Given the potential for toxicity with the routine use of probiotic therapy in critically ill patients, and the lack of a mortality benefit in the available meta-analyses,19-21 how should clinicians caring for critically ill patients proceed? One approach would be to identify select patients who are at the greatest risk for developing VAP or non-ventilator-associated respiratory infections, but who are also at low risk for complications from probiotic therapy (eg, absence of valvular heart abnormalities, pancreatitis, GI tract injury). Through careful patient selection, iatrogenic injury can be avoided. It is also important to note that meta-analyses can be misleading, especially when the number of articles reviewed or the number of patients included is small. In situations where a meta-analysis and a subsequent, large, randomized trial are available, discrepancies are not uncommon. Unfortunately, a large, multicenter, high-level RCT analyzing probiotic therapy vs placebo is not available. Based on the available evidence, such a trial seems warranted and should include adequate numbers of patients to evaluate secondary outcomes including mortality, lengths of stay, and nonrespiratory infections, including the occurrence of Clostridium difficile infection. Until such a RCT is performed, clinicians should tread carefully on the use of probiotics in critically ill patients, given their overall lack of proven benefit and potential for harm.