Probiotics Effective for Primary Prevention of C. Diff

By Will Boggs MD

NEW YORK (Reuters Health) - Probiotics are effective for preventing Clostridium difficile infection (CDI) in patients treated with antibiotics, according to findings from two research groups.

"Probiotics are considerably more effective in settings where the risk for Clostridium difficile infection is moderate to high," Dr. Bradley C. Johnston from Dalhousie University, in Halifax, Canada, told Reuters Health by email.

"For instance, among participants in outbreak hospital settings where the risk of Clostridium difficile is high (>=5%), the number needed to treat is approximately 12," said Dr. Johnston, who worked on one of the studies. "Based on the more likely baseline risk of Clostridium difficile infection in typical hospital settings (a 1.6% risk based on the median of all studies), the number needed to treat is 96."

Current clinical practice guidelines on CDI prevention focus on core strategies (e.g., staff education, patient isolation, antimicrobial stewardship and utilization of disinfectants), but none recommend probiotics for prophylaxis.

Dr. Johnston and colleagues conducted a meta-analysis using data from 6,851 individual participants in 18 trials to determine whether adding probiotics to an antibiotic regimen reduces the incidence of CDI among children and adults when adjusting for a variety of factors.

The incidence of CDI was 1.1% in the intervention groups and 2.5% in the control groups of the 18 studies. Probiotic prophylaxis reduced the odds of CDI by 63% in unadjusted analyses (P<0.0001).

The reduction was slightly greater, 65%, in the 13 studies included in the analysis that adjusted for other factors, the researchers report in Infection Control and Hospital Epidemiology, online April 26.

The use of two or more antibiotics increased the odds of CDI 2.20-fold, whereas age, sex, hospitalization status and high-risk antibiotic exposure did not.

Multispecies probiotics significantly reduced the odds of CDI, whereas there was a nonsignificant reduction with single-species probiotics. Probiotic doses below 1 billion colony forming units per day did not significantly reduce CDI risk.

"Moderate-certainty evidence suggests that probiotic prophylaxis is a useful and safe Clostridium difficile infection prevention strategy," Dr. Johnston said. "Based on a recent systematic review we conducted on prophylactic strategies for Clostridium difficile, probiotics offer the highest certainty of evidence among the existing strategies that are typically considered during Clostridium difficile outbreaks (e.g., contact precautions, antimicrobial stewardship interventions, cleaning with sporicidal agent)."

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The study had no specific funding.

In related work, published simultaneously in the same journal, Dr. William E. Trick from Cook County Health and Hospitals System in Chicago and colleagues examined the effectiveness of their quality-improvement intervention of probiotics for primary prevention of CDI at a 694-bed teaching hospital.

"There were substantial challenges in implementing the intervention in a 'real-world' setting, outside of a randomized clinical trial," Dr. Trick told Reuters Health. "Since we wanted probiotic to be administered soon after the start of antibiotics, many patients were excluded because they came in on antibiotics or were started on antibiotics in the emergency department. Our intervention was focused on patients in the inpatient hospital setting."

The incidence of CDI did not differ significantly between the baseline period (6.9 cases per 10,000 patient-days) and the intervention period (7.0 per 10,000 patient-days). But the incidence of CDI during the second six-month period of the intervention period was significantly lower than during the first six months of the intervention period (5.4 vs. 8.6 per 10,000 patient-days, P=0.009).

"The delayed effect is consistent with prior literature and may have been related to poor fidelity to the protocol for probiotic administration and a delayed gradual reduction in environmental contamination," the researchers note.

In a case-control study of 68 matched pairs of patients, however, there was no protective effect from probiotics.

"Many patients are at risk for complications due to exposure to antibiotics and these should only be given when necessary," Dr. Trick said. "I expect that in the not-too-distant future, we will have several options to protect and restore a patient's microbiome. Probiotics are one such option, but will not be completely effective without hand washing and good environmental cleaning-especially in rooms that previously housed a patient with C. difficile infection."

Dr. Lynne V. McFarland from the University of Washington, Seattle, who recently reviewed the difficulty of preventing CDI, told Reuters Health by email, "It is surprising how hard it is to prevent hospital-associated diseases, especially such clever pathogens as Clostridium difficile. This pathogen is loaded with an arsenal of ways to infect people and cause disease. Despite infection control 'bundles' that have several different ways to prevent this infection, outbreaks continue to plague us."

"Probiotics fill in a niche that standard infection-control practices (hand washing, isolation of infected patients, room cleaning, contact precautions, etc.) don't cover," said Dr. McFarland, who was not involved in the new studies. "They help the normally protective intestinal microflora recover and have ways to fight the pathogen while this recovery of microflora occurs. It takes 6-8 weeks for this recovery to be complete!"

"Just because a product lists itself as a 'probiotic' does not mean it is useful for the specific purpose you want to use it for," she cautioned. "The efficacy of probiotics is both strain-specific and disease-specific. Not every probiotic is created equal."

SOURCE: https://bit.ly/2HNlGOE and https://bit.ly/2HMROln

Infect Control Hosp Epidemiol 2018.

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