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Biomedical subjects

D Honeybourne

Publications and source records attributed to D Honeybourne.

At least 55 records · Page 3Linked to original sources
PubMed1994

Chlamydia pneumoniae.

Chlamydia pneumoniae, a fairly recent addition to the genus Chlamydia, has been shown to cause community-acquired and nosocomial pneumonias, and to be a common infectious agent in human populations throughout the world. It has a wide variety of clinical presentations, and may be associated with ischaemic heart disease. Like other species in the genus, it is difficult to isolate by cell culture: clinical diagnosis therefore rests on other techniques, each of which presents particular problems. Those discussed in this review are cell culture, antigen detection by direct immunofluorescence and enzyme immunoassay, serological methods (exemplified by micro-immunofluorescence) and the polymerase chain reaction. Currently available treatments and the prospect of vaccination are also discussed.

Chlamydia Infections↗
PubMed1994

Concentration of amoxycillin and clavulanate in lung compartments in adults without pulmonary infection.

BACKGROUND: The efficacy of an antibiotic is usually predicted from serum levels and MIC90 values for likely pathogens, but in the lung tissue concentrations may be more informative. This study compares concentrations of amoxycillin and clavulanate in serum, epithelial lining fluid (ELF), alveolar macrophages, and bronchial mucosa in 15 adults. METHODS: Amoxycillin 500 mg and clavulanic acid 250 mg were given 1-2 hours before diagnostic bronchoscopy for haemoptysis or radiological abnormality. Mucosal biopsy samples were taken from macroscopically normal sites, alveolar macrophages harvested by lavage, and ELF volume derived from urea concentrations in bronchial lavage fluid and blood. Amoxycillin was assayed by inhibition of growth of Micrococcus lutea, and clavulanate (in serum, ELF, and bronchial mucosa) by inhibition of growth of Klebsiella pneumoniae; in macrophages clavulanate was measured by high performance liquid chromatography. RESULTS: The median concentrations in serum were 6.90 mg/l for amoxycillin and 5.25 mg/l for clavulanate. The median bronchial mucosal concentration of amoxycillin was 2.99 mg/l and of clavulanate was 1.65 mg/l; the median concentrations in ELF were 0.89 and 0.96 mg/l, and in macrophages 0 and 0.76 mg/l, respectively. In macrophages amoxycillin levels were undetectable in 10 of 14 subjects (71%); by contrast, only 6 of 14 subjects (43%) had no detectable clavulanate. CONCLUSIONS: Clavulanate levels exceeded quoted MIC90 values (around 0.25 mg/l) for Legionella pneumophila both in ELF and in macrophages. Amoxycillin-clavulanate may therefore have a clinical role in infections with Legionella pneumophila.

Adult↗
PubMed1994

The levels of clarithromycin and its 14-hydroxy metabolite in the lung.

Clarithromycin is a new macrolide that has a longer half-life than erythromycin and is claimed to reach higher tissue concentrations. We aimed to investigate whether, following oral administration, the drug and its 14-hydroxy metabolite reach levels in lung tissue that are likely to be clinically effective against common respiratory pathogens. Ten patients undergoing diagnostic bronchoscopy received seven doses of clarithromycin, 500 mg b.i.d. orally. Bronchoscopy was performed at a mean time of 4.25 h after the last dose. At bronchoscopy, bronchial biopsies and bronchoalveolar lavage were performed. Clarithromycin and its 14-OH metabolite were measured in serum, bronchial biopsies, epithelial lining fluid (ELF) and alveolar cells. Mean levels of clarithromycin were 4.0 mg.l-1 in serum, 16.8 mg.kg in bronchial biopsies, 20.5 mg.l-1 in ELF and 372.7 mg.l-1 in alveolar cells. The equivalent levels of 14-OH metabolite were 0.7, 2.7, 1.9 and 38.6 mg.l-1, respectively. We conclude that there is considerable concentration of clarithromycin and its 14-OH metabolite in alveolar cells, and to a lesser extent in bronchial tissue and ELF; this implies efficacy against susceptible organisms at these sites.

Clarithromycin↗
PubMed1993

Comparative bronchoalveolar concentrations of ciprofloxacin and lomefloxacin following oral administration.

In a comparative study, the concentrations of two fluoroquinolone antimicrobials, ciprofloxacin and lomefloxacin, were measured in serum, bronchial mucosal biopsies, epithelial lining fluid (ELF) and alveolar macrophages (AM). Thirty-four subjects received either ciprofloxacin 250 mg b.d. (17 subjects) or lomefloxacin 400 mg o.d. for 4 days prior to sampling by bronchoscopic bronchial biopsy and bronchoalveolar lavage. Both ciprofloxacin and lomefloxacin showed favourable accumulation in the sites of infection with bronchial biopsy concentrations of 1.6 and 1.7 times those of serum respectively; ELF concentrations of 2.1 and 1.9 times serum; and AM concentrations of 11.8 and 20.1 times serum respectively. The MIC90 for most of the common chest pathogens was reliably exceeded by both agents except for that of Streptococcus pneumoniae.

Administration, Oral↗
PubMed1993

The penetration of rufloxacin into sites of potential infection in the respiratory tract.

The concentrations of rufloxacin in the bronchial mucosal, pulmonary epithelial lining fluid and alveolar macrophages were determined in specimens obtained at fibreoptic bronchoscopy. A single oral dose of rufloxacin 400 mg was administered and the samples obtained in the following 72 h. The mean peak serum concentration was 3.56 mg/L, yet the agent was concentrated 1.8-fold in bronchial mucosa, 21.6-fold in alveolar macrophages and 7.7-fold in epithelial lining fluid (as measured by AUC ratios).

Anti-Infective Agents↗
PubMed1992

Concentrations of cefpodoxime in serum and bronchial mucosal biopsies.

Cefpodoxime proxetil is a new orally administered cephalosporin which has a favorable spectrum of activity against respiratory pathogens. Concentrations of cefpodoxime in serum and bronchial mucosal biopsy were measured in 13 patients without active respiratory tract infection undergoing fibreoptic bronchoscopy. Samples were taken between 1 and 6 h after a single oral dose of cefpodoxime proxetil equivalent to 200 mg of cefpodoxime base. In twelve patients who completed the study, mean serum concentrations were 1.7 mg/L (S.E.M. 0.4) and in ten patients mean bronchial biopsy concentrations were 0.9 mg/L (S.E.M. 0.2). The mean penetration was 54% (S.E.M. 6.1). Cefpodoxime was undetectable in biopsies from two patients. The majority of serum and biopsy concentrations were in excess of the MIC90S for Haemophilus influenzae and Streptococcus pneumoniae. Cefpodoxime proxetil may be worthy of further study in clinical trials in patients with respiratory infections.

Administration, Oral↗
PubMed1992

Bronchoalveolar distribution of cefuroxime axetil and in-vitro efficacy of observed concentrations against respiratory pathogens.

The concentrations of cefuroxime in human alveolar macrophages (AM), epithelial lining fluid (ELF), bronchial mucosal biopsies and serum were measured after a single dose, equivalent to 500 mg of cefuroxime base, given in the form of the orally-administered pro-drug, cefuroxime axetil. Fourteen patients undergoing fibreoptic bronchoscopy with bronchoalveolar lavage were studied. The mean ELF concentration was 0.7 mg/L, that of bronchial biopsies was 1.8 mg/kg and that of serum 3.5 mg/L. AM-associated cefuroxime was detected in nine patients. To assess the in-vitro activity of the concentrations achieved at the potential sites of infection, clinical isolates of common respiratory pathogens were exposed to two concentrations of cefuroxime, based on the observed concentrations in ELF and bronchial mucosa. ELF and mucosal site concentrations were effective against Streptococcus pneumoniae (except one strain with reduced susceptibility to benzyl penicillin) and Haemophilus influenzae. The ELF concentration was less effective against Moraxella catarrhalis.

Aged↗
PubMed1992

Quantitative morphology and water distribution of bronchial biopsy samples.

BACKGROUND: An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial biopsy specimens consist of more than one tissue type and that drugs are often not distributed evenly. The morphology of bronchial biopsy specimens and the distribution of water between the extracellular and the intracellular compartments is therefore important. METHODS: Fifteen subjects undergoing fibreoptic bronchoscopy each had four bronchial biopsy samples taken. Thirty sections from 10 patients were examined and the proportion of tissue types noted, a morphometric analysis computer being used. The water distribution was investigated in the other biopsy specimens with radiolabelled markers. RESULTS: There was pronounced variation in the relative proportions of tissue types. Ciliated epithelium occupied a mean of 22.3% of the biopsy sample, submucosa 53.4%, muscle 17.6%, and glandular tissue 7.0%. There were no differences between second and the fourth generation subcarinae and macroscopic normality of the mucosa was a good predictor of histological normality. The extracellular water content was 40% of the total weight of the specimen and the total water content was 70%. CONCLUSIONS: These data provide the basis for pharmacokinetic study of drugs in bronchial mucosa. They show for pharmacokinetic study that macroscopically normal mucosa may be assumed to be histologically normal; that multiple biopsy specimens should be taken for any study, as there is considerable variation in the proportion of tissue types; that specimens from second and fourth generation subcarinae are the same; and that extracellular water contributes 40% to the total weight of the biopsy specimen.

Biopsy↗
PubMed1992

The distribution of temafloxacin in bronchial epithelial lining fluid, alveolar macrophages and bronchial mucosa.

The concentrations of temafloxacin, a new fluoroquinolone antimicrobial, in the potential sites of pulmonary infection were assessed by fibreoptic bronchoscopy with bronchoalveolar lavage. Fourteen patients received a course of temafloxacin, 600 mg twice daily, for three days prior to sampling. The mean serum concentration was 9.6 (SEM 1.2) mg.l-1, compared with 14.9(SEM 1.8) mg.kg-1 for bronchial mucosa, 26.5 (SEM 3.6) mg.l-1 for epithelial lining fluid and 83.0 (SEM 11.5) mg.l-1 for alveolar macrophage. In the ten patients who completed the protocol, site concentrations correlated well with serum concentrations. Temafloxacin was concentrated in each of the potential sites of infection examined and is, therefore, a promising new agent for the treatment of respiratory tract infection.

Anti-Infective Agents↗
PubMed1991

The penetration of cefpirome into the potential sites of pulmonary infection.

The concentrations of cefpirome, a new semi-synthetic cephalosporin, in the bronchial mucosa and serum were assessed after a single 1 g intravenous dose in 37 patients. Bronchoalveolar lavage allowed epithelial lining fluid (ELF) concentrations to be measured in eight subjects. The mean concentration for serum was 34.5 mg/L (S.E.M. 3.3), for bronchial mucosa 19.3 mg/kg (S.E.M. 1.9) and for ELF 7.2 mg/L (S.E.M. 1.1). The progressive reduction in cefpirome concentration in serum compared to that in bronchial mucosa and ELF is consistent with the permeability characteristics of beta-lactam antimicrobials and the barriers to movement of antimicrobial agents present in the lung.

Adult↗
PubMed1991

Comparative pharmacokinetic disposition of fluoroquinolones in the lung.

The problems associated with the study of the penetration of quinolones into the respiratory tract are discussed. New techniques allow the study of the penetration of these agents into bronchial mucosa, alveolar macrophages and epithelial lining fluid. In general quinolones are concentrated in bronchial mucosa approximately 1.5 times compared with serum. In alveolar macrophages, the agents are concentrated 14- to 18-fold compared with serum and the ratio of alveolar macrophage levels to those in epithelial lining fluid are 7.7 to 5.7:1. The concentrations of temafloxacin and ciprofloxacin in these sites suggests that these agents will be efficacious in the therapy of respiratory infections caused by Streptococcus pneumoniae.

Administration, Oral↗