Bactericidal activity of ramoplanin against antibiotic-resistant enterococci

Abstract

Ramoplanin, a new lipoglycodepsipeptide antibiotic, was uniformly active against 65 strains of enterococci, including strains higly resistant to vancomycin, penicillin G, and gentamicin. MBCs were usually within a fourfold dilution of the MICs. In time-kill studies, ramoplanin alone demonstrated dose-dependent bactericidal activity against enterococcal strains that resisted killing by vancomycin or penicillin in combination with gentamicin.

Vancomycin-Resistant Enterococci

“…In all investigations, all strains of all species, including vancomycin-resistant E. faecalis and E. faecium, were inhibited by 8 g/ml and the MIC 90 s (in all but one study) ranged from Յ0.25 to 1.6 g/ml (18,54,132,170,234). Ramoplanin is also bactericidal for enterococci, with the MBCs being only fourfold higher than the MICs (132). Ramoplanin inhibits cell wall synthesis by acting at the level of lipid-intermediate formation, whereas vancomycin and daptomycin interfere with peptidoglycan synthesis by preventing transglycosylation (223).…”

“…In preliminary studies, ramoplanin has been poorly tolerated following intravenous or intramuscular injection, and it seems unsuitable for systemic use because of its toxicity; however, it is being developed for topical use (261). It has been suggested that ramoplanin could be used for the clearance of glycopeptide-resistant enterococci from the gastrointestinal tract (132), and it might well be used to eradicate C. difficile without a risk of colonization by glycopeptide-resistant enterococci (22).…”

Bactericidal activities of peptide antibiotics against multidrug-resistant Enterococcus faecium

“…Ramoplanin is a lipoglycopeptide antibiotic which inhibits peptidoglycan synthesis by inhibiting the formation of lipid intermediate 11 (18). Cross-resistance between these drugs and older peptide antibiotics does not routinely occur (4,11,12). Therefore, these newer peptide antibiotics may retain activity against vancomycin-resistant strains.…”

“…Ramoplanin is a new lipoglycopeptide antibiotic with activity against most gram-positive organisms (2,17), including enterococci resistant to penicillin or vancomycin (11). Bactericidal activity against a small number of vancomycin-resistant enterococci has been demonstrated elsewhere (4,11).…”

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin: Minimal structural requirements for intermolecular complexation and fibril formation

“…1) is a promising candidate to replace vancomycin. Produced by fermentation of Actinoplanes ATCC 33076, ramoplanin A2 is highly active against numerous Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) (2-6), vancomycin-resistant Enterococcus faecium (VRE), and those resistant to ampicillin and erythromycin (6)(7)(8)(9)(10)(11). Ramoplanin factor A2 is currently under Phase III clinical development for eradication of VRE and MRSA.…”