Inclusion Criteria:

At the time of screening, participant:

• Has suspected or confirmed CDI, as evidenced by the following:
  • had a change in normal bowel habits for 2 or more calendar days with either watery diarrhea (for participants using diapers or other type of fecal collection device, Bristol Stool Scale types 6 or 7) or at least 6 UBMs (eg, takes shape of container, or Bristol Stool Scale types 5, 6, or 7) within a 48-hour period, and  produced a stool sample that has tested positive for toxigenic C. difficile according to local diagnostic criteria.
  • is receiving or is planning to receive a 10- to 21-day course of antibacterial drug treatment for CDI, which is defined as oral vancomycin, oral metronidazole, or oral fidaxomicin. Additionally, IV metronidazole may be given concurrently with oral vancomycin or oral fidaxomicin.
• At the time of randomization/study infusion, participant:
  • has a diagnosis of CDI confirmed by a diagnostic assay which detects the presence of C. difficile toxin in stool (see Appendix 7 for additional information regarding C. difficile assay requirements), and
  • is still receiving antibacterial drug treatment for CDI.

Demographics

• Participant is of either sex and of any race, and ≥1 year to <18 years of age at the time of randomization.

Female participants:

• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP); OR
  • A WOCBP who agrees to use any contraceptive method listed in Table 14 in Appendix 5 (including those classified as “acceptable”) from Day 1 through at least 12 weeks after the single infusion of study treatment.

Informed Consent/Assent

• The participant (or legally acceptable representative [LAR] if applicable) provides written informed consent/assent for the trial. The participant or LAR may also provide consent/assent for Future Biomedical Research (FBR). However, the participant may participate in the main trial without participating in FBR.

Adherence to Study Procedures

• Participant must be able to adhere to the study visit schedules.
• Participant and/or parent or caregiver must be able to read, understand, and complete the daily diary.

Exclusion Criteria

• Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

• Participant has an uncontrolled chronic diarrheal illness such as, but not limited to, Crohn’s disease, ulcerative colitis, or with a condition such that their normal 24-hour bowel movement habit is 3 or more UBMs. Participants with a history of IBD who are controlled (ie, had no recent active diarrhea/UBMs prior to current CDI episode) may be enrolled if in the opinion of the investigator, the symptoms are more likely due to CDI than a flare of the IBD.
• Has a known hypersensitivity to bezlotoxumab, its active substance and/or any of its excipients (refer to the Investigator’s Brochure for a list of excipients).

Prior/Concomitant Therapy

• Participant for whom, at the time of randomization, the planned course of antibacterial drug treatment for CDI is longer than 21 days.
• Participant has received any treatment or procedure listed in Table 2 within the indicated exclusion window.

TABLE 2:  Treatment/Procedure | Exclude if Given in the Window Indicated

Treatments

• Rifaximin
  • Within 14 days prior to receipt of study infusion
• Nitazoxanide
  • Within 14 days prior to receipt of study infusion

Procedures

• Surgery for episode of CDI under treatment at time of randomization
  • Any time prior to screening or during screening period

Prior/Concurrent Clinical Study Experience

• Participant has previously participated in this trial, has previously received bezlotoxumab, has received an experimental mAb against C. difficile toxin B, or has received a vaccine directed against C. difficile or its toxins.
• Participant has received an investigational trial agent within the previous 30 days, or is currently participating in or scheduled to participate in any other clinical trial with an investigational agent during the 12-week trial period.

Other Exclusions

• Participant is not expected to survive for 72 hours.
• Participant has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant, would make it unlikely for the participant to complete the trial, or would confound the results of the trial.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.