The looming threat of C-diff


The risk of a major gut-bug epidemic looms behind the search for a stronger antibiotic. Neil Dowling reports.


Australian researcher Tom Riley in a playful depiction of a very serious subject.

Murdoch and Edith Cowan University

The freshly rolled lawn you walk on, the potatoes you boil, the bacon under the eggs on a brunch plate and the handshake of a friend in hospital can transmit a bug so tenacious, so resistant to eradication and so adept at being invisible to detection that it will kill you.

It is so clever at outwitting attempts to destroy it because the anaerobic Clostridium difficile – dubbed C-diff – bacteria has existed for hundreds of millions of years. Only in the past 40 has it come onto the radar of medical researchers and only in the last 15 has it been the subject of increasingly intense research.

C-diff, now well known to hospitals around the world, is, in layman’s terms, a particularly nasty tummy bug. It survives because the patient has a gut that has poor bacterial flora, allowing it to, literally, flourish.

Infection can be facilitated by issues such as poor health and ingesting spores of the bacteria which establish in a gut compromised by doses of antibiotics that have killed off the good bacteria.

But it is clouded by myths. People presume that, as with a lot of infections found in hospital patients, C-diff is the result of hospitalisation. It is also seen as a disease that affects only the elderly and infirm.

But more recent research finds that C-diff infection has no preference for age, and is now regarded as a community-borne disease not necessarily sourced from a hospital. It has been found on root vegetables in suburban grocery stores, for instance, and in roll-out lawn that was fertilised by faeces from animal farms.

In 1978, US researcher John Bartlett was the first to find what was causing an outbreak of diarrhoea-related illnesses and, in many cases, deaths. What brought the bug to international infamy was a spectacular and alarming increase in reported cases in North America in the early 2000s.

Clostridium difficile was identified as one of the most virulent causes of colitis, the inflammation of the colon wall, and subsequent diarrhoea.

Cases spiked in 2002, rising from 40 to 160 patients per 100,000 in Canada. Most were elderly – in a single year, 860 people aged over 68 were hospitalised.

But the real problem hit in 2004 in Quebec when, dramatically and with unprecedented speed, 7004 cases of C-diff were diagnosed.

To put that in perspective, Quebec Province has a population of seven million, meaning that the bug infected one citizen in every 1000. There were not many options for treatment, and very, very few people even knew what it was. As many as 2000 died.

Australia’s leading researcher on C-diff, Thomas Riley of Murdoch and Edith Cowan University in Perth, Western Australia, describes the Quebec outbreak as “massive”.

“The Canadian government spent millions and millions of dollars trying to deal with it,” he says.

They were unsuccessful. It began to spread, and Australia, at the other end of the globe, wasn’t immune. In 2009, six cases were recorded.

“But it never established itself in Australia because it was in a different environment,” Riley says.

“Three hundred million years ago C-diff was everywhere. All the continents were joined, and the bacterium was the same across the entire land mass. Now we have different clades (or types) and we know that certain parts of the globe have certain clades of C-diff.

“We also have increased migration of people, and that has brought the different clades into new parts of the world. The clade from Africa, for example, has been recently identified in Europe and Australia because of migration.

“Asian strains have likely been in California since the gold rush of the late 1800s brought Chinese migrants. At one stage, the Chinese represented 10% of the Californian population.”

So the bug proliferated. In 2013, it was responsible for 29,000 deaths in the US alone. The annual reported cases in the US total 400,000.

Now the job is to find the antibiotic that will kill C-diff but not kill the beneficial bacteria in the human gut.

The search is heavily funded by private and public donations in the US. Globally, it is the subject of four international conferences each year.

C-diff cannot survive in a normal human gut,” Riley says.

“We now know it’s also a community-acquired infection and that patients are getting younger. There is very little cross-infection in Australia, and only 25% of cases have links to the patient visiting a hospital.

“We do know that it is coming from animals. In Australia, 60% of dairy calves tested had C-diff. In intensive pig farming, piglets at the age of seven days are full of it. Yet at age 21 days, they have none.”

Su-Chen Lim, who did her PhD with Riley on the presence of C-diff in root vegetables, says 50% of potatoes in Australian supermarkets were contaminated. Onions imported from California were likely a major source of the bacteria during a shortage some years ago.

“The rate in compost and mulch sold at gardening shops is 30% containing C-diff while in roll-out lawn the rate is double, at 60% of samples being found with the bacteria,” she says. “It comes from animal manure.”

The problem with food is that scrubbing root vegetables will just contaminate the kitchen environment with the bacteria.

“And conventional cooking temperatures won’t kill the C-diff spores because they are resistant,” she warns. “Curing of meat also doesn’t kill the bacteria.”

But there is an answer. In fact, two. One is a drug called Fidaxomicin – very expensive and definitely not government subsidized. The other, the one in which researchers including Riley hold great hope, is a new drug Ridinilazole.

Ridinilazole is now in Phase-3 clinical trials and is expected to become available in about two years.

Ironically, without this type of antibiotic to kill a bug that thrives because its competition has been killed by other antibiotics, Riley warns: “We have the potential for a nasty outbreak.”

  1. https://www.cdc.gov/cdiff/what-is.html
  2. https://academic.oup.com/cid/article/59/suppl_2/S66/544275
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805733
  4. http://www.cmaj.ca/content/173/9/1020
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304170/
  6. https://www.nps.org.au/australian-prescriber/articles/fidaxomicin-for-clostridium-difficile
  7. https://clinicaltrials.gov/ct2/show/NCT03595566
Latest Stories
MoreMore Articles