In vitro activity of ramoplanin against Clostridium difficile, including strains with reduced susceptibility to vancomycin or with resistance to metronidazole.
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 microg/ml (MICs at which 50 and 90% of isolates were inhibited, 0.25 microg/ml; geometric mean MIC, 0.22 microg/ml). All isolates, independently of their levels of susceptibility to vancomycin or metronidazole, were considered susceptible to ramoplanin (MICs, < or =0.5 microg/ml).
Peláez
T
T
Deparment of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain. terepelaez@teleline.es
Alcalá
L
L
Alonso
R
R
Martín-López
A
A
García-Arias
V
V
Marín
M
M
Bouza
E
E
D016360:Clostridioides difficile / Q000187:drug effects*; D047630:Depsipeptides / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014640:Vancomycin / Q000494:pharmacology*
D047630:Depsipeptides; C041438:ramoplanin; D008795:Metronidazole; D014640:Vancomycin
Antimicrob Agents Chemother. 2002 Jun;46(6):1647-50
12019070
N Engl J Med. 2002 Jan 31;346(5):334-9
11821511
J Antimicrob Chemother. 2003 Jun;51 Suppl 3:iii31-5
12801940
Antimicrob Agents Chemother. 2003 Jul;47(7):2334-8
12821492
Lancet. 1977 Nov 26;2(8048):1103-6
73011
Arch Intern Med. 2001 Feb 26;161(4):525-33
11252111
J Hosp Infect. 2001 Jul;48(3):233-7
11439012
Clin Infect Dis. 2001 Nov 1;33(9):1476-82
11588692
J Antimicrob Chemother. 2001 Nov;48(5):741-2
11679570
Scand J Infect Dis Suppl. 1980;(Suppl 22):16-29
7010532
Ann Intern Med. 1989 Feb 15;110(4):255-7
2643913
Diagn Microbiol Infect Dis. 1989 May-Jun;12(3):279-82
2507218
Antimicrob Agents Chemother. 1990 Mar;34(3):413-9
2334153
J Clin Microbiol. 1991 Jan;29(1):33-7
1993763
Antimicrob Agents Chemother. 1991 Jan;35(1):195-7
1826593
Cytobios. 1991;65(262-263):149-53
1828756
Rev Infect Dis. 1991 Nov-Dec;13(6):1053-60
1775837
N Engl J Med. 1994 Jan 27;330(4):257-62
8043060
J Clin Microbiol. 1994 Jul;32(7):1629-33
7929748
Diagn Microbiol Infect Dis. 1999 May;34(1):1-6
10342100
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7384-9
12032292