Quasiexperimental Study of the Effects of Antibiotic Use, Gastric Acid-Suppressive Agents, and Infection Control Practices on the Incidence of Clostridium difficile -Associated Diarrhea in Hospitalized Patients

Abstract

The objective of this study was to evaluate the effects of antimicrobial drug use, gastric acid-suppressive agent use, and infection control practices on the incidence of Clostridium difficile-associated diarrhea (CDAD) in a 426-bed general teaching hospital in Northern Ireland. The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (time-series analysis) model was built to relate CDAD incidence with antibiotic use, gastric acid-suppressive agent use, and infection control practices within the hospital over a 5-year period (February 2002 to March 2007). The findings of this study showed that temporal variation in CDAD incidence followed temporal variations in expanded-spectrum cephalosporin use (average delay ‫؍‬ 2 months; variation of CDAD incidence ‫؍‬ 0.01/100 bed-days), broad-spectrum cephalosporin use (average delay ‫؍‬ 2 months; variation of CDAD incidence ‫؍‬ 0.02/100 bed-days), fluoroquinolone use (average delay ‫؍‬ 3 months; variation of CDAD incidence ‫؍‬ 0.004/100 bed-days), amoxicillin-clavulanic acid use (average delay ‫؍‬ 1 month; variation of CDAD incidence ‫؍‬ 0.002/100 bed-days), and macrolide use (average delay ‫؍‬ 5 months; variation of CDAD incidence ‫؍‬ 0.002/100 bed-days). Temporal relationships were also observed between CDAD incidence and use of histamine-2 receptor antagonists (H2RAs; average delay ‫؍‬ 1 month; variation of CDAD incidence ‫؍‬ 0.001/100 bed-days). The model explained 78% of the variance in the monthly incidence of CDAD. The findings of this study highlight a temporal relationship between certain classes of antibiotics, H2RAs, and CDAD incidence. The results of this research can help hospitals to set priorities for restricting the use of specific antibiotic classes, based on the size-effect of each class and the delay necessary to observe an effect.Clostridium difficile, a spore-forming gram-positive anaerobic bacillus, is a common pathogen in hospitals, with gastrointestinal colonization giving rise to increased morbidity, mortality, and health care costs (32). The clinical spectrum of Clostridium difficile-associated diarrhea (CDAD) ranges from uncomplicated diarrhea to severe life-threatening pseudomembranous colitis (23). Established risk factors for CDAD include host factors (for example, advanced age and comorbidities [21,28]), poor infection control practices (relating to the health care environment, health care workers' hand hygiene, etc.) (4, 21), exposure to factors that disrupt the normal protective intestinal microflora (i.e., broad-spectrum antibiotics) (6,24,25), and the use of gastric acid-suppressive agents, i.e., proton pump inhibitors (PPIs) (1, 8, 9) and histamine-2 receptor antagonists (H2RAs) (10). In a systematic review, which was undertaken to summarize the strength of the evidence for a relationship between antibiotic use and the occurrence of CDAD, most studies cited were limited in their ability to establish a causal relationship due to the presence of bias, small sample sizes, and the inadequ...

Seasonal Variations in Clostridium difficile Infections Are Associated with Influenza and Respiratory Syncytial Virus Activity Independently of Antibiotic Prescriptions: a Time Series Analysis in Québec, Canada

“…The temporal relationships between FQ and ML prescriptions in the community and CDAD incidence in hospitals detected in our study are congruent with those observed in other ecologic studies using similar statistical methods relating antibiotic use within hospitals and CDAD incidence in hospitals (2,40). In our study, an increase in FQ and ML prescriptions in the community was associated with an increase in the CDAD incidence with delays of 2 months and 1 month, respectively.…”

Multihospital Outbreak ofClostridium difficileRibotype 027 Infection: Epidemiology and Analysis of Control Measures

“…The model parameters were then estimated by the unconditional least squares method. Finally, the adequacy of the model was checked, 11 and the statistical significance of the parameters was determined. After identification of the multivariate transfer function models, the cross-correlation function was determined by estimating the correlations between the series describing antibiotic use at different time lags and the CDI series.…”

“…Autoregressive integrated moving average (ARIMA) models, using the BoxJenkins method for analysis, 19 were used to evaluate whether relationships existed between antibiotic use and the incidence of CDI, as described elsewhere. 11 To evaluate the effect of the antibiotic restriction policy, dummy variables were created, whereby 0 and 1 represent the pre-and postintervention periods, respectively. A transfer function model that models a time series as a function of its past values and random errors was built.…”

The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease?

“…PPIs and H2-receptor antagonists are associated with suppression of gastric acid which increases intragastric bacterial counts and small bowel colonization [Dial et al 2005[Dial et al , 2006Aldeyab et al 2009]. These effects may occur by antimicrobial-independent or antimicrobial-dependent mechanisms.…”