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

We studied the activity of human alveolar macrophages (HAMs) obtained by bronchoalveolar lavage (BAL) from human lungs. In particular, we studied in vitro phagocytosis and bacterial killing in basal conditions and in the presence of miocamycin (MOM), a macrolide antibiotic. At a dose of 600 mg every 12 hours, MOM concentrations in the serum were 2.60 micrograms/ml 1 hour after administration and 0.75 microgram/ml 8 h after. The antibiotic cannot be assayed by the microbiological method in the acellular liquid of alveolar lavage. After penetrating the HAMs, it can be detected at a concentration of about 0.4 mcirograms/1.10(6) HAMs. MOM was able to penetrate HAM cytoplasm without altering their vitality. As a matter of fact, the Trypan blue exclusion dye test was not modified after long incubation in the presence of MOM. The HAMs, resuspended in a RPMI 1640 enriched medium, were able to phagocytize either live Staphylococci or inert Latex beads of 1 micron. MOM stimulated the HAM phagocytosis on both Staphylococci and Latex beads. The increase in Latex phagocytosis, a relatively inert substance on which MOM should not be active, is a confirmation of the antibiotic's directed stimulation of the HAMs. Finally, we have seen that the HAMs, which were noteworthy in killing the phagocytized bacteria, were stimulated by MOM after only 30 minutes of contact with the antibiotic.

Results of clinical studies in advanced and, recently, also in early breast cancer have shown a clear protective effect of high dose medroxyprogesterone acetate (MPA) on the bone marrow toxicity induced by chemotherapy. The underlying mechanism of this phenomenon is unsettled and in vitro studies have yielded contradictory results. The results of these clinical and in vitro studies are summarized. The myeloprotective effect may have important therapeutical implications.

The in vitro antibacterial activity of teicoplanin, a new glycopeptide antibiotic, previously named teichomycin A2, has been compared to that of five other chemoantibiotics: netilmicin, clindamycin, rifampicin, enoxacin and vancomycin. The minimum inhibitory concentration (MIC) values against 588 gram-positive strains, 561 facultative aerobes and 27 anaerobes, recently isolated from clinical specimens, were evaluated. Teicoplanin showed the highest activity against all the tested strains, with a geometrical mean of the MICs (GMM), a MIC50 and MIC90 of 0.123, 0.12 and 0.5 micrograms/ml respectively.

In an open study aztreonam was evaluated for efficacy and safety in 20 hospital in-patients presenting with presumptive or confirmed hospital acquired aerobic gram-negative infections. The overall clinical cure rate was 100% (19/19) with a corresponding microbiological cure rate of 100% in those patients in whom an organism was isolated initially (17/17). Reinfection with enterococcus occurred in 2 patients with UTI within a week of stopping aztreonam and one patient developed superinfection during treatment, but none were given any additional therapy. No evidence of drug-associated toxicity was found on any of the laboratory evaluations. One patient developed diarrhea 3 days after starting therapy, was withdrawn from the study and subsequently excluded from the analysis. One other patient remained febrile despite evidence of clinical and microbiological cure. Both these incidents were thought to be possibility drug-related. This study confirms aztreonam as a safe and effective way to treat patients with serious gram-negative infections.

The in vitro activity of the novel monobactam carumonam (RO17-2301) was evaluated on 311 gram-negative clinical isolates in comparison to aztreonam, cefotaxime, ceftazidime, cefotetan and ceftriaxone. Carumonam showed an antibacterial potency equal to or higher than any other reference compound; in particular it was the most effective against Proteus indole positive and Klebsiella sp. Its antipseudomonal activity was comparable to that of ceftazidime and it showed, together with aztreonam, the highest activity against the Citrobacter, Enterobacter and Escherichia coli isolates. The minimal inhibitory concentrations performed on permeability altered organisms indicated that carumonam has a penetration rate comparable to aztreonam and higher than cefotetan and ceftriaxone. Carumonam demonstrated excellent stability to chromosomal and plasmid-mediated beta-lactamases and that correlated with its antibacterial activity against the producing strains and inoculum size effect.

We estimated the relationship of Post Antibiotic Effect (PAE) induced by ofloxacin in both gram-positive and gram-negative bacteria, with the Percent Growth Rate Average (PGRA) considered on an increase of 1 log (CFUs/ml). The results showed a good correlation between parameters (0.84, p less than 0.001), and enabled us to find out that the drug-induced effect persisted after the period of time considered in the standard procedure. Where the values of PAE are much greater, the growth curve rates were faster after the apparent termination of the phenomenon.

The cardiac morphology of CD 1 mice undergoing two different schedules of acute (5 day) starvation and that of animals treated with a single dose (15 mg/kg i.p.) of doxorubicin, epirubicin or mitoxantrone were studied by light microscopy. Determinations of heart catalase were also carried out. Mice subjected to moderate starvation had a mean weight reduction of 18.7% and did not show heart morphological damage. A slight increase (38%) of heart catalase specific activity occurred in these animals. In animals subjected to severe starvation the weight loss was 32.2%. In this case considerable heart damage, in the form of myofibrillar loss, and a striking increase of catalase (158.5%) were seen. In the drug groups comparable weight reductions (about 15%) occurred 5 days after the treatment. Moderate heart lesions, represented by myolysis and especially by myocytic microvacuolation, were observed and appeared to be of similar degree in the 3 drug groups. Catalase specific activity increased by 119.9% in the doxorubicin animals, by 73% in the epirubicin mice and by 30.3% in the mitoxantrone ones. Light microscopy made it possible to distinguish between cardiac alterations induced by starvation and those specifically induced by antiblastics. Catalase may be helpful to indicate the existence of heart damage but it does not correlate well with the severity of the lesions by antiblastics. An additional cause of heart catalase elevation might be the free radical generation induced by the anthracyclines but not by mitoxantrone.

Since the early '50s, radiation therapy has been regarded as the mainstay of treatment for testicular seminoma. In the last decade, however, several reports claimed optimal control (about 80% of lasting complete remissions) of advanced disease with cisplatin-containing chemotherapy regimens, consequently questioning the opportunity of irradiation in bulky retroperitoneal presentation. The respective role of radiotherapy and chemotherapy in the management of advanced locoregional seminoma has been reviewed, in view of the fact that our data, previously unpublished, show a 10-year disease-free survival probability of 70% for 27 bulky stage II patients submitted to irradiation. On the grounds of currently available data, a prospective randomized trial of chemotherapy versus radiotherapy in stage II testicular seminoma seems justified, in order to identify the optimal treatment policy for this disease.

This study evaluates the susceptibility of sucrose-negative Candida tropicalis and Candida lusitaniae strains to amphotericin B (AMB), miconazole (MCZ) and ketoconazole (KTZ). The susceptibility tests were carried out in different media: Antibiotic Medium 3 (AM-3m) and Earle Minimum Essential Medium (E-MEM) for AMB: Yeast Nitrogen Base (YNB) and E-MEM for imidazole compounds. The minimal fungicidal concentrations (MFCs) of AMB were slightly higher than minimal inhibitory concentration (MICs) except against Candida lusitaniae strains; whereas the MFCs of MCZ and KTZ were higher than the MICs by almost two-fold for all strains tested. AMB was more efficacious against sucrose-negative Candida tropicalis and the MICs were very definite; on the contrary, the MICs with KTZ were difficult to read. The MICs of AMB in E-MEM were essentially the same as those in AM-3m; whereas for KTZ and MCZ determined in YNB the MICs were generally higher than those obtained in E-MEM.

The urinary concentrations of fosfomycin trometamol, norfloxacin, pipemidic acid and cotrimoxazole were studied at various times after oral administration of drugs in healthy volunteers. Using the same urine, the bactericidal activity of four antimicrobial agents against Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae in an in vitro model simulating the treatment of bacterial cystitis was also evaluated. The results obtained show that very high concentrations of the drugs were achieved in urine particularly after the oral administration of the fosfomycin trometamol. In the bladder model bactericidal activity of fosfomycin trometamol, norfloxacin and pipemidic acid were higher than that of cotrimoxazole; no resistant mutants to drugs were selected over a period of 24 h.