Are glycopeptide-resistant enterococci in animals a threat to human beings?
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Biomedical subjects
Publications and source records attributed to R Wise.
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An anonymized point-prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) carriage was conducted amongst a stratified random sample of nursing home residents in Birmingham, UK, during 1994. Microbiological sampling from noses, fingers and the environment was undertaken. Information about potential risk factors for the acquisition of MRSA was gathered. MRSA was isolated from cultures of the nose or fingers of 33 of the 191 residents who took part in the study (17%) but only 1 of the 33 positive residents had a clinical infection. Although just 10 of the 87 environmental samples were MRSA positive, there was some environmental contamination in most homes. Risk factors for MRSA carriage were hospital admission within the last year (relative prevalence 2.09, 95% CI 1.13-3.88; P < 0.05) and surgical procedures within the last year (relative prevalence 4.02, 95% CI 2.18-7.43; P = 0.002). Phage-typing of the strains revealed similarities with those circulating in Birmingham hospitals. These findings suggest that the prevalence of MRSA in nursing homes in Birmingham was high, and that the strains may have originated in hospitals.
This work explores the cerebral structures involved in the appreciation of music. We studied six young healthy subjects (right handed, French, without musical talent), using a high resolution PET device (CTI 953B) and 15O-labelled water. In three tasks, we studied the effects of selective attention to pitch, timbre and rhythm; a final task studied semantic familiarity with tunes (considered as divided attention for pitch and rhythm). These four tasks were performed on the same material (a tape consisting of 30 randomly arranged sequences of notes). We selected a paradigm, without a reference task, to compare the activations produced by attention to different parameters of the same stimulus. We expected that the activations recorded during each task would differ according to the differences in cognitive operations. We found activations preferentially in the left hemisphere for familiarity, pitch tasks and rhythm, and in the right hemisphere for the timbre task. The familiarity task activated the left inferior frontal gyrus, Brodmann area (BA) 47, and superior temporal gyrus (in its anterior part, BA 22). These activations presumably represent lexico-semantic access to melodic representations. In the pitch task, activations were observed in the left cuneus/precuneus (BA 18/19). These results were unexpected and we interpret them as reflecting a visual mental imagery strategy employed to carry out this task. The rhythm task activated left inferior Broca's area (BA 44/6), with extention into the neighbouring insula, suggesting a role for this cerebral region in the processing of sequential sounds.
The in-vitro activity of faropenem, a novel oral penem, was studied in comparison with other beta-lactam antimicrobials against 711 recent clinical isolates including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that faropenem was active against most members of the Enterobacteriaceae (MICs < or = 4 mg/L), with reduced activity against Serratia spp. (MIC90 = 32 mg/L). In common with its comparators, faropenem had weak activity against Pseudomonas aeruginosa and Stenotrophomonas maltophilia (MIC > 128 mg/L). Faropenem was active against staphylococci, although for MRSA MICs were raised (MIC90 = 2 mg/L) compared with those for MSSA (MIC90 = 0.12 mg/L). Faropenem was also found to be active against streptococci, Neisseria spp., Enterococcus faecalis and beta-lactamase-producing and non-producing strains of Haemophilus influenzae and Moraxella catarrhalis. Of the anaerobic bacteria studied, faropenem was most active against peptostreptococci and Clostridium perfringens (MIC90 < or = 1 mg/L) and Bacteroides fragilis (MIC90 = 4 mg/L). An increase in inoculum from 10(4) to 10(6) cfu raised faropenem MICs for Morganella morganii from 0.06-1 mg/L to 2-4 mg/L and for MRSA from 0.25-2 mg/L to 8 mg/L (a similar increase was not observed for MSSA). The MICs of faropenem were not affected by the presence of either 20% or 70% (v/v) serum. MICs for faropenem to 11 well characterized beta-lactamase producers were similar to those of non-producers. In hydrolysis studies, faropenem was shown to be highly stable to a number of beta-lactamases, including TEM-1, SHV-1, the extended spectrum beta-lactamases, TEM-3 and TEM-9, and the beta-lactamase produced by Staphylococcus aureus (NCTC 11561).
The in-vitro activity of colistin sulphomethate sodium was compared with that of other commonly used antimicrobial agents against 377 recent clinical isolates of Gram-negative bacteria (including 94 strains of Pseudomonas aeruginosa from patients with cystic fibrosis) and 16 organisms with defined resistance patterns. Colistin was active against most strains of P. aeruginosa (MIC90 4 mg/L), Shigella spp. (MIC90 0.5 mg/L), Salmonella spp. (MIC90 1 mg/L), Acinetobacter spp. (MIC90 2 mg/L), Citrobacter spp. (MIC90 1 mg/L), Escherichia coli (MIC90 1 mg/L), Klebsiella spp. (MIC90 8 mg/L) and Enterobacter spp. (MIC50 1 mg/L). No useful activity was demonstrated against Providentia spp. or Serratia spp. The results show that colistin remains a useful antimicrobial agent against Gram-negative bacteria, particularly those strains which are resistant to more commonly used antibiotics.
The pharmacodynamic properties of faropenem, a new oral penem antibiotic, were investigated by studying time-kill kinetics and postantibiotic effect. Time-kill kinetics were employed against strains of Bacteroides fragilis, Escherichia coli, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. The postantibiotic effects of faropenem were studied using strains of E. coli, S. aureus, H. influenzae and Streptococcus pneumoniae. The time-kill kinetic data demonstrated that faropenem has bactericidal activity. Faropenem exhibited a significant postantibiotic effect against all strains except H. influenzae.
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The in-vitro activity of CG 5501 against a wide range of recent clinical isolates was compared with that of three fluoroquinolones. CG 5501 inhibited 90% of the species of the family Enterobacteriaceae at 0.5 mg/L or less, exceptions being Enterobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Ninety per cent of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter spp. were inhibited by 16, 4 and 1 mg/L respectively. CG 5501 had high activity against Gram-positive cocci, 90% of staphylococci being inhibited at 2 mg/L. Methicillin-resistant Staphylococcus aureus strains were generally ciprofloxacin-resistant yet were all susceptible to 4 mg/L or less of CG 5501. Isolates of Streptococcus pneumoniae were eight-fold more susceptible to CG 5501 (MIC90 0.5 mg/L) than to ciprofloxacin (MIC90 4 mg/L) and the former had a similar activity to that of trovafloxacin and sparfloxacin. Enterococcus faecalis was generally two- to four-fold more susceptible to CG 5501 or trovafloxacin than to ciprofloxacin. CG 5501 and trovafloxacin had high activity against Bacteroides fragilis (MIC90 0.25 mg/L). Five strains of Chlamydia spp. were inhibited by < or =0.12 mg/L of CG 5501; sensitive and multiresistant strains of Mycobacterium tuberculosis were inhibited by < or =0.5 mg/L of CG 5501. The high activity and breadth of its antibacterial spectrum suggests that CG 5501 should be useful in a wide range of clinical infections.
Concentrations of trovafloxacin were measured in serum, alveolar macrophages, epithelial lining fluid and bronchial mucosa following single and multiple oral doses. Concentrations were determined using a microbiological assay method. There were 18 subjects in the single dose and nine subjects in the multiple dose groups. After single dosing, mean concentrations in serum, alveolar macrophages, epithelial lining fluid and bronchial mucosa at 6, 12 and 24 h were as follows: 6 h, 1.41 mg/L, 19.06 mg/L, 3.01 mg/L and 1.52 mg/kg; 12 h, 0.85 mg/L, 16.22 mg/L, 4.8 mg/L and 1.01 mg/kg; 24 h, 0.37 mg/L, 10.23 mg/L, 0.93 mg/L, and no measurable concentration, respectively. After multiple dosing (approximately 6 h post-dose) the corresponding concentrations were 1.47 mg/L, 34.3 mg/L, 10.21 mg/L and 1.67 mg/kg, respectively. These concentrations exceed the MIC90s for the common respiratory pathogens, Haemophilus influenzae 0.06 mg/L, Moraxella catarrhalis 0.008 mg/L and Streptococcus pneumoniae 0.12 mg/L and suggest that trovafloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infections.
The postantibiotic effect (PAE) of trovafloxacin (CP 99,219) was investigated with six strains of Pseudomonas aeruginosa at concentrations equivalent to 0.5, 1, 2 and 4 x MIC. Trovafloxacin exhibited a significant PAE with four out of the six strains of P. aeruginosa studied. The PAE values obtained for trovafloxacin with P. aeruginosa ranged from 0.3 h to 2.3 h, increasing with increased exposure time and trovafloxacin concentration.
Some strains of staphylococci have raised MBCs of quinupristin/dalfopristin compared with their MICs. In this study, the time-kill kinetics of quinupristin/dalfopristin at 2 mg/L on two strains of Staphylococcus aureus were determined by viable count and intracellular ATP measurement. After 24 h exposure to quinupristin/dalfopristin, the percentage survival of the strain with a raised MBC was 5.9 and that of the strain with a normal MBC was 0.04. The time-kill kinetics of the strain with a raised MBC were analogous to those associated with phenotypic tolerance.
A new semi-synthetic glycopeptide, LY333328, was tested for in-vitro activity against 197 strains of enterococci including strains resistant to other glycopeptides. Activity was also assessed against species with intrinsic resistance to glycopeptides. For strains of enterococci tested the LY333328 MIC90s were < or = 0.5 mg/L. Enterococcus faecalis was less susceptible to LY333328 than other enterococci with a maximum MIC of 2.0 mg/L. Glycopeptide-resistant strains of enterococci were not more resistant to LY333328 than glycopeptide-susceptible strains but intrinsically resistant species had MICs between 4 and 8 mg/L.
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Concentrations of levofloxacin were measured in bronchial biopsies, alveolar macrophages (AM), epithelial lining fluid (ELF) and serum following a single oral dose. Concentrations were measured by a microbiological assay method. A total of 35 patients undergoing fibre-optic bronchoscopy were studied. Mean serum, AM, ELF and biopsy concentrations were as follows. 0.5 h: 4.73 mg/L, 19.1 mg/L, 4.74 mg/L and 4.3 mg/kg; 1 h: 6.6 mg/L, 32.5 mg/L, 10.8 mg/L and 8.3 mg/kg; 2 h: 4.9 mg/L, 41.9 mg/L, 9.0 mg/L and 6.5 mg/kg; 4 h: 4.1 mg/L, 27.7 mg/L, 10.9 mg/L and 6.0 mg/kg; and 6-8 h: 4.0 mg/L, 38.4 mg/L, 9.6 mg/L and 4.0 mg/kg respectively. Mean serum and AM concentrations at 12-24 h were 1.2 and 13.9 mg/L respectively (concentrations in biopsy and ELF were only measurable in three of the six patients). These concentrations exceed the MIC90s of the common respiratory pathogens, Haemophilus influenzae (0.015 mg/L), Moraxella catarrhalis (0.06 mg/L) and Streptococcus pneumoniae (1 mg/L) and suggest that levofloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infection.
The in-vitro activity of grepafloxacin was compared with that of other antimicrobials against respiratory tract pathogens collected from 15 UK laboratories over the winter of 1995-96. Penicillin-resistant Streptococcus pneumoniae was not encountered, but macrolide resistance was seen in approximately 10% of strains. Grepafloxacin (MIC90 0.25 mg/L) was four- to eight-fold more active than ciprofloxacin. Twelve percent of Haemophilus influenzae were beta-lactamase producers, macrolides were relatively inactive yet fluoroquinolones were highly active. Moraxella catarrhalis were highly susceptible to fluoroquinolones and macrolides. The activity of grepafloxacin against respiratory tract pathogens should make it a useful agent in the treatment of infections at this site.
OBJECTIVE: To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population. STUDY DESIGN: A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case. RESULTS: The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses). CONCLUSION: Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found.
The in vitro activity of BAY 12-8039, a new fluoroquinolone, was studied in comparison with those of ciprofloxacin, trovafloxacin (CP 99,219), cefpodoxime, and amoxicillin-clavulanate against gram-negative, gram-positive, and anaerobic bacteria. Its activity against mycobacteria and chlamydia was also investigated. BAY 12-8039 was active against members of the family Enterobacteriaceae (MIC at which 90% of strains tested were inhibited [MIC90S] < or = 1 microgram/ml, except for Serratia spp. MIC90 2 microgram/ml), Neisseria spp. (MIC90S, 0.015 microgram/ml), Haemophilus influenzae (MIC90, 0.03 microgram/ml), and Moraxella catarrhalis (MIC90, 0.12 micrgram/ml), and these results were comparable to those obtained for ciprofloxacin and trovafloxacin. Against Pseudomonas aeruginosa, the quinolones were more active than the beta-lactam agents but BAY 12-8039 was less active than ciprofloxacin. Strains of Stenotrophomonas maltophilia were fourfold more susceptible to BAY 12-8039 and trovafloxacin (MIC90S, 2 micrograms/ml) than to ciprofloxacin. BAY 12-8039 was as active as trovafloxacin but more active than ciprofloxacin against Streptococcus pneumoniae (MIC90, 0.25 microgram/ml) and methicillin-susceptible Staphylococcus auerus (MIC90S, 0.12 micrograms/ml). The activity of BAY 12-8039 against methicillin-resistant S. aureus (MIC90, 2 micrograms/ml) was lower than that against methicillin-susceptible strains. BAY 12-8039 was active against anaerobes (MIC90S < or = 2 micrograms/ml), being three- to fourfold more active against Bacteroides fragilis, Prevotella spp., and Clostridium difficile than was ciprofloxacin. Against Mycobacterium tuberculosis, BAY 12-8039 exhibited activity comparable to that of rifampin (MICs < or = 0.5 micrograms/ml). Against Chlamydia trachomatis and Chlamydia pneumoniae BAY 12-8039 was more active (MICs < or = 0.12 microgram/ml) than either ciprofloxacin or erythromycin and exhibited a greater lethal effect than either to these two agents. The protein binding of BAY 12-8039 was determined at 1 and 5 micrograms/ml as 30 and 26.4%, respectively. The presence of human serum (at 20 or 70%) had no marked effect on the in vitro activity of BAY 12-8039.