A new class of cis-monobactam derivatives bearing a sulfamoyloxymethyl or an N-alkylsulfamoyloxymethyl group at position 4: synthesis and antibacterial activity.

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.

MEN 10700, a new penem antibiotic: in-vitro activity and its correlation with beta-lactamase stability, PBP affinity and diffusion through the bacterial cell wall.

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.

Genotypic differentiation of Gardnerella vaginalis by amplified ribosomal DNA restriction analysis (ARDRA).

In total 34 strains of Gardnerella vaginalis were analyzed with various molecular techniques in order to find the possibility of dividing this single species into different genotypes. Classical ribotyping, PCR-ribotyping and restriction analysis of 16S-23S rRNA intergenic spacer sequences were all unsuccessful in genotype differentiation of these bacteria. Only amplified ribosomal DNA restriction analysis (ARDRA) was suitable in recognizing different G. vaginalis genotypes. At least 3-4 genotypes were identified with different restriction enzymes, some of which showed a prevalent distribution in certain of the centers from which they were collected. Although in this study no correlation was found between bacterial vaginosis and any of the genotypes identified, the ARDRA method could prove to be a useful tool for studying the etiopathology and epidemiology of G. vaginalis.

Synthesis and antibacterial activity of C-4 thio- and dithiocarbamate monobactam derivatives.

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.

Structure-activity relationship of new 2-substituted penem antibiotics.

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.

2-Substituted penems with amino acid-related side chains: synthesis and antibacterial activity of a new series of beta-lactam antibiotics.

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.

In vitro activity of azithromycin against Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis in comparison with erythromycin, roxithromycin and minocycline.

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.

Chlamydial genital infections and laparoscopic findings in infertile women.

Several studies have shown that previous chlamydial genital infection, reflected by serological markers, is strongly associated with tubal damage leading to tubal infertility. In 105 women undergoing laparoscopy, multiple samples were collected from the lower (urethra and cervix) and upper (endometrium, peritoneal fluid, tubal lumen) genital tract, in order to isolate Chlamydia trachomatis in cell culture. Chlamydia trachomatis was isolated from at least one site in 13 (30.9%) of 42 infertile women with tubal infertility, in 5 (12.1%) of 41 women with unexplained infertility, in 1 of 4 women affected by acute salpingitis and in 1 (5.5%) of 18 women with endometriosis or uterine malformations. The latter group was the control group. Thirteen (65%) of the 20 positive women harboured Chlamydia trachomatis in their upper genital tract alone and 16 women were positive in one or both tubes. Only one of the positive women showed laparoscopic signs of acute pelvic infection. Four of the 5 positive women with unexplained infertility harboured Chlamydia trachomatis in the tubal lumen. This study confirms that chlamydial infection is strongly associated with tubal damage. It suggests that cervical cultures are inadequate for excluding a tubal infection and that chlamydial colonization of the tubal mucosa is possible in the absence of symptoms and laparoscopic signs of active infection.