In February 2012, the FDA warned that proton pump inhibitors (PPIs) such as Nexium, Prevacid, and Prilosec may increase the risk of Clostridium difficile (C. diff) associated diarrhea. In ecological terms, then, we could view PPIs as an environmental insult on the microecology of the stomach.

C. diff infection is one of the more familiar bacterial GI illnesses. Its signature symptoms are watery diarrhea, abdominal tenderness, nausea, loss of appetite, and fever. In worst case scenarios, patients manifest a potentially fatal inflammatory state called pseudomembranous colitis. In wellness circles, C. diff problems occur less often than among sicker populations. People generally get C. diff colonization only after prolonged antibiotic therapy. Health-conscious individuals try to avoid unneeded antibiotic use. Adding insult to injury, the treatment for severe C. diff infection involves other powerful antibiotics such as fearsome vancomycin; so for some patients, this is a no-win scenario!

According to the Mayo Clinic, C. diff incidence is growing in severity, frequency, and recalcitrance. Broad-spectrum antibiotics such as cephalosporins, fluoroquinolones, penicillins, and clindamycin kill off competing bacteria so that C. diff can thrive. Now, the FDA is admitting that PPIs are contributing to the C. diff rise as well. And we know that some of the increase in C. diff outbreaks has to do with a newer, tougher strain—NAP1—that carries aggressiveness and antibiotic resistance in its toolkit. In response to changes in its environment, this strain is synthesizing more potent and abundant toxins A and B than were ever seen in prior C. diff infections (those occurring before 2000).

These toxins A and B seem responsible for the diarrhea and inflammation of C. diff infections. Other toxins are produced by this bug, but the most studied are A and B. While toxin A has been prevalent, ELISA testing of both toxins is recommended, as both are potently cytotoxic. There are now strains that produce only toxin B (Lyras D et al. Nature, 2009, p. 1176).

Unlike what is common with EIA stool tests for C. diff, DNA-based determinations of stool C. diff will yield no false positives.  It is also common for small amounts of the bacteria to be present in asymptomatic individuals. So what do you do if your patient comes back positive on the GIfx stool test?

If diarrhea is present in a patient who:

• has recently taken antibiotics

• is 65 or older

• has been hospitalized

• is immuno-compromised AND/OR

• lives in a long term care facility

...a positive GIfx C. diff may warrant further testing for the toxins. Short of that, many clinicians put their mildly symptomatic patients on high-dose probiotics—emphasizing a friendly yeast species called Saccharomyces boulardii (S. boulardii), in addition to various Lactobacillus and Bifidobacter strains. This intervention is a safe and effective means of remediating the host microenvironment.

In a related study, (Erdeve O, J Trop Pediatr, 2004, p. 234) Erdeve demonstrated the efficacy of Saccharomyces boulardii as adjunctive therapy in antibiotic-associated diarrhea: in 466 children, 11.4% of those on azithromycin alone had diarrhea, but only 5.5% had diarrhea if S. boulardii was added to the protocol. Likewise, 25.6% of those children on sulbactam-ampicillin had diarrhea, but only 5.7% if S. boulardii was added during the antibiotic treatment.

So the lesson here is the safety and effectiveness of treating a “bad bug” with good ones! Reflecting natural processes that occur in any ecosystem, diverse and robust gut microecology is vital to keeping overgrowth of C. diff (or any single bacterial species) from happening in the first place!

The Bigger Picture – It’s the Microbiome, Silly!

On GIfx testing for anaerobic bacteria, there are several major beneficial players that are detected/quantified per gram of stool. One dominant genus is—you guessed it—Clostridium! In light of the havoc that one of its species (C. diff) can wreak, it’s hard for some to believe that its own genus could be beneficial, but it is. (It helps to think of many “good guys” keeping the few “bad guys” at bay, so to speak.) The Clostridium genus, like its cohort genera of Bacteroides, Prevotella, Bifidobacteria, Collinsella, and others, includes many scores of species providing vital services. These include synthesizing vitamins K, B12, and biotin, preventing colonization by potential pathogens, and producing many factors that assist in GI and systemic health. Perhaps most importantly, the normal anaerobic flora “teaches” the immune system how to develop and perform properly! So encouraging their health is priority one. Collectively (this amalgam of bacterial species in our GI tract is continually being explored), the anaerobic flora will then help prevent harmful overgrowth by a single species, such as Clostridium difficile.

~Terry Arden Pollock, MS