摘要:

The pharmacokinetics of cefroxadine, a new orally active broad-spectrum cephalosporin, was studied in healthy volunteers and patients with impaired renal function after a single oral dose of 500 mg. The pharmacokinetic parameters of cefroxadine were obtained by analysing the serum level data of the drug based on a one-compartment open model. The mean serum half-life of cefroxadine was 0.97 h in healthy subjects, and was prolonged to 41.7 h in patients with a creatinine clearance of < 5 ml/min. There was a significant linear correlation (p < 0.001) between the elimination rate constant of the drug and the creatinine clearance. In healthy subjects, 71% of the administered dose was excreted in the urine collected over the first 6 h.

ISSN:0009-3157    

DOI:10.1159/000237971

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

A high-pressure-liquid chromatographic (HPLC) procedure for quantitative assay of cefotaxime (CT) and its major metabolite in serum of normal individuals, desacetyl cefotaxime (DACT), is described. It employs Lichrosorb RP-8, elution with phosphoric-acid-methanol and UV absorption at 310 nm. The method is optimized for cefotaxime and allows differentiation between the parent compound and the biotransformation product DACT. The lower assay sensitivity level of CT and DACT is 0.3 μg/ml. Correlation between HPLC and microbiological assay with Escherichia coli or Proteus rettgeri of pooled serum with CT added is r = 0.99. The method is rapid; processing of one sample takes 17 min. Use of HPLC avoids the errors of microbiological assays which derive from the presence in patient sera of different ratios of CT and DACT. The apparent rate of serum elimination is linearly related to the sensitivity of the microbial assay indicator strain to DACT. There is synergistic antibacterial activity between CT and DACT regardless of relative minimum inhibitory concentrations of the agents

ISSN:0009-3157    

DOI:10.1159/000237972

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Cefamandole penetration was studied in 32 normal bone specimens. No antibiotic bone binding was found. Blood contamination of bone samples was measured by the haemoglobin method. Mean corrected levels attained (5.8 μg/g) exceed MIC values of sensitive Staphylococcus aureus, Haemophylus influenzae and Enterobacteriaceae. Similar diffusion was observed in cortical and trabecular bone. The results obtained invite further studies on preoperative prophylaxis and treatment of osteomyelitis

ISSN:0009-3157    

DOI:10.1159/000237973

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

The pharmacokinetics of cefotaxime after repeated doses of intramuscular injections were studied in 8 healthy volunteers receiving 1 g cefotaxime every 8 h for 6 days. Mean peak serum level after the first 1 g intramuscular dose was 26.8 ± 6.4 μg/ml and the peak serum concentration was reached within 75 min. The half-life of cefotaxime was 1.35 ± 0.33 h and the total apparent clearance 263 ± 63 ml/min. After the last injection (day 6), the mean peak serum level reached 19.1 ± 3.2 μg/ml and the areas under the curve were significantly lower than on day 1. No body accumulation of the drug could be detected. Serum levels of cefotaxime monitored throughout the study 5 min prior to and 30 min after the intramuscular injection were found above the minimum inhibitory concentration for most aerobic gram-positive and gram-negative sensitive orga

ISSN:0009-3157    

DOI:10.1159/000237974

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Nine purine or pyrimidine analogues or other inhibitors of DNA synthesis were studied for their inhibition of vaccinia virus multiplication by a plaque inhibition test with a fluid overlay in Vero cell cultures, either as single substances or in combination. Experiments on combined inhibition were made with substance concentrations leading to 80–90% plaque inhibition; indifference, additive, or synergistic interaction were evaluated from normalized plaque counts. 12 substance pairs acted in a synergistic manner and 22 showed indifference. A comparison was made with the results of other DNA viruses (adenovirus, herpes simplex virus

ISSN:0009-3157    

DOI:10.1159/000237975

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Experiments have been performed using rifampicin (RIF) and tetracycline (TET) to establish whether the use of the combination prevents the emergence of bacterial resistance to either drug. Experiments were performed using repeated 4-hour cycles of exposure of large bacterial populations to varying concentrations of antibiotics in order to reproduce in vitro the conditions of treatment of a systemic infection in man. When exposed to both RIF and TET the doubly-sensitive test organism was eliminated from the test cultures in 92 h without emergence of resistance. When the organism was exposed to RIF alone it became massively RIF-resistant in 20 h. The organism was eliminated in 104 h when exposed to TET alone. Under the test conditions there was no significant difference in experimental outcome when RIF was added to TET compared to that when TET alone was used.

ISSN:0009-3157    

DOI:10.1159/000237976

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Dihydrofolate reductases (DHFR) were studied in two groups of trimethoprim (TMP)-resistant Enterobacteria 1,000 mg/l) and all of them were found to harbour an additional TMP-insensitive DHFR thought to be responsible for the high degree of resistance. Three Proteus mirabilis strains in this group synthesized chromosomal reductases with reduced TMP sensitivity as well. A second group of six strains, exhibiting MIC values for TMP between 16 and 512 mg/l was seen to be resistant by the production of a chromosomally altered TMP-insensitive DHFR, produced either in normal or slightly elevated amounts. With one exception these strains were all fully susceptible to sulfadiazine and strong synergism with TMP was present. Resistance to nalidixic acid was also frequently observed in this group. In conclusion, three different basic mechanisms were found to be responsible for TMP resistance in Enterobacteria from Finland and these were seen to occur not only independently but also simultaneously in the same strain.

ISSN:0009-3157    

DOI:10.1159/000237977

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Bacterial elimination kinetics under different simulated administration schedules of amoxicillin was followed in vitro by using a simple model for simulation of pharmacokinetic parameters. The results were compared to those obtained in lethally infected mice by determining the viable bacterial count in the blood at various times post-infection and under different schedules of amoxicillin administration. A satisfactory correlation could be established between the in vitro and invivo results. Multiple administration of amoxicillin was found to induce a β-lactamase in vitro as well as in vivo in the Escherichia coli strain used. No difference was however found between the various administration schedules of amoxicillin in terms of surviving animals. Taking into account the lasting elimination of viable bacteria from the blood, the best treatment of E. coli-infected mice was found to be a twice daily administration of the higher amoxicillin dose

ISSN:0009-3157    

DOI:10.1159/000237978

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

In the studies conducted, arginine deficiency suppressed herpes simplex virus replication in tissue culture. Lysine, an analog of arginine, as an antimetabolite, antagonized the viral growth-promoting action of arginine. The in vitro data may be the basis for the observation that patients prone to herpetic lesions and other related viral infections, particularly during periods of stress, should abstain from arginine excess and may also require supplemental lysine in their diet.

ISSN:0009-3157    

DOI:10.1159/000237979

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Therapy of listeriosis with ampicillin was examined in two murine models with compromised defense mechanisms. In mice treated with dextran sulfate paralysing the function of the macrophage system, ampicillin was less able to reduce death rates as well as bacterial counts in the spleens than after infection of normal mice. In nude mice with chronic listeriosis, treatment with ampicillin was started 8 days after infection. The numbers of viable listeria cells decreased under therapy, but a bacteriologic cure was not achieved in a 6-day schedule. Relapse followed cessation of therapy.

ISSN:0009-3157    

DOI:10.1159/000237980

出版商:S. Karger AG    

年代:1981

数据来源: Karger