What is C. Diff Recurrence?

C. diff (Clostridioides difficile) is a bacterium that causes diarrhea and inflammation of the colon (colitis). C. diff infections are most common in individuals over the age of 65 who have been recently hospitalized or prescribed antibiotics. Recurrence is the greatest barrier to the treatment of C. diff infections—individuals who recover from C. diff infection once are much more likely to be infected again. Recurrences are most likely a week or two after successful treatment, but patients can experience recurrence two months or more after completing treatment.

Why do C. Diff Infections Recur?

C. diff infection recurrence is most likely in individuals who are...

  • exposed to hospitals and long term care facilities, especially repeatedly or for prolonged periods of time. These environments are often sites of bacteria proliferation.
  • over the age of 65. The exact reason for more cases of C. diff in individuals over the age of 65 is unknown, but it is possible a weakened immune system may inhibit the body’s ability to fight a C. diff infection.
  • starting, finishing, or currently taking a course of antibiotics not related to  C. diff treatment. Antibiotics can disturb the healthy balance in the gut, especially acid composition in the colon which promotes C. diff growth.
  • completing a course of antibiotics related to C. diff treatment. For those who have had C. diff in the past, antibiotics, like vancomycin, are prescribed to target toxin-producing C. diff bacteria.  However, there may be other dormant forms of the bacteria that remain in the gut. Once a course of antibiotics is complete, the dormant C. diff spores may become active, causing recurrence. For example, C. diff recurrence after a course of vancomycin is common. Antibiotics, like investigational drug ridinilazole, meant to target C. diff bacteria specifically may potentially reduce chance of repeat infection—destroying C. diff bacteria without disturbing healthy gut balance.
  • taking medication to reduce stomach acid. Lowered acidity in the gut may increase the risk of a C. diff infection.
  • suffering from weakened immune system and/or severe underlying illness

Antibiotics and Risk of C. Diff Recurrence

Most antibiotics carry a risk for C. diff infections, however, some antibiotics carry a higher risk due to their spectrum of coverage. The below table provides select antibiotics and their associated risk level for C. diff recurrence.

Select Antibiotics and Risk of C. Diff Recurrence
Drug Name/Class Approved Uses
Drug Examples
C. diff Risk Level


Administered orally or by injection.

Serious infections in the lungs, skin and soft tissue, blood, intra-abdomen and female genitals, specifically caused by susceptible anaerobic bacteria. Cleocin®  High


Administered orally or by injection.

Skin infections
Bone and joint infections
Intra-abdominal infections
Infectious diarrhea such as C. diff
Typhoid fever
Anthrax inhalation
Bacterial prostatitis
Lung infections
Urinary tract infections (UTI)

Sinus infection
Kidney infection

Inflammation caused by Chlamydia

Bladder infection 

Cipro® (ciprofloxacin) Levaquin® (levofloxacin)

Floxin® (ofloxacin) 

Cephalosporins (2nd and 3rd generation) Administered orally or by injection.  

Lung infections
Skin infections
Urinary tract infections (UTI)

Pelvic inflammatory disease (PID)
Blood infections (sepsis)
Bone and joint infections
Intra-abdominal infections

Meningitis (inflammation of the brain)

Disinfecting surgical sites 

Rocephin® (ceftriaxone)

Claforan® (cefotaxime)



Administered orally or by injection.


Blood infections (sepsis, bacteremia)
Empyema (pus filling around the lungs)


Pericarditis (inflammation of the tissue surrounding the heart)

Endocarditis (heart valve inflammation)

Meningitis (inflammation of the brain)

Anthrax inhalation
Fusospirochetosis (severe infections of the oropharynx, lower respiratory tract, and genital area)
Haverhill fever

Rat bite fever

Disseminated gonococcal infections


Ear infections

Nose infections

Throat infections

Skin infections

Urinary tract infections (UTI)

Lung infections



penicillin G 






Administered orally most commonly.

Sinus infections



Skin infections

Inflammation caused by Chlamydia

Genital ulcer disease


Mycobacterial infections


Zithromax® (azithromycin)

Klacid® (clarithromycin)



Administered orally typically.

C. diff-associated diarrhea

Inflammation of the small intestine and colon



Administered orally or by injection.


C. diff


Amoebic dysentery

Intra-abdominal infections

Skin infections

Gynecologic infections

Blood infections (sepsis)

Bone and joint infections

Central nervous system infections (such as meningitis)

Endocarditis (heart valve inflammation)


Signs a C. Diff Infection is Coming Back

Symptoms of a repeat C. diff infection will mirror the symptoms of previous infections.

Common symptoms:

  • Watery diarrhea (at least 3 loose stools in 24 hours)
  • Fever
  • Abdominal pain/tenderness
  • Loss of appetite

How Common are Repeat C.Diff Infections?

The rate of repeat infection varies from 5% to 50% among patients with a resolved first infection—the recurrence rate varies according to risk factors like age, exposure to hospital environments, and an underlying disease like kidney failure. However, the typical recurrence rate among patients is approximately 20%.

Among patients who have already experienced a C. diff infection twice, the rate of reinfection is approximately 45% to 65%.

How to Reduce the Risk of C.Diff Recurrence

  • Take extra precautions to disinfect and minimize skin-to-skin contact. Contact precautions should extend beyond the period when diarrhea persists; C. diff spores can remain on the skin, dormant, for 7 or more days after treatment of the diarrhea.
  • Hand washing and patient isolation are often overlooked, but very important. Hand sanitizer is not enough—hand washing is more effective! Environmental disinfection using a product like bleach is also key.
  • Be aware that antibiotics can negatively impact the gut—broad spectrum antibiotics can kill healthy bacteria increasing susceptibility to a repeat C. diff infection.
  • Consult with your doctor about taking antacids/acid reducers—both prescribed and over-the-counter. Examples include:
  • Over-the-Counter
    • Tums®
    • Pepto-Bismol®
    • Alka-seltzer®
  • Prescription
    • Pepcid®
    • Zantac®
    • Prilosec OTC®
  • Be aware of possible risk of reinfection in certain health facilities. For example, over 60% of cases of healthcare related C. diff infection cases may have began in long term care facilities.  
  • Identify relapse as soon as possible — early detection of a repeat C. diff infection lessens the risk of spreading the bacteria.

Recurrent C. Diff Treatment Options

While there is no definitive treatment for repeat C. diff infections, vancomycin, fidaxomicin, and fecal microbiota transplants (FMT) are believed to be the best options at the moment.

For more information about C. diff treatment options click here.

New recurrent C. diff treatments being researched

Summit Pharmaceuticals is evaluating an investigational drug called Ridinilazole to determine its safety and efficacy in treating Clostridioides difficile (C. diff) and to help reduce the risk of C. diff coming back. Ridinilazole is designed specifically to target the C. diff bacteria, which could potentially mean less damage to the gut and a reduced chance of another infection.

If you’re ready to help researchers put a stop to repeat C. diff infections, click here to learn more about the clinical study.

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