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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1994

Evaluation of three culture media and their combinations for the isolation of Mycobacterium tuberculosis from pleural aspirates of patients with tuberculous pleurisy.

The abilities of three culture systems to detect Mycobacterium tuberculosis from 480 pleural aspirate specimens in 347 patients were compared. The systems were the Bactec 12B radiometric detection system (Bactec 12B), the Middlebrook 7H9 broth (7H9), and two solid media including one pyruvate enriched Lowenstein-Jensen slope (LJP) and one non-selective Middlebrook 7H11 agar slope (7H11). In the 116 specimens obtained from 85 patients of confirmed pleural tuberculosis for the isolation of Mycobacterium tuberculosis, the diagnostic yields were 33 (39%) cases from Bactec 12B, 24 (28%) cases from 7H9 and 21 (25%) cases from LJP/7H11, with median detection times of 18, 47.5 and 44 days respectively. Thirteen isolates were recovered by the Bactec 12B only, 9 by the 7H9 broth only, and 2 by the LJP/7H11 agar only. The use of a combination of the three culture systems substantially increased the diagnostic yield to 47% over the individual systems. These results show that a significantly greater and faster diagnostic yield can be obtained by including Bactec 12B in pleural aspirate cultures for the recovery of Mycobacterium tuberculosis.

Biopsy, Needle↗
PubMed1993

Multiple-dose pharmacokinetics of rufloxacin in patients with cirrhosis.

The multiple-dose pharmacokinetics of rufloxacin were investigated in 13 patients with biopsy-proven cirrhosis and in 5 healthy controls. Rufloxacin was administered once a day for 5 consecutive days, starting with a loading dose of 400 mg on day 1 and 200 mg on the subsequent days. Plasma and urinary drug concentrations were determined by high-performance liquid chromatography and a microbiological assay. A one-compartment model applied to the high-performance liquid chromatography data was used to calculate the pharmacokinetic parameters of rufloxacin. In the controls rufloxacin had a low plasma clearance (41 +/- 4 ml/min, mean +/- S.E.M.), a long half-life (30.1 +/- 3.9 hr), a large area under the plasma concentration vs. time curve (171 +/- 18 micrograms.hr/ml) and a low renal clearance (18 +/- 2 ml/min). No appreciable differences were observed in the pharmacokinetic parameters between patients with various degrees of liver-function impairment (modified Child-Pugh score ranging from 5 to 13). In these patients plasma clearance was slightly reduced (-32%), but this decrease was caused by a marked reduction in renal clearance (-65%) rather than nonrenal clearance, which remained unchanged (22 ml/min in cirrhotic patients vs. 23 ml/min in controls). A significant (p < 0.01) correlation was found between creatinine clearance and both rufloxacin renal clearance (r = 0.769) and rufloxacin plasma clearance (r = 0.681). The elimination half-life and the area under the plasma concentration vs. time curve were moderately increased in cirrhotic patients (+33% and +26%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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 in-vitro activity of Bay y 3118, a new chlorofluoroquinolone.

The in-vitro activity of Bay y 3118, a new quinolone antimicrobial was compared with that of ciprofloxacin, sparfloxacin and three beta-lactams against 620 clinical isolates. Bay y 3118 was the most active quinolone against the majority of Enterobacteriaceae and Staphylococcus spp. The MIC90 for the members of the Enterobacteriaceae were < or = 0.12 mg/L except for Serratia spp. (1 mg/L) and in general Bay y 3118 was two-fold more active than ciprofloxacin or sparfloxacin. Strains of Pseudomonas aeruginosa were more susceptible to ciprofloxacin (MIC90 0.25 mg/L) than to Bay y 3118 (MIC90 0.5 mg/L) or sparfloxacin (MIC90 1.0 mg/L). Staphylococcus aureus was more susceptible to Bay y 3118 (MIC90 0.03 mg/L) and sparfloxacin (MIC90 0.06 mg/L) than to ciprofloxacin (MIC90 1 mg/L) and similar differences were noted for Staphylococcus saprophyticus and Staphylococcus epidermidis. Streptococcus pneumoniae was susceptible to Bay y 3118 (MIC90 0.03 mg/L) as were other streptococci. Enterococcus spp. was four-fold more susceptible to Bay y 3118 and sparfloxacin than to ciprofloxacin. All strains of Haemophilus influenzae and Moraxella spp. were inhibited by Bay y 3118 < or = 0.015 mg/L. Anaerobes were more susceptible to Bay y 3118 than to other quinolones; the MIC90 of Bay y 3118 for Bacteroides fragilis being 0.06 mg/L. Little effect was seen by increasing the inoculum from 10(4) cfu to 10(6). Bay y 3118 inhibited Chlamydia sp. at concentrations < or = 0.015 mg/L.

Anti-Bacterial Agents↗
PubMed1993

The in-vitro activity of OPC-17116, a new 5-methyl substituted quinolone.

The in-vitro activity of the new 5-methylated fluoroquinolone OPC-17116 was compared with that of other fluoroquinolines and beta-lactams against a total of 690 bacterial strains. With the exception of Klebsiella and Serratia spp., 90% of the Enterobacteriaceae were inhibited by 0.25 mg/L. OPC-17116 inhibited 90% of Serratia spp. at 8 mg/L and Klebsiella spp. at 4 mg/L. Moraxella catarrhalis and Haemophilus influenzae were highly susceptible (MIC90 < or = 0.03 mg/L). Pseudomonas aeruginosa were more susceptible to ciprofloxacin (MIC90 0.25 mg/L) than OPC-17116 (MIC90 1 mg/L). Generally, OPC-17116 was more active than ciprofloxacin against Gram-positive cocci, 90% of Staphylococcus spp. being inhibited by < or = 0.25 mg/L. OPC-17116 displayed greater activity than ciprofloxacin against Chlamydia spp. (MICs < or = 0.12 and < or = 2 mg/L, respectively).

Amoxicillin↗
PubMed1993

The antimicrobial activity and beta-lactamase stability of cefpirome, a new fourth-generation cephalosporin in comparison with other agents.

The antimicrobial activity of cefpirome was compared with amoxycillin/clavulanic acid, ampicillin/sulbactam, cefuroxime, ceftazidime, gentamicin and amikacin against 743 non-duplicate clinical isolates. MIC50 and MIC90 showed that the antibiotic was active against both Gram-negative and Gram-positive organisms. Cefpirome was highly active against most of the Enterobacteriaceae, including indole-positive Proteus spp., Aeromonas spp. (MIC < or = 1 mg/L) and Salmonella spp. (MIC < or = 0.5 mg/L). Neisseria gonorrhoeae and Haemophilus influenzae (including beta-lactamase producers) were all susceptible, with MIC less than 0.5 and 0.25 mg/L respectively. Cefpirome was more active than cefuroxime and ceftazidime against Campylobacter spp. (MIC < or = 2 mg/L), but less active than ceftazidime against Pseudomonas aeruginosa. Cefpirome was active against Streptococcus pneumoniae. Streptococcus bovis and coagulase-negative staphylococci (MIC < or = 0.5 mg/L) and methicillin-sensitive Staphylococcus aureus (MIC < or = 2 mg/L). Methicillin-resistant S. aureus, Gram-positive and Gram-negative anaerobes were resistant to cefpirome. The stability of cefpirome to TEM-1, TEM-2, PSE-1, SHV-1 and the chromosomal-mediated P99 and K-1 beta-lactamases was comparable to ceftazidime.

Acinetobacter↗
PubMed1993

The efficacy and safety of piperacillin/tazobactam in the therapy of bacteraemia.

The efficacy of the combination of piperacillin plus tazobactam was studied in 142 patients who had a bacteriologically proven bacteraemia. Seventy-three patients were bacteriologically evaluable and, of these, 55 had a follow-up blood culture; there was no follow-up culture in the other 18 patients, so that any cure could only be presumptive. Of the 55 patients who were fully followed up, 32 received only piperacillin and tazobactam and 23 also received an aminoglycoside. Overall, there were 67 cures and six failures out of 73 evaluable cases (three Staphylococcus aureus, two Staphylococcus epidermidis and one Streptococcus bovis). There were 11 deaths, eight of which occurred in neutropenic patients. In no case was death drug related. Side-effects were mild; the commonest adverse events noted were mild elevations of liver enzymes. Piperacillin plus tazobactam appeared efficacious and safe in the therapy of bacteraemia.

Abdomen↗
PubMed1993

The pharmacokinetics, tissue penetration and in-vitro activity of loracarbef, a beta-lactam antibiotic of the carbacephem class.

The pharmacokinetics of loracarbef in plasma and a mild inflammatory exudate were studied in human volunteers. After a single oral dose of 400 mg, a mean maximum drug concentration (Cmax) of 17.8 mg/L was achieved in the plasma at 1.2 h (mean Tmax). The mean plasma elimination half-life (T1/2) was 1.3 h. In the inflammatory exudate the mean Cmax was 8.9 mg/L at a mean Tmax of 2.0 h and with a mean T1/2 of 1.7 h. The mean penetration into the inflammatory exudate was 90.1%. The in-vitro activity of loracarbef was determined against Haemophilus influenzae and Moraxella catarrhalis (MIC90s of 4 mg/L and 1 mg/L respectively, regardless of beta-lactamase production), as well as Streptococcus pneumoniae (MIC90 of 2 mg/L). Loracarbef was also active against Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae (MIC90s of < or = 2 mg/L). The in-vitro activity and pharmacokinetics of loracarbef suggest that it would be efficative therapy for patients with community-acquired respiratory and urinary tract infections caused by the most frequently-encountered bacterial pathogens.

Adult↗