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Biomedical subjects

H A Holt

Publications and source records attributed to H A Holt.

At least 37 records · Page 2Linked to original sources
PubMed1997

Gas exchange and water relations of Fraxinus americana affected by flurprimidol.

Effects of flurprimidol on plant water relations and leaf gas exchange were investigated in one-year-old white ash (Fraxinus americana L.) seedlings subjected to soil water deficits. Flurprimidol (20 mg kg(-1) of soil equivalent) was applied to the soil surface of pot-grown seedlings after shoot growth was completed. Two months after flurprimidol application, water was withheld from one-half of the seedlings. Leaf water relations and gas exchange parameters were measured 5, 7, 10, 14, 18 and 22 days after withholding water. Under both irrigated and nonirrigated conditions, flurprimidol treatment resulted in reduced net CO(2) assimilation rate and transpirational water loss of seedlings as a result of decreased stomatal conductance. Consequently, flurprimidol-treated seedlings had higher leaf water potential and relative water content than untreated seedlings. Nonirrigated flurprimidol-treated seedlings also had greater turgor and sap osmolality and lower osmotic potential at full turgor than seedlings in the other treatments, indicating that flurprimidol increased osmotic adjustment. Under water-stress conditions, water use efficiency was lower and gas exchange efficiency was higher in flurprimidol-treated seedlings than in untreated seedlings, suggesting that flurprimidol treatment enhances survival of plants subjected to soil water deficits.

Journal Article↗
PubMed1996

A new time-kill method of assessing the relative efficacy of antimicrobial agents alone and in combination developed using a representative beta-lactam, aminoglycoside and fluoroquinolone.

A time-kill curve employing nine sampling times over 6 h was used to provide data which were then used to develop a theoretical (best-fit) curve. From the theoretical curve parameters describing the rate of kill (alpha), time from addition of antibiotic to initiation of killing (d) and a function of the degree of killing observed (Ym/Yo) were defined. The area-under-the-curve (AUC) was calculated from the theoretical curve. The variability of each parameter was assessed using a theoretical curve to fit the data from experiments done on three occasions and in triplicate. In terms of the parameters alpha, d, Ym/Yo and AUC, no synergy was demonstrated with combinations of piperacillin/tazobactam plus ciprofloxacin or gentamicin when compared with single antibiotics. The AUC represents the best summary parameter of a time-kill curve but should be supported by other parameters describing the best-fit curve.

Acinetobacter↗
PubMed1996

The in-vitro activity of trovafloxacin and nine other antimicrobials against 413 anaerobic bacteria.

The in-vitro activity of trovafloxacin and nine other antimicrobials was determined for 413 non copy anaerobic clinical isolates. Trovafloxacin was the most active quinolone tested with an MIC90 of 0.5 mg/L against Gram-positive cocci (n = 75); MIC90 of 4 mg/L against Gram-positive bacilli (n = 151); MIC90 of 0.5 mg/L for Gram-negative cocci (n = 12) and MIC90 of 1 mg/L for Gram-negative bacilli (n = 175). Overall the MIC90 of trovafloxacin was 1 mg/L which was equivalent to co-amoxiclav and one dilution higher than that of imipenem. The other seven comparators, including clindamycin and metronidazole, had higher MIC90 values than trovafloxacin. Trovafloxacin is likely to have clinically useful activity against anaerobes from human infection.

Anti-Bacterial Agents↗
PubMed1996

Bactericidal activity, post antibiotic effect and modified controlled effective regrowth time of meropenem at high concentrations.

The effect of increasing meropenem concentrations up to 250 mg/L, as might occur if 3 g was given as a single daily intravenous dose, was investigated in terms of bactericidal activity, post antibiotic effect (PAE) and modified controlled effective regrowth time (mCERT). Increasing the meropenem concentration above 50 mg/L did not result in increased bacterial killing, while concentrations over 75 mg/L did not result in longer PAE or mCERT.

Enterobacter↗
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↗
PubMed1995

A critical assessment of the agar dilution chequerboard technique for studying in-vitro antimicrobial interactions using a representative beta-lactam, aminoglycoside and fluoroquinolone.

The agar dilution chequerboard technique of studying antimicrobial interactions was assessed by testing a representative beta-lactam (piperacillin/tazobactam), aminoglycoside (gentamicin) and fluoroquinolone (ciprofloxacin) against themselves, that is piperacillin/tazobactam plus piperacillin/tazobactam, gentamicin plus gentamicin and ciprofloxacin plus ciprofloxacin. In addition, combinations of piperacillin/tazobactam plus gentamicin or ciprofloxacin were also tested against Enterobacteriaceae and Acinetobacter spp. in triplicate. The agar dilution chequerboard technique did not reliably show addition when agents were combined with themselves, and there was also considerable variation when beta-lactam plus aminoglycoside or fluoroquinolone combinations when tested in triplicate. These observations, and problems with the design of the method, indicate that the chequerboard technique should be used only with adequate controls and replication, and then interpreted with extreme caution; ideally, it should not be used as a method of assessing antimicrobial interactions.

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↗
PubMed1993

The activity of cefpirome and ten other antibacterial agents against 2858 clinical isolates collected from 20 centres.

Two thousand eight hundred and fifty-eight aerobic clinical isolates of Enterobacteriaceae, Pseudomonas species, staphylococci, streptococci and Haemophilus species were collected in 19 geographically separated centres in the UK and one in Ireland. The identity of each isolate was confirmed at Southmead Hospital and the MIC of cefpirome, cefotaxime, ceftazidime, cefuroxime, cephradine, amoxycillin, piperacillin, imipenem, gentamicin, ciprofloxacin and trimethoprim was determined by an agar dilution method. Against species of Enterobacteriaceae not associated with producing an inducible cephalosporinase, cefpirome had a similar degree of activity to cefotaxime and was more active than ceftazidime and earlier cephalosporins. Against species with a high prevalence of inducible beta-lactamase production, cefpirome was superior to other cephalosporins; imipenem was also active against these isolates. Cefpirome was active against Pseudomonas aeruginosa, methicillin-sensitive staphylococci, non-enterococcal streptococci and Haemophilus spp. When the isolates were exposed to 0.1 mg/L of imipenem in agar plus the test agent, cefpirome had superior activity compared with the other cephalosporins tested for the Enterobacteriaceae, except Proteus vulgaris and Proteus penneri. 8.7% of Enterobacter spp., 7% of Citrobacter spp. and 6.7% of Morganella morganii had susceptibilities to beta-lactams suggesting constitutive hyperproduction of chromosomal cephalosporinase; cefpirome, unlike the other cephalosporins tested, was active against these isolates, although to a lesser degree than against the wild-type inducible isolates. No isolates were thought to produce an extended-spectrum beta-lactamase.

Anti-Bacterial Agents↗
PubMed1993

An eight-year survey of the antimicrobial susceptibility patterns of 85,971 bacteria isolated from patients in a district general hospital and the local community.

Antimicrobial susceptibilities were determined for 85,971 bacteria isolated from clinical specimens in the microbiology department of a single district general hospital during the eight-year period between 1984 and 1991. The isolates included 45,786 coliforms, 4483 Proteus spp. and 2644 Pseudomonas spp. from urine and 13,324 Staphylococcus aureus, 7311 beta-haemolytic streptococci, 4741 coliforms, 3643 Pseudomonas spp., 2778 Haemophilus influenzae, 638 Proteus spp. and 623 Streptococcus pneumoniae from other sites (excluding blood). Patterns of susceptibility remained largely unchanged during the study period, except for a decline in the susceptibility of Proteus spp. to trimethoprim between 1984 and 1988 which had reversed itself by 1990 and a reduction in the susceptibilities of Pseudomonas spp. and S. aureus to ciprofloxacin between 1986 and 1991. The susceptibilities of coliforms which had been isolated from sites other than the urinary tract to ampicillin, cefazolin and cefuroxime decreased between 1984 and 1988 but a more variable pattern was noted in subsequent years. Susceptibility of S. aureus to penicillin fell during the first five years of the study but has remained stable since. No change was observed in the susceptibility pattern of H. influenzae. In our experience, gentimicin-resistant Gram-negative bacilli, methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were rarely isolated.

Bacterial Infections↗
PubMed1993

The activity of piperacillin/tazobactam against clinical isolates collected in 20 UK centres and the design of a disc test for susceptibility testing.

The in-vitro activities of piperacillin plus tazobactam at ratios of 4:1, 8:1 and 16:1 were determined against 952 non-copy clinical aerobic bacterial isolates collected from 20 UK centres. Tazobactam enhanced the activity of piperacillin against Enterobacteriaceae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis. No enhancement was noted for Pseudomonas aeruginosa, other Pseudomonas spp., streptococci and enterococci. For 95.6% of strains MICs were either the same or only one two-fold dilution different with all the three ratios of tazobactam, and for most of the remaining strains the piperacillin MIC was lowest with the highest proportion of the tazobactam (4:1). The percentage of strains which remained resistant was also lowest with the 4:1 ratio. Regression analysis of MICs versus inhibition zone size with a variety of disc strengths tested on DST agar indicated that for Enterobacteriaceae, and H. influenzae 30 +4 micrograms, and 5 +1 microgram piperacillin/tazobactam discs gave the most reliable results. However, for S. aureus no disc gave good discrimination. Zone sizes obtained on DST and Iso-Sensitest agar were similar, with 96.1% of 1450 paired tests showing agreement to within 3 mm.

Bacteria, Aerobic↗
PubMed1993

Resistance to third-generation cephalosporins in Barbados.

Resistance to third-generation, or extended-spectrum, cephalosporins caused by induction of class I beta-lactamases has been reported rarely from developing countries. Seven isolates of cephalosporin-resistant Gram-negative rods were recovered recently from urine, burns and ulcers in the Queen Elizabeth Hospital, Barbados. The isolates were identified as Acinetobacter calcoaceticus (2), Citrobacter freundii (1), Enterobacter cloacae (1), Morganella morganii (1), Providencia stuartii (1) and Proteus sp. (1). Induction of beta-lactamase by cefoxitin was demonstrated, and minimal inhibitory concentrations (MIC) were determined by agar dilution. beta-lactamases were demonstrated by isoelectric focusing; the presence of chromosomal beta-lactamases was confirmed in at least three of the resistant isolates. The only antibiotics which were uniformly active against these resistant strains were imipenem and ciprofloxacin. These data confirm the existence of resistance to the third-generation cephalosporins in Barbados, and emphasise the necessity for continuous surveillance of resistance patterns in the Caribbean region.

Barbados↗