In vitro activities of ramoplanin and four glycopeptide antibiotics against clinical isolates of Clostridium difficile

Biavasco, Francesca; Manso, Esther; Varaldo, Pietro E.

doi:10.1128/aac.35.1.195

Cited by 38 publications

(15 citation statements)

References 23 publications

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“…Published information (2,5,8) showing the activity of ramoplanin against all isolates of C. difficile is available for a limited number of strains, but all of those isolates were susceptible to MTZ and VAN. In this study, ramoplanin showed excellent in vitro activity against a large and heterogeneous collection of C. difficile isolates.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Ramoplanin against Clostridium difficile , Including Strains with Reduced Susceptibility to Vancomycin or with Resistance to Metronidazole

Peláez

Alcalá

Alonso

et al. 2005

Antimicrob Agents Chemother

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We evaluated the in vitro activity of ramoplanin, an antimicrobial compound that inhibits cell wall synthesis by acting at the level of lipid intermediate formation, against Clostridium difficile. We included strains with reduced susceptibilities to vancomycin (vancomycin-intermediate [Van i ] strains) or with resistance to metronidazole (Mtz r ), in order to assess the potential utility of ramoplanin for the treatment of C. difficile-associated diarrhea. We tested the activity of ramoplanin against a total of 105 nonduplicate clinical isolates of toxigenic C. difficile, including 8 Van i isolates and 6 Mtz r isolates, obtained from our laboratory. Ramoplanin was active against all strains tested at concentrations ranging from 0.03 to 0.5 g/ml (MICs at which 50 and 90% of isolates were inhibited, 0.25 g/ml; geometric mean MIC, 0.22 g/ml). All isolates, independently of their levels of susceptibility to vancomycin or metronidazole, were considered susceptible to ramoplanin (MICs, <0.5 g/ml).Rates of Clostridium difficile-associated diarrhea (CDAD) are increasing in hospitals worldwide as a consequence of the widespread use of broad-spectrum antibiotics, and the organism may also be an important cause of community-acquired diarrhea (1,9,14,17). The drugs of choice for the treatment of CDAD are metronidazole (MTZ) and oral vancomycin (VAN).Our group recently reported on the isolation of MTZ-resistant (Mtz r ) and VAN-intermediate (Van i ) C. difficile strains (19). The roles of these nonsusceptible strains in clinical failures and relapses remain unknown, but therapeutic alternatives must be sought.Ramoplanin, a lipoglycodepsipeptide antibiotic obtained from the fermentation of an Actinoplanes strain (ATCC 33076), is being developed as an oral, nonabsorbable agent for the gastrointestinal decontamination of patients infected or colonized with 15,24). No cross-resistance between ramoplanin and VAN has been so far described, due to differences in their structures and mechanisms of action (6, 21).Our objective was to evaluate the in vitro activity of ramoplanin against C. difficile, with a special interest in those strains that have reduced susceptibilities to VAN MATERIALS AND METHODSThe activity of ramoplanin was tested against a total of 105 nonduplicate clinical isolates of toxigenic C. difficile obtained in our laboratory over a 9-year period (1994 to 2002). Eight of the strains had reduced susceptibility to VAN, and six strains were MTZ resistant. The MICs of VAN for the C. difficile Van i isolates were 4 g/ml (six strains) and 8 g/ml (two strains); and the MTZ MICs for the Mtz r isolates were 16 g/ml (three strains), 32 g/ml (two strains), and 64 g/ml (one strain).C. difficile isolates were presumptively identified by their colony morphology, yellow color, ground-glass texture, and characteristic horse dung smell and by Gram staining (16). Additional biochemical tests (Rapid ID 32A system; bio Mérieux, Marcy l'Etoile, France) were also used. All the strains with reduced susceptibilities to VAN and resist...

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Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Ramoplanin against Clostridium difficile , Including Strains with Reduced Susceptibility to Vancomycin or with Resistance to Metronidazole

Peláez

Alcalá

Alonso

et al. 2005

Antimicrob Agents Chemother

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“…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).…”

Section: Treatmentmentioning

confidence: 99%

Vancomycin-Resistant Enterococci

Çetinkaya

Falk

Mayhall

2000

Clinical Microbiology Reviews

642

344

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confidence: 99%

“…It has demonstrated activity against a wide spectrum of gram-positive organisms, including antibiotic-resistant strains of staphylococci and enterococci and less frequently encountered pathogens such as Corynebacterium jeikeium, Listeria monocytogenes, and Bacillus spp. (5,9,10,11,12,14,16); however, limited data are available on the drug's activity against anaerobic bacteria (3,14). Broad-spectrum antimicrobials with activity against anaerobes may disrupt the ecological balance of the intestinal flora and promote colonization with VRE and Clostridium difficile (6,7,8,15,19), while antimicrobials with minimal antianaerobe activity preserve the normal intestinal anaerobic flora responsible for colonization resistance (18).…”

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In Vitro Activities of Ramoplanin, Teicoplanin, Vancomycin, Linezolid, Bacitracin, and Four Other Antimicrobials against Intestinal Anaerobic Bacteria

Citron¹,

Merriam²,

Tyrrell³

et al. 2003

Antimicrob Agents Chemother

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By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at <2 g/ml against 287 of 300 (95.7%) gram-positive organisms, including 18 strains of Clostridium difficile for which MICs of ramoplanin were 0.25 to 0.5 g/ml; for 3 of these, linezolid MICs were 8 to 16 g/ml. Nineteen Clostridium innocuum strains for which the vancomycin MIC at which 90% of strains were inhibited was 16 g/ml were susceptible to ramoplanin at 0.06 to 0.25 g/ml and to teicoplanin at 0.125 to 1.0 g/ml. All strains of Eubacterium, Actinomyces, Propionibacterium, and Peptostreptococcus spp. were inhibited by <0.25 g of ramoplanin per ml and <1 g of vancomycin per ml. Ramoplanin was also active at <4 g/ml against 15 of 22 of the Prevotella and Porphyromonas strains tested, but ramoplanin MICs for all 31 strains of the Bacteroides fragilis group, the Fusobacterium mortiferum-Fusobacterium varium group, and Veillonella spp. were >256 g/ml. Ramoplanin displays excellent activity against C. difficile and other grampositive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.Ramoplanin, a glycolipodepsipeptide antibiotic that inhibits peptidoglycan synthesis, is currently being developed as an oral, nonabsorbable agent for the prevention of vancomycinresistant Enterococcus (VRE) infection in patients with VRE gastrointestinal tract colonization (17). It has demonstrated activity against a wide spectrum of gram-positive organisms, including antibiotic-resistant strains of staphylococci and enterococci and less frequently encountered pathogens such as Corynebacterium jeikeium, Listeria monocytogenes, and Bacillus spp. (5,9,10,11,12,14,16); however, limited data are available on the drug's activity against anaerobic bacteria (3,14). Broad-spectrum antimicrobials with activity against anaerobes may disrupt the ecological balance of the intestinal flora and promote colonization with VRE and Clostridium difficile (6,7,8,15,19), while antimicrobials with minimal antianaerobe activity preserve the normal intestinal anaerobic flora responsible for colonization resistance (18). Since ramoplanin is intended as treatment for intestinal colonization of VRE, we examined its potential effects on colonic flora by determining its in vitro activity against anaerobic organisms of intestinal origin, including both gram-positive and gram-negative species.Selected for this study were strains from our collection of anaerobic gram-positive bacilli and cocci that had been isolated from bowel flora or clinical intra-abdominal specimens.Smaller numbers of gram-negative anaerobes of intestinal origin were also included. The majority of the test strains were isolated during the past 3 years. The species and numbers of strains te...

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In vitro activities of ramoplanin and four glycopeptide antibiotics against clinical isolates of Clostridium difficile

Cited by 38 publications

References 23 publications

In Vitro Activity of Ramoplanin against Clostridium difficile , Including Strains with Reduced Susceptibility to Vancomycin or with Resistance to Metronidazole

In Vitro Activity of Ramoplanin against Clostridium difficile , Including Strains with Reduced Susceptibility to Vancomycin or with Resistance to Metronidazole

Vancomycin-Resistant Enterococci

In Vitro Activities of Ramoplanin, Teicoplanin, Vancomycin, Linezolid, Bacitracin, and Four Other Antimicrobials against Intestinal Anaerobic Bacteria

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