摘要:

Two dosages of clindamycin, 300 and 600 mg, were given orally to 10 patients each. The patients were admitted for minor elective surgery. Their mean age was 39.3 years; mean weight was 67.5 kg. None of them had taken antibiotics for at least 1 month. After administration of a single dose, blood samples were obtained at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h after dosing. Drug levels were determined by the bioassay method using Micrococcus luteus as test organism. Serum inhibitory and bactericidal activities against five isolates each of Staphylococcus aureus and Streptococcus pyogenes were determined by the microdilution method according to the National Committee for Clinical Laboratory Standards guidelines. The mean peak serum level was 3.4 mg/l for the 300-mg dose and 4.8 mg/l for the 600-mg dose. The mean reciprocal peak inhibitory titers for the 300-/600-mg doses were 13.7/23.8 and 15.2/ 34.7 against S. aureus and S. pyogenes, respectively. Most serum samples did not show bactericidal activity against S. aureus.

ISSN:0009-3157    

DOI:10.1159/000239571

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

No data on the genetic analysis of penicillin-resistant Streptococcus pneumoniae (PRP) in Japan has been reported. The Smal restriction endonuclease digested patterns of chromosomal DNAs from 15 PRP serotyped 23F isolated in Japan were analyzed by pulsed-field gel electrophoresis (PFGE). The isolates were genetically heterogeneous and seven different PFGE patterns were identified. Nine strains were also resistant to erythromycin and tetracycline. Four strains revealed resistance to ceftriaxone. The PFGE patterns of some strains isolated in Nagasaki University Hospital were identical to each other and closely resembled those of isolates from three different areas of Japan. These results indicate a need for additional studies by PFGE to determine the possibility of clonal spread in Japan.

ISSN:0009-3157    

DOI:10.1159/000239572

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The in vitro antimicrobial activities of AM-1155, a new fluoroquinolone, tosufloxacin and fleroxacin were tested against 55 clinical isolates of Neisseria gonorrhoeae using the agar dilution method. In our previous study, all the strains had been examined for mutations in the region corresponding to the quinolone-resistance determining region of the Escherichia coli gyrA gene and the analogous region of the parC gene, and tested for susceptibility to ciprofloxacin. In this study, the 55 isolates of N. gonorrhoeae were assigned to one of three categories based on the presence or absence of alterations in GyrA and ParC. In each category, the antimicrobial activity of AM-1155 against the isolates was compared with those of tosufloxacin and fleroxacin. The MICs of AM-1155 for 11 highly fluoroquino-lone-resistant isolates with alterations in both GyrA and ParC ranged from 0.06 to 1.0 μg/ml. The MICs inhibiting 50% (MIC50) and 90% (MIC90) of these isolates were 0.125 and 1.0 μg/ml, respectively. The MICs of AM-1155 for 20 moderately fluoroquinolone-resistant isolates with alterations only in GyrA ranged from 0.03 to 0.25 μg/ ml (MIC50, 0.06 μg/ml; MIC90, 0.125 μg/ml). The MICs of AM-1155 for 24 of the quinolone-susceptible isolates without alterations in either GyrA or ParC ranged from 0.004 to 0.03 μg/ml (MIC50, 0.008 μg/ml; MIC90, 0.015 μg/ml). There were significant differences between the MIC distribution of AM-1155 and each corresponding MIC distribution of tosufloxacin and fleroxacin in these three categories to which the 55 isolates were assigned (p < 0.05). Based on the MIC90S of the tested fluoroquinolones, AM-1155 was two- and eightfold more active against the highly fluoroquinolone-resistant isolates than tosufloxacin and fleroxacin, respectively. Against the moderately fluoroquinolone-resistant isolates, AM-1155 was four-and sixteenfold more active than tosufloxacin and fleroxacin, respectively. Against the quinolone-susceptible strains, AM-1155 was also two- to fourfold more active than the other fluoroquinolones. Overall, AM-1155 exhibited more potent in vitro activity against both quinolone-resistant and quinolone-susceptible isolates of N. gonorrhoeae than tosufloxacin and fleroxacin. In ciprofloxacin treatment failures of gonorrhea at single doses of 500 mg. MICs for the causative organisms have ranged from 1.0 to 16.0 μg/ml. The MICs of AM-1155 for the isolates harboring quinolone resistance-associated genetic alterations, including strains exhibiting ciprofloxacin MICs of 2.0 and 8.0 μg/ml, still ranged from 0.03 to 1.0 μg/ml. A single-dose study in humans has demonstrated higher peak serum concentrations and longer half-lives of AM-1155, resulting in the AUC0-∞ values of AM-1155, which are threefold greater than those of ciprofloxacin at the single doses of 400 and 600 mg. Because of its potent in vitro antimicrobial activity and advantageous pharmacokinetic behavior, AM-1155 may be a clinically useful agent for treating gonorrhea including that caused by quinolone-resis

ISSN:0009-3157    

DOI:10.1159/000239573

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Extended-spectrum β-lactamases (ESBLs) are found in numerous Enterobacteriaceae, mainly in Klebsiella pneumoniae. We investigated the pharmacodynamics of two new extended-spectrum cephalosporins, cefepime and cefpirome, alone and combined with either amikacin or gentamicin or ciprofloxacin by means of time-kill curves against ESBL-producing, amino-glycoside-resistant K. pneumoniae. When used alone, cefepime (8 and 16 mg/l) resulted in a 2 and 3 log decrease at 6 h, respectively, but at 24 h regrowth occurred. The combination of cefepime (8 mg/l) with amikacin (4 mg/l) resulted in a 4 log decrease at 6 h, but there were no surviving bacteria at 6 h when combined with amikacin (8 mg/l). The combination of cefepime (16 mg/l) with gentamicin (4 mg/l) resulted in a 4 log decrease in 24 h. The antimicrobial combiantion of cefepime (32 mg/l) with ciprofloxacin (2 mg/l) resulted in a 4 log decrease in 24 h. Cefpirome (8 mg/l) induced a 2 log decrease at 4 h; 32 mg/l cefpirome resulted in a 3 log decrease followed by regrowth at 24 h. The regrowth observed in the late phase with cefpirome alone disappeared when combined with aminoglycoside. When cefpirome (32 mg/l) was used in combination with ciprofloxacin (1 mg/l), it resulted in a 4 log decrease in 24 h

ISSN:0009-3157    

DOI:10.1159/000239575

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Compound MDL 62,879 (GE2270 A) is a thiazolyl peptide antibiotic that appears to inhibit aminoacyl-tRNA binding to elongation factor Tu. In the present study, it was shown that MDL 62,879 broth microdilution MIC values were generally 2-4 doubling dilutions lower in the presence of 0.02% bovine serum albumin. Using US clinical isolates and BSA-supple-mented media, MDL 62,879 was more active than teicoplanin and vancomycin against the staphylococci and glycopeptide-resistant and glycopeptide-susceptible enterococci and equally active against the streptococci. Broth microdilutions MIC values were not appreciably affected by inoculum concentrations of 5 x 104 to 5 x 108 cfu/ml or in the presence of 3.5% human serum albumin.

ISSN:0009-3157    

DOI:10.1159/000239576

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Rifabutin is a lipophilic antibacterial with high in vitro activity against many pathogens involved in bacterial meningitis including pneumococci. Resistance to β-lactam antibiotics in pneumococci is not associated with a decreased sensitivity to rifabutin (30 strains from Germany with intermediate penicillin resistance; MIC range of penicillin: 0.125-1 mg/l, MIC of rifabutin: < 0.008-0.015 mg/l). Rifabutin at doses of 0.625, 1.25, 2.5, 5 and 10 mg/kg/h i.v. was investigated in a rabbit model of meningitis using a Streptococcus pneumoniae type 3 (MIC/MBC of rifabutin: 0.015/ 0.06 mg/l). The bacterial density in CSF at the onset of treatment was 7.3 ± 0.6 log CFU/ml (mean ± SD). Rifabutin decreased bacterial CSF titers in a dose-dependent manner [δlog CFU/ml/h (slope of the regression line log CFU/ml vs. time) at a dose of 0.625 mg/kg/h: -0.16 ± 0.06 (n = 3), at 1.25 mg/kg/h: -0.20 ± 0.12 (n = 4), at 2.5 mg/kg/h: -0.24 ± 0.04 (n = 4), at 5 mg/kg/h: -0.31 ± 0.10 (n = 8), and at 10 mg/kg/h: -0.29 ± 0.10 (n = 5)]. At high doses rifabutin was as active as ceftriaxone at 10 mg/kg/h (δlog CFU/ml/h: -0.29 ± 0.10, n = 10). Two and 5 h after initiation of therapy, CSF TNF-α activities were lower with rifabutin 5 mg/kg/h than with ceftriaxone (medians 2 vs. 141 U/ml, p = 0.005 at 2 h; median 51 vs. 120 U/ml 5 h after initiation of therapy, p = 0.04). This did not result, however, in a decrease of indicators of neuronal damage. In conclusion, intravenous rifabutin was bactericidal in experimental pneumococcal meningitis. Provided that a well-tolerated i.v. formulation will be available it may qualify as a reserve antibiotic for pneumococcal meningitis, in particular when strains with a reduced sensitivity to β-lactam antibiotics are the causati

ISSN:0009-3157    

DOI:10.1159/000239577

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The effects of midazolam (MID) on the in vitro growth and differentiation of two murine myeloid leukemia WEHI 3B (JCS) and M1 cells were studied. MID inhibits the proliferation of both Ml and JCS cells in a dose-dependent manner. At the concentration of 10 μg/ml, MID was found to induce both monocytic and granulocytic differentiation of the JCS but not Ml cells. Induction of morphological differentiation of the JCS cells was also associated with the enhanced expression of the differentiation antigens Mac-1, F4/80, and Gr-1 for the cells. Results from mRNA phenotyping experiments also indicated that the expression of tumor necrosis factor (TNF-α) and neutrophil-specific J11d differentiation marker was significantly upregulated in MID-treated JCS cells. In addition, the phagocytic activity of MID-treated JCS cells was increased towards opsonized yeast cells. Results from this investigation suggested that MID may be used as an inducer for further study on the mechanisms of differentiation in these myeloid leukemia cell

ISSN:0009-3157    

DOI:10.1159/000239578

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The dose response and time course of micronucleated polychromatic erythrocytes (mPCE) in cat peripheral blood induced by various doses (150-250 mg/m2) of carboplatin in vivo was determined. The data indicate that carboplatin produced a significant (p < 0.05) dose-dependent increase in the number of mPCE over baseline values; however, the times following carboplatin administration when mPCE were first observed differed significantly (p < 0.05) between the three carboplatin dose groups. mPCE were present in significantly greater numbers (p < 0.05) on smears at an earlier time interval following a single carboplatin dose of 150 mg/m2 than for a dose of either 200 or 250 mg/m2. The peak number of mPCE occurred on days 7, 14 and 17.5 following administration of a carboplatin dose of 150,200 and 250 mg/m2, respectively. The pattern of time course delay following carboplatin administration suggests that the block of erythropoietic stem cells in G2 is dose dependent. Indeed, the administration of carboplatin arrested the cell cycle in the G2 phase and, at higher doses, diminished the number of cycling erythroid precursor cells. mPCE were apparent in blood smears only after recovery from this arrest and resumption of replication. This observation has implications for the scheduling of carboplatin administration when used in combination with other anticancer drugs.

ISSN:0009-3157    

DOI:10.1159/000239579

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We carried out a randomized study of 49 consecutive patients with unresectable primary lung cancer to determine whether clarithromycin (CAM), a 14-membered ring macrolide, can improve outcome. A total of 49 patients (42 patients with non-small-cell lung cancer and 7 patients with small-cell lung cancer) had received prior chemotherapy, radiotherapy or both during their hospital stay. They were randomly allocated into two study groups on the first visit after discharge: 25 patients (22 patients with non-small-cell lung cancer, 3 patients with small-cell lung cancer) were assigned to receive CAM (400 mg/day, orally), and 24 patiens (20 patients with non-small-cell lung cancer, 4 patients with small-cell lung cancer) did not receive CAM. CAM treatment after randomization was open and the treatment was to be continued as long as the patients could tolerate CAM. There was no significant difference in the median survival time for small-cell lung cancer between the CAM group and the non-CAM group. However, CAM treatment significantly increased the median survival time for non-small-cell lung cancer patients, the median survival for the CAM group was 535 days and that for the non-CAM group was 277 days. Analyses of prognostic factors showed that only treatment with CAM was predictive of longer survival for non-small-cell lung cancer, and other tested covariates had no effects on the prognosis. There were no remarkable side effects observed in the CAM group throughout treatment. We conclude that long-term treatment using CAM is beneficial for unresectable non-small-cell lung cancer patiens and that it can increase the median survival of patients with advanced disease.

ISSN:0009-3157    

DOI:10.1159/000239580

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The efficacy and tolerability of once- or twice-daily ceftibuten (400 mg daily) were compared with three-times daily amoxicillin/clavulanate (AMX/CA, 500 mg/l25 mg) in the treatment of acute exacerbations of chronic bronchitis (AECB) in an open, parallel-group 10- to 14-day study in 443 patients. Patients were assessed at baseline and on days 5, 10-14 and after 4-6 weeks of treatment, and the clinical response defined as cured, improved, stabilized or failed. Clinical efficacy between the 3 groups was equivalent (p = 0.002) with 90% of patients in each group responding to treatment (cured or improved) and the incidence of complete cures (with no clinical signs of relapse) was also equivalent. In conclusion, this study showed that ceftibuten is clinically equivalent to a standard regimen of amoxicillin/clavulanate in the treatment of AECB, including those patients infected with Streptococcus pneumonia. Ceftibuten was better tolerated than AMX/CA and was associated with significantly fewer gastrointestinal side effects. Furthermore, once-daily was a well tolerated and effective as twice-daily ceftibuten.

ISSN:0009-3157    

DOI:10.1159/000239581

出版商:S. Karger AG    

年代:1997

数据来源: Karger