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Use of Proton Pump Inhibitors a Significant Factor in Community Acquired C-Difficile Infection

Use of Proton Pump Inhibitors a Significant Factor in Community Acquired C-Difficile Infection.


Although community-associated CDI is defined based on the interim surveillance recommendations as the absence of inpatient overnight stay in a health care facility, we found that 82.0% of patients acquiring C difficile in the community had either a recent outpatient health care exposure or an inpatient health care exposure without an overnight stay. Outpatient settings such as physicians’ offices, emergency departments, and dialysis facilities can be the source of C difficile acquisition by exposure to contaminated environmental surfaces, as well as the prescription of antibiotics that disrupt the lower intestinal microbiota. In our study, 64.1% of patients with CDI received outpatient antibiotics within 12 weeks before infection, and the most common indications for antibiotic therapy were ear, sinus, or upper respiratory tract infection or a dental procedure. Multiple studies have noted that ear, sinus, or upper respiratory tract infections are common reasons for inappropriate antibiotic use in outpatient settings. The many patients receiving antibiotics for dental procedures was notable because the current American Heart Association guideline for prevention of infective endocarditis restricts prophylactic antibiotic use for dental procedures to patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis. Therefore, it is likely that a substantial proportion of patients in our study received antibiotics inappropriately, emphasizing that antibiotics should be prescribed more judiciously by outpatient health care providers and that the overuse of outpatient antibiotics may have an adverse effect on community-associated CDI rates. Antimicrobial stewardship programs in acute care facilities have been associated with decreases in CDI rates up to 60%; aspects of these strategies may need to be considered for use in outpatient health care settings as well.

Thirty-six percent of patients in our study did not report antibiotic exposure in the 12 weeks before infection. Since discovery of the causal role for C difficile in pseudomembranous colitis was made in the late 1970s, there have been occasional reports of CDI occurring without precedent antibiotic exposure. However, the overall importance of community-associated CDI and its frequent occurrence in the absence of antibiotic exposure were not appreciated until approximately 8 years ago. Our study is the largest assessment of antibiotic exposures among patients with community-associated CDI in the United States to date, and the proportion we identified without such exposure is consistent with other recent estimates. Although it is unknown from these or other data whether CDI in the absence of antibiotic exposure is increasing, other emerging factors may have a role similar to that of antibiotics in weakening the important host defense afforded by intact lower intestinal microbiota.

We found that patients having community-associated CDI without antibiotic exposure had a trend toward having received PPIs more frequently than patients with antibiotic exposure. In some studies, PPIs have been shown to increase the risk of community-associated CDI, and the US Food and Drug Administration issued a recent warning advising physicians of the increased CDI risk in patients receiving PPIs. However, no data indicating the effect of restricting PPI use on CDI incidence are available to date. In addition, the mechanism by which PPIs may increase the risk of CDI is not fully understood, and it has been suggested that PPIs may have a more important role in patients with minimal antibiotic exposure. Based on our data, if the effect of reducing unnecessary PPI use on community-associated CDI is limited to those patients who have not received recent antibiotics, such an intervention would prevent only 11.2% of community-associated CDI.

Clostridium difficile spores can survive for prolonged periods in the environment and the health care environment where patients with C difficile are treated can serve as a source of transmission. To identify sources of C difficile in the community other than the outpatient health care environment and the transiently contaminated hands of health care personnel, we compared C difficile patients by level of health care exposure. In these exploratory analyses adjusted for antibiotic use, a plausible association existed between low-level health care exposure and exposure to household members younger than 1 year. Infants younger than 1 year are known to be frequent asymptomatic carriers of C difficile, with the results of some studies suggesting up to a 70% colonization rate. Our findings are consistent with a study by Wilcox et al, which found that contact with children younger than 2 years was associated with an increased risk of community-associated CDI. Although C difficile–colonized infants and children can shed the organism into the environment and a study has reported a C difficile outbreak in a day care center, additional studies in day care, home day care, and household settings are needed before setting-specific environmental recommendations can be made. We also found higher odds of having a household member with CDI among the no and low-level health care exposure groups. However, due to the low prevalence of household members with CDI, this association was not statistically significant. This finding is consistent with a recent Canadian study, which demonstrated that household contacts with patients having active CDI are at increased risk of infection. Our data provided no evidence to support a role for food or animal exposure as a source of C difficile acquisition beyond health care exposure. Only 6.7% of culture-positive isolates were NAP7 or NAP8, strains primarily detected in food and animals. In recent studies in North America, C difficile detection in retail meat samples has ranged from 0% to 10%. This low prevalence of C difficile among retail meat in conjunction with our findings suggests that food and animal exposures could account for only a small proportion of community-associated CDI. Furthermore, antibiotics may be present in consumed foods, and it is unclear at this point whether food can be a source of C difficile or another potential factor that can disturb the gut microbiota and predispose patients to CDI.

Despite that a large sample of patients across multiple geographic locations was included in our analyses, the study is subject to several limitations. First, only a sample of patients having community-associated CDI was interviewed, and these patients were more likely to be female and white compared with patients having CDI who refused to be interviewed. In addition, only a convenience sample of the patients interviewed had stool specimens sent for further testing. Therefore, patients and C difficile isolates included in this analysis may not be representative of all US patients with community-associated CDI, and the data should be interpreted cautiously because women of perimenopausal age, for example, may be submitted to more medical maneuvers or may be receiving other medications to counteract menopause symptoms. Second, because interviews were conducted up to 12 weeks after detection of C difficile and because exposures to medications and sources of C difficile acquisition were self-reported, it is possible that these exposures were misclassified. Nevertheless, this study assesses exposures for C difficile using medical records and health interviews and may provide a more accurate description of exposures compared with studies that solely relied on data collected from medical records. Third, the lack of a comparison group without CDI precluded us from confirming risk factors for community-associated CDI that we observed in this study. Fourth, because few patients had CDI without outpatient health care exposure, we were likely limited in our ability to detect any statistically significant association among this group. Nonetheless, our findings raise important hypotheses to be tested in future studies.

Most patients identified with community-associated CDI had received antibiotics and had outpatient health care exposure. Prevention of community-associated CDI should primarily focus on reducing inappropriate antibiotic use and better infection control practices in outpatient settings. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of PPI use.

To read the original study from the Journal of JAMA Internal Medical click the link:
http://archinte.jamanetwork.com/article.aspx?articleid=1697791


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