摘要:

Rufloxacin is a new broad-spectrum fluoroquinolone antibacterial agent. The pharmacokinetics and safety of rufloxacin were evaluated after repeated oral administration to healthy volunteers. The drug was administered once a day for 6 consecutive days following two different dose schedules. The first group of 11 subjects was given a loading dose of 300 mg on the first day and 150 mg on the subsequent 5 days. The second group of 12 subjects was given a loading dose of 400 mg and 200 mg for 5 days. Serum levels and urine concentrations of rufloxacin were determined by microbiological assay. A simultaneous fit of all data points for each subject was done according to a one-compartment open model. The drug was rapidly absorbed (absorption half-life 17 ± 6 min in the 300 + 150 mg and 11 ± 5 min in the 400 + 200 mg dose regimen group) and reached maximal serum concentrations (2.77 ± 0.24 and 3.62 ± 0.35 μg/ml) 4.2 ± 0.4 and 4.0 ± 0.9 h after the first administration. Steady-state serum concentrations (3.19 ± 0.31 and 4.06 ± 0.33 μg/ml) were reached in 3.7 ± 0.7 and 4.5 ± 0.4 days. Elimination half-lives were 29.5 ± 2.4 and 36.0 ± 2.8 h. Apparent volumes of distribution were Ill ± 8 and 136 ± 16 liters and apparent plasma clearances were 46 ± 5 and 44 ± 4 ml/min. Renal clearances were 18 ± 3 and 17 ± 2 ml/min. The percentage of the total dose excreted in urine throughout the study was 36.1 ± 4.0% in the 300 + 150 mg and 43.7 ± 2.5% in the 400 + 200 mg dose schedule group. Mean extents of accumulation were 2.4 ± 0.2 and 2.5 ± 0.1. Treatments were well tolerated, with only minor side effects (nausea, insomnia and postprandial vomiting) in 3 subjects and with no abnormalities being noted in routine laboratory examinations. Two and 3 days after the last administration, measurable antimicrobial activity was still observed in plasma and urine, indicating that the long half-life of rufloxacin assures valuable antibacterial coverage even after disco

ISSN:0009-3157    

DOI:10.1159/000238885

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

BRL 42715 is a new penem which inhibits a wide range of plasmid as well as chromosomally mediated bacterial β-lactamases. We used a total of 902 recent clinical isolates, consisting of 455 Enterobacteriaceae, 247 staphylococci and 200 other gram-negative bacteria to evaluate its ability for potentiation of amoxycillin. MICs for all the 104 strains of methicillin-susceptible Staphylococcus aureus 32.0 μg/ml) to a ‘susceptible’ range (≤ 8.0 μg/ml). Commonly resistant bacteria like Klebsiella, Enterobacter, Citrobacter, Morganella, Serratia, Acinetobacter and Aeromonas were rendered susceptible to amoxycillin in the presence of 1.0

ISSN:0009-3157    

DOI:10.1159/000238886

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The comparison of a clinical Acinetobacter baumanii isolate (strain No. 4852/88) and its selected imipenem-resistant (IMR) clone exhibited a complex reorganization of the penicillin-binding proteins (PBPs) with diminished labelling of all PBPs except the 24-kD PBP which showed an increased binding of 14C-penicillin. This protein could not be saturated by preincubation of membranes with imipenem at 8-fold the MIC of imipenem, thus indicating PBP alterations responsible for imipenem resistance. In A. baumanii 4852/88 seven PBPs with the apparent molecular weights of 94, 84, 65, 61, 48, 40 and 24 kD could be detected. β-Lactamase production was barely detectable in any case and could not be enhanced in the presence of various β-lactams as the inducer. The outer membrane proteins were found identical in both the wild-type strain and the ImR clone. So far, imipenem-resistant A. baumanii isolates have been isolated twice in our diagnostic laboratory; hovewer, no implications on the future relevance of the above findings can be mad

ISSN:0009-3157    

DOI:10.1159/000238887

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The minimum inhibitory concentration (MIC) of the new penem ALP 201 was tested against 243 recent clinical isolates of which 95 were from the family Enterobacteriaceae, 50 were from the genus Streptococcus,50 were Staphylococcus aureus and 48 were Staphylococcus epidermidis.An agar dilution technique was used to determine the MIC50 and MIC90 of ALP 201 in comparison with cefotaxime, cefuroxime, clindamycin, imipenem, piperacillin, tobramycin and vancomycin. Overnight cultures were suspended to produce inocula of 105 colonies from a replicator. ALP 201 was shown to have an activity similar to imipenem against most species; ALP 201 was less active than imipenem against Serratia spp. and was more active against S. epidermidis.β-Lactamase production did not affect the activity of ALP 201. All the other compounds tested were less active than ALP 201 and imipenem

ISSN:0009-3157    

DOI:10.1159/000238888

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The antimicrobial activity (minimal inhibitory concentration, MIC, and killing kinetics) and postantibiotic effect (PAE) of different concentrations (MIC and 6 mg/l) of ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, fleroxacin and lomefloxacin on pure cultures of Staphylococcus aureus and Escherichia coli were compared in vitro. The MIC, killing kinetics and PAE were determined by standard methods. Ciprofloxacin displayed the lowest MICs, while the highest were those of norfloxacin against S. aureus and lomefloxacin against E. coli.The killing curves showed ciprofloxacin to be the most and norfloxacin the least active. The bactericidal power was dependent on the concentration. At MIC, the fluoroquinolones, with the exception of norfloxacin, induced PAEs of 1–2 h. The effect was, in all cases, greater against E. coli.When assayed at 6 mg/l the PAEs were increased to 2–5 h, the best results being obtained by ciprofloxacin followed by ofloxacin. Norfloxacin produced no PAE on S. aureus and scarcely reached 1.3 h against E. coli.There was a close relationship between bactericidal power and

ISSN:0009-3157    

DOI:10.1159/000238889

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Twelve clinical and 102 fecal isolates from healthy carriers of Clostridium perfringens type A were tested for virulence in juvenile, outbred NMRI mice (intramuscular route). There were marked differences (up to 1,000-fold) in virulence among strains of both groups of isolates. On average, clinical isolates were not more virulent than fecal isolates. Fresh epinephrine (10 μg/mouse and given concurrently with bacterial inocula) significantly augmented virulence. The murine model of Hill and Osterhout for experimental gas gangrene yielded reproducible results. Myelosuppressed (cyclophosphamide-pretreated) mice were somewhat more susceptible to C perfringens as contrasted with mice that had been pretreated with either carrageenan type II or with zymosan. The murine virulence of C. perfringens was enhanced significantly by Escherichia coli

ISSN:0009-3157    

DOI:10.1159/000238890

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Daunorubicin (DNR) and l-β-D-arabinofuranosylcytosine (Ara-C) act in a schedule-dependent fashion on leukemic cells. The present study was undertaken to determine whether the inhibition exerted by DNR on Ara-C cytotoxicity on HL 60 cells could be accounted for by an impairment of its uptake. After 250 ng/ml DNR treatment for 30 min, the time course of Ara-C uptake was measured, up to 128 min of incubation at 37°C and at 4°C, compared with controls. We found that DNR inhibits Ara-C uptake both at 37 and 4°C, mostly acting on passive diffus

ISSN:0009-3157    

DOI:10.1159/000238891

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The K562 cell line provides a unique population of primitive human myeloid leukaemia cells which can be induced to differentiate along the erythroid, granulocytic, macrophage and megakaryocytic lineages in response to several agents. Cytarabine is not only the most widely used drug in the treatment of myeloid leukaemia but also the most effective agent in K562 cells. The effects of five recombinant human cytokines – interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-α, interferon-β and interferon-γ on cytarabine-induced growth inhibition and differentiation of K562 cells was studied in liquid suspension cultures. GM-CSF and to a lesser extent IL-3 enhanced the antiproliferative effect of cytarabine in K562 cells, whereas the three interferons reduced it. The efficacy of cytarabine in inhibiting the growth of K562 cells was doubled by its combination with GM-CSF or IL-3 but was halved by its combination with interferons. The five cytokines did not significantly affect cytarabine-induced erythroid differentiation of K562 cells. The present results appear to favour the use of GM-CSF and IL-3 but not of interferons in future treatment strategies based on a combined cytokine and chemotherapy approach for myeloid leuka

ISSN:0009-3157    

DOI:10.1159/000238892

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

An oral chemotherapy schedule based on idarubicin and cyclophosphamide was evalutated in 31 advanced breast cancer patients. Out of 27 patients evaluable for response, 1 (3.7%) achieved a complete response and 5 (18.5%) a partial response, with an objective response rate of 22.2% (95% confidence limits 8.6–42.3%). The median time to progression was 7 months (range 3–12). Fourteen patients (51.9%) showed a disease stabilization, and 7 progressed (25.9%). Toxicity was mild. Considering the low response rate, but also the advantages of oral chemotherapy and the mild toxicity observed, oral idarubicin plus cyclophosphamide can be considered as a second-choice regimen in advanced breast can

ISSN:0009-3157    

DOI:10.1159/000238893

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0009-3157    

DOI:10.1159/000238894

出版商:S. Karger AG    

年代:1991

数据来源: Karger