Chemioterapia : international journal of the Mediterranean Society of Chemotherapy最新文献

The therapeutic effectiveness of a single oral dose (60 and 200 mg/kg body weight) of fosfomycin trometamol (FT), norfloxacin, trimethoprim sulfamethoxazole (Bactrim) and pipemidic acid against experimental cystitis in the rat were compared. Infections were produced with clinical isolates of Klebsiella pneumoniae, Proteus mirabilis and Escherichia coli in a total of 135 Sprague-Dawley albino rats. Oral treatment with all four drugs consistently lowered the numbers of CFU in bladder tissue, especially E. coli and P. mirabilis. Fosfomycin trometamol appeared to be as effective as norfloxacin for treatment of E. coli cystitis even thoughs its minimal inhibitory concentration (MIC) in vitro is 100 times greater than that of the quinolonic antibiotic. Fosfomycin trometamol, pipemidic acid and Bactrim were equally effective against P. mirabilis infection, but FT was less active than norfloxacin or Bactrim for treatment of K. pneumonia cystitis. In conclusion, single dose treatment with fosfomycin trometamol was effective for treatment of experimental cystitis in the rat and might, by extrapolation, be of use in clinical practice for single dose treatment of uncomplicated urinary tract infections.

The aim of this prospective, randomized, open study was to survey the frequency course and to evaluate the therapy of peritonitis induced by staphylococci in patients on continuous ambulatory peritoneal dialysis (CAPD). From June 1983 to November 1986, 20 patients (9 men, 11 women) aged from 25 to 73 were treated. During 258 months of the CAPD treatment they had 54 episodes of peritonitis. Staphylococcus saprophyticus was the most frequent offender of peritonitis, isolated from peritoneal effluent in 44% of the cases, Staphylococcus epidermidis was isolated in 7% of the cases. Staphylococcus aureus was isolated in 5% of the cases and caused a more severe form of peritonitis. The combination of gentamicin and methicillin was used in 14 cases, in 2 cases this treatment was unsuccessful. A combination of gentamicin and cloxacillin was used in 5 cases and a combination of clindamycin and mezlocillin in 12 cases of peritonitis, giving good results in all cases. The last combination seemed to be the most effective in the treatment of staphylococcus induced peritonitis.

This study was undertaken to investigate aclacinomycin distribution in the rat, using a method based on the histofluorescence of tissues treated in vivo with anthracyclines. The target organs were the kidney, lung and pancreas; a fainter fluorescence was also detected in the heart compared with adriamycin due to a quantitatively different fixing of the two anthracyclines. Our findings revealed a preferential uptake into the cell nucleus in all tissues examined except the adrenal gland medulla where a slight fluorescence appeared only in the cytoplasm.

LY121019 is a cyclic peptide antibiotic of the echinocandin group, which is characterized by strong anti-Candida activity (in particular against Candida albicans) as well as by low experimental toxicity. Its anti-Candida activity is thought to be due to an inhibition of the synthesis of beta-glucan, an essential cell wall polysaccharide. The different composition of culture media or the presence of animal serum did not show adverse effects on LY121019's anti-Candida activity and the addition of reducing compounds such as cysteine and hydroquinone did not manifest a negative influence. Analogously the anti-Candida activity was not influenced when C. albicans was grown under aeration. The activity of LY121019 was very high against the mycelial form of C. albicans even when this form was developed in the presence of animal serum.

The activity of fosfomycin trometamol (FOT) was compared with that of cotrimoxazole (COT) and norfloxacin (NOR) using urine as medium and 10(7) bacteria as inoculum, conditions as close as those found by the administration of the drugs in vivo during the course of a urinary tract infection. The minimum inhibitory concentrations (MIC) of all antibiotics against 100 strains isolated from urinary tract infections were found to be higher than the breakpoint. Concentrations of FOT corresponding to mean and maximal values found in urine after single dose administration within the 0-48 h interval killed the great majority of strains. COT and NOR, when tested under similar conditions, exhibited an antibacterial activity lower than and equal to that of FOT, respectively. In several strains belonging to different species the frequency of mutation to resistance to 2000 and 1000 micrograms/ml of FOT was very low (greater than 10(-7], whereas it was relatively high (1 x 10(-5) to 1 x 10(-7] for 150 micrograms/ml, the two former and the latter being the respective maximal, mean and minimal values found in urine after administration of a single dose.

Twenty-six postmenopausal consecutive patients with advanced breast cancer were treated with very high medroxyprogesterone acetate doses (4000 mg/day orally for 30 days and then 3000 mg/day orally until progression or intolerance). The dominant metastatic lesion was bone in 13 patients, soft tissue in 3 patients and viscera in 10 patients (C.I. = V/ST + 0 = 0.62). An objective partial remission was achieved in 16 pts (61%), no change in 8 (31%), progression in 2 (8%). The median duration of objective remission was 7.5+ months with a median survival of 14.5+ months in responders. Toxicity was minor and only two patients discontinued the treatment because of side-effects. These results confirm the utility of medroxyprogesterone acetate at very high doses in these patients and the feasibility of this kind of dose.

Cis-diamminedichloroplatinum (DDP) or cyclophosphamide (Cy) were given to mice bearing L1210 or LSTRA leukemia in H-2 compatible tumor-host combinations. Little anti-tumor activity was afforded by DDP against both leukemias inoculated in entirely histocompatible recipients. However, when the drug was given to mice incompatible for minor histocompatibility loci (MMHL) with the tumor, the efficacy of the treatment was markedly augmented and a substantial number of long-term survivors was found among BALB/c mice inoculated with L1210 cells. On the other hand, no difference in survival times was found between histocompatible or allogeneic mice inoculated with both leukemias, not subjected to chemotherapy. The LSTRA model was much less susceptible to this type of DDP-mediated antineoplastic immuno-chemotherapy synergism. Moreover no synergistic effects with allograft reaction were detected with Cy in both L1210 and LSTRA models, although Cy was markedly more active than DDP against leukemic cells in histocompatible recipients.

The purpose of this study was to evaluate VAP combination chemotherapy in advanced breast cancer: prednimustine 80 mg/m2 p.o. days 1-5, adriamycin 40 mg/m2 and vincristine 1.4 mg/m2 1st day in cycles of 3 weeks. Twenty-one women entered the study and 19 were evaluable. The mean age was 54.5 years (25-69) with an average performance status of 60 according to Karnofsky. Hormonal receptors were unknown in 10, positive in 6 and negative in 3. The dominant site of disease was soft tissues in 11, bones in 1, liver in 3 and lung in 4. Fourteen patients had as prior treatment cyclophosphamide, methotrexate and 5-fluorouracil (CMF), two had tamoxifen and three none. Ten patients (52.6%) had a partial response with a mean survival of 7.8+ months, 5 patients (26.3%) had stable disease with a mean survival 6.6+ months and 4 patients (21.1%) had progressive disease with a mean survival of 3 months. Regarding toxicity all patients had alopecia, most of the patients had nausea grade I, whereas 5 patients developed mild leukopenia. We conclude that VAP is an effective, well tolerated chemotherapy combination in patients with advanced breast cancer which deserves further clinical trials.

We studied the effects of rifamycin SV, rifampicin and rifapentine on human phagocyte functions. Rifamycins inhibited in vitro neutrophil chemotaxis in the range of their therapeutic levels, and they significantly affected the survival of a rifamycin-sensitive strain of Staphylococcus aureus inside human monocytes. Both effects were related to the intraphagocytic penetration of these antibiotics. For the ex vivo studies, 600 mg of rifampicin were orally administered to five subjects with defective S. aureus killing. A significant reduction of neutrophil chemotaxis and increased activity against S. aureus were shown 150 and 210 min after administration of the drug.

Forty-eight fully assessable previously treated patients with biopsy-proven recurrent squamous cell carcinoma of the oral cavity were randomized to receive either methotrexate (MTX), 40 mg/m2 iv push weekly, or sequential MTX and 5-fluorouracil (5-FU) (MTX 150 mg/m2 iv for 1 h; 1 h after the end of MTX, 5-FU 600 mg/m2 iv for 2 h; 24 h later, leucovorin rescue 10 mg/m2 iv and the same dose was given orally every 6 h 4 times; the treatment was repeated every 10 days). There were 1 complete response (CR) and 5 partial responses (PR) in the MTX group; median remission duration = 84 days. There were 3 CR and 11 PR in the MTX-5-FU group (overall response 14/24, 58.3%--p less than 0.05); median remission duration = 125 days. Median survival was 6.2 months in the MTX group and 8.1 months in the MTX-5-FU group. There was no difference in mucositis between the two groups, and a prevalence of leukopenia and moderate gastro-intestinal toxicity in the MTX-5-FU group.