strains was greater than that observed with lomefloxacin or ciprofloxacin. In experiments in a model of the treatment of bacterial cystitis, concentrations of lomefloxacin well within those readily achievable in urine suppressed growth of nalidixic acid sensitive and resistant strains for more than 20 h without causing any decline in susceptibility of surviving bacteria.

Newer Antibiotics Active Against Bacteroides Fragilis: Comparison with Older Agents

The activity of eleven antibiotics against a high inoculum (ca 108 cfu./ml) of Bacteroides fragilis was examined in an anaerobic turbidimeter which allowed the removal of samples during the course of the experiment for the parallel investigation of bactericidal activity and morphological effects. When comparative bacteriostatic and bactericidal activities were related to achievable blood levels, imipenem, clindamycin and the combination of benzylpenicillin with clavulanic acid exhibited the highest activity. Surprisingly, fusidic acid also showed good activity. Although metronidazole displayed only moderate bacteriostatic and bactericidal activity in relation to achievable blood levels it was the only agent found to be bactericidal to cultures in the stationary phase of growth, and this may help to explain its excellent activity in vivo.