Gastric Acid Suppression by Proton Pump Inhibitors: DISCUSSION
In studies evaluating PPIs as a risk factor for CDAD, results have been mixed. This relationship has been somewhat ambiguous, and the exact mechanism of action is only speculative. C. difficile is a gram-positive, spore-forming anaerobic bacillus. The spores are acid-resistant, and they are not affected by the gastric pH. By contrast, a vegetative inoculum of C. difficile is easily destroyed by stomach acid. Suppressing gastric acid secretion may allow actively growing bacteria and ingested spores that germinate in the stomach to survive until they pass into the bowel, increasing the likelihood of colonization. PPIs have also been implicated in diminishing neutrophil activity, thereby further increasing the risk of an infectious disease. Overall, it has been proposed that PPIs either suppress the body’s natural barrier defense to infection or alter the immune response to infection.
To assess potential differences between the case and control groups that might explain our results, we evaluated several demographic characteristics and well-documented risk factors for CDAD. Both groups of subjects were similar in age, LOS, and antibiotic exposure. These three risk factors, arguably, are the most important in the development of CDAD. canadian antibiotics
On average, our study population was older than 65 years of age. Most C. difficile infections occur in the elderly, who are more likely to have pre-existing hypochlorhydria. PPIs might not affect the risk of CDAD in older patients, because the change in gastric pH induced by PPIs might be less profound. This might partially explain our study results.
As supported in other studies, penicillin plus a beta-lacta-mase inhibitor was associated with less C. difficile overgrowth, compared with other broad-spectrum antibiotics. Piper-acillin-tazobactam (Zosyn, Wyeth) significantly alters the intestinal flora, but it does not increase the germination of C. difficile spores.
We analyzed therapy for CDAD to determine whether either patient group was receiving more empirical treatment before C. difficile toxin assay testing. IV metronidazole (Baxter) has also been infrequently implicated in the development of CDAD. There was no statistical difference between case and control groups for any antibiotic exposures except penicillin with a beta-lactamase inhibitor.
LIMITATIONS OF THE STUDY
Our results should be viewed in the context of the study’s according to their location; therefore, we could not detect outbreaks of CDAD that were potentially specific to a particular patient- care area within the institution. We considered it unnecessary to match subjects in this fashion, because they were matched according to other robust controlling factors in play.
buy antibiotics without prescription
The laboratory test used in this study detects toxin A exclusively. Some strains of pathogenic C. difficile produce only toxin B or scant amounts of toxin A. To control for this, we excluded all clinical diagnoses of CDAD that were not confirmed by laboratory testing.
We analyzed antibiotic exposure only 30 days before toxin A assay testing. However, it has been reported that CDAD symptoms can develop six weeks or longer following antibiotic exposure.
As for the small number of patients enrolled in the study, we analyzed consecutive patients admitted to the hospital over a recent 10-month period in order to limit the data to the most recent C. difficile diagnoses and to be consistent with our institution’s current PPI usage. To increase the number of patients in the study, it might have been prudent to match each case subject to several control subjects. Although the low number of subjects could imply a lack of statistical power, our results show credibility, in that cases and controls were markedly similar in age, LOS, and antibiotic exposure, as well as in the other predefined matching criteria that assessed for severity of illness.
CONCLUSION
CDAD is a problem of growing concern as both the incidence and the severity of this disease continue to escalate. One possible explanation for the results of inpatient studies associating PPI exposure with CDAD includes a potential detection of a regional strain of C. difficile; it is also possible that the case subjects were already more susceptible to a C. difficile infection because of an increased incidence of other comorbid conditions when they were compared with control groups. The few studies that evaluated risk factors for CDAD development in the hospital have not implicated PPIs as increasing the risk of CDAD. Our results support this conclusion; in our study, PPIs were not associated with CDAD in hospitalized patients.
CDAD is a complicated disease process, with multiple factors contributing to significant infection. It is difficult to assess whether one single factor, such as PPI exposure, contributes significantly to the development of CDAD. It is more likely that a combination of multiple factors causes CDAD in susceptible patients.
Until further definitive research is conducted, practitioners should focus on modifying well-known and accepted risk factors for CDAD, such as improving hygiene practices among health care providers and using broad-spectrum antibiotics appropriately. PPIs remain effective for various gastrointestinal conditions, and they are well tolerated.
Our study conclusions do not support suggestions of an increased risk of CDAD with PPIs. These medications should be considered in hospitalized patients when indicated. Further prospective research is warranted to evaluate the potential risks for CDAD development.