Adverse Effects and Safety
When ingested orally, probiotics are generally considered safe and well tolerated. The most common adverse effects include bloating and flatulence; however, these are typically mild and subside with continued use.[24,57,58] Constipation and increased thirst have also rarely been associated with S. boulardii. One theoretical concern associated with probiotics includes the potential for these viable organisms to move from the gastointestinal tract and cause systemic infections. Although rare, probiotic-related bacteremia and fungemia have been reported. It is estimated that the risk of developing bacteremia from ingested lactobacilli probiotics is less than 1 per 1 million users, and the risk of developing fungemia from S. boulardii is estimated at 1 per 5.6 million users. Another theoretical risk associated with probiotics involves the possible transfer of antibiotic resistance from probiotic strains to pathogenic bacteria; however, this has not yet been observed.[65,66]
Although no serious adverse events have been described in clinical trials, systemic infections associated with specific probiotics have been noted in isolated reports. These include sepsis or endocarditis with lactobacilli, fungemia with S. boulardii, and liver abscess with LGG.[24,65] Bacteremia due to lactobacilli rarely occurs, but predisposing factors include immunosuppression, prior hospitalization, severe underlying comorbidities, previous antibiotic therapy, and prior surgical interventions. There have been several documented cases of fungemia associated with use of S. boulardii. Those at greatest risk include critically ill or highly immunocompromised patients or those with central venous catheters in place. When S. boulardii capsules are opened at the bedside for administration through the nasogastric tube, central venous catheters may become contaminated and serve as the source of entry for the organism. Although there have been infrequent reports of lactobacillemia and fungemia, to date there have been no reports of bifidobacterial sepsis associated with the use of a probiotic, supporting the low pathogenicity of bifidobacteria species. Fortunately, most cases of probiotic bacteremia or fungemia have responded well to appropriate antibiotic or antifungal therapy.
In a review of the literature, Boyle et al. identified major and minor risk factors for probiotic-associated sepsis. Major risk factors included immunosuppression (including a debilitated state or malignancy) and prematurity in infants. Minor risk factors were the presence of a central venous catheter, impairment of the intestinal epithelial barrier (such as with diarrheal illness), cardiac valvular disease (Lactobacillus probiotics only), concurrent administration with broad-spectrum antibiotics to which the probiotic is resistant, and administration of probiotics via a jejunostomy tube (this method of delivery could increase the number of viable probiotic organisms reaching the intestine by bypassing the acidic contents of the stomach). The authors recommended that probiotics be used cautiously in patients with one major risk factor or more than one minor risk factor.
It is important to remember that the overall risk of developing an infection from ingested probiotics is very low, particularly when used by generally healthy individuals. In Finland, LGG has been routinely added to dairy products since 1990. Despite a substantial increase in the consumption of LGG-containing products from 1995 through 2000, there was no significant change in the incidence of Lactobacillus-associated bacteremia observed during the surveillance period of 1990–2000.
A recent study found an increased risk of mortality when probiotics were used to prevent infectious complications in patients with predicted severe acute pancreatitis. These patients had acute pancreatitis and an elevated Acute Physiology and Chronic Health Evaluation (APACHE) II score, Imrie/modified Glasgow score, or C-reactive protein value, predicting a severe disease course and putting them at risk for developing infectious complications, including infected pancreatic necrosis. This multicenter, randomized, double-blind, placebo-controlled trial involved 298 patients who received a multispecies probiotic preparation (L. acidophilus, L. casei, Lactobacillus salivarius, Lactobacillus lactis, B. bifidum, and B. lactis) or placebo, administered enterally twice daily for a maximum of 28 days. The study found that this combination of six probiotic strains did not decrease infectious complications in patients with predicted severe acute pancreatitis but rather was associated with significantly more deaths than was placebo (24 versus 9, p = 0.01) and an increased risk of bowel ischemia in the probiotics group compared with placebo (9 versus 0, p = 0.004). The authors stated that probiotics should not be routinely given to patients with predicted severe acute pancreatitis and should be used cautiously in critically ill patients or those at risk for nonocclusive mesenteric ischemia.
Am J Health Syst Pharm. 2010;67(6):449-458. © 2010 American Society of Health-System Pharmacists
Cite this: Probiotics - Medscape - Mar 15, 2010.