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Biomedical subjects

D S Reeves

Publications and source records attributed to D S Reeves.

At least 127 records · Page 7Linked to original sources
PubMed1989

Pharmacokinetics and tolerance of a new film-coated tablet of sodium fusidate administered as a single oral dose to healthy volunteers.

Single oral doses of 250, 500, 750 and 1000 mg of sodium fusidate as one, two, three and four film-coated 250 mg tablets were compared in a cross over design trial with a solution dose of 500 mg in 12 healthy male volunteers. The effect of food on absorption of two-film coated tablets was also studied. Compared with the dose given as a solution, tablets gave complete oral absorption, the area under the curve (AUC) for blood concentration being virtually identical. After administration of 250, 500, 750 and 1000 mg the mean of the maximum serum concentrations (Cmax) was 11.6 +/- 1.1, 30.6 +/- 2.2, 48.1 +/- 3.0 and 65.2 +/- 4.2 mg/l, respectively, indicating a greater than expected increase in Cmax with increasing dose. This was also apparent with AUC, while there was a significant trend for beta, the terminal slope of the serum/concentration time curve, to decrease. Food significantly reduced Cmax and delayed Tmax but did not affect AUC or beta. Dosage had no effect on parameters of renal, hepatic or haemopoietic function but 25% of the volunteers complained of upper gastro-intestinal symptoms mainly at the highest dose studied.

Administration, Oral↗
PubMed1989

Pharmacokinetics of FCE 22101 in man following different modes of administration.

Twelve healthy volunteers received single iv doses of either 500 and 1000 mg or 750 and 1500 mg of the sodium salt of FCE 22101; in addition, five of the volunteers received a further dose of 2000 mg. In the second part of the study, 11 of the volunteers received 1000 mg doses of FCE 22101 in a four-way randomized fashion by iv bolus (1000 mg, with and without probenecid), im injection (1000 mg plus lignocaine) and a continuous infusion (280 mg/h) to steady state. All doses were well tolerated by the volunteers with no serious side effects and no significant haematological or biochemical changes following drug administration. Plasma and urine concentrations of FCE 22101, and in the cross-over study also its open ring metabolites P1 and P2, were determined by HPLC. Good linearity was observed between the peak plasma levels or AUC and the dose given. Plasma concentrations were fitted to a two-compartment model and the mean pharmacokinetic parameters determined after iv bolus were: Cmax 117 mg/l, T1/2 beta 36 min, Vss 181, AUC 2179 mg/min/l with urinary recoveries of FCE 22101 37%, P1 36% and P2 6%. With probenecid the values were Cmax 116 mg/l, T1/2 beta 47 min, Vss 141, AUC 4540 mg/min/l and urinary recoveries of FCE 22101 20%, P1 40% and P2 7%. Following im injection the mean values were Cmax 15 mg/l, Tmax 30 min, T1/2abs 14 min, T1/2 beta 61 min, AUC 2117 mg/min/l and urinary recoveries of FCE 22101 33%, P1 37% and P2 6%. At steady state during continuous infusion, mean values were Css 12.7 mg/l, Vss 131 and T1/2 beta after steady state was 22 min. Although urinary recoveries varied widely between volunteers there was a tendency towards consistency of recovery within individual volunteers. We conclude that FCE 22101 is a well tolerated penem with pharmacokinetic properties broadly similar to those of other penem and carbapenem antibiotics.

Adolescent↗
PubMed1989

Evaluation of API 20 STREP system for identifying Listeria species.

The API 20 STREP system was used to identify 146 known strains from seven species of the genus Listeria, including both pathogenic and environmental strains. The gallery was easy to use and tests, with the exception of leucine arylamidase (LAP) and starch fermentation (AMD), were simple to interpret. Identification to genus level was satisfactory but differentiation between species was poor. Using the API 20 STREP the haemolytic species L monocytogenes, seeligeri, and ivanovii could easily be differentiated from the non-haemolytic species L welshimeri, innocua, grayii and murrayi. Of the haemolytic species, L monocytogenes could not be distinguished from L seeligeri but L ivanovii could be separated from the two other haemolytic species because it fermented ribose. Non-haemolytic L welshimeri could not be differentiated from non-haemolytic L innocua, but mannitol and ribose fermenting non-haemolytic L grayi and L murrayi were easily differentiated from the other two non-haemolytic species. The API 20 STREP identified Listeria in four hours and therefore might be used for rapid identification of strains causing infection in man. It would, however, not be useful to identify environmental isolates when speciation is important.

Bacteriological Techniques↗
PubMed1988

The laboratory interpretation of coagulase-negative staphylococcal bacteraemia in neonates.

In an attempt to detect markers of significance of coagulase-negative staphylococci (CNS) isolated from neonatal blood cultures, epidemiological data and the rate of appearance of positive blood cultures were examined. The main epidemiological factor studied was the relative abundance of the different biotypes of CNS in blood cultures, on neonatal skin and the hands of neonatal unit staff. Our results showed that the relative recovery rates of biotypes found from these sources showed no significant differences. The number of positive blood culture bottles in each set and the number of days taken for growth to appear showed wide variations. A higher proportion of aminoglycoside-resistant strains were found in the group showing both blood culture bottles positive and in the group where isolates were obtained by 24 h of incubation. We conclude that there is no advantage in biotyping CNS in assessing clinical significance, but the association of aminoglycoside resistance with the isolation pattern of CNS in neonatal blood cultures requires further examination.

Bacterial Typing Techniques↗
PubMed1988

Cloning and characterization of an AAC(6') gene from Serratia marcescens.

A gene encoding AAC(6') mediated resistance to netilmicin and amikacin was cloned from the chromosome of a nosocomial strain of Serratia marcescens into the BamHI site of pACYC184. The resistance determinant was localized to a sequence of approximately 1 kb. A 490 base pair BamHI-PvuII restriction fragment from the cloned DNA was used as a probe in Southern hybridization studies. Homology with a 920 base pair fragment of PvuII digested S. marcescens DNA from AAC(6')-producing strains was observed. No homology was detected with aminoglycoside sensitive S. marcescens or Escherichia coli.

Acetyltransferases↗
PubMed1988

The pharmacokinetics of norfloxacin in the aged.

Eight patients aged over 65 years (mean age 81 years), with microbiologically proven urinary tract infections were treated with 400 mg norfloxacin bd daily for six days. Blood samples were taken on day 1 and day 6 to give a concentration-time profile, and on each of the other days samples were obtained before the first dose of the day. Urine was collected throughout. The mean of the maximum serum concentration of norfloxacin after the first dose was 1.5 mg/l (range 1.1-1.8 mg/l) at a mean of 3.2 h (range 1-6 h). After the last dose the mean maximum concentration was 2.2 mg/l (range 1.6-3.7 h) at 3 h (range 1-4 h). The mean serum half life was 5 h (range 3.7-6.5 h) on day 1 and 5.3 h range (4.4-6.2 h) on day 6. Serum pre-dose norfloxacin levels showed no evidence of accumulation. Mean urinary concentrations varied between 95 and 288 mg/l from day 1 to day 6. No significant adverse reactions were noted. No alteration of norfloxacin dose is suggested in the aged with normal renal function.

Aged↗
PubMed1988

The in-vitro degradation at 37 degrees C of vancomycin in serum, CAPD fluid and phosphate-buffered saline.

Solutions of vancomycin in phosphate-buffered saline, peritoneal dialysis effluent fluid and human serum were incubated at 37 degrees C for ten days and sampled at daily intervals. The samples were assayed for vancomycin content by a microbiological assay, HPLC and polarisation fluoroimmunoassay (Abbott TDX). The results obtained by HPLC and microbiological assay agreed well and indicated approximately 50% loss over ten days in serum and buffered saline and over 70% loss in dialysate. TDX results indicated losses of only 20% and 40%, respectively. Degradation products were prepared from vancomycin by acid hydrolysis and purified by HPLC. These purified products were shown to cross-react in the TDX assay. It is suggested that the TDX assay becomes non-specific in the presence of vancomycin breakdown products and thus overestimates true vancomycin concentrations.

Bacteriological Techniques↗
PubMed1988

Resistance of bacterial pathogens to four aminoglycosides and six other antibacterials and prevalence of aminoglycoside modifying enzymes, in 20 UK centres.

A total of 5116 non-fastidious bacterial strains isolated from either blood or urine culture were collected from 20 geographically distributed centres within the UK. Upon receipt the strains were identified and the minimum inhibitory concentrations of ten antimicrobial agents in hospital usage were determined for each of the strains. All laboratories submitted a similar range of bacterial species and in species normally considered as sensitive the overall rates of resistance to the different antibiotics tested were: amikacin 2.4%, gentamicin 3.7%, netilmicin 2.6%, tobramycin 3.4%, ampicillin 41.7%, cefadroxil 11.6%, cefotaxime 1.4% [corrected], cefuroxime 4.3%, ciprofloxacin 0.6% and trimethoprim 13.0%. For those strains resistant to one or more aminoglycosides the mechanisms of resistance responsible were determined from the aminoglycoside-resistance patterns of the strains to 16 different aminoglycoside antibiotics. The predominant mechanisms of resistance found were APH(2") + AAC(6') production in staphylococci. AAC(2') production in Providencia spp., and AAC(3) production in the other Gram-negative genera.

Aminoglycosides↗
PubMed1988

The pharmacokinetics of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide in haemodialysis patients with end-stage renal failure.

Six patients with end-stage chronic renal failure undergoing haemodialysis were given ofloxacin (600 mg) orally and blood samples were taken at intervals up to 32 h. In four patients samples were also taken before and after haemodialysis. Serum concentrations of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide were measured by HPLC. The drug was well tolerated. Mean pharmacokinetic parameters for ofloxacin were Cmax 5.5 h (S.D. 1.97 h), Tmax 3.9 h (S.D. 3.25 h), T1/2 28 h (S.D. 17.37 h), AUC0-24 83.1 mg/1 h (S.D. 32.69 mg/l h). The desmethyl metabolite was produced in all patients but only half produced N-oxide. Cmax values were 0.21 mg/l (desmethyl) and 0.37 mg/l (N-oxide). Ofloxacin and desmethyl ofloxacin were variably and only slightly removed by haemodialysis whilst ofloxacin N-oxide was not removed at all. These results confirm that dosage reduction of ofloxacin is required in haemodialysis patients. Therapeutic drug monitoring by HPLC is recommended because of the observed variability in absorption and plasma half life.

Adolescent↗
PubMed1988

Fluoroquinolone antibiotics. Microbiology, pharmacokinetics and clinical use.

The newer fluoroquinolones are a major advance in antimicrobial chemotherapy. They inhibit the supercoiling activity of the DNA gyrase enzyme, thus exerting their antibacterial action on DNA and RNA synthesis, resulting in a biphasic response and killing of susceptible organisms. The newer fluoroquinolones have an extended antimicrobial spectrum compared to their older congeners, and are highly active against most Gram-negative pathogens including the Enterobacteriaceae and Pseudomonas aeruginosa. While Staphylococcus aureus and coagulase-negative staphylococci are usually susceptible to the fluoroquinolones, streptococci are generally more resistant and enterococci are resistant. All of the newer fluoroquinolones may be administered orally and most of them have been administered parenterally. They are widely distributed in the body, attaining therapeutic concentrations in most tissues. All of the fluoroquinolones have long half-lives and may be administered once or twice daily. The fluoroquinolones have proved effective in many infections, including uncomplicated or complicated urinary tract infections, respiratory tract infections, gonorrhoea, bacterial gastroenteritis, and soft tissue infections due to Gram-negative organisms. In general, success has been notable in the management of Gram-negative infections but less so with Gram-positive infections. Resistance has occurred and is proving a problem with P. aeruginosa in some cystic fibrosis patients, but as yet no plasmid-mediated resistance has developed. Cross-resistance occurs between the quinolones but only rarely with other classes of antibacterial drugs. The fluoroquinolones have an excellent safety record and their adverse effects, which include hypersensitivity reactions, dizziness, headache, gastrointestinal disturbance and minor haematological abnormalities are usually mild and transient. However, the fluoroquinolones have been found to damage juvenile weight-bearing joints in animals and are therefore only to be used with caution in children; transient arthralgia has been reported in a cystic fibrotic teenager on long term ciprofloxacin therapy. All of the fluoroquinolones except ofloxacin are associated with a variable increase in the serum concentration of theophylline, warfarin and caffeine. Thus, the fluoroquinolones are an attractive option in the management of many infections. Cost and possible resistance, however, should counsel caution in their use, and may limit them to situations where a cheaper antimicrobial of equivalent efficacy is not available.

4-Quinolones↗