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

Abstract

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...

Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

“…Exposure to these agents also brought about a decrease in the proportion of reads assigned to the Bacteroidetes. Metronidazole brought about a greater decrease in Bacteroidetes proportions than vancomycin, which is not surprising given the greater activity of the former against representatives of this phylum (29). Lacticin 3147 also impacted on the microorganisms within the Bacteroidetes.…”

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

“…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.…”

“…difficile susceptibility tests are not very often performed in microbiology laboratories because to date the first-line drugs, MTZ and VAN, have been considered universally active against the microorganism (4,5,9).…”

Four Cases of Bacteremia Caused by Oscillibacter ruminantium, a Newly Described Species

“…The apparent vancomycin susceptibility is unusual for Gram-negative rods but is also found in other anaerobic rods, such as Clostridium clostridioforme and Clostridium symbiosum, that persistently stain Gram negative (17).…”