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ABSTRACT: The in-vitro activity of MEN 10700, a novel penem, was compared with that of imipenem, ritipenem, ampicillin/sulbactam, cefotaxime, ciprofloxacin and amikacin against 1088 strains taken from 21 genera, including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that MEN 10700 was very active against staphylococci and streptococci (MIC90 < or = 0.5 mg/L) and against most members of the Enterobacteriaceae (MIC90 < or = 2 mg/L), with reduced activity only against Providencia stuartii (MIC90 = 8 mg/L). MEN 10700 was also active against anaerobic species such as Clostridium perfringens and Bacteroides fragilis as well as Moraxella catarrhalis. It was moderately active against Enterococcus faecalis and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Aeromonas spp. and Acinetobacter spp. Its antibacterial spectrum was thus slightly narrower than that of imipenem, but compared favourably with those of a third-generation cephalosporin and ritipenem. MEN 10700 was highly stable to a number of beta-lactamases and was a poor inducer of class I enzymes. It bound penicillin-binding protein 2 with the highest affinity and easily permeated the outer membrane of Escherichia coli.
Journal of Antimicrobial Chemotherapy 06/1998; 41(5):513-25. · 5.07 Impact Factor
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ABSTRACT: A new series of monobactam derivatives, bearing unsubstituted or N-monosubstituted sulfamoyloxymethyl groups in position 4 was synthesized either in racemic or in optically active form. Their in vitro antibacterial activity was tested in comparison with carumonam 1a and its methoxyimino derivative 1b.
Il Farmaco 04/1998; 53(3):173-80.
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ABSTRACT: New series of monobactam antibiotics, bearing thio-and dithiocarbamate derivatives as C-4 side chain, were synthesized. Some compounds were found to have good antibacterial activity against Gram-negative bacteria.
Il Farmaco 04/1996; 51(3):189-96.
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ABSTRACT: The antibacterial activities of three new penems with 4-hydroxyprolinamide, 1-prolinamide and N-methyl-N-2-propionamide substituents, respectively, in position 2 and of their stereoisomers were examined against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli and Pseudomonas aeruginosa. All substitutes conferred a broad antibacterial spectrum on the penem moiety. Changes in stereoisomerism selectively improved the activity against E. coli, S. aureus or enterococci. The structure-activity relationships of each compound were discussed in relation to minimum inhibitory concentrations, penicillin-binding protein (PBP) affinity and outer membrane permeability coefficient in E. coli. In this microorganism, PBP 2 was the target for all compounds. Changes in stereoisomerism influenced the affinity for PBPs 1A/B and 2. All antibiotics easily permeated the outer membrane of E. coli and, within each group of compounds, the penetration rate correlated with the antibacterial activity.
The Journal of Antibiotics 01/1996; 48(12):1488-93. · 1.65 Impact Factor
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ABSTRACT: Lymphokines produced by T-helper 1 (Th1) and Th2 cells are mutually inhibitory and/or self stimulatory and this may be exploited to inactivate or downregulate the subset of choice in order to achieve controlled and specific immunosuppression. Attempts to specifically activate normal human Th precursor cells into the Th2 subset are reported. Cholera toxin and forskolin increased intracellular cyclic AMP levels, but this had no discriminatory effect on Th1 and Th2 secretions. Primary activation with calcium ionophores, alone or in combination with phorbol esters, high concentrations of anti-CD3 monoclonal antibody and selective inhibition IL-2 synthesis with cyclosporin A or FK506 were unable to skew lymphokine production, away from vigorous IL-2 synthesis, to IL-4 predominance. However, it was possible to selectively activate the Th2 component in unprimed, normal human T-lympocytes by primary stimulation in mixed lymphocyte culture in the presence of IL-2 and high concentrations of IL-4, followed by restimulation. Ex vivo activation of these cells may have clinical significance in situations where suppression of Th1-like responses or IFN-( synthesis is desirable for example, in autoimmunity and transplant rejection.
African journal of health sciences 12/1995; 2(4):395-398.
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ABSTRACT: A new series of 6-(hydroxyethyl)penems 2-substituted with amino acid-related side chains was synthesized. The nature of the amino acyl derivative proved to be crucial both from a synthetic point of view, as beta-lactam ring opening can compete with C-2 nucleophilic substitution, and for antibacterial activity. Primary amino acid amides emerged as the most suitable side chains for enhancing permeability through a Gram-negative outer membrane. In vitro activity of the new 2-[(aminoamido)methyl]penems 3a-u was influenced by the nature and position of the amide moiety, the ring size for cyclic amides, and the configuration of the amino acid. Compounds bearing amides derived from small N-methyl amino acids (such as 3a) or from cyclic amino acids (such as prolinamide 3p and 4-hydroxyprolinamide 3r) showed broad spectrum in vitro activity against both Gram-positive and Gram-negative microorganisms.
Journal of Medicinal Chemistry 11/1995; 38(21):4244-56. · 5.25 Impact Factor
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ABSTRACT: Rats may be rendered tolerant to allografts by a single intrathymic injection (IT) of donor cells given 0-21 days before transplantation with or without immunosuppression. This prompted us to use these procedures in subhuman primates given renal allografts after lymphoablation. Timing of donor antigen was adapted to circumstances of clinical cadaver transplantation. Median survival (MS) of recipient baboons given IT donor spleen cells after immunosuppression with anti-thymocye globulin (ATG; MS=7d) or in combination with cyclosporin A and dexamethasone (MS=13d) was disappointing when compared with untreated controls (MS=11d). Immmunosuppression with total lymphoid irradiation (TLI) + ATG and IT donor spleen cells increased MS to 22d and 41d respectively. IT donor glomeruli in combination with TLI increased MS to 242d, a value previously obtained with TLI alone. Some animals given IT spleen a week before transplant showed evidence of sensitization. Immunosuppression reduced interleukin-2 synthesis in recipient lymphocytes and MLC suppressive serum factors occurred in 4 long-surviving baboons which had received TLI. Injection of donor cells into the atrophied thymus of adult baboons is difficult, and leakage of foreign cells or soluble antigen might have triggered host immunity in early rejectors. This is an important consideration in the clinical application of the approach.
African journal of health sciences 09/1995; 2(3):344-348.
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ABSTRACT: The in vitro activity of azithromycin against 40 strains of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis was investigated in comparison with erythromycin, roxithromycin and minocycline. All C. trachomatis strains were inhibited by azithromycin at a concentration < or = 0.5 microgram/ml. The initial minimum inhibitory concentration (MIC) of the drug for U. urealyticum was 4 microgram/ml, whereas some resistance against the drug was shown by M. hominis. Erythromycin and roxithromycin presented almost comparable activities, whereas minocycline was slightly more active than macrolides against C. trachomatis (MIC < or = 0.25) and more active against M. hominis (initial MIC < or = 1 micrograms/ml). Only 97% of U. urealyticum strains were susceptible to 8 micrograms/ml of minocycline.
Journal of chemotherapy (Florence, Italy) 06/1993; 5(3):155-8. · 1.08 Impact Factor
