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Biomedical subjects

K A Bedford

Publications and source records attributed to K A Bedford.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) in neonates.

The pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) was studied in 16 neonates, divided for analysis into three groups according to gestational age: group 1 >36 weeks (n=7); group II between 34-36 weeks (n=4); and group III <34 weeks (n=5). The serum netilmicin (mean +/- SD) 4h and 24h after the first dose were 4.7 +/- 0.8 and 0.8 +/- 0.5 mg/L; 4.9 +/- 0.8 and 1.9 +/-0.2 mg/L; 4.9 +/- 0.5 and 1.7 +/- 0.5 mg/L in groups I, II and III respectively. After the second dose, concentrations at 2, 4, 8, 16 and 24 h were 7.2 +/- 1.0, 5.0 +/- 0.8, 3.0 +/- 0.6, 1.7 +/- 0.4 and 0.9 +/- 0.2 mg/L (group I); 8.6 +/- 0.2, 6.1 +/- 0.5, 4.2 +/- 0.7, 2.6 +/- 0.1 and 1.4 +/- 0.4 mg (group II); 9.0 +/- 1.2, 6.3 +/- 0.9, 4.1 +/- 0.7, 2.6 +/- 0.5 and 1.7 +/- 0.3 mg/L (group III). There was a large degree of inter-patient variability in serum concentrations and serum half-life (t1/2), volume of distribution (VD), area-under-the-curve (AUC), relative serum clearance (Clp) such that these parameters could not be correlated to age or weight. Absolute serum clearance (L/h) was correlated with gestational age (r = 0.672, P <0.01). There was no statistically significant evidence of accumulation between the first and second doses for any patient group. One baby from each group II and group III had concentration >2 mg/L 24h after the first dose and one baby from group III had concentration >2 mg/L 24h after the second dose. There are no established correlations between serum netilmicin concentrations and efficacy or toxicity in neonates and keeping 24 h trough concentration below 2 mg/L with a once-a-day dose of 4.5 mg/L would have to be validated in terms of its clinical efficacy and potential toxicity in a neonatal population.

Drug Administration Schedule↗
PubMed1996

Pharmacokinetics of once-a-day netilmicin (6 mg/kg) in neonates.

The pharmacokinetics of once a day netilmicin (6 mg/kg) was studied in 21 neonates. The babies were divided into three groups according to gestational age: group I aged > 36 weeks; group II between 34-36 weeks and group III < 34 weeks. Serum concentrations were variable between patients and the concentration 24 h after the first dose ranged from 0.8 to 3.8 mg/L with only two babies having concentrations of < 1 mg/L while seven had concentrations of > 2 mg/L. There were also large patient-to-patient variations in serum half-life, volume of distribution, area under the curve and relative plasma clearance such that these parameters could not be correlated to gestational age or weight. Absolute plasma clearance was correlated with both gestational age and weight. There was evidence of accumulation between the first and second dose for all three patient groups and for patients of gestational age < 34 weeks (group III) these observations were statistically significant. A netilmicin dosage of 4.5 mg/kg once a day may be more suitable for all neonates supported by assay of serum concentrations.

Female↗
PubMed1995

The comparative inhibitory and bactericidal activities of meropenem and imipenem against Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins.

The inhibitory and bactericidal activities of meropenem and imipenem were compared using Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins. The inhibitory activity of both agents was similar for Acinetobacter spp. but meropenem was more active against the Enterobacteriaceae. Bactericidal activities were compared employing time-kill curves which indicated meropenem was more bactericidal than imipenem against Enterobacteriaceae at pharmacologically achievable concentrations while imipenem was more bactericidal than meropenem against Acinetobacter spp.

Acinetobacter↗
PubMed1994

An evaluation of three new immunoassays for determination of serum gentamicin concentrations.

Three new immunoassays for determination of serum gentamicin concentration were assessed: a latex agglutination assay (Technicon), an enzyme immunoassay (EMIT 2000) and a multi-layer thin-film immunoassay (Opus). All three were easy to use, had good within- and between-assay reproducibility, good reliability and acceptable linearity. The standard curve stability was shortest with the latex agglutination assay and longest with the thin-film. The thin-film assay calibrators gave approximately double the expected concentration when assayed by polarisation fluoroimmunoassay but this did not effect the assay's performance. When compared with the polarisation fluoroimmunoassay results of patient samples, all three methods gave an excellent correlation. The technical aspects of these three methods make them acceptable for clinical use.

Calibration↗
PubMed1994

The pharmacokinetics of once daily gentamicin in neutropenic adults with haematological malignancy.

Seven febrile neutropenic adults with normal renal function were treated with intravenous gentamicin 4.5 mg/kg once a day in combination with azlocillin. Gentamicin serum concentrations 1, 2, 4, 8, and 24 h after a 30 min infusion were 10.9 +/- 0.6, 7.1 +/- 0.4, 4.2 +/- 0.2, 1.8 +/- 0.1 and 0.16 +/- 0.003 mg/L respectively. The pharmacokinetics were best described by a triphasic plot including a distribution phase (about 1/2 h) and two elimination phases, an early and late.

Adolescent↗
PubMed1981

Cefoperazone and cefotiam--two new cephalosporins: an in-vitro comparison.

The in vitro activity of cefoperazone (CPZ) and cefotiam (CTM) was compared to other available cephalosporins. Using an agar dilution procedure both CTM and CPZ were more active against the Enterobacteriaceae tested than cefoxitin, cefuroxime and cefazolin; CTM being slightly more active than CPZ, in particular against Klebsiella spp Haemophilus influenzae were more susceptible to CPZ. CTM had no activity against Pseudomonas aeruginosa but CPZ exhibited considerable activity (mode MIC 4 mg/l). Against Bacteroides fragilis CPZ had a similar activity to cefuroxime, but CTM was less active. CTM was about twice as active as CPZ against Staphylococcus aureus, cefazolin being the most active agent tested. The MBC was about twice the MIC for each compound and the presence of 75% serum had only a modest effect on the MIC and MBC. The protein binding of CPZ was 94% and CTM 62%.

Ampicillin↗
PubMed1981

Epimers of moxalactam: in vitro comparison of activity and stability.

Moxalactam exists in two epimeric forms, R and S. The in vitro activity of these two epimers was compared with that of material available for clinical and laboratory use (R + S moxalactam). Generally, R moxalactam was twice as active as the S form. The stability of R + S moxalactam was studied at 37, 20, 4 and -20 degrees C in buffer and serum. Only in serum at 37 degrees C was there any appreciable loss of activity (half-life, 8 h). The stability of R and S epimers was studied separately, and the composition of the resulting equilibrium was investigated. At 37 degrees C in serum, one-half of the excess of either R or S over the equilibrium mixture was converted into the equilibrium mixture in 1.5 h. The proportions of R to S in an equilibrium mixture in buffer were 50:50, but in serum they were 45:55. It is doubtful whether these differences in stability and activity will have any significant clinical importance.

Anti-Bacterial Agents↗
PubMed1980

Activity of the cefotaxime (HR756) desacetyl metabolite compared with those of cefotaxime and other cephalosporins.

The desacetyl metabolite (DES) of cefotaxime (HR756) is formed in vivo to a significant extent. The in vitro activities of DES, the parent compound, and cefazolin, cefoxitin, and cefuroxime were compared against 70 bacterial isolates. DES was found to possess approximately 1/10th the activity of the parent compound against the common Enterobacteriaceae, but was somewhat more active than the other three compounds tested. DES had no useful activity against Pseudomonas aeruginosa and was less active than cefotaxime or cefoxitin against Staphylococcus aureus or Bacteroides fragilis. Because DES may accumulate in renal failure or be concentrated in the biliary tract, its antimicrobial activity may have considerable clinical significance.

Bacteria↗
PubMed1980

UK31214, a new aminoglycoside and derivative of kanamycin B.

The in vitro activity of UK31214, a kanamycin B derivative, was studied against 250 recent isolates and compared with other aminoglycosides. Against the Enterobacteriaceae (with the exception of Proteus mirabilis and Providencia stuartii) UK31214 and amikacin had similar degrees of activity (mode minimum inhibitory concentration [MIC], 1 microgram/ml). Proteus mirabilis and P. stuartii strains were four- to eight-fold more susceptible to amikacin than to UK31214. Pseudomonas aeruginosa strains were equally susceptible to both amikacin and UK31214 (mode MIC, 4 microgram/ml), but tobramycin was the most active antimicrobial agent tested (mode MIC, 0.25 microgram/ml). The gentamicin-resistant strains of P. aeruginosa were equally susceptible to UK31214 and amikacin. Strains of Staphylococcus aureus were more susceptible to gentamicin or tobramycin than to UK31214 or amikacin (mode MIC, 0.5 microgram/ml). A synergistic interaction between UK31214 and carbenicillin was demonstrated.

Drug Resistance, Microbial↗
PubMed1980

Comparison of in vitro activity of GR 20263, a novel cephalosporin derivative, with activities of other beta-lactam compounds.

The in vitro activity of GR 20263, a new cephalosporin, was compared primarily with the activities of moxalactam (LY 127935), cefotaxime, cefoxitin, cefuroxime, and cefazolin against 293 clinical isolates of a variety of gram-positive and -negative bacteria. The minimal inhibitory concentrations of GR 20263 for 90% of group isolates were between 0.06 and 0.5 microgram/ml for the Enterobacteriaceae, Haemophilus influenzae, Neisseria gonorrhoeae, and Lancefield group A beta-hemolytic streptococci; 2 micrograms/ml for Pseudomonas aeruginosa; 16 micrograms/ml for Staphylococcus aureus; and in excess of 128 micrograms/ml for Bacteroides fragilis and Lancefield group D streptococci. In comparison with the other agents, GR 20263 was markedly more active against the Enterobacteriaceae than cefuroxime, cefoxitin, and cefazolin, but marginally less active than moxalactam or cofotaxime. Aganist S. aureus, cefazolin was 16-fold and cefotaxime was 4-fold more active than GR 20263 and moxalactam. GR 20263 was eight-fold more active than cefotaxime and moxalactam against P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1979

LY127935, a novel oxa-beta-lactam: an in vitro comparison with other beta-lactam antibiotics.

The in vitro activities of LY127935 (LY) were compared with those of other beta-lactam antibiotics. LY was highly active (minimal inhibitory concentration [MIC] range 0.06 to 0.25 micrograms/ml) against the common Enterobacteriaceae (including Providencia stuartiia, Enterobacter, and Serrati marcescens), 8 to 16 times more active than cefoxitin, cefuroxime, or cefazolin, and from one-half to one-eighth as active as cefotaxime (HR756). The activity of LY against Pseudomonas aeruginosa (with MICs of 4 and 64 micrograms/ml for 50 and 90% of test strains, respectively) was essentially similar to that of cefotaxime, but was only one-half as active as CGP 7174/E. LY, cefoxitin, and cefotaxime were essentially equally active against Bacteroides fragilis--each was more active than cefuroxime and cefazolin. Against Staphylococcus aureus, LY (50% MIC and 90% MIC of 4 and 16 micrograms/ml, respectively) was less active than cefotaxime, cefoxitin, or cefuroxime and one-eighth as active as cefazolin. The composition and pH of the culture medium had little effect on the activity of LY, although 7.2 appeared to be the optimum pH.

Anti-Bacterial Agents↗