evernimicin and Gram-Positive-Bacterial-Infections

Ziracin is produced by Micromonospora carbonacea and is highly active against Gram-positive bacteria. In particular it is highly active against methicillin resistant staphylococci and vancomycin resistant enterococci. Ziracin, C71H97NO38Cl2, contains two orthoester linkages, a nitro sugar, a methylene dioxy group, two aromatic ester residues and thirty five centres of assymmetries. In this paper a brief description of the structural elucidation of ziracin is presented along with the chemical modification of the antibiotic which has led to the identification of several potent antibacterials.

Topics: Aminoglycosides; Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Molecular Structure; Oligosaccharides; Structure-Activity Relationship

The in vitro activity of SCH27899, a novel oligosaccharide antimicrobial agent, was compared with those of representatives of six classes of antimicrobial agents (piperacillin, clarithromycin, clindamycin, vancomycin, sitafloxacin and metronidazole) against clinical isolates of anaerobic bacteria and Propionibacterium acnes. Against Peptostreptococcus: spp. and Clostridium difficile, SCH27899 was the most potent (MIC(90) < 0.125 mg/L) of the agents examined. Besides these Gram-positive anaerobes, SCH27899 showed a moderate level of activity against Prevotella bivia, Prevotella intermedia and Porphyromonas: spp. (MIC(90)< or = 4 mg/L).

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria, Anaerobic; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Propionibacterium acnes

SCH27899 is an oligosaccharide, everninomicin antibiotic with activity primarily against Gram-positive pathogens. The activity of SCH27899 was evaluated against 360 routine clinical isolates by the broth microdilution (BMD), agar dilution (AD), disk diffusion (DD), and Etest (AB BIODISK, Solna, Sweden) methods. In addition, results from a nine center SCH27899 quality control (QC) trial were used to establish QC ranges. SCH27899 MICs for 330 Gram-Positive strains, including multiply-resistant staphylococci and enterococci, ranged from 0.015 to 1 microgram/ml with MIC90s of 0.12 to 0.5 microgram/ ml. SCH27899 had no measurable activity against the 30 selected Gram-negative strains tested (MICs, > 256 micrograms/ml), with the exception of Moraxella catarrhalis MICs, 0.12 microgram/ ml). Etest MICs for SCH27899 correlated well with AD and BMD results with > 90% of MICs within +/- one log2 dilutions of the reference test results. Three disk concentrations (2.5-, 5-, 10-microgram) of SCH27899 were evaluated, but minimal difference of zone diameters between disk drug contents was observed (+/- 2 mm). SCH27899 disk zone diameters correlated poorly with reference MICs due to small zone diameters (range, 11 to 22 mm) attributed to poor diffusion through agar mediums, a product of this compound's high molecular weight and solubility. The use of the DD method for SCH27899 was not recommended. The proposed MIC quality assurance limits for SCH27899 using Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 was 0.06 to 0.25 microgram/ml for both QC strains and methods. SCH27899 appears to be a eveminomicin-derivative widely active against important Gram-positive cocci, and in vitro dilution testing methods would be preferred for clinical use, validated by the recommended MIC control ranges cited in this report.

Topics: Aminoglycosides; Anti-Bacterial Agents; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Laboratories; Microbial Sensitivity Tests; Quality Control; Reference Standards

The emergence of multiresistant bacteria has increased the need for new antibiotics or modifications of older antibiotics. One promising agent might be the everninomicin SCH 27899, an oligosaccharide antibiotic recently developed by Schering Plough. However, another oligosaccharide, avilamycin, that is structurally very similar has been used as a growth promoter for food animals in the EU for several years, and a very frequent occurrence of resistance to avilamycin has been found among Enterococcus faecium isolates from broilers in Denmark. This study was conducted to investigate whether the resistance to avilamycin was associated with decreased susceptibility to everninomicin. From broilers, a total of 31 avilamycin susceptible and 55 avilamycin resistant (MIC >16 microg/mL) E. faecium isolates were selected. From pigs, 21 avilamycin-susceptible and eight avilamycin-resistant Enterococcus faecalis and 50 avilamycin-susceptible and two avilamycin-resistant E. faecium isolates were selected. All isolates were tested for susceptibility to everninomicin by E-test. The avilamycin-susceptible enterococci isolates had MICs to everninomicin from 0.064 to 0.75 microg/mL (MIC50 = 0.38 microg/mL) and the avilamycin-resistant isolates had MICs from 1.5 to 16 microg/mL (MIC50 = 3 microg/mL). Complete agreement between decreased susceptibility to avilamycin and everninomicin was found. This study showed that the use of avilamycin as a growth promoter for broilers and pigs has created a reservoir of E. faecium and E. faecalis isolates with decreased susceptibility to everninomicin among food animals already before this antibiotic have been finally developed for human use.

Topics: Aminoglycosides; Animal Feed; Animals; Anti-Bacterial Agents; Chickens; Drug Resistance, Microbial; Drug Utilization; Enterococcus; Gram-Positive Bacterial Infections; Growth Substances; Humans; Microbial Sensitivity Tests; Oligosaccharides; Swine