In vitro antibacterial activity of AZD0914, a new spiropyrimidinetrione DNA gyrase/topoisomerase inhibitor with potent activity against Gram-positive, fastidious Gram-Negative, and atypical bacteria.

AZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potent in vitro antibacterial activity against key Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzae and Neisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance in S. aureus, and if mutants were obtained, the mutations mapped to gyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, ß-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration and in vitro time-kill studies. In in vitro checkerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potent in vitro antibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.

[Clinical basis of macrolides apply in diseases of the respiratory tract]. / Kliniczne podstawy stosowania makrolidów w chorobach ukladu oddechowego.

Macrolides are applied to control bacterial infection of the respiratory tract. Because of their possibility to penetrate into bacterial cell, they are used in inflammatory diseases caused mainly by atypical bacteria. Many macrolide gidelines have been accepted for antibiotic therapy. In the paper recommendations for macrolide treatment have been based on Polish results of bacterial resistance in pneumonia, asthma and COPD exacerbations, sinusitis and otitis.

Acción del Agua del Volcán Copahue (Neuquén, Argentina) sobre la morfología de las microbacterias / Action of the Copahue Volcano (Neuquén, Argentine) water of mycobateria morphology

Se efectuó un estudio de la acción del Agua del Volcán Copahue (AVC), Neuquén, Argentina, sobre 15 cepas de microbacterias Mycobacterium tuberculosis: M. bovis y los mycobacterum no tuberculosos ("Atipicos"), poniendo especial interés en los que forman "cuerdas". Se utilizó AVC con su pH l,3 y se la llevó a pH 6,5. En los bacilos que resistieron la acción del agua hasta el momento de la coloración, se advirtieron elementos más o menos alterados. Al aumentar el tiempo de contacto se llegó a la destrucción total, observándose en algunos casos muy pocos bacilos aislados, material deteriorado y formas granulares. Estas alteraciones fueron mucho más marcadas en las suspensiones que en el líquido del sedimento con el AVC; en las primeras directamente no se llegó a reparar la formación de cuerdas en ningun momento aun en bacilos que deberían formarla. Su acción no estaría asociada a una reacción bioquímica responsable en la síntesis de la pared celular, como la transpeptidación. El AVC actuaría sobre la síntesis del ácido micólico y se trataría de un agente bacteriolítico. Además se realizaron estudios en el "Laboratorio de tratamiento de imágenes", INEUCI (Instituto de Neurociencia), CONICET