Antimicrobial activity of RU-66647, a new ketolide

A new macrolide subclass called ketolides, possess a mode of action similar to the macrolide-lincosamide-streptogramin (MLS) compounds. Utilizing reference in vitro tests, the in vitro activity of RU-66647 (a ketolide) was compared to other MLS compounds against 376 Gram-positive organisms and over 400 representative strains of Gram-negative bacilli. The ketolide's spectrum was most similar to clindamycin and an earlier drug in the series (RU-64004 or RU-004) against staphylococci and streptococci. However, RU-66647 was more active than erythromycin and azithromycin against oxacillin-resistant Staphylococcus spp. and vancomycin-resistant enterococci. Ketolide activity was more potent than other MLS drugs against vancomycin-susceptible enterococci (MIC90, 0.25-4 micrograms/ml) and all streptococci (MICs, < or = 0.25 microgram/ml). Erythromycin-resistant (constitutive) strains were generally inhibited by < or = 2 micrograms RU-66647/ml (staphylococci, 31 to 36%; streptococci, 100%; enterococci, 72%). RU-66647 was active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 microgram/ml), and pathogenic Neisseria spp. (MIC90 0.5 microgram/ml). The ketolide failed to inhibit Enterobacteriaceae, nonfermentative Gram-negative bacilli, and Bacteriodes fragilis group strains. RU-66647 was observed to be a promising new compound directed toward some organisms resistant to other MLS-class drugs.     

Ultratight DNA binding of a new bisintercalating anthracycline antibiotic

Differential scanning calorimetry and absorption spectroscopy were used to characterize the interaction of the new bisintercalating anthracycline antibiotic, WP631, with DNA. The method of continuous variations revealed five distinct binding modes for WP631, corresponding to 6, 3, 1.3, 0.5, and 0.25 mol of base pairs (bp) per mole of ligand. The binding of one drug to 6 bp corresponds to the bisintercalative binding mode determined previously, and was the mode studied in detail. UV melting experiments and differential scanning calorimetry were used to measure the ultratight binding of WP631 to DNA. The binding constant for the interaction of WP631 with herring sperm DNA was determined to be 3.1 (+/- 0.2) x 10(11) M-1 at 20 degrees C. The large, favorable binding free energy of -15.3 kcal mol-1 was found to result from a large, negative enthalpic contribution of -30.2 kcal mol-1. DNA melting curves at different concentrations of WP631 were fitted to McGhee's model of DNA melting in the presence of ligands, yielding an independent estimate of DNA binding parameters. The salt dependence of the WP631 binding constant was examined, yielding a slope SK = delta (log K)/delta (log[Na+]) = 1.63. The observed salt dependence of the equilibrium constant, interpreted according to polyelectrolyte theory, indicates that there is a significant nonpolyelectrolyte contribution to the binding free energy. DNA melting studies using a homogeneous 214 bp DNA fragment showed that WP631 binds preferentially to the GC-rich region of the DNA.     

HP17, a new pigment-like antibiotic produced by a new strain of Spirillospora

Spirillospora strain 719 produces several antibiotics. On solid and liquid media, a deep red pigments is formed and diffuses throughout the culture. It was extracted with methanol from the mycelium cake and from the fermentation broth after precipitation at pH 2 and purified using TLC and HPLC. Its u.v. absorption spectrum and its physicochemical characteristics place this antibiotic in the 3.3.2.2.8 of the Berdy et al. classification. In most respects, it resembles proteinaceous pigment from Spirillospora 1655 and 1309-b that was studied and named spirillomycin. However, HP17 differs from spirillomycin principally in molecular weight and chemical nature.     

The structure of antibiotic G-52, a new aminocyclitol-aminoglycoside antibiotic produced by Micromonospora zionensis

Antibiotic G-52, a new aminocyclitol-aminoglycoside antibiotic produced in the fermentation of Micromonospora zionensis, has been shown to be 6'-N-methylsisomicin on the basis of its spectral characteristics. This assignment was confirmed by synthesis of the antibiotic from sisomicin.     

Antiviral and interferon-inducing activity of a new glutarimide antibiotic, 9-methylstreptimidone

Leucocyte migration inhibition by autologous breast tumour cell fractions was mediated by a soluble factor synthesized and released by mononuclear leucocytes and active against migrating granulocytes. This mechanism is similar to that previously described in respect to cell-mediated sensitivity to microbial antigens. Alternative mechanisms involving directly reactive granulocytes or cytophilic antibodies were rarely operative in the migration tests.     

AH17, a new non-polyenic antifungal antibiotic produced by a strain of Spirillospora

An antibiotic (AH17) was produced by Spirillospora strain 719. This substance was obtained only from the broth filtrate after precipitation with acetic acid followed by extraction with n-butanol. Its purification was carried out by thin layer chromatography on silica gel followed by HPLC procedures. It showed activity against Gram-positive and Gram-negative bacteria and fungi. The spectroscopic and chemical properties were examined and indicated that AH17 was a quinone. It seems that this is a new antibiotic from Spirillospora.     

In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic

The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against experimental murine septicemia caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli and against murine respiratory infections caused by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection by penicillin-susceptible and penicillin-resistant S. pneumoniae, sanfetrinem cilexetil was more effective than amoxicillin in reducing the number of bacteria in infected lungs. These results were reflected in its potent in vitro activity and high levels in plasma.     

Pharmacokinetics of azlocillin, a new semisynthetic, wide-spectrum antibiotic (author's transl)

Azlocillin, a new semisynthetic penicillin with a wide spectrum of antimicrobial activity and a member of the ureidopenicillin group, was administered to ten adults in a dosage of 2 g by intravenous bolus injection. The determination of antibiotic activity in serum and urine demonstrated an average concentration of 58.9 mug/ml after one hour, 28.1 mug/ml after two hours and 6.1 mug/ml after four hours. The total urinary excretion was 60% within six hours. The pharmacokinetic parameters were calculated for the one and two compartment models, respectively. Mathematical analysis according to an open two-compartment model resulted in better curve adjustment as judged from the sum of the deviant squares. The resulting parameters for volume of distribution and rate of elimination show only minor differences however. Similar results were seen on comparison with the respective data for ampicillin.     

In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae

The in vitro activities of HMR 3647, roxithromycin, erythromycin, and azithromycin against 19 strains of Chlamydia pneumoniae were tested. The MIC at which 90% of the isolates are inhibited and the minimum bactericidal concentration at which 90% of the isolates are killed of HMR 3647 were 0.25 microgram/ml (range, 0.015 to 2 micrograms/ml). Nine recently obtained clinical isolates from children with pneumonia were more susceptible (MICs, 0.015 to 0.0625 microgram/ml) than older strains that had been passaged more extensively.     

Sorbistin, a new aminoglycoside antibiotic complex of bacterial origin. III. Structure determination

The structures of sorbistins A1, A2, B, C and D have been determined including stereo-chemistry. Sorbistins A1, A2 and B are composed of a 4-acyl-amino-4-deoxy-D-glucose and 1,4-diamino-1,4-dideoxy-D-sorbitol, the latter compound being hitherto undescribed in literature. Sorbistins C and D have the same aglycone of 1,4-diamino-1,4-dideoxy-D-sorbitol, which is linked with D-glucose and 4-amino-4-deoxy-D-glucose, respectively, through a glycosidic bond.     

In vitro activity of RU 64004, a new ketolide antibiotic, against gram-positive bacteria

The comparative in vitro activity of RU 64004 (also known as HMR 3004), a new ketolide antibiotic, was tested by agar dilution against approximately 500 gram-positive organisms, including multiply resistant enterococci, streptococci, and staphylococci. All streptococci were inhibited by < or = 1 microg of RU 64004 per ml. The ketolide was more potent than other macrolides against erythromycin A-susceptible staphylococci and was generally more potent than clindamycin against erythromycin A-resistant strains susceptible to this agent. Clindamycin-resistant staphylococci (MIC, > 128 microg/ml) proved resistant to the ketolide, but some erythromycin A- and clindamycin-resistant enterococci remained susceptible to RU 64004.     

Samarosporin, a new peptide antibiotic. I. Fermentation, isolation ahd characterization

A new antibiotic, samarosporin, was isolated in a crystalline state from a mycelial extract of a strain of Samarospora species (an ascomycete). Samarosporin is a neutral cyclopeptide and has a molecular formula of C72H111N15O19. Samarosporin shows a broad antimicrobial activity against various test microorganisms.