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Clostridioides difficile (C.diff)

A major health threat affecting people of all ages, C. diff is leading cause of healthcare associated infections. In the US each year, C. diff causes ½ million illnesses and worldwide incidents are on the rise. 15,000 deaths in the US were attributable to C. diff infections. Strains increasingly resistant to first line antibiotics are becoming much more prevalent, some spreading regionally and some across all European countries.

The Pathogen

C. diff is a Gram-positive, spore-forming bacterium. It is an opportunistic pathogen, infecting the colon of patients following antibiotic treatment. C. difficile bacteria are found throughout the environment — in soil, air, water, human and animal feces, and food products, such as processed meats. A small number of healthy people naturally carry the bacteria in their large intestines and don't have ill effects from the infection. C. difficile produces two toxins, TcdA and TcdB, which damage intestinal cells and cause inflammation in the gut. The toxins destroy cells, produce patches (plaques) of inflammatory cells, and decaying cellular debris inside the colon, and cause watery diarrhea. An aggressive strain of C. difficile has emerged that produces far more toxins than other strains do. The new strain may be more resistant to certain medications and has shown up in people who haven't been in the hospital or taken antibiotics. This strain of C. difficile has caused several outbreaks of illness since 2000.

C. Difficile Infection (CDI)

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Most cases of CDI occur when you’ve been taking antibiotics, with people taking antibiotics 7-10 times more likely to get a CDI while on the drugs or in the month following. Other risk factors include being over 65 years of age, recently hospitalized or extended hospital/nursing home stay, a weakened immune system, or a previous CDI (20% of people will get a CDI again) or known exposure to C. diff. The spread of C.diff is through the oral-fecal route. Infected patients shed C. diff in their feces, and C. diff spores can survive for extended time on surfaces. CDI is spread when contaminated surfaces are touched and spores are ingested. Symptoms develop within a few days after taking antibiotics and include diarrhea or frequent bowel movements for several days, fever, stomach pain, loss of appetite, and nausea. Potential complications are dehydration, kidney failure, toxic megacolon (pictured on the right), a hole in the large intestine, and death. For those with repeat infections, fecal microbiota transplants have shown promising results.

C. Diff Antibiotic Resistance 

All antibiotic classes may promote CDI by disrupting the current microbes residing in the intestine, allowing C. diff to grow, colonize and infect. This means that resistance to multiple antibiotics is a selective advantage for C.diff strains, because it would enhance their survival and spread. This is seen in the majority of epidemic and emergent strains (~60% of analyzed strains), which show resistance to multiple antibiotics. The majority of resistance in C.diff clinical isolates are to cephalosporins (stop bacterial cell wall), fluoroquinolones (stops bacterial DNA replication), and erythromycin and clindamycin (stops bacterial protein synthesis). C. diff has multiple methods to become resistant to antibiotics, include resistance genes, forming a biofilm, and changing the target of the antibiotic.