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Biomedical subjects

D S Reeves

Publications and source records attributed to D S Reeves.

At least 181 records · Page 10Linked to original sources
PubMed1981

The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers.

1 Cefoxitin was given by acute intravenous injection to six healthy volunteers, in a crossover study to investigate the effects of concurrent probenecid administration. 2 Serum antibiotic concentrations were determined by microbiological assay. Cefoxitin concentrations were simultaneously determined in the fluid of blisters produced by topical cantharides. All antibiotic was accounted for in the urine. 3 Cefoxitin was administered by intravenous infusion, subsequent to a loading dose, to produce steady state levels in the region of 10 microgram/ml, in one volunteer. The procedure was later repeated after prior administration of probenecid in the same subject. 4 Pharmacokinetic analyses indicated significant changes only in the parameters associated with renal excretion of drugs. Clearance was reduced by half. 5 The absolute and relative amounts of antibiotic in the central and peripheral compartments were calculated for both modes of administration. In the acute study probenecid produced a small change in distribution away from the peripheral or tissue compartment, towards the central compartment. 6 There was no elevation of initial serum concentrations and sustained levels of antibiotic could be accounted for principally by retarded excretion produced by probenecid, with little contribution by alteration in the disposition of antibiotic. 7 The sustained serum levels of cefoxitin that resulted from its decreased excretion were also reflected in blister fluid. It was concluded that the sustained cefoxitin levels produced by probenecid resulted in similar raised levels in the peripheral or "tissue' compartment, since the redistribution away from the peripheral compartment did not contribute materially to other changes in disposition of drug.

Adult↗
PubMed1981

Resistance of Pseudomonas species to beta-lactam antibiotics.

Resistance of Pseudomonas species to beta-lactam compounds involves both drug exclusion and hydrolytic inactivation. Exclusion is effected by a permeability barrier in the cell envelope, whereas hydrolysis is effected by beta-lactamases, encoded either by the chromosome or by R-plasmids. Chromosomally-mediated beta-lactamases are generally inducible and have a high activity against cephalosporins. They are virtually universally present in P. aeruginosa. Conversely, the generally infrequent R-plasmid-mediated beta-lactamases are constitutive, with substrate profiles specific to each enzyme type. Four Pseudomonas-specific R-plasmid-mediated beta-lactamases are responsible for high level resistance to carbenicillin. Resistance to carbenicillin may also be associated with isolates not possessing this type of beta-lactamase: the permeability barrier effect is probably highly significant in these isolates.

Anti-Bacterial Agents↗
PubMed1980

Therapeutic drug monitoring of aminoglycoside antibiotics.

Aminoglycosides are widely used antibacterial agents, particularly for serious infections. They have a narrow therapeutic margin of efficacy over toxicity relative to many other agents, a disadvantage which can be obviated to some extent by precise dosing regulated by blood concentration monitoring. The relationships of efficacy and toxicity to concentrations are discussed, as are the practical aspects of clinical indications for monitoring and specimen collection. Dosing by predictive methods is useful but not always of sufficient precision. A large number of methods for assay are now available. With care, microbilogical plate assays can give results of adequate accuracy and selectivity, and with sufficient speed. Immunoassays give more accurate, specific and rapid answers; EMIT, in particular, seems the best method available at the present time. Whichever method is used, control of its accuracy is essential.

Aminoglycosides↗
PubMed1980

Comparison of sensititre dried microtitration trays with a standard agar method for determination of minimum inhibitory concentrations of antimicrobial agents.

A total of 222 clinical isolates were used to test the accuracy of Sensititre dried microtitration trays for determining minimum inhibitory concentrations (MICs) of antimicrobial agents. In comparison with an agar dilution technique, 89.5% of all the pairs of results were within one doubling dilution. The 2,420 pairs of MIC results with finite values gave a corresponding figure of 86.8%. Exclusion of sulfisoxazole results, which demonstrated a significant interlaboratory variation in accuracy, raised this value to 89.1%. Very good differentiation of beta-lactamase-producing strains of Staphylococcus aureus (24 of 24 giving an MIC greater than or equal to 0.25 micrograms/ml) and Haemophilus influenzae (3 of 3 giving an MIC greater than or equal to 32 micrograms/ml) was obtained with the Sensititre system. This method also clearly distinguished erythromycin-resistant S. aureus strains (7 of 7 giving an MIC greater than 32 micrograms/ml) from the susceptible strains (26 of 28 giving an MIC less than or equal to 0.5 microgram/ml plus 1 strain at 1.0 microgram/ml and 1 at 2.0 micrograms/ml). Sensititre offers an accurate and convenient method of determining MICs comparable to those obtained with the agar dilution procedure, with the advantage of an extended shelf life when stored at room temperature.

Aminoglycosides↗
PubMed1980

Double-blind clinical trial of a nitrofurantoin/sulphadiazine combination at two dosage levels in acute symptomatic urinary infections.

A double-blind trial was carried out in 177 patients with acute symptomatic urinary tract infections to assess the efficacy and tolerability of nitrofurantoin plus sulphadiazine at two dosage levels. Patients were allocated, at random, to receive 7-days' treatment with either 50 mg nitrofurantoin plus 150 mg sulphadiazine 3-times daily or 100 mg nitrofurantoin plus 500 mg sulphadiazine 3-times daily, and were followed-up 10 to 14 days later. Only the 73 (41%) patients with significant bacteriuria on entry were included in the analysis of the efficacy results. There were no statistically significant differences between the two treatments either in bacteriological cure rates, which were approximately 90% in both groups, or in the complete or partial resolution of symptoms, recorded in over 90% of patients at the 2-week follow-up visit. The main side-effects recorded were anorexia, nausea, vomiting and/or headache, and were fewer in the group treated with the lower dosage.

Adult↗