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R Wise

Publications and source records attributed to R Wise.

At least 55 records · Page 3Linked to original sources

Establishing MIC breakpoints and the interpretation of in vitro susceptibility tests.

The purpose of undertaking susceptibility testing, by whatever method, is to attempt to integrate the susceptibility of a population of potential pathogens with the pharmacokinetics of the antimicrobial and, whenever possible, to review this relationship in the light of clinical experience following therapy in clinical trials. Breakpoints are discriminatory antimicrobial concentrations used in the interpretation of results of susceptibility testing to define isolates as susceptible, intermediate or resistant. Clinical, pharmacological and microbiological considerations are important in setting breakpoints, and the ideal mix of these factors is unknown. Different countries have different approaches to this problem but, by and large, these approaches have much in common. This paper attempts to summarize the philosophy of the British Society for Antimicrobial Chemotherapy (BSAC) Working Party in its approach to setting breakpoints and to update the activities of the Working Party since it initially published breakpoints, approximately 10 years ago. The formula outlined by the BSAC Working Party in 1991 has been used to set the breakpoints presented here. The Working Party accepts that in the light of new knowledge, there is a need to reassess how breakpoints are defined, and this paper also summarizes the future activities of the Working Party.

Anti-Bacterial Agents↗

Cell-autonomous expression of barley Mla1 confers race-specific resistance to the powdery mildew fungus via a Rar1-independent signaling pathway.

The barley Mla locus encodes 28 characterized resistance specificities to the biotrophic fungal pathogen barley powdery mildew. We describe a single-cell transient expression assay using entire cosmid DNAs to pinpoint Mla1 within the complex 240-kb Mla locus. The MLA1 cDNA encodes a 108-kD protein containing an N-terminal coiled-coil structure, a central nucleotide binding domain, and a C-terminal leucine-rich repeat region; it also contains a second short open reading frame at the 5' end that has a possible regulatory function. Although most Mla-encoded resistance specificities require Rar1 for their function, we used the single-cell expression system to demonstrate that Mla1 triggers full resistance in the presence of the severely defective rar1-2 mutant allele. Wheat contains an ortholog of barley Mla, designated TaMla, that is tightly linked to (0.7 centimorgan) but distinct from a tested resistance specificity at the complex Pm3 locus to wheat powdery mildew. Thus, the most polymorphic powdery mildew resistance loci in barley and wheat may have evolved in parallel at two closely linked homeoloci. Barley Mla1 expressed in wheat using the single-cell transformation system failed to trigger a response to any of the wheat powdery mildew Avr genes tested, indicating that AvrMla1 is not genetically fixed in wheat mildew strains.

Alleles↗

Pharmacokinetics and tissue penetration of linezolid following multiple oral doses.

The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 microg/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 microg/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) microg x h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.

Acetamides↗

Extensive surface phenotyping of alveolar macrophages in interstitial lung disease.

There is increasing evidence implicating activated macrophages in the pathogenesis of interstitial and other lung diseases. We investigated whether there was a unique pattern of cell surface expression that constituted a disease-specific phenotype on alveolar macrophages from patients with interstitial lung disease (ILD). Macrophage cell surface receptor expression of 19 selected markers was assessed by indirect immunofluorescence and flow cytometry in bronchoalveolar lavage (BAL) fluids from patients with idiopathic pulmonary fibrosis (IPF, n = 4), scleroderma (SCL-ILD, n = 14), mild asthma (n = 7), allergy without asthma (n = 2), and normal subjects (n = 9). There was increased expression of adhesion receptors (CD11c, CD29, CD36, CD44, CD49e, CD54), receptors involved in signal transduction and/or inflammation (CD13, CD45, CD53), and other markers (CD9, CD52, CD71, CD98, HLA Class I) on macrophages from ILD patients compared to the non-ILD group. Most markers upregulated on macrophages in ILD were significantly inversely correlated with clinical parameters of disease activity such as FEV(1), FVC, and DL(CO) and positively correlated with numbers of BAL neutrophils and eosinophils. Increased expression of several cell surface markers suggests that activated alveolar macrophages may contribute to the pathophysiology of IPF and SCL-ILD.

Adult↗

Outer-membrane proteins pattern and detection of beta-lactamases in clinical isolates of imipenem-resistant Acinetobacter baumannii from Brazil.

In order to compare imipenem-sensitive and -resistant Acinetobacter baumannii strains isolated from three patients, ribotyping, plasmid, beta-lactamase detection and outer-membrane analysis were performed. Ribotyping and the use of a beta-lactam during the period when the strains were isolated suggested that they had a common origin and that resistance occurred in vivo. Outer membrane analysis showed no difference between susceptible and resistant strains with the exception of an A2 imipenem-resistant strain that lost a protein band of 31-36 kDa. Beta-lactamases were detected using isoelectric focusing in all strains (pI of 7.4). In addition, two beta-lactamases (pI of 5.9 and 6.7) were found in imipenem-resistant isolates. The double-disc technique demonstrated the presence of a beta-lactamase capable of imipenem inactivation in resistant strains. Plasmid analysis showed that all susceptible strains had the same pattern, one resistant strain did not have any plasmid, one had the same plasmid pattern of its susceptible pair and only one had a different pattern when compared with its susceptible pair.

Acinetobacter↗

A comparison of antimicrobial resistance rates in Gram-positive pathogens isolated in the UK from October 1996 to January 1997 and October 1997 to January 1998.

Rates of resistance for two consecutive years for 28 centres (10 Teaching, nine Associate Teaching and nine District General hospitals) in the UK were compared. Combined rates of resistance for each of the hospital types of Staphylococcus aureus to methicillin revealed an increase in the rate of resistance in Teaching hospitals (12.5% year 1, 23.5% year 2), but, for Associate Teaching and District General hospitals rates fell (Associate Teaching 19.1% year 1, 11.9% year 2; District General 16.5% year 1 and 11.3% year 2). Using conventional methodology to determine MICs, no strain was considered to have reduced susceptibility to vancomycin. Among coagulase-negative staphylococci, increased resistance was observed for Staphylococcus epidermidis to rifampicin, for Staphylococcus haemolyticus to clindamycin, for Staphylococcus saprophyticus to penicillin and for Staphylococcus spp. to clindamycin, methicillin and rifampicin. For Streptococcus pneumoniae an upward trend in low-level resistance to penicillin was observed (18 of the 28 centres), however, for high-level resistance the trend was in the opposite direction (only four centres showed an increase). For Enterococcus faecalis there was a trend to a fall in levels of resistance, the only exception being an increase in high-level gentamicin resistance (10.5% year 1, 15.1% year 2, P = 0.0388). For Enterococcus faecium rates of resistance were not significantly different except for increases in resistance to nitrofurantoin and rifampicin.

Anti-Bacterial Agents↗

Evaluation of the Oxoid Aura image system for measuring zones of inhibition with the disc diffusion technique.

In this study the Oxoid Aura image antibiotic sensitivity test system, used as a stand-alone device, was compared with manual zone measurement and use of a template, for the determination of sensitivities. An overall correlation coefficient of 0.99 was observed for zone diameters measured using the Aura image system and zones measured manually, when the differences between zones were within 3 mm; 5.4% of zones showed a difference in zone diameter between manual and automated measurement of >3 mm. The results obtained using the template method for interpretation were less reliable than zone measurement, with cefuroxime and ampicillin tested against Enterobacteriaceae and Acinetobacter spp. When linked to a laboratory patient database, the bar code and disc identification facilities avoided errors that were associated with manual data entry.

Acinetobacter↗

The in vitro activity of ABT773, a new ketolide antimicrobial agent.

The in vitro activity of ABT773, a ketolide antimicrobial agent, was investigated and compared with those of seven other antibiotics. Type strains and 733 Gram-positive, Gram-negative and anaerobic isolates of clinical origin and four CHLAMYDIA: isolates were used. The activity of ABT773 was very similar to that of telithromycin, the other ketolide tested. The MIC(90) was < or = 0.5 mg/L for all bacteria examined except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae and BACTEROIDES: spp. The antichlamydial activity of ABT773 was greater than that of telithromycin, erythromycin and ciprofloxacin. Neither an increase in the size of the inoculm nor the addition of human serum had any marked affect on the in vitro activity of ABT773.

Anti-Bacterial Agents↗

Preface.

Although the clinical presentation and the treatment of lower urinary tract infection (UTI) have changed little in the 60 to 70 years of the 'antibiotic era', uropathogenic bacteria have not been slow to respond to the selecting pressure of antimicrobials. This is because such infections are common. Approximately 3% of all consultations made to general practitioners are for symptoms of UTI and approximately 12-20% of all antibiotic prescriptions are for this indication. Between one-quarter and one-half of all women experience a UTI at some time. The problem, therefore, is a considerable one and warrants reevaluation. This supplement is based upon papers presented at a meeting held in March 2000 in Vienna, Austria and sponsored by Leo Pharmaceutical Laboratories. It draws together the current views on the diagnosis and the treatment of UTIs at a time when the disease-causing microorganisms are most certainly changing. Antibiotic resistance to commonly used agents, such as trimethoprim and ampicillin, often now exceeds 30-50%. The clinician may be tempted to choose an agent such as a fluoroquinolone for the treatment of this disease, yet it is known that fluoroquinolone resistance can develop rapidly. Views on the length of treatment have also changed over the years and a 3 day regimen is usually now advocated. Pivmecillinam, which is hydrolysed to mecillinam after absorption, has a novel mode of action, rapid bacterial cell penetration and lower affinity for common beta-lactamases. Its spectrum of activity and good safety profile make it an ideal candidate for the treatment of this common condition. Experience in several countries over many years confirms this assessment and it may be time to reconsider the potential role of pivmecillinam in the treatment of UTIs. The Editors would like to thank Inge Boe and Paul Menday of Leo Laboratories for their untiring support and assistance in the preparation of this supplement.

Journal Article↗

Clinical efficacy and antimicrobial pharmacodynamics.

Changes in the susceptibility of bacterial pathogens and the availability of new antimicrobial drugs mean that physicians need to understand the underlying pharmacodynamics of each antimicrobial therapy. Antimicrobial pharmacodynamics determine clinical efficacy and should therefore be carefully considered when selecting appropriate antibiotic agents in the therapeutic setting.

Anti-Bacterial Agents↗

Short test of semantic and phonological fluency: normal performance, validity and test-retest reliability.

Tests of verbal fluency, whether of Semantic Fluency (SF) or Phonological Fluency (PF), are often used as a standard method of neuropsychological assessment. However, very little normative data, standardized on a UK sample, is available, and little is known about the utility of popularly used 'short-forms' of these tasks. Additionally, very little is known about verbal fluency test-retest reliability. In this report we describe the performance of N = 365 normal participants on a version of SF requiring the generation of exemplars of the category 'animals' and a version of the PF task requiring participants to generate words beginning with the letter 'B'. From this data we have derived a percentile distribution for both tasks. We also addressed the impact of sex, age, years of education and IQ upon both SF and PF performance. No sex differences were found on either the PF or the SF tasks. A significant but small correlation between age and SF, but not PF, was observed. Modest correlations between both years of education and IQ and PF and SF performance were also seen. We also report test-retest reliability scores for performance on both SF and PF tasks. Performance on the longer 'FAS' version was found to correlate highly with scores obtained using just the letter 'B'. This suggests that little additional advantage obtains from administering three-letter versions of PF. An extremely high degree of correlation between SF tasks in which participants are given 1 minute and scores obtained when participants are given 1 minute 30 seconds was also observed. Finally, in order to assist users in deciding whether a changed retest score is due to error measurement or a real effect, we calculated Standard Error of Prediction (SEP) scores.

Adult↗

Preface.

Although the clinical presentation and the treatment of lower urinary tract infection (UTI) have changed little in the 60 to 70 years of the 'antibiotic era', uropathogenic bacteria have not been slow to respond to the selecting pressure of antimicrobials. This is because such infections are common. Approximately 3% of all consultations made to general practitioners are for symptoms of UTI and approximately 12-20% of all antibiotic prescriptions are for this indication. Between one-quarter and one-half of all women experience a UTI at some time. The problem, therefore, is a considerable one and warrants reevaluation. This supplement is based upon papers presented at a meeting held in March 2000 in Vienna, Austria and sponsored by Leo Pharmaceutical Laboratories. It draws together the current views on the diagnosis and the treatment of UTIs at a time when the disease-causing microorganisms are most certainly changing. Antibiotic resistance to commonly used agents, such as trimethoprim and ampicillin, often now exceeds 30-50%. The clinician may be tempted to choose an agent such as a fluoroquinolone for the treatment of this disease, yet it is known that fluoroquinolone resistance can develop rapidly. Views on the length of treatment have also changed over the years and a 3 day regimen is usually now advocated. Pivmecillinam, which is hydrolysed to mecillinam after absorption, has a novel mode of action, rapid bacterial cell penetration and lower affinity for common beta-lactamases. Its spectrum of activity and good safety profile make it an ideal candidate for the treatment of this common condition. Experience in several countries over many years confirms this assessment and it may be time to reconsider the potential role of pivmecillinam in the treatment of UTIs. The Editors would like to thank Inge Boe and Paul Menday of Leo Laboratories for their untiring support and assistance in the preparation of this supplement.

Journal Article↗