摘要:

The pharmacokinetics of intramuscular doses of 1.0 g cefotaxime (HR 759) was studied in 19 persons with normal or reduced renal function. Quantitation was done by both microbiological and high pressure liquid chromatography (HPLC) methods. The HPLC determined unchanged cefotaxime and desacetyl cefotaxime and up to 2 more metabolites in serum, whether unchanged or biotransformed. Patients with renal functions within the normal range (inulin clearance above 100 ml/min) had a mean serum peak concentration of 24.5 ± 10.5 μg/ml. In renal failure, both serum concentrations and the terminal serum half-life (t½β) increased. The mean terminal serum half-life was 2.1 h according to the microbiological assay and 1.5 h according to the HPLC procedure at a glomerular filtration rate (GFR) of 100 ml/min. At an inulin clearance of 10 ml/min, the serum half-life was 6.0 h for the total microbiologically assayed activity and 3.6 h for unchanged drug. There is a linear relationship between log serum half-life of the three moieties of unchanged cefotaxime, total antimicrobial activity (agar diffusion assay with Escherichia coli as indicator), and the major metabolite desacetyl cefotaxime and log clearance of both inulin (ClI) and p-amino-hippuric acid (CIPAH) down to CII, of 10 ml/min. The excretion of unchanged drug in urine during 24 h was reduced gradually upon reduction in renal function from a mean of 59.4 ± 10.2% (range 52.1–77.1) in 5 subjects with GFR above 100 ml/min. The area volume of distribution, e.g. the area of the one-compartment linear open model or during the β-phase of the two-compartment model, Vd,area, was 34.3 ± 10.4 litres according to the microbiological assay and 27.3 ± 13.4 litres for unchanged cefotaxime in patients with renal function within the normal range. The patients with reduced renal function had only insignificantly different distribution volumes. The volumes in normal individuals correspond to 53% of the body weight. The deasacetyl cefotaxime metabolite is excreted more slowly than the parent compound and elimination is relatively longer compared to the parent compound in patients with reduced renal functions. Doses for patients with reduced renal function are discussed. Because nonrenal mechanisms of elimination assume importance when the renal route becomes inefficient, elimination is only moderately prolonged, even in patients with severe renal impairment. Therefore, only moderate reduction in dosage seems

ISSN:0009-3157    

DOI:10.1159/000238063

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Chloramphenicol and thiamphenicol were tested by the agar dilution method against 105 Salmonella typhi, 15 S. paratyphi A, 6 S. paratyphi B, 8 S. paratyphi C, 57 Haemophilus influenzae and 60 Neisseriagonorrhoeae strains. The two drugs showed similar in vitro activity against strains of H. influenzae and N. gonorrhoeae irrespective of their β-lactamase production. In contrast, while all the tested isolatels of typhoid and paratyphoid fever Salmonella 8 μg/ml. The significance of these findings are discusse

ISSN:0009-3157    

DOI:10.1159/000238064

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

A simple screening method served to detect β-lactam antibiotic-tolerant variants of clinical isolates and laboratory control strains of Staphylococcus aureus, S. epidermis, group B β-hemolyticstreptococci, and Listeria monocytogenes. The β-lactamase(s) of a multiple drug-resistant strain of Enterobacter cloacae (isolate No. 19) yielded most consistent results as compared with several other β-lactamase producers; the E. cloacaeβ-lactamase(s) was neutralized by clavulanic acid. Spot inocula of E. cloacae isolate No. 19, following overnight ‘induction’ with 1 μg/ml of ampicillin and 3 μg/ml of cephalothin in tryptic soya broth, were applied centrally to β-lactam antibiotic inhibition zones of Bauer-Kirby antibiogram plates (Mueller-Hinton agar, MHA, and diagnostic sensitivity test agar, DSTA) following removal of the appropriate disks. The spot-inoculated plates were incubated overnight at 35 °C and inspected for satellite growths of tolerant variants around the E. cloacae spot inocula. Satellite growths of ≥ 10 colonies were interpreted to indicate tolerance to the relevant cell wall synthesis inhibitor. The method readily permitted detection of variants tolerant for ampicillin, cephalothin, penicillin G, piperacillin, azlocillin, and mezlocillin. However, strains documented by minimal inhibitory and minimal bactericidal concentrations to be tolerant for cefotaxime, cefoxitin, fosfomycin, and vancomycin only rarely gave rise to respective satellite growths. DSTA proved superior to MHA with respect to ‘rescue’ of inhibited tolerant staphylococcal variants; furthermore, the diameters of inhibition zones obtained on DSTA correlated well with those on MHA. Therefore, DSTA was adopted as the routine test medium for clinical staph

ISSN:0009-3157    

DOI:10.1159/000238065

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The effects of chloramphenicol (CAP) and thiamphenicol (TAP) on the outcome of Chlamydiapsittaci infection in chick embryos were compared. CAP administered along with Chlamydia reduced embryo mortality rates but showed no appreciable effects when its injection was delayed. On the contrary, TAP caused a high rate of embryo survival in both experimental situations. Statistical analysis of the results showed that differences in the survival rates following CAP and TAP administration are significant. Metabolic pathways in chick embryos of the antibiotics assayed differed remarkably in that CAP undergoes a quicker inactivation, which could even justify the better activity showed by TAP.

ISSN:0009-3157    

DOI:10.1159/000238066

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Chemoprophylaxis of anaerobic pulmonary infection due to aspiration was studied in a rabbit model with the view of comparing the efficacy of procaine penicillin, clindamycin, chloramphenicol, doxycycline and cefoxitin. The antibiotic treatment was commenced immediately following transtracheal inoculation of a mixture of Bacteroidesfragilis, Streptococcusmorbillorum, Fusobacterium nucleatum and Eubacterium lentum. Treatment was stopped after 48 h and lungs were examined for evidence of infection on the 10th day. Only clindamycin and carbencillin were highly efficacious in chemoprophylaxis and both drugs prevented pulmonary infection in 7 of 8 (87%) of the animals tested.

ISSN:0009-3157    

DOI:10.1159/000238067

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The filamentous forms of a serum resistant Escherichia coli strain developed under in vitro exposure to subminimal inhibitory concentration of the compound LY 127935 showed a higher resistance against host defence than the nontreated control bacteria. Significantly diminished LD50 values and a longer lasting persistence in the peritoneal cavity of the mouse were found after intraperitoneal infection. In order to exclude the suggestion that the enhanced virulence was only due to the separation of filaments into normal virulent bacilli, the course of experimental infection with normal virulent germs was investigated under treatment with subtherapeutic doses of the antibiotic. When animals treated with repeated doses of 10–15 μg/kg of LY 127935 were intraperitoneally infected a significantly smaller elimination rate of bacteria was observed in the peritoneal cavity than in animals injected with sali

ISSN:0009-3157    

DOI:10.1159/000238068

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Niridazole was shown to be an effective chemotherapeutic agent for mice infected intravenously with a niridazole-sensitive strain of Salmonella typhimurium. Death rates as well as bacterial counts per spleen were reduced, even in compromised animals. Histologic examination of spleens proved the reduction of inflammatory reaction due to Salmonella infection. A suppressive effect of niridazole treatment on immunity to challenge infection with S. typhimurium was not found, as demonstrated by infection with a niridazole-resistant strain of S. typhimurium.

ISSN:0009-3157    

DOI:10.1159/000238069

出版商:S. Karger AG    

年代:1982

数据来源: Karger