摘要:

The pharmacokinetics of metronidazole (M), hydroxymetronidazole (OH-M), and acetylhydroxymetronidazole (A-M) were determined after a single intravenous dose of 0.5 g metronidazole. This was administered as an intravenous infusion during 30 min to 10 healthy volunteers and 24 patients with varying degrees of reduced renal function. Serum and urine concentrations were assayed by high-pressure liquid chromatography. The peak concentrations of the hydroxymetabolite appeared within an hour in the healthy volunteers and after a mean of 2.6 h (range 0.5–12.5 h) in the patients with reduced renal function. Analogously, the peak of the acetylmetabolite appeared later, at an average of 6.9 h and a range of 0.5–36.5 h. A-M was not observed in serum of the healthy subjects nor in 6 of the patients, but was recovered in urine of all subjects. The serum concentrations of M and OH-M were detectable throughout the 48 h monitored. Total urinary recovery in healthy subjects was 108.0% of the dose. This breaks down to 18.4% metronidazole, 62.4% OH-M, and 27.2% A-M. In the patients with reduced renal function, the relative contribution of A-M is higher than that of the other two products. The serum half-life of metronidazole was 7.1 h in the healthy subjects and similar in reduced renal function (range 3.5–12.4 h). The serum half-life of OH-M was 18.0 h in the healthy and ranged 9.6–85.5 h in renal impairment. Long half-life values of 8.5–36.5 h were observed for A-M. Accumulation of OH-M and particularly of A-M was marked in reduced renal function. In the normal healthy volunteers, the coefficient of the steady-state distribution volume averaged 0.404 liter/kg, of the terminal phase distribution volume 0.542 liter/kg, and the total body clearance 3.1 liter/h. The total body clearance of the unchanged compound was not influenced by reduced renal

ISSN:0009-3157    

DOI:10.1159/000238429

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The penetration into suction skin blisters and pharmacokinetics of 4 sulfonamides (sulfacarbamide, sulfadimidine, sulfadiazine, sulfamethoxazole) and two dihydrofolate reductase inhibitors (methioprim, trimethoprim) have been compared in healthy volunteers. The concentrations were monitored after the first dose and for the subsequent 4 days when approximate steady state conditions could be assumed to have been established. The serum or plasma half-life of the agents in the above order was 3.1, 6.3, 13.9, 12.1, 9.3, and 12.0 h. The respective areas under the serum curves were 97.1, 607.8, 942.6, 1423.1, 128.1 and 175.4 mg/l per dose of 1.0 g. With the sulfonamides, there was a distinct correlation between serum protein binding and pKa and the ability of the compounds to penetrate into blister fluid as shown by the 12-hour ratios between areas under the concentration curves in blister fluid relative to serum.

ISSN:0009-3157    

DOI:10.1159/000238430

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The antibacterial activity of aztreonam, 9 other β-lactam antibiotics and gentamicin was tested in vitro on 383 recently isolated bacteria. The activity of aztreonam against the gram-negative bacteria is similar to the activity of the 3rd generation cephalosporins and gentamicin. With regard to β-lactamase stability only PSE-2 out of 14 plasmid mediated β-lactamases and K-1 out of 2 chromosomally mediated β-lactamases could hydrolyze aztreonam. With its β-lactamase stability, high antibacterial activity and narrow-spectrum aztreonam seems to be a valuable addition to the antibiotic ars

ISSN:0009-3157    

DOI:10.1159/000238431

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

A total of 432 clinical isolates of Staphylococcus aureus (128), coagulase-negative staphylococci (123), group A and B β-hemolytic streptococci (61), group D streptococci (30), Streptococcus pneumoniae (29), Haemophilus influenzae (19), Haemophilus parainfluenzae (12), and Legionella pneumophila (30) were examined with the agar dilution and Bauer-Kirby agar disk diffusion tests for susceptibility to josamycin as compared with erythromycin. On a weight-for-weight basis, erythromycin was more active than josamycin against all bacterial species, including L. pneumophila. Josamycin inhibited 18 of 23 S. aureus and 11 of 16 coagulase-negative staphylococcal strains resistant to erythromycin. Utilizing minimal inhibitory concentrations (MIC) breakpoints of ≤ 2 μg/ml (sensitive), 4 μg/ml (intermediate) and of ≥ 8 μg/ml (resistant), and inhibition zone criteria of ≥ 18 mm diameter (sensitive), 14–17 mm (intermediate), and ≤ 13 mm (resistant), and excluding L. pneumophila, there was good correlation between erythromycin MIC and corresponding disk diffusion data for staphylococci and streptococci, but not for Haemophilus species. In comparison, josamycin yielded a significant number of minor discrepant data for group D streptococci and Haemophilus species. It is suggested that erythromycin and josamycin should not be tested against Haemophilus species, and that josamycin should be excluded from test batteries against enterococci. Erythromycin-resistant staphylococci require separate testing w

ISSN:0009-3157    

DOI:10.1159/000238432

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Cefpirome and six other antimicrobial agents were tested against 884 blood culture isolates from cancer patients. Cefpirome was highly active against aerobic gram-negative bacilli including Acinetobacter spp., and the Enterobacteriaceae. Only imipenem was more active than cefpirome against Pseudomonas aeruginosa. Cefpirome was also extremely active against β-hemolytic streptococci and methicillin-susceptible staphylococci

ISSN:0009-3157    

DOI:10.1159/000238433

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

A procedure dating back to the early penicillin era is adapted in order to determine the activity of the new cephalosporins ceftizoxime and ceftriaxone against Treponema pallidum in vitro. While the well-known activity of penicillin G is confirmed for the virulent Nichols strain (0.002 μg/ml lead to 50% immobilisation) the new cephalosporins turn out to be almost as efficacious. The concentration of ceftizoxime leading to 50% inhibition amounts to 0.004 μg/ml. The corresponding figure for ceftriaxone is 0.01 μg/ml. The potential importance of these findings for the treatment of syphilis in man are discuss

ISSN:0009-3157    

DOI:10.1159/000238434

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Two human squamous carcinomas of the cervix, established by serial passage in nude mice, are described. The reponse of the tumours to cis-diamminedichloro-platinum (CDDP) was assessed by comparing tumour weights and by histological observations. Tumours treated with CDDP 10 mg/kg/week for 2 weeks regressed significantly and microscopy revealed extensive degeneration. Treatment with CDDP 5 mg/kg/week produced tumour growth retardation and microscopy showed some degenerative changes, however, viable cells, many of which were mitotic, were evident. There was, therefore, a dose-response relationship. The sensitivity of the tumours to CDDP lends support to its use in humans with this malignancy.

ISSN:0009-3157    

DOI:10.1159/000238435

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The efficacy of azlocillin + amikacin was compared to ciprofloxacin (with and without amikacin) in 96 rabbits with right-sided endocarditis due to Pseudomonas aeruginosa. Animals received either: (1) no therapy (controls); (2) amikacin (15 mg/kg/day) + azlocillin (400 mg/kg/day); (3) ciprofloxacin (80 mg/kg/day) or (4) amikacin + ciprofloxacin (above dosages). All three antibiotic regimens were significantly more effective than no therapy in reducing mortality (p < 0.0005), preventing pulmonary infarction (p < 0.0005) and reducing mean vegetation titers of P. aeruginosa (p < 0.0005). Also, the three therapy regimens were equivalent in preventing bacteriologic relapse after discontinuing therapy. No development of antibiotic resistance in vivo was observed.

ISSN:0009-3157    

DOI:10.1159/000238436

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effect of several antibiotics on rat platelet membrane fluidity was examined by ESR spectrometry using 5-doxyl stearate as the spin probe. Latamoxef, cefamandole, cefotaxime and carbenicillin had negligible effects on the order parameters, the indices of membrane fluidity, of platelet-rich plasma or washed platelets at high concentrations that would inhibit ADP-induced rat platelet aggregation in vitro. A further in vivo study with one of these antibiotics, latamoxef, showed no significant effect on the fluidity based on ESR data.

ISSN:0009-3157    

DOI:10.1159/000238437

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effects of three macrolide antibiotics were studied on rat polymorphonuclear leukocyte chemotaxis. Rats were given 25 mg/kg twice a day of either erythromycin, josamycin or spiramycin by gastric intubation for 5 days. In all cases, chemotaxis was found to be impaired by 10–20% only. As macrolides are known to reach high intracellular concentrations within polymorphonuclear leukocytes, our results suggest that these antibiotics are unlikely to exert a deleterious influence on the chemotactic response of treated patient

ISSN:0009-3157    

DOI:10.1159/000238438

出版商:S. Karger AG    

年代:1986

数据来源: Karger