Cadazolid: A new hope in the treatment of Clostridium difficile infection

Abstract

Clostridium difficile infection (CDI) is a potential life-threatening consequence of antibiotic therapy. Although the risk increases with duration of treatment, it can also occur after a short treatment course. In addition to broad-spectrum antibiotics, anti-neoplastic agents, proton pump inhibitors, H(2) blockers, and several other drugs have been reported to induce intestinal dysbiosis, which is central to the pathogenesis of CDI. There is an increase in incidence and mortality attributed to CDI globally. Moreover, the epidemiology of C. difficile-associated diseases has changed significantly with an increasing occurrence of community-acquired CDI. Metronidazole and oral vancomycin are the first-line antibiotics used to treat CDI. However, metronidazole has limited effectiveness in severe cases and vancomycin use is associated with increasing risk of vancomycin resistance among Enterococcus spp. Cadazolid, a novel oxazolidinone antibiotic, has recently shown potent antimicrobial activity against C. difficile and has a lower propensity to induce resistance. The implications of its use in treating CDI have been reviewed based on current evidence.

Update on Antimicrobial Resistance in Clostridium difficile: Resistance Mechanisms and Antimicrobial Susceptibility Testing

“…The transposons are also involved in the resistance to chloramphenicol in C. difficile. Two mobile transposons, Tn4453a and Tn4453b, are able to transfer the catP gene, which encodes a chloramphenicol acetyltransferase enzyme that is responsible for the chloramphenicol resistance (25,41).…”

Clostridium difficile infection: a review of current and emerging therapies

“…CRS3123 is a favorable therapeutic agent that selectively inhibits the growth, spore and toxin production of C. difficile . The use of oral CRS3123 in hamsters resulted in a long lasting efficacy with essentially no recurrence, in significant contrast to existing CDI therapy with vancomycin [ 79 ]. CRS3123 has not demonstrated any cross-resistance to existing antibiotics and remains active against all tested C. difficile strains, more importantly the epidemic fluoroquinolone-resistant NAP1/BI/027 strain.…”

“…Cadazolid, an oxazolidinone antibiotic, has demonstrated its potency in vitro against C. difficile , in addition to the epidemic BI/NAP1/027 strain [ 79 ]. A recent phase 2 multicenter, randomized, double-blinded study (NCT01222702; EUDRA-CT 2010-020941-29) assessed the efficacy and safety of oral cadazolid in treatment of CDI.…”

Antimicrobial Peptides Targeting Gram-Positive Bacteria

“…The same is true for gut residing Enterococcus and Clostridia species. The former are associated with urinal infection in patients with catheter or catheter-related bloodstream infections and the latter is causing severe diarrhea by prolonged treatment with antibiotics or proton pump inhibitors [ 3 , 4 ]. In fact, a study involving 19 US hospitals during 2007 and 2010 revealed that the percentage of isolates of E. faecium being resistant to vancomycin was highest (87.1%) followed by S. aureus resistance to oxacillin–methicillin (56.8%) [ 5 ].…”