CHARACTERIZATION OF CLOSTRIDIUM DIFFICILE ISOLATED FROM DIARRHEAL PATIENTS IN A TERTIARY-CARE HOSPITAL, KARNATAKA, SOUTH INDIA
SOUTHEAST ASIAN JOURNAL OF TROPICAL MEDICINE AND PUBLIC HEALTH
Authors: Rituparna, Chakraborty; Mamatha, Ballal; Mukhyaprana, Prabhu M.; Manjunatha, Hande H.; Gururaja, Pazhani P.; Thandavarayan, Ramamurthy
Increase in Clostridium difficile infection in tertiary-care hospitals in Karnataka, South India with a paucity of data on antibiotic susceptibility and genetic characteristics of the pathogen from this region of the country necessitated this study. From April 2012 to December 2014, 480 hospitalized antibiotic-associated diarrhea cases with a history of antibiotic treatment in the previous three weeks were enrolled. Sixteen percent of the samples were positive for C. difficile toxins A and B by rapid enzyme immunoassay, anaerobic culture and multiplex PCR. In 40 representative strains, minimum inhibitory concentrations (MICs) determined by E-test revealed that 39 strains were resistant to imipenem and moxifloxacin (MIC > 32 mu g/ml), 38 to clindamycin (MIC > 256 mu g/ml) and 19 to tetracycline (MIC > 4 mu g/ml), while all 40 strains were susceptible to ampicillin (MIC < 2 mu g/ml), ampicillin sulbactam (MIC < 8 mu g/ml), metronidazole (MIC < 8 mu/ml) and vancomycin group (MIC <2 mu g/ml). Pulsed field gel-electrophoresis (PFGE) of 13 representative strains grouped them into three clusters: cluster A consisting of two strains having > 65% similarity, cluster B of 6 strains with 100% similarity (considered clonal) and 3 strains with > 85% similarity, and cluster C of 2 strains with 50% similarity. Clusters A and C contained unrelated strains having different antibiograms. Periodic monitoring of resistance profiles with epidemiological typing by PFGE should aid in interpretation of emerging drug resistant C. difficile clones.
Host-targeted niclosamide inhibits C. difficile virulence and prevents disease in mice without disrupting the gut microbiota
Authors: Tam, John; Hamza, Therwa; Ma, Bing; Chen, Kevin; Beilhartz, Greg L.; Ravel, Jacques; Feng, Hanping; Melnyk, Roman A.
Clostridium difficile is the leading cause of nosocomial diarrhea and colitis in the industrialized world. Disruption of the protective gut microbiota by antibiotics enables colonization by multidrug-resistant C. difficile, which secrete up to three different protein toxins that are responsible for the gastrointestinal sequelae. Oral agents that inhibit the damage induced by toxins, without altering the gut microbiota, are urgently needed to prevent primary disease and break the cycle of antibiotic-induced disease recurrence. Here, we show that the anthelmintic drug, niclosamide, inhibits the pathogenesis of all three toxins by targeting a host process required for entry into colonocytes by each toxin. In mice infected with an epidemic strain of C. difficile, expressing all three toxins, niclosamide reduced both primary disease and recurrence, without disrupting the diversity or composition of the gut microbiota. Given its excellent safety profile, niclosamide may address an important unmet need in preventing C. difficile primary and recurrent diseases.