摘要:

To complement a study on aminoglycoside dosing regimen and ototoxicity in the guinea pig, we designed an experiment to examine: (1) the effect of dosing regimen on guinea pig pharmacokinetic parameters, and (2) possible differential accumulation after repeated intramuscular administrations of netilmicin and amikacin (150 mg/ kg/day) for 7 days by 1 or 3 daily injections. The area under the curve (AUC∞) and the maximum plasma concentration (Cmax) were dose-dependent. Within each regimen, no significant difference was observed between days 1 and 7. Little or no accumulation was observed after 21 days of treatment. The results show a good dose-dependence of AUC∞ and Cmax and are in accordance with data from human studies. Moreover, the fact that no accumulation occurred in the guinea pig suggests that it is a suitable animal model to evaluate the relation between aminoglycoside ototoxicity and dosing regi

ISSN:0009-3157    

DOI:10.1159/000238746

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

A double-blind, double-dummy trial comparing a single dose treatment with fosfomycin trometamol (FT, 3 g) versus trimethoprim (TMP, 200 mg) was carried out in women with uncomplicated urinary tract infections. From 51 clinically evaluable patients, 44 were bacteriologically assessable at the 6-week follow-up. The results were as follows in the FT group (n = 22): eradiction in 17 (77.3%); recurrence in 2 (9%); reinfection in 2 (9%), and persistence in 1 (4.5%). For the TMP group (n = 22) the results were: eradication in 12 (54.5%); recurrence in 1 (4.5%); reinfection in 1 (4.5%), and persistence in 8 (33.3%). There were no significant adverse events reported with either agent.

ISSN:0009-3157    

DOI:10.1159/000238814

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

A randomized trial, comparing a single dose treatment of fosfomycin trometamol (FT, 3 g) versus a 3-times daily regimen of cotrimoxazole (CTX, 960 mg) was carried out in women with uncomplicated urinary tract infections. Of 36 evaluable patients, 19 were treated with FT and 17 with TMP. The bacteriological results after 4 weeks of follow-up were in the FT group (n = 19): cure in 17 (89%), and failure in 2 (11%). For the CTX group (n = 17) the results were cure in 13 (76%), and failure in 4 (24%). Adverse events were reported in 3 patients on FT (2 diarrhoea, 1 epigastralgia) and in 2 on CTX (1 stain rash, 1 asthenia).

ISSN:0009-3157    

DOI:10.1159/000238815

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Fosfomycin trometamol (FT), an antibiotic active against the common urinary pathogens, may be demonstrated in adequate urine concentrations up to 36–48 h after a single oral dose of 1–2 g. This pharmacokinetic peculiarity seems to indicate that this antibiotic may be used in single doses in the therapy of lower urinary tract infections (UTIs) in infants and children. The efficacy and safety of FT in single oral doses was compared with those of netilmicin (NM), an aminoglycoside antibiotic with a demonstrated efficacy in bolus doses against UTIs, shown in a multicentric study. One hundred and thirty-five children with lower UTI, diagnosed on the basis of fever ( < 38°C), erythrocyte sedimentation rate ( < 25 mm/1 h) and C-reactive protein ( < 20 μg/ml), were included in the study: 71 received 2 g of FT, 64 5 mg/kg of NM. Cure, defined as persistence of sterile urine up to 30 days after therapy, was reached in 80.2% of children in the FT group and in 81.2% of children in the NM group. Persistence of infection was demonstrated in 7 and in 3 children, respectively. Recurrence of infection was noticed in 7 patients in the FT group and in 9 in the NM group. No differences between FT- and NM-treated children are demonstrable even if the patient population is analyzed according to the higher risk of UTI because of the presence of an anatomical and/or functional abnormality of the urinary tract or due to a previous tendency to recurrent UTIs. FT is as effective as NM in the treatment of lower UTIs in infants and chi

ISSN:0009-3157    

DOI:10.1159/000238816

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Ten years of controlled clinical trials supported single-dose therapy efficacy and safety in uncomplicated lower urinary tract infections (UTI). Both local and systematic factors contribute to the high UTI prevalence seen in elderly people. A controlled open randomized study was undertaken to evaluate the clinical efficacy and safety of a new fosfomycin derivative (fosfomycin trometamol) given in a single dose in the treatment of uncomplicated lower UTIs in 60 elderly subjects (mean age 68.4 years). A single 3-gram fosfomycin trometamol dose was compared to a 7-day treatment with norfloxacin 400 mg b.i.d. Midstream urocultures and susceptibility tests were performed to diagnose a UTI and at 3–5 and 25–35 days after discontinuation of therapies. Our results, showing comparable clinical and bacteriological resolution rates in both groups (76.6 and 73.3% in the fosfomycin-trometamol- and norfloxacin-treated subjects, respectively), support the single-dose fosfomycin trometamol efficacy in uncomplicated lower UTIs in an elderly population, suggesting it as a convincing alternative to longer therapeutic regim

ISSN:0009-3157    

DOI:10.1159/000238817

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The Italian multihospital study of bacteriuria in pregnancy randomized 153 pregnant bacteriuric patients to receive fosfomycin trometamol (FT) as a single dose of 3 g and 138 such patients to receive conventional therapy with pipemidic acid (PA), 400 mg b.i.d. for 7 days. The two groups were well matched for age, parity, pregnancy course, symptoms and past history of cystitis. Infecting organisms were eradicated in 147 (96%) of FT and 129 (94%) of PA patients. Similar recurrence rates occurred. Minimal side effects (mostly nausea and dyspepsia) occurred (9% FT; 15% PA). Single-dose FT appeared equivalent to conventional treatment with PA.

ISSN:0009-3157    

DOI:10.1159/000238818

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Differentiation induction therapy provides an alternative for treatment of patients with acute myeloid leukaemia (AML) who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + low concentration of cytarabine (Ara-C) + dimethylformamide (DMF) on the differentiation of blasts from 24 AML patients was studied. Nonadherent mononuclear cells were cultured at a concentration of 5 x 105 cells/ml in 24-well tissue culture plates containing RPMI 1640 culture medium with 20% fetal calf serum, 10% autologous serum and 10% 5637-conditioned medium and incubated with 10––6M RA, 10––6M Ara-C and/or 100 mM DMF alone and in combination with each other for 6 days in primary culture at 37°C in a humidified incubator under 5% CO2. The triple combination of 10––6 M RA+ 10––6M Ara-C + 100 mMDMF induced 90% of blasts from 22 out of 24 AML patients to differentiate. These highly effective results justify a clinical trial of this triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytoto

ISSN:0009-3157    

DOI:10.1159/000238748

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0009-3157    

DOI:10.1159/000238819

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0009-3157    

DOI:10.1159/000238820

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

2-Acetylpyridine semicarbazone (APSC), 2-acetylpyridine thiosemicarbazone (APTSC) and 2-acetylpyridine-4-methyl-3-thiosemicarbazonoe (APMTSC) were evaluated against type-2 herpes simplex virus (HSV-2)-induced genitalis and encephalitis in mice and guinea pigs. The antiviral activity of these compounds was compared with that of acyclovir. With 1,3-butanediol as a topical treatment vehicle, 1 % APSC and APTSC showed significant activity against the genital infection in mice, as evidenced by increased survivors and decreased severity of vaginal lesions. Reduced titers of virus recovered from the lesions were also observed with APTSC treatments. Eight different commercially available vehicles were compared to determine in which topically administered 1% APTSC would be most efficacious against the vaginal disease induced in mice. Significant results were observed with Squibb cream base, Eucerin base, and K-Y jelly; these effects were essentially equivalent to using 1,3-butanediol Unibase, Aqua-phor, polyethylene glycol, polyvinyl alcohol and petrolatum were less effective as carrier vehicles. The herpesvirus genital infection in guinea pigs was treated with 1% APMTSC and APTSC comparing Squibb cream, Eucerin and K-Y jelly bases; while neither compound exerted striking effects against this infection in any vehicle, 1% APMTSC in Squibb cream was effective in increasing mean survival time and reducing lesion score and titers of recoverable virus. In this experiment, treatments with 1 and 5 % acyclovir in polyethylene glycol base were effective in reducing titers of virus from the vaginal area. Orally administered APTSC (12.5, 25, 50 mg/kg/day given twice daily for 7 days) caused moderate prevention of death of mice infected intraperitoneally with HSV-2; subcutaneous injection of the compound was markedly effective with efficacy comparable to that of acyclovir at 120 mg/kg/day.

ISSN:0009-3157    

DOI:10.1159/000238749

出版商:S. Karger AG    

年代:1990

数据来源: Karger