In the September 2009 issue of CHEST, Zilberberg and colleagues1 reported on the association between patients receiving prolonged acute mechanical ventilation (PAMV) and Clostridium difficile-associated disease (CDAD). The reported infection rate (5.3%) in the current study was significantly higher than previously reported by the same authors in the general hospital population (0.112%).2 The authors point out that the causality of the association between PAMV and CDAD cannot be established based on the results of the current study. Zilberberg and colleagues1 do, however, discuss several concomitant risk factors for CDAD that are likely in the mechanically ventilated patient, including increased exposure to antibiotics and C difficile spores. Perhaps one overlooked additional risk factor in the study population was exposure to acid-suppressive therapy (ie, proton-pump inhibitors and histamine-receptor blockers) for stress ulcer prophylaxis. These medications have previously been associated with CDAD,3 and exposure to these agents may be an important potential confounder of the current study. Evidence-based guidelines emphasize that stress ulcer prophylaxis is appropriate in a select group of critical care patients, including those on prolonged mechanical ventilation.4 It is plausible that the majority of patients included in the current study would have had exposure to acid-suppressive therapy. Murphy and colleagues5 reported that stress ulcer prophylaxis is often inappropriately continued when patients transfer out of a critical care unit. The results of the current study clearly show increased costs and length of stay with concurrent PAMV and CDAD. The authors of the current study conclude that “aggressive measures aimed at preventing [CDAD] need to be examined ….” Diligent medication reconciliation when transferring patients from the critical care unit to a lower level of care, particularly focusing on acid-suppressive therapy, may be one simple measure clinicians can take to aid in the prevention of CDAD.