Abstract In the presence of phosphate-citrate buffers, nystatin and amphotericin B are optimally stable between pH 5 and 7. Loss of biological activity followed first-order kinetics, except under acid conditions. Apparent energies, enthalpies, free energies and entropies of activation of the two antibiotics have been calculated at pH 7, and the two sets of figures are similar. Variation in pH between 5 and 8 appeared to have little effect of the activity of amphotericin B against Candida albicans, while nystatin was more active at pH values between 6 and 8. Nystatin was more active at lower incubation temperatures (30-25°), while amphotericin B appeared to be more active at 41°.
Twenty-four general practitioners completed a questionnaire on behalf of their partners in the practices before attending the symposium. The main points that emerged were that trimethoprim was the most popular antibiotic for treatment of acute urinary infection and that the most common duration of treatment was 5 to 7 days. A panel discussion, with audience participation, covered duration of treatment, antibiotic resistance, specimen collection, management of different patient groups and availability of information concerning resistance patterns. Nineteen of the original 24 general practitioners returned the post-meeting questionnaire, and stated that, as a result of what they had heard at the symposium, they were contemplating changing the way in which they managed urinary infections. Information concerning bacteriuria in pregnancy and changing patterns of bacterial resistance to antibiotics were of particular interest.
Virtually all the agents now available for the treatment of infections were discovered by chance, or at best developed without a specific plan rather than on the basis of a sequence of logical experiments. An element of reason went into the original decision to screen samples of soil for the presence of microorganisms (usually molds) capable of producing antibiotic substances, but thereafter the procedures used were, of necessity, entirely empirical. Although there are notable exceptions, such as hexamine, mandelic acid, nalidixic acid, the nitrofurans, sulfonamides, p-aminosalicylate, and isoniazid, nearly all the clinically useful antibacterial compounds such as the (3-lactam compounds, aminoglycosides, tetracyclines, and macrolides were developed by observation and experiment without any background theory. Admittedly, some of the more sophisticated refinements have been planned by chemical methods, and the introduction of the semisynthetic penicillins and cephalosporins was a major advance in antimicrobial therapy. Nevertheless, empiricism was inevitable, and history has shown that the mode of action of an antibacterial compound is rarely known until some time after its introduction into clinical practice. The best example is penicillin. The explanation for selective toxicity of penicillin was not known until more than 20 years after its discovery, and the method of transport of wall components by lipid intermediates in the membrane remains to be elucidated.
A five-way crossover study in 10 volunteers was carried out to determine the bioavailability by the oral route of 4 brands of ampicillin and of talampicillin. There were no significant differences between the 4 ampicillins in terms of maximum serum levels, times of peak levels, serum concentrations at each sampling time, area-under-curves, half-lives and percentage urinary excretion (including peniciloate). A significantly higher proportion of the dose of ampicillin (65.6%) appeared in the urine after giving talampicillin than after giving any of the ampicillins (mean value = 38%). Thus, while there is no bioinequivalence amongst these ampicillin brands, talampicillin is a more effective way of delivering ampicillin. There were some indications that females absorb ampicillin less well than do males, and that there may be ‘good’ and ‘bad’ absorbers of ampicillin.
Abstract Three different intramuscular formulations of cefonicid (a new long acting cephalosporin) have been tested for bioavailability in 12 healthy volunteers, using a triple crossover design. No significant differences were detectable between the bioequivalence of the three formulations in terms of area‐under‐curve and 24‐h urinary excretion. However, one of the formulations (A) was absorbed significantly more rapidly from the site of injection, causing higher serum levels for up to 1.5 h after administration. A significantly greater urinary excretion was also found up to 8 h after admininstration of formulation A. All three formulations were well tolerated, and no side‐effects or significant changes in laboratory tests were observed.
Journal Article The susceptibility of nosocomial pathogens to ceftazidime Get access W. Brumfitt, W. Brumfitt Royal Free HospitalPond Street, London NW3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. T. Hamilton-Miller J. M. T. Hamilton-Miller Royal Free HospitalPond Street, London NW3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 8, Issue suppl_B, 1981, Pages 15–21, https://doi.org/10.1093/jac/8.suppl_B.15 Published: 01 April 1981
Phenotypes of resistance to the macrolide-lincosamide-ketolide-streptogramin (MLKS) group of antibiotics have been determined in 540 clinical isolates of staphylococci (210 Staphylococcus aureus and 330 coagulase-negative species). Results of disc diffusion tests using erythromycin A, oleandomycin, rokitamycin, clindamycin, telithromycin, quinupristin and dalfopristin delineated four main groups corresponding to those defined classically using erythromycin and clindamycin only, but with sub-divisions. Resistance to erythromycin was more common in coagulase-negative strains (56%) than in S. aureus (16%); telithromycin, clindamycin, quinupristin–dalfopristin and rokitamycin were active against >97% of S. aureus strains and >88% of the coagulase-negative strains. The commonest resistance phenotype was 'inducible MLSB' (12% in S. aureus, 31% in coagulase-negative strains); this group could be divided in terms of the different inducing abilities of erythromycin and oleandomycin. 'Constitutive MLSB' and 'MS' phenotypes were more often found in coagulase-negative strains (11 and 13%, respectively) than in S. aureus (2 and 1%). Novel phenotypes were found during the isolation of constitutively resistant mutants from inducible strains, and of resistant mutants from 'MS' strains. This extended phenotyping scheme has revealed further complexities and evolutionary possibilities in patterns of resistance to this group of antibiotics.
SUMMARY The activities of azlocillin and ticarcillin against Pseudomonas aeruginosa were compared by estimating minimum inhibitory and bactericidal concentrations (MIC and MBC) in liquid and solid media, and by constructing killing curves from sequential viable counts. In MIC studies, azlocillin was about three times more active than ticarcillin in solid medium (agar dilution test) and in liquid media (tube and microdilution tests). When the MBC was measured, however, results varied according to the technique used. On agar and in microdilution tests, both azlocillin and ticarcillin were bactericidal, the MBC being 1.3-3 MIC. In the tube test, the MBC for ticarcillin was again about 3 MIC, but azlocillin appeared not to be bactericidal (MBC < 1 mg/ml). However, sequential viable counts of four clinical isolates showed that at 4 MIC both antibiotics reduced viable counts by a factor of 104 in 8 h. Our results stress the importance of methodology when assessing the antibacterial activity of an antibiotic.
Journal Article Paldimycin: a novel antibiotic highly active against Gram-positive bacteria Get access W. BRUMFITT, W. BRUMFITT Department of Medical Microbiology, The Royal Free Hospital School of MedicinePond Street, Hampstead, London NW3 2QG, England Search for other works by this author on: Oxford Academic PubMed Google Scholar J.M.T. HAMILTON-MILLER, J.M.T. HAMILTON-MILLER Department of Medical Microbiology, The Royal Free Hospital School of MedicinePond Street, Hampstead, London NW3 2QG, England Search for other works by this author on: Oxford Academic PubMed Google Scholar GAYNOR WHITER GAYNOR WHITER Department of Medical Microbiology, The Royal Free Hospital School of MedicinePond Street, Hampstead, London NW3 2QG, England Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 19, Issue 3, March 1987, Pages 405–406, https://doi.org/10.1093/jac/19.3.405 Published: 01 March 1987
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