In vitro activity of the tribactam GV104326 against gram-positive, gram-negative, and anaerobic bacteria

Abstract

GV104326 is the first member of a new class of antibiotics (tribactams) selected for development. It combines a particularly broad spectrum (including gram-negative and gram-positive aerobes and anaerobes) with high potency, resistance to beta-lactamases, and complete stability to dehydropeptidases. Comparative MICs were determined for GV104326 against 415 recent clinical isolates (including beta-lactamase producers), using representative antibacterial agents (imipenem, amoxicillin-clavulanic acid, cefpirome, ciprofloxacin, gentamicin, and erythromycin). GV104326 was particularly active against gram-positive bacteria; in general, its in vitro activity was equivalent to that of imipenem, equivalent to or better than that of amoxicillin-clavulanic acid, and superior to that of cefpirome, ciprofloxacin, and erythromycin. Against gram-negative bacteria, GV104326 possessed activity similar to that of imipenem and cefpirome against enterobacteria and Haemophilus spp. but its activity was superior to that of amoxicillin-clavulanic acid. GV104326 showed excellent antianaerobe activity. GV104326 was stable to all clinically relevant beta-lactamases and was rapidly lethal to susceptible bacteria. In Escherichia coli, GV104326 bound predominantly to PBPs 1a and 2 and at low concentrations osmotically stable round forms were observed. GV104326 showed an affinity for PBPs 2 and 4 of Staphylococcus aureus.

Syntheses and Antibacterial Activities of Diterpene Catechol Derivatives with Abietane, Totarane and Podocarpane Skeletons against Methicillin-Resistant Staphylococcus aureus and Propionibacterium acnes

“…13,23) 12,13-Dihydroxy-8,11,13-totaratriene-6-one 13) 9 was synthesized from 5 as follows. Oxidation of 5 with Ag 2 O gave a mixture of 6-deoxymaytenoquinone 6 and 8(14),9(11)-totaradiene-12,13-dione (25) as reported in the literature.…”

Syntheses of Carnosic Acid and Carnosol, Anti-oxidants in Rosemary, from Pisiferic Acid, the Major Constituent of Sawara

“…Biological Activities Minimun inhibitory concentration (MIC mg/ml) of the synthetic carnosic acid 2 and carnosol 3 were measured against Propionibacterium acnes (ATCC 6919) 18) and Staphylococcus aureus ME/GM/TC Resistant (ATCC 33592) 19) to show the potential of these compounds as antibacterial drugs. Both of the synthetic compounds showed potent antibacterial activities against P. acnes and S. aureus ( Table 1).…”

“…synthetic carnosol, 212-213°C 15) ; natural carnosol, 219.5°C 22) ). Methods of Anti-microbial Activities in vitro Assays Minimun inhibitory concentration (MIC mg/ml) of the synthetic carnosic acid 2 and carnosol 3 were performed under conditions described in the literatures for each assay against Propionibacterium acnes (ATCC 6919) 18) and Staphylococcus aureus ME/GM/TC Resistant (ATCC 33592). 19) Two compounds 2 and 3 were tested at half-log concentrations ranging from 0.03 to 100 mg/ml in the P. acnes and S. aureus in vitro growth inhibition assays.…”

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

“…Nomenclature in the literature varies, some authors referring to them as'round forms' [76,100], 'round cells' [63, 101,102], 'spherical forms', 'spherical cells' [54,78,103], or 'coccoid forms' [104,105]. In a few papers, these descriptors are used interchangeably with the term 'spheroplast' [54,101,102] but this is incorrect.…”

“…In a few papers, these descriptors are used interchangeably with the term 'spheroplast' [54,101,102] but this is incorrect. Unlike spheroplasts, ovoid cells are osmotically stable [63,75,76,100,106]. This difference can be demonstrated by comparing impression smears of the antibiotic-treated bacteria overlaid with drops of distilled water or 0.85% (w/v) NaCl [53], or by performing the antibiotic treatment itself in media with and without osmotic support [69].…”