The bioavailability for four different commerically available brands of ampicillin compared with that of talampicillin.
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Biomedical subjects
Publications and source records attributed to W Brumfitt.
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1 The biliary excretion of erythromycin has been studied following parenteral administration in 23 patients. 2 Mean bile levels of the drug were approximately ten times higher than corresponding serum concentrations 1 h after i.v. (erythromycin lactobionate) and i.m. (erythromycin ethylsuccinate) injection. 3 Thus, unlike many antimicrobial agents, these compounds are well concentrated in the bile.
Over an 18-month period (October 1973 to April 1975), 133 strains of gram-negative bacteria with acquired resistance to trimethoprim (TM) were isolated from infected urines cultured at the Royal Free Hospital. The overall frequency of resistance was 3.2%. A disproportionately high number of resistant strains (63.1%) were Kebsiella aerogenes. Resistance to TM mediated by R plasmids occurs infrequently (9% of all resistant strains); the majority of TMR plasmids isolated belonged to one incompatability group (W). Chromosomally mediated resistance to TM in most Escherichia coli and K. aerogenes strains appears to be due mainly to production of a dihydrofolate reductase with a reduced susceptibility to TM. In some strains, increased activity of the DHFR was also a contributing factor. Increase in enzyme level alone was only great enough to account for the level of resistance to TM in a small number of cases.
42 strains of gram-negative bacteria, isolated from clinical material, resistant to trimethoprim (TM), sulphamethoxazole (SMZ) or both, have been tested for synergistic sensitivity to TM + SMZ. The combination showed no synergy against strains 'highly resistant' to SMZ (MIC greater than 1 mg/ml). Indifference was invariably observed. However, synergy was seen with strains 'moderately resistant' to SMZ (MIC 100--1,000 microgram/ml). Our results indicate that present techniques for the testing of urinary tract isolates for sensitivity to co-trimoxazole need revision.
48 non-pregnant domiciliary patients referred by general practitioners and 50 pregnant women were treated for bacteriuria with either 500 mg cephradine or 400 mg pivmecillinam every 6 h for 7 days. In the pregnant women, cure rates were over 90% after 2 weeks for both compounds, and after 6 weeks were 86% for cephradine and 78% for pivmecillinam. Cure rates in the non-pregnant were 83% for cephradine and 95% for pivmecillinam at 6 weeks. Seven patients (3 given cephradine, 4 given pivmecillinam) stopped treatment due to side-effects. Overall, side-effects (many of which were trivial) were more common in patients treated with cephradine (51%) than in those receiving pivmecillinam (33%). It is concluded that both drugs are highly effective in these two common types of urinary infection.
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Specimens from 95 patients attending a venereal diseases clinic were examined for gonococci by three methods--a conventional culture technique using modified Thayer-Martin medium, microscopy of a Gram-stained direct smear, and the Microcult system. For 56% of the specimens the results by all three methods agreed. Assuming the results obtained by culture on Thayer-Martin medium to be correct, the largest source of error was due to false-positive results: microscopy gave 26 and Microcult gave 15 such results. False-negative results were less common: Microcult gave 14, microscopy six. Microcult gave positive results more quickly than the conventional Thayer-Martin cultural method, but the gonococci were difficult to isolate by subculture from the Microcult culture pads. The Microcult medium was not absolutely specific for Neisseria gonorrhoeae. Nevertheless, the Microcult test may well prove to be a useful adjunct to the diagnosis of gonorrhoea, especially when laboratory facilities are not readily available.
Five nitrofurans- nitrofurantoin, nifuratel, nitrofurazone, furazolidone and and SQ 18,506--have been tested against 201 microbial strains. Escherichia coli, Streptococcus faecalis, micrococci and Staphylococcus epidermidis were sensitive to all five compounds; furazolidone and SQ 18,506 were the most active against these species. Klebsiella aerogenes was less sensitive, and Proteus spp., Providencia stuartii and Pseudomonas aeruginosa strains were resistant. Nifuratel was inhibitory for some Candida albicans strains, and SQ 18,506 was highly active against this species. Nifuratel was judged overall to have superior in vitro antimicrobial properties to nitrofurantoin.
Data on the incidence of primary resistance to rifampicin in Mycobacterium tuberculosis strains have been collected from various countries. Strains isolated from those countries where rifampicin is used for both tuberculous and non-tuberculous conditions (Italy, Argentina, Brazil, and Spain) did not show a higher incidence of primary resistance than did strains from other countries (France, U.K., and U.S.A.) where rifampicin use is confined to tuberculosis. It is concluded that there is no evidence to justify fears of an increased incidence of resistance to rifampicin in M. tuberculosis if rifampicin were used discreetly for treating non-tuberculous infections.
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Mecillinam (MC) was found to be inhibitory at low concentrations to a wide range of Gram-negative bacteria; the sensitivity of such strains could be predicted by using a 10 microgram disk. Resistance to MC did not appear to be associated with beta-lactamase-mediated destruction of the antibiotic. Ampicillin-resistant strains tended to be less sensitive to MC. MC and cephradine acted synergistically against Proteus mirabilis, Pr. vulgaris, Prov. stuartii and Serratia marcescens, and the combination was additive against most Klebsiella aerogenes, Enterobacter spp. and Escherichia coli.
The Microstix system has been tested, in parallel with dipslides, for suitability as a screening technique for the detection of bacteriuria. Results obtained using each method on 228 urine specimens were assessed by comparison with the results of quantitative counts. Dipslides had a higher sensitivity (86-7%) than Microstix. The best specificity (100%) was obtained from those results (77-6%) where both components of the Microstix system were in agreement. Advantages of Microstix are its greater shelf-life and its compactness.
Techniques for the microbiological assay of nitrofurans are described. In one the indicator strain is Bacteroides fragilis; use of this system enables concentrations of nifuratel and furazolidone of down to 0.7 micrograms/ml to be estimated. The other system uses a recombination-deficient (recA-uvrA-) mutant of Escherichia coli; with this indicator, concentrations of 0.2 micrograms/ml, or less, of five nitrofurans can be assayed.
The activities of formaldehyde and of mandelic and hippuric acids, alone and in combination, have been tested against some 300 strains of bacteria typical of those causing urinary tract infections. In a chemically defined medium, which resembles urine in many respects, formaldehyde had a mean minimal inhibitory concentration of 13 mug per ml. Activity was several fold lower in media (nutrient agar and tryptic soy agar) that contained significant amounts of protein. The activity of formaldehyde is virtually unaffected by pH in the range of 5 to 8. Mandelic and hippuric acids (2 mg per ml) have limited antimicrobial activity at acid pH values only. The combination of formaldehyde with mandelic acid (2 mg per ml) was additive, most markedly at pH 5; the formaldehyde-hippuric acid combination, however, did not appear to be additive. Our findings suggest that, at pH values between 5 and 6, an antibacterial concentration of formaldehyde will be generated from methenamine within approximately 1 hr after being excreted into the urine.
The bacterial flora of the female periurethral area was studied by impression cultures taken by polystyrene sponges, the results being recorded by photographic contact printing. With this technique it is possible to observe the preferential colonisation of different areas by different organisms and to detect persistent colonisation by pathogens. In assessing the possible aetiological importance of these results, and especially in comparing them with the findings of other workers, it is essential to use correct anatomical nomenclature.
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