Lab result explainedInflammationLast updated November 11, 2026

C. diff test: results explained, including PCR positive with toxin negative and testing after treatment

C. diff test (C. diff) · Stool test (GDH antigen, toxin A/B immunoassay and nucleic acid amplification test, usually in a two- or three-step algorithm) · reported in Qualitative: positive or negative for GDH antigen, toxin A/B and toxin B gene (PCR/NAAT); some PCR platforms also report the 027/NAP1 strain

A C. diff test looks for Clostridioides difficile, a spore-forming bacterium that overgrows in the colon after antibiotics disturb the normal gut bacteria and produces toxins that inflame the bowel. It is ordered when someone has three or more loose stools in 24 hours, usually with recent antibiotic use, a hospital or nursing home stay, or age over 65. C. difficile causes about half a million infections and more than 12,000 deaths a year in the US, and about 1 in 5 people who recover have a recurrence within 8 weeks.

There is no single perfect test, so labs combine two or three. The GDH antigen test detects an enzyme made by every C. difficile strain, toxin-producing or not; it is very sensitive but not specific. The toxin A/B immunoassay detects the toxins themselves, which is what actually causes disease; it is specific but misses 25 to 50 percent of true infections. A PCR or NAAT detects the gene for toxin B; it is highly sensitive but cannot tell whether the toxin is being produced, and it is positive in the 5 to 15 percent of hospital patients who simply carry the organism. A typical report therefore reads as a combination: GDH positive and toxin positive is infection; GDH negative is negative; GDH positive with toxin negative is resolved by PCR, and if that is positive the result is read with your symptoms.

Two rules about the test cause more confusion than anything else. First, it should only be run on unformed stool from someone with diarrhea who has not taken laxatives in the previous 48 hours; most labs reject formed stool, and infants under 12 months are not tested because up to half of them carry C. difficile harmlessly. Second, there is no test that confirms the infection has cleared. PCR and even toxin tests can stay positive for weeks after successful treatment, so repeating the test to confirm the infection has gone is not recommended, and a positive result in that window does not by itself mean treatment failed.

C. diff at a glance

What it is: a stool test for the bacterium Clostridioides difficile and its toxins, run on loose stool from someone with diarrhea, usually after antibiotics.
Three components: GDH antigen (sensitive screen for the organism), toxin A/B immunoassay (detects active toxin, specific but misses 25 to 50 percent), PCR/NAAT (detects the toxin gene, very sensitive, also detects carriers).
Positive infection: GDH positive plus toxin positive, or PCR positive with toxin positive. Negative: GDH negative, or PCR negative.
PCR positive but toxin negative: either colonization or infection with low toxin levels; about half of these people have outcomes like uninfected patients, so the result is read with symptoms, white count and alternatives.
How long: PCR and immunoassays run in 1 to 4 hours and most labs report the same day; toxigenic culture, rarely used, takes 2 to 4 days.
After treatment: do not retest unless diarrhea returns; tests stay positive for weeks in up to 60 percent of people who are better. Severe infection is flagged by a white count of 15,000 or more or creatinine above 1.5 mg/dL.

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What C. diff measures

C. difficile causes disease through two large toxins, toxin A (an enterotoxin) and toxin B (a cytotoxin about ten times more potent), which damage the colon lining and provoke the intense inflammation that produces watery diarrhea, cramps, fever and, in severe cases, the yellow plaques of pseudomembranous colitis. Some strains carry a third binary toxin, and the hypervirulent ribotype 027 strain produces more toxin and more severe disease. Strains that lack the toxin genes are harmless. The tests therefore try to answer two different questions: is the organism present, and is it making toxin?

Glutamate dehydrogenase (GDH) is a metabolic enzyme produced in large amounts by all C. difficile strains, so an immunoassay for it is a fast, cheap screen with sensitivity of 90 to 95 percent; a negative GDH effectively rules C. difficile out. Toxin A/B enzyme immunoassays detect toxin protein in stool with specificity above 95 percent but sensitivity of only 50 to 75 percent, because toxin degrades quickly at room temperature and can be below the detection limit early in illness. Nucleic acid amplification tests (PCR, loop-mediated amplification) detect the tcdB gene, with sensitivity above 95 percent and specificity around 95 percent, but they detect the gene whether or not it is being expressed. The reference methods, toxigenic culture and the cell cytotoxicity neutralization assay, are too slow for routine use.

The 2017 IDSA/SHEA guideline and the 2021 ACG guideline recommend a multistep algorithm: GDH plus toxin, with PCR to arbitrate discordant results, or PCR followed by a toxin test on positives. Laboratories that only accept stool meeting strict criteria (unformed, from a patient with three or more stools in 24 hours and no laxatives in 48 hours) may use PCR alone. The sample should be liquid or soft enough to take the shape of its container, reach the lab within 2 hours or be refrigerated, and should not be collected on a swab. Only one sample is tested; repeating within 7 days after a negative result changes the answer in fewer than 5 percent of cases.

Normal range for C. diff

Reference ranges vary between labs and by age, sex and pregnancy. Use the range printed on your own report.

Group	Typical range (Qualitative: positive or negative for GDH antigen, toxin A/B and toxin B gene (PCR/NAAT); some PCR platforms also report the 027/NAP1 strain)	Notes
GDH negative, toxin negative	Negative	C. difficile is not present in meaningful amounts. Look for another cause of diarrhea. Do not repeat within 7 days unless symptoms change markedly.
GDH positive, toxin positive	Positive: C. difficile infection	Toxin-producing organism and active toxin in a person with diarrhea. Treatment is started; isolation precautions apply in hospital.
GDH positive, toxin negative, PCR negative	Negative (non-toxigenic strain or false GDH)	The organism present cannot make toxin, or the GDH was a false positive. Not an infection; no treatment.
GDH positive, toxin negative, PCR positive	Indeterminate: toxigenic strain detected, no free toxin found	Either colonization with another cause of diarrhea, or true infection with toxin below the assay's limit. The clinician weighs symptoms, white count, antibiotic history and alternatives; many are not treated, some are.
PCR positive (PCR-only laboratory)	Toxigenic C. difficile detected	Read as infection if the stool met strict submission criteria. Without those criteria, roughly half of PCR-only positives are colonization rather than disease.
Toxin positive alone	Positive	Free toxin is the most specific single finding and indicates active infection when diarrhea is present.
Formed stool, infant under 12 months, or laxatives in the last 48 hours	Test rejected or not recommended	Formed stool means no C. difficile diarrhea by definition. Up to half of healthy infants carry toxigenic strains without illness, so a positive is uninterpretable. Laxatives create diarrhea that mimics infection.
Severity markers reported alongside	WBC 15,000/µL or more, or creatinine above 1.5 mg/dL = severe; low blood pressure, ileus or megacolon = fulminant	These blood findings, not the stool result, decide how aggressively the infection is treated.

Positive C. diff test

A positive test with diarrhea means C. difficile infection, and treatment is started the same day, usually with oral vancomycin or fidaxomicin rather than the metronidazole that was first-line until 2018. The antibiotic that triggered the infection is stopped if at all possible, acid-suppressing drugs are reviewed, and anti-motility medicines such as loperamide are avoided because slowing the bowel can tip a colitis into toxic megacolon. Most people improve within 2 to 3 days and diarrhea resolves in 7 to 10 days. In hospital you will be placed in contact isolation, and staff will wash with soap and water because alcohol gel does not kill spores.

How the result was reached matters for how confident the diagnosis is. Toxin positive is the most specific finding: free toxin in stool means the organism is actively causing disease. A result that is PCR positive but toxin negative is the gray zone. In a large study of hospital patients, those who were PCR positive but toxin negative had complication and death rates similar to patients who tested negative altogether, and almost all of them recovered without specific treatment, which suggests that many are carriers with diarrhea from another cause. Others, particularly those with a high white count, fever, cramping and no alternative explanation, do have early or low-toxin infection and are treated. Your clinician decides which group you fall into; the stool test cannot.

A positive result also carries a warning about the future. Around 20 to 25 percent of people have a recurrence within 8 weeks of finishing treatment, and the risk rises to 40 to 60 percent after a second episode. Recurrence is more likely with age over 65, further courses of antibiotics, continued proton pump inhibitor use, kidney disease and a weakened immune system. For repeated recurrences, fecal microbiota transplantation or the newer FDA-approved microbiome products resolve the problem in 80 to 90 percent of cases, which is why recurrent infection is referred to a gastroenterologist or infectious disease specialist.

Common causes

Recent antibiotics
The dominant trigger. Clindamycin, fluoroquinolones, third- and fourth-generation cephalosporins and carbapenems carry the highest risk, but almost any antibiotic can do it. Risk is highest in the month after a course, when it is 7 to 10 times normal, and stays about 3 times normal for 3 months.
Hospital or nursing home exposure
Spores survive on surfaces for months and resist alcohol and most cleaners. Carriage rises from 2 to 5 percent in the community to 10 to 25 percent after a hospital stay, and most healthcare-associated infections start with a colonized patient or contaminated room.
Age over 65
Older adults have more antibiotic exposure, more healthcare contact, weaker antibody responses to toxin and a less resilient microbiome. More than 80 percent of C. difficile deaths occur in people over 65.
Proton pump inhibitors and H2 blockers
Meta-analyses link proton pump inhibitor use to a 1.7- to 2-fold higher risk of initial infection and of recurrence, probably by allowing more vegetative organisms to survive the stomach. The FDA added a warning to PPI labels in 2012.
Inflammatory bowel disease
People with ulcerative colitis or Crohn's disease are infected 2 to 5 times more often, often without prior antibiotics, and infection is easily mistaken for a flare. Guidelines recommend testing for C. difficile at every flare.
Immunosuppression, cancer treatment and transplantation
Chemotherapy, solid organ and stem cell transplantation, and advanced HIV increase the risk of infection, severity and recurrence; some chemotherapy drugs disturb gut bacteria in the same way antibiotics do.
Previous C. difficile infection
The strongest predictor of another episode. About 1 in 5 first episodes recur, 2 in 5 second episodes, and more than half of those with two or more recurrences.
Community-acquired infection without obvious risk factors
About a third of US cases now begin in the community, and roughly a third of those have had no recent antibiotics or hospital contact. Younger people, women, and those with recent outpatient healthcare, household contact with a case, or PPI use make up most of this group.
Colonization rather than infection
A positive PCR in someone whose diarrhea has another cause (laxatives, tube feeds, a flare of IBD, another infection) reflects carriage. This is the main reason PCR-only testing is paired with strict stool criteria or a toxin test.

Symptoms that can go with it

Watery diarrhea three or more times a day, often with a characteristic strong odor, starting during or up to 2 to 3 months after a course of antibiotics
Lower abdominal cramping, tenderness and bloating
Fever, usually low-grade but can be high in severe colitis
Nausea and loss of appetite
Mucus or occasionally blood in the stool
Dehydration: dizziness, dry mouth, reduced urine, rising creatinine
A high white blood cell count, sometimes above 15,000 or even 30,000/µL, which can appear before the diarrhea
Warning signs of fulminant colitis: severe abdominal pain and distension with diarrhea that suddenly stops (ileus), low blood pressure, confusion or a very high white count

Read it alongside

White blood cell count — 15,000/µL or above defines severe infection; a count that is rising while diarrhea paradoxically slows suggests toxic megacolon.
Creatinine — above 1.5 mg/dL marks severe disease and reflects dehydration and kidney injury.
Albumin — below 3 g/dL predicts a worse course and is one of the markers used in severity scores.
Lactic acid — raised lactate with low blood pressure signals fulminant colitis needing surgical review.
Potassium, sodium and bicarbonate — depleted by profuse diarrhea and replaced as part of treatment.
Stool culture or GI PCR panel — other infections cause identical symptoms; many GI panels include a C. difficile target, which is read with the same caveats as a standalone PCR.
Fecal calprotectin or lactoferrin — markedly raised in C. difficile colitis; helps distinguish colonization from infection and infection from an IBD flare when read alongside the toxin result.
Abdominal X-ray or CT — ordered when the abdomen is distended or tender to look for colonic dilatation above 6 cm (megacolon) or wall thickening.

What usually happens next

If positive, treatment usually starts the same day; ask which antibiotics you were taking can be stopped, whether your acid-suppressing medicine is still needed, and avoid loperamide and other anti-diarrheals.
If the result is PCR positive but toxin negative, expect a conversation rather than an automatic prescription: your clinician will weigh your symptoms, white count, antibiotic exposure and other possible causes of diarrhea, and may treat, observe or test for something else.
If negative with ongoing diarrhea, do not ask for a repeat within 7 days; the next tests are usually a stool culture or PCR panel, fecal calprotectin, a medication and laxative review, and consideration of an inflammatory bowel disease flare.
Do not retest at the end of treatment to prove the infection is gone. If diarrhea comes back after you have improved, usually within 8 weeks, that is when a repeat test is appropriate, and a second episode is treated differently from the first.
After a first episode, ask how to lower the recurrence risk: avoiding unnecessary antibiotics for at least 3 months, reviewing PPI use, and in high-risk people a discussion of bezlotoxumab or, after multiple recurrences, fecal microbiota-based therapy.
At home, wash hands with soap and water after the bathroom and before eating, clean the bathroom with a 1:10 bleach solution, and do not share towels until diarrhea has stopped for 48 hours.

Diet, lifestyle and natural levers with evidence

What can move C. diff once the cause is known. Nothing here replaces finding the cause.

Avoid unnecessary antibiotics

Strong evidence

Nothing natural clears an established C. difficile infection, which needs a specific antibiotic or microbiome therapy. The most powerful preventive lever is not taking antibiotics you do not need. Hospital stewardship programs that cut use of fluoroquinolones and cephalosporins have been followed by 30 to 60 percent falls in C. difficile rates, and after an episode each further antibiotic course roughly doubles the chance of recurrence. Ask whether a prescription is truly necessary, whether a narrower drug or a shorter course would do, and tell every prescriber about your history for at least a year.

Review proton pump inhibitor use

Moderate evidence

Meta-analyses of observational studies associate PPIs with a 1.7- to 2-fold higher risk of initial infection and about a 1.5-fold higher risk of recurrence, and the FDA placed a C. difficile warning on PPI labels in 2012. Many people take PPIs long after the original reason has passed. Stopping is not always appropriate (Barrett's esophagus, erosive esophagitis and people on NSAIDs with bleeding risk need them), so this is a decision to make with your clinician, but a trial of stepping down to an H2 blocker or stopping is reasonable for most others.

Probiotics taken during an antibiotic course to prevent a first infection

Moderate evidence

A 2017 Cochrane review of 31 trials in 8,672 people found that probiotics started within 2 days of an antibiotic course reduced C. difficile diarrhea from 4.0 percent to 1.5 percent (a 60 percent relative reduction), with the benefit confined to people whose baseline risk was above 5 percent, such as hospital inpatients. The largest single trial, PLACIDE, in nearly 3,000 older inpatients, found no benefit, and the IDSA guideline considers the evidence insufficient to recommend routine use. Saccharomyces boulardii and Lactobacillus rhamnosus GG are the best-studied strains.

Avoid in people with central venous lines, severe immunosuppression, critical illness or a damaged gut barrier, in whom bloodstream infections with the probiotic organism have been reported. Probiotics are not a treatment for an active infection.

Saccharomyces boulardii as an add-on to reduce recurrence

Preliminary evidence

In a 1994 randomized trial of 124 people treated with standard antibiotics for C. difficile, adding Saccharomyces boulardii 500 mg twice daily for 4 weeks reduced recurrence from 65 percent to 35 percent in those who had already had a prior episode, with no benefit in first episodes. A follow-up trial found benefit only when combined with high-dose vancomycin. The evidence is old, limited to one research group and not endorsed by current guidelines, but the yeast is low-risk in otherwise healthy people.

Same restrictions as above; discuss with your clinician rather than adding it yourself to a treatment course.

Soap-and-water hand washing and bleach cleaning

Strong evidence

C. difficile spores are not killed by alcohol-based hand sanitizer or by most household disinfectants, but they are physically removed by washing with soap and running water and are killed by sodium hypochlorite (household bleach diluted 1 part to 9 parts water, left wet for at least a minute) and by EPA-registered sporicidal products. In hospitals, bleach-based room cleaning has reduced transmission by about 50 percent in before-and-after studies. At home, focus on the toilet, flush handle, taps and door handles, and launder soiled items on a hot cycle.

When to see a clinician promptly

Severe abdominal pain or a swollen, rigid abdomen, especially if diarrhea suddenly stops while you still feel unwell: possible toxic megacolon or perforation, which is a surgical emergency.
Fever above 101.5 °F (38.6 °C), a fast heart rate, dizziness on standing or confusion with diarrhea: signs of severe or fulminant infection and dehydration that need same-day assessment, by emergency services if blood pressure is low.
Six or more watery stools in 24 hours, blood in the stool, or inability to keep fluids down.
Diarrhea that returns within 8 weeks of finishing treatment for C. difficile; recurrence is treated differently and promptly.
Any diarrhea after antibiotics in someone over 65, immunosuppressed, with inflammatory bowel disease, kidney disease or a previous C. difficile infection, in whom the illness is more likely to be severe.
New diarrhea in a household member of someone recently treated for C. difficile, since spread within homes does occur.

Frequently asked questions

What does C. diff PCR positive, toxin negative mean?

It means the stool contains C. difficile carrying the toxin gene, but the lab could not detect toxin protein. That is either colonization (you carry the organism and something else is causing the diarrhea) or genuine infection with toxin below the test's detection limit. In a large study, people in this category had complication rates like those who tested negative, and most recovered without treatment, so many clinicians observe rather than treat unless there is fever, a high white count, cramping and no other explanation. It is a judgment call, not a lab call.

How long does a C. diff test take?

The GDH and toxin immunoassays run in about an hour and PCR in 1 to 4 hours, so most hospital labs report a result within a few hours and outpatient labs the same or next day. If the lab runs an algorithm, a discordant GDH/toxin result adds the PCR step and can push the final report to the next day. Toxigenic culture, used mainly for outbreak typing, takes 2 to 4 days.

Should I be retested after C. diff treatment to make sure it is gone?

No. Guidelines recommend against a test to confirm clearance because PCR, GDH and even toxin tests stay positive for weeks after successful treatment in up to 60 percent of people, and a positive result in someone who is better does not need treatment. The only reason to retest is if watery diarrhea returns, usually within 8 weeks, which is how recurrence is diagnosed.

Can I have C. diff with a negative test?

Rarely. A negative GDH or negative PCR rules out C. difficile with better than 95 percent confidence, which is why labs discourage repeat testing within 7 days (fewer than 5 percent become positive). False negatives can happen if the sample sat at room temperature for hours before testing, if a toxin-only test was used (which misses 25 to 50 percent), or very early in illness. If diarrhea with fever and a high white count persists after antibiotics and nothing else is found, a clinician may repeat the test or, rarely, look directly at the colon.

Why will the lab not test my formed stool?

Because C. difficile infection causes diarrhea by definition, so a formed stool means either no infection or an infection that has already resolved. Testing formed stool mainly finds carriers (5 to 15 percent of hospital patients), who would then be treated unnecessarily. The accepted sample is stool loose enough to take the shape of its container, from someone with three or more such stools in 24 hours who has not taken laxatives in the last 48 hours. The exception is suspected ileus, where the bowel has stopped and a rectal swab may be accepted.

Is C. diff contagious to my family?

It can be, although household spread is much less common than hospital spread. Spores pass in stool and survive on bathroom surfaces for months, and family members who are older, on antibiotics or on acid suppressants are most at risk. Washing hands with soap and water (sanitizer does not kill spores), cleaning the toilet and taps with diluted bleach, using a separate towel and, if possible, a separate bathroom until diarrhea has stopped for 48 hours are the practical measures. Healthy household members do not need testing unless they develop diarrhea.

What is the difference between C. diff colonization and infection?

Colonization means C. difficile lives in your colon without causing illness; it affects 2 to 5 percent of healthy adults, 10 to 25 percent of hospital or nursing home residents and up to half of infants, and it needs no treatment. Infection means the organism is producing toxin and causing diarrhea and colitis. A toxin-positive test with diarrhea is infection; a PCR-positive test without diarrhea, or with diarrhea clearly due to something else, is colonization. Treating colonization does not help and may increase the chance of later infection by further disturbing the gut bacteria.

What counts as severe C. diff?

The IDSA/SHEA guidelines call an infection severe when the white blood cell count is 15,000/µL or higher or the serum creatinine is above 1.5 mg/dL, and fulminant when there is low blood pressure or shock, ileus (the bowel stops moving and diarrhea paradoxically ceases) or megacolon (colon dilated beyond 6 cm on imaging). Severe and fulminant disease is treated in hospital with higher-dose or combined antibiotics and early surgical review, and it carries a mortality of 5 to 10 percent in severe and over 30 percent in fulminant cases.

References

McDonald LC, Gerding DN, Johnson S, et al.. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clinical Infectious Diseases (2018)
Johnson S, Lavergne V, Skinner AM, et al.. Clinical practice guideline by the IDSA and SHEA: 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clinical Infectious Diseases (2021)
Kelly CR, Fischer M, Allegretti JR, et al.. ACG Clinical Guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. American Journal of Gastroenterology (2021)
Polage CR, Gyorke CE, Kennedy MA, et al.. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Internal Medicine (2015)
Crobach MJT, Planche T, Eckert C, et al.. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clinical Microbiology and Infection (2016)
Guh AY, Mu Y, Winston LG, et al.. Trends in U.S. burden of Clostridioides difficile infection and outcomes. New England Journal of Medicine (2020)
Goldenberg JZ, Yap C, Lytvyn L, et al.. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database of Systematic Reviews (2017)
Allen SJ, Wareham K, Wang D, et al.. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet (2013)
McFarland LV, Surawicz CM, Greenberg RN, et al.. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA (1994)
Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. American Journal of Gastroenterology (2012)
Clostridioides difficile infection: information for patients. Centers for Disease Control and Prevention (2024)
C. difficile infection. Mayo Clinic (2023)View source
Clostridioides (formerly Clostridium) difficile-induced diarrhea. Merck Manual Professional Version (2024)

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This page is educational and is not medical advice or a diagnosis. Lab results have to be interpreted together with your history, symptoms and other results by a clinician who knows you. Do not start or stop a supplement to change a lab value before the cause is known.