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Biomedical subjects

A Bryskier

Publications and source records attributed to A Bryskier.

At least 73 records · Page 4Linked to original sources
PubMed1995

In-vitro and in-vivo activities of roxithromycin in combination with pyrimethamine or sulphadiazine against Toxoplasma gondii.

The efficacy of roxithromycin alone or in combination with pyrimethamine or sulphadiazine was examined in vitro and in a murine model of acute toxoplasmosis. In-vitro studies were performed with MRC5 fibroblast tissue cultures, with quantification of toxoplasma growth by an enzyme-linked immunosorbent assay. For in-vivo studies, mice were infected with 10(4) tachyzoites of the virulent RH strain and then treated perorally for 10 days from day 1 after infection. The efficacy of each drug regimen was assessed by determination of survival rates and sequential titration of parasites in blood, brain and lungs, using a tissue culture method. In vitro, roxithromycin inhibited toxoplasma growth at a concentration of > or = 0.02 mg/L; the 50% inhibitory concentration was estimated to be 1.34 mg/L. No synergistic effect was observed when it was combined with pyrimethamine or sulphadiazine. In vivo, roxithromycin alone at 50 or 200 mg/kg/day slightly prolonged survival compared with untreated mice, but a striking synergistic effect was observed when roxithromycin was administered in combination with pyrimethamine or sulphadiazine at subtherapeutic doses, i.e., 12.5 and 100 mg/kg/day, respectively. Combination regimens consistently resulted in a marked reduction fo the parasite burdens in blood and tissue, compared with those in mice treated with any of the agents alone. These results suggest that in-vivo activities of either pyrimethamine or sulphadiazine against T. gondii are reinforced by roxithromycin and such combinations should be considered in development of alternative treatments for human toxoplasmosis.

Animals↗
PubMed1995

Intracellular activities of roxithromycin used alone and in association with other drugs against Mycobacterium avium complex in human macrophages.

Recent reports have shown that roxithromycin possesses significant activity against atypical mycobacteria, including the Mycobacterium avium complex (MAC), and that its extracellular anti-MAC activity is further enhanced in two- or three-drug combinations with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine. In accordance with the above data, the anti-MAC potential of roxithromycin used alone and in combination with the above-mentioned antituberculous drugs was screened intracellularly against five clinical MAC isolates (from both human immunodeficiency virus-positive and human immunodeficiency virus-negative patients), phagocytized by human monocyte-derived macrophages. The results showed that roxithromycin used alone and within clinically achievable levels was active against all of the MAC isolates tested. Screening of two-drug combinations showed that both rifampin and clofazimine further increased the intracellular activity of roxithromycin against all five isolates by 35 to 80% (ethambutol, ofloxacin, and amikacin resulted in increased intracellular activity against one, two, and four isolates, respectively). For the three-drug combinations, the combination of roxithromycin plus ethambutol used with rifampin or clofazimine was the most uniformly active against all five MAC isolates, with activity increases of 42 to 90%, followed by roxithromycin plus ethambutol used with amikacin, which resulted in activity increases of 15 to 90%. The overall level of intracellular killing after 5 days of drug addition, in comparison with growth in untreated controls, varied from 1 to 3 log units depending on the individual MAC isolate and/or drug combination used.

Cells, Cultured↗
PubMed1995

Pharmacokinetics of cefodizime following single doses of 0.5, 1.0, 2.0, and 3.0 grams administered intravenously to healthy volunteers.

Cefodizime is a new expanded-spectrum cephalosporin for parenteral use which possesses a broad antibacterial spectrum and potent antibacterial activity and is stable against most beta-lactamases. The aim of this study was to assess the pharmacokinetics of cefodizime, administered intravenously, over the dose range of 0.5 to 3.0 g in healthy volunteers. Concentrations of cefodizime in the serum and urine were determined by high-performance liquid chromatography. The area under the concentration-time curve from 0 h to infinity and the amount of drug excreted in urine from 0 to 34 h increased in a linear, dose-dependent manner with increasing doses of antibiotic from 0.5 to 3.0 g. Mean concentrations of cefodizime in plasma at the end of infusion increased from 97 to 440 mg liter-1 over the dose range 0.5 to 3.0 g and displayed a slight deviation from linearity at doses in excess of 2.0 g. Total plasma clearance (3.11 liters h-1), volume of distribution at steady state (10.5 liters), terminal elimination half-life (3.3 h), and renal clearance (1.91 liters h-1) remained constant over the doses administered. Cefodizime was well tolerated in this study.

Adolescent↗
PubMed1995

Classification and structure-activity relationships of fluoroquinolones.

Fluoroquinolones are potent broad spectrum antibacterial agents. Two classifications have been described: chemical and biological. Quinolones can be classified into 4 groups according to their chemical structures: monocyclic, bicyclic, tricyclic and tetracyclic derivatives. Each group can be subdivided into subgroups if a fluorine atom is fixed at the 6-position. The biological classification recognised 4 groups. Groups 1 and 2 are composed of compounds showing limited spectra (Enterobacteriaceae) and groups 3 and 4 contain compounds displaying broad antibacterial spectra. Compounds that are highly metabolised fall into groups 1 and 3 and those poorly metabolised (< 5%) into groups 2 and 4. The structure of fluoroquinolones may help to predict antibacterial activity, pharmacokinetics, physicochemical properties, toxicity and adverse events.

Animals↗
PubMed1994

[Macrolides. New therapeutic prospects].

The aim of the development of semisynthetic derivatives was to overcome the problem of chemical stability of erythromycin A in acid medium, with less variability in gastro-intestinal absorption and leading to renewed interest in macrolides. The new macrolides have the same antibacterial spectrum as erythromycin A including Gram-positive and Gram-negative cocci, intracellular bacteria, mycoplasma, Campylobacter sp., Helicobacter pylori, mycobacteria spp., Gram-negative bacilli including Haemophilus influenzae, Bordetella pertussis, Pasteurella multocida, Gram-positive bacilli including Corynebacterium diphtheriae and anaerobic species. In vitro activity against Haemophilus influenzae is still a controversial subject. Macrolides are among the best tolerated antibacterial agents. Theoretically, macrolides could be given to a large range of patients even those suffering from underlying diseases. The new macrolides, roxithromycin, azithromycin, clarithromycin, dirithromycin, rokitamycin and miokamycin, are indicated for the treatment of upper respiratory tract infections and lower respiratory tract infections due to intracellular bacteria or Mycoplasma pneumoniae. Macrolides could be used as first line therapy for non-gonococcal urethritis, especially those due to Chlamydia trachomatis or Ureaplasma urealyticum. In pelvic inflammatory infections in which Chlamydia trachomatis is involved macrolides could also be used. Other non-conventional indications under discussion are H. pylori and Lyme's disease. Macrolides in combination with other antibacterials could be an alternative for Mycobacterium avium-intracellulare infections. The antiparasite effect of erythromycin has been known since the 1950s. Extensive experimental work is currently underway to determine the potential use of these drugs in this setting. Research during the 80s in the macrolide field, led to enhanced pharmacokinetic properties. Current research is focused on expanding the antibacterial spectrum and to overcome cross-resistance among 14-membered-ring macrolides.

Animals↗
PubMed1994

Activities of roxithromycin used alone and in combination with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine against Mycobacterium avium complex.

Preliminary studies showed that roxithromycin possessed significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii and rare pathogens such as M. chelonae and M. fortuitum. In this investigation, radiometric MICs of roxithromycin, ethambutol, rifampin, amikacin, ofloxacin, and clofazimine for 10 clinical isolates of the M. avium complex (5 each from human immunodeficiency virus [HIV]-positive and HIV-negative patients) were determined. Roxithromycin MICs against all the isolates were below the reported maximum concentration of drug in serum at the routine pH of 6.8, and the MICs were further lowered by 1 to 2 dilutions at a pH of 7.4. In vitro enhancement of roxithromycin activity against all strains was further investigated by the previously established Bactec 460-TB method by combining the drugs at sub-MIC levels. Antibacterial activity of roxithromycin was enhanced in all 10 strains by ethambutol, in 3 strains each by rifampin and clofazimine, in 2 strains by amikacin, and in 1 strain by ofloxacin. In vitro screening of three-drug combinations showed that combinations of roxithromycin, ethambutol, and a third potential anti-M. avium drug (rifampin, amikacin, ofloxacin, or clofazimine) resulted in further enhancement of activity in 13 out of 20 drug combinations screened.

Amikacin↗
PubMed1993

In vitro activity of roxithromycin against 16 species of atypical mycobacteria and effect of pH on its radiometric MICs.

The antimycobacterial spectrum of roxithromycin, a semisynthetic 14-membered ring macrolide, was determined against 28 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs by BACTEC methodology at two different pH values, i.e., 6.8 and 7.4. The MICs obtained at pH 7.4 were 1 to 2 dilutions lower or more than those obtained at pH 6.8 for some of the species. Roxithromycin possessed promising MICs against such potential pathogens as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, and rare pathogens like M. chelonei subsp. chelonei and M. chelonei subsp. abscessus but not against M. simiae. Roxithromycin showed lower MICs against M. fortuitum var. peregrinum than M. fortuitum var. fortuitum.

Hydrogen-Ion Concentration↗
PubMed1992

Antibacterial activity of RU44790, a new N-tetrazolyl monocyclic beta-lactam.

RU44790 belongs to a new class of synthetic monocyclic beta-lactam antibiotics which feature a bioisosteric tetrazole moiety instead of the more classical acidic functions at the N-1 position of the beta-lactam ring. Its antibacterial activity was evaluated against some 900 strains and was compared with those of other recent beta-lactam derivatives, especially aztreonam. RU44790 is endowed with potent activity against gram-negative bacteria. At less than or equal to 0.6 micrograms/ml, RU44790 inhibited 90% of all strains of the family Enterobacteriaceae with the exception of Citrobacter spp. (MIC for 90% of strains tested, 1.2 micrograms/ml). The activity was similar to that of aztreonam against strains that are normally susceptible to expanded-spectrum cephalosporins. On the other hand, the new compound was 10 to 100 times more potent than aztreonam and most of the other antibiotics tested against enterobacteria that produce chromosome-encoded or plasmid-mediated extended-spectrum beta-lactamases. Pseudomonas aeruginosa isolates were equally susceptible to both monobactams. RU44790 was inactive against staphylococci and had only marginal activity against streptococci (MIC for 50% of strains tested, 2.5 micrograms/ml). RU44790 was highly resistant to hydrolysis by various beta-lactamases, particularly cephalosporinases such as P99. The latter enzyme was also inhibited by the compound. RU44790 showed a high affinity for penicillin-binding protein 3 of Escherichia coli. The results suggest that RU44790 has good potential in the treatment of infections caused by gram-negative microorganisms.

Anti-Bacterial Agents↗
PubMed1990

Cefodizime, a new 2-aminothiazolyl cephalosporin: physicochemical properties, toxicology and structure-activity relationships.

Cefodizime is a 2-aminothiazolyl cephalosporin for parenteral use. Cefodizime has a bisubstituted thiothiazole moiety in position 3 of the cephem nucleus. The presence of this moiety does not alter the in-vitro antibacterial activity, or safety in animal studies, which are similar to those of cefotaxime, but results in an apparent long elimination half-life in rodents and dogs, and in novel immunological properties.

Animals↗
PubMed1990

Pharmacokinetics of cefodizime administered intravenously as a single-dose (1.0 and 2.0 g) to healthy adult volunteers.

Cefodizime is a new third generation cephalosporin for parenteral use. The purpose of this study was to define the pharmacokinetic profile of cefodizime after intravenous dosing with 1.0 and 2.0 g in healthy adult volunteers. Concentrations in plasma were determined over a period of 34 h and in urine over 48 h, using high-pressure liquid chromatographic procedures. Cefodizime displays a long elimination half-life (3.5-3.7 h). Mean total clearance was 2.63 +/- 0.19 l/h and mean renal clearance was 1.37 +/- 0.15 l/h. Areas under the curve were 422 +/- 43 mg.h/l and 757 +/- 39 mg.h/l for 1.0 and 2.0 g respectively. The apparent volumes of distribution were 12.8 +/- 1.81 and 14.3 +/- 1.11. After 1.0 g administration the residual concentrations were 3.94 +/- 0.79 mg/l and 0.38 +/- 0.10 mg/l at 12 and 24 h, respectively; after 2.0 g administration the residual concentrations were 6.80 +/- 1.40 mg/l and 0.65 +/- 0.18 mg/l, at 12 h and 24 h. Cefodizime is mainly eliminated via the kidneys. This profile supports once-daily administration of cefodizime, when indicated in non-life-threatening infections.

Adult↗
PubMed1990

Pharmacokinetics of cefodizime in elderly patients with moderate or severe renal impairment.

In young adults, the elimination half-life of cefodizime is 3.5-4 h. A pharmacokinetic study was performed in eight patients, aged 63 to 85 years, divided into two groups with the following creatinine clearances (group I: greater than or equal to 50 ml/min and group II: less than 30 ml/min). Cefodizime was administered as a 1.0-g iv bolus. In group I, pharmacokinetic parameters did not differ from those observed in young healthy volunteers in a previous study. In group II, the half-life was increased (3.42-7.41 h). There is a linear correlation between the creatinine clearance and total clearance. The daily dose given needs to be based not on the age of the patient but on the degree of renal impairment. In elderly patients with severe renal impairment, the daily dose should be reduced if the creatinine clearance falls below 30 ml/min.

Adult↗
PubMed1990

[Preparation of monodesethylamodiaquine from human urine].

60 mg of monodesethylamodiaquine, the active metabolite of amodiaquine were prepared by extraction from human urine, at pH 11-12, using ethyl acetate. The purification was carried out by medium pressure liquid chromatography. The identity and the purity of the compound were checked by thin layer chromatography, 1H nuclear magnetic resonance and mass spectrometry.

Amodiaquine↗
PubMed1989

[Comparative in vitro bacteriostatic and bactericidal effect of 5 macrolides: roxithromycin, erythromycin, oleandomycin, josamycin and spiramycin against 284 hospital bacterial strains].

The bacteriostatic and bactericidal activities of five macrolides (roxithromycin, erythromycin, troleandomycin, josamycin and spiramycin) were tested against 284 bacterial strains belonging to various species of Gram positive (staphylococci, streptococci, pneumococci, Listeria sp, Corynebacterium sp, Bacillus sp) and Gram negative bacteria (Neisseria sp, H. influenzae, P. multocida). The activity of these compounds on the whole strains showed near results: 71.8% of susceptible strains to erythromycin and spiramycin, 70% to josamycin, 67.6% to roxithromycin, 65.5% to troleandomycin. Resisting strains were MLSB resistant cocci Gram positive, H. influenzae and P. multocida strains. Species usually less studied (nongroupable streptococci, Corynebacterium sp, Bacillus sp) were very susceptible to macrolides with MICS equal or inferior to 1 mg/l for the two last genus. A bactericidal effect was observed for 38.8% of 72 tested strains (erythromycin), 36.1% (josamycin), 34.7% (spiramycin), 31.9% (roxithromycin), 20.8% (troleandomycin). Among various tested species, this bactericidal effect concerned especially group A streptococci, N. meningitidis and Corynebacterium (except D2 and JK species).

Cross Infection↗