In vitro activity of linezolid against Clostridium difficile

Sir, The increasing rates of infections due to multiresistant Gram-positive bacteria have intensified the search for treatment alternatives. Streptogramin combinations, ketolides, new glycopeptides and the oxazolidinones were developed to overcome problems with multidrug-resistant Gram-positive bacteria. Linezolid is the first compound of a novel class of synthetic antimicrobial agents, the oxazolidinones. The compound reached the market in the USA in 2000 and in Europe in 2001. The major binding sites of oxazolidinones are the large (50S) ribosomal units. The effect on a variety of clinically important human pathogens is predominantly bacterio-static. 1,2 Linezolid has inhibitory activity against a broad range of Gram-positive aerobic cocci, including methicillin-resistant Staphylococcus aureus, glycopeptide-resistant enterococci (GRE) and penicillin-resistant Streptococcus pneumoniae. Linezolid is much less active against Gram-negative aerobes. In vitro activity of linezolid against common anaerobic bacteria shows MICs in the range 1–8 mg/L, with some studies reporting bactericidal effect against Bacteroides fragilis and Clostridium perfringens. 1,3 Resistance against linezolid can be induced in vitro by spiral plating against S. aureus and vancomycin-resistant Enterococcus faecalis. Genomic characterization of these strains revealed specific mutations in the peptidyl transferase centre of the 23S rRNA region (G2447→U for S. aureus and G2576→U for E. faecalis). 3,4 The activity of linezolid is unaffected by mutations or mechanisms responsible for resistance against macrolide– lincosamide–streptogramin B (MLS B) antibiotics, amino-glycosides, chloramphenicol or tetracycline. Resistance to linezolid in clinical isolates was rarely observed and occurred only during prolonged therapy (i.e. of an undrained focus of infection). 1 Clostridium difficile is the major cause of nosocomial diarrhoea and antimicrobial-associated colitis. Patients often (15–20%) suffer from relapsing infections after treatment with vancomycin or metronidazole. In addition, the search for alternative treatments is driven by reports of decreased susceptibility of C. difficile against vancomycin and metro-nidazole and the known potency for the selection of GRE due to a prolonged therapy with vancomycin. 5–7 Several studies have investigated the activity of linezolid against C. difficile. 5,8,9 The MICs of the tested isolates were less than or equal to the suggested susceptibility breakpoint for linezolid of ≤4 mg/L. 3 One study reported an impact of linezolid on the aerobic and anaerobic intestinal microflora with reduced numbers of enterococci, bifidobacteria, lacto-bacilli, Clostridia and Bacteroides spp. 10 However, further studies are needed to prove the activity of linezolid against C. difficile and to evaluate clinical efficacy. It has been shown that antimicrobial resistance in C. difficile is growing and is …