Probiotic Ineffective in Preventing C. difficile Infection

WASHINGTON — The probiotic Lactobacillus GG failed to prevent Clostridium difficile infection when given at the same time as systemic antibiotics to hospitalized adults in two prospective, randomized, double-blind, placebo-controlled trials.

Lactobacillus GG (LGG) is an L. rhamnosus isolate named after the initials of the two scientists—Sherwood Gorbach and Barry Goldin—from whom the strain was derived and who hold the patents for it. The strain is marketed as a dietary supplement under the name Culturelle by the ConAgra Foods Co., which funded the two studies.

The organism is acid- and bile-stable and has high affinity to mucosal cells of the gastrointestinal tract, thus rendering it a potential gut probiotic that could prevent disruptions in normal flora that occur with antibiotic use, Dr. Mark Miller said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Virtually all cases of Clostridium difficile infection (CDI) are preceded by antibiotic consumption in the previous 60 days, and perturbation of normal flora is almost certainly responsible for the mechanism that “turns on” CD spore germination and toxin production. Yet no study has demonstrated the effectiveness of a probiotic to prevent CDI, said Dr. Miller, head of the division of infectious diseases and chief of the department of microbiology at SMBD-Jewish General Hospital, McGill University, Montreal.

In the first study, 95 hospitalized patients who were receiving oral or parenteral antibiotics for 14 days or less were randomized to receive LGG in an oral dose of 2 × 1010 bacteria twice daily for 14 days; 94 patients received placebo. No patient was severely immunocompromised, and all were able to take medications by mouth.

Over the subsequent 30 days, four of the LGG patients (4.2%) and seven of the placebo patients (7.4%) developed documented CDI (diarrhea plus positive toxin B assay), but this difference was not significant.

Two of the LGG patients (2.1%) and four placebo patients (4.3%) died; none of the deaths were deemed to be related to the study drug.

The larger, second study employed a higher dose of LGG (6 × 1010) twice daily for 14 days. Again there was no significant difference between groups, with CDI developing in 2 (1.3%) of 157 the LGG patients and in 0 of the 159 placebo patients.

Four (2.6%) of the LGG patients died—none deemed related to the study drug—while none of the placebo patients died. Watery diarrhea was reported by 5.1% of the LGG patients and 2.5% of the placebo group, also not a significant difference.

Study medication compliance was similar for the two groups.

It's possible that the low rate of CDI in the study population may have obscured an effect of LGG, or that monitoring the effects of “lesser” diarrhea than “watery” may have shown an effect, Dr. Miller commented.

In general, probiotic prophylaxis studies are hampered by the large number of study subjects needed to show an effect. Also, whether the failure of LGG is a product-specific effect or is representative of all probiotics is an open question.

Dr. Miller received research support from ConAgra Inc.