Erik R. Dubberke

US estimates of the Clostridium difficile infection (CDI) burden have utilized International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Whether ICD-9-CM code rank order affects CDI prevalence estimates is important because the National Hospital Discharge Survey (NHDS) and the Nationwide Inpatient Sample (NIS) have varying limits on the number of ICD-9-CM codes collected. ICD-9-CM codes for CDI (008.45), C. difficile toxin assay results, and dates of admission and discharge were collected from electronic hospital databases for adult patients admitted to 4 hospitals in the United States from July 2000 through June 2006. CDI prevalence per 1000 discharges was calculated and compared for NHDS and NIS limits and toxin assay results from the same hospitals. CDI prevalence estimates were compared using the χ(2) test, and the test of equality was used to compare slopes. CDI prevalence measured by NIS criteria was significantly higher than that measured using NHDS criteria (10.7 cases per 1000 discharges versus 9.4 cases per 1000 discharges; P<.001) in the 4 hospitals. CDI prevalence measured by toxin assay results was 9.4 cases per 1000 discharges (P=.57 versus NHDS). However, the CDI prevalence increased more rapidly over time when measured according to the NHDS criteria than when measured according to toxin assay results (β=1.09 versus 0.84; P=.008). Compared with the NHDS definition, the NIS definition captured 12% more CDI cases and reported significantly higher CDI rates. Rates calculated using toxin assay results were not different from rates calculated using NHDS criteria, but CDI prevalence appeared to increase more rapidly when measured by NHDS criteria than when measured by toxin assay results.

Objective.: To compare incidence rates of Clostridium difficile infection (CDI) during a 6-year period among 5 geographically diverse academic medical centers across the United States by use of recommended standardized surveillance definitions of CDI that incorporate recent information on healthcare facility (HCF) exposure.Methods.: Data on C. difficile toxin assay results and dates of hospital admission and discharge were collected from electronic databases. Chart review was performed for patients with a positive C. difficile toxin assay result who were identified within 48 hours after hospital admission to determine whether they had any HCF exposure during the 90 days prior to their hospital admission. CDI cases, defined as any inpatient with a stool toxin assay positive for C. difficile, were categorized into 5 surveillance definitions based on recent HCF exposure. Annual CDI rates were calculated and evaluated by use of the χ² test for trend and the χ² summary test.Results.: During the study period, there were significant increases in the overall incidence rates of HCF-onset, HCF-associated CDI (from 7.0 to 8.5 cases per 10,000 patient-days; P < .001); community-onset, HCF-associated CDI attributed to a study hospital (from 1.1 to 1.3 cases per 10,000 patient-days; P = .003); and community-onset, HCF-associated CDI not attributed to a study hospital (from 0.8 to 1.5 cases per 1,000 admissions overall; P < .001). For each surveillance definition of CDI, there were significant differences in the total incidence rate between HCFs.Conclusions.: The increasing incidence rates of CDI over time and across healthcare institutions and the correlation of CDI incidence in different surveillance categories suggest that CDI may be a regional problem and not isolated to a single HCF within a community.

Dubberke ER, Reske KA, Srivastava A, Sadhu J, Gatti R, Young RM, Rakes LC, Dieckgraefe B, DiPersio J, Fraser VJ. Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes. Clin Transplant 2009. DOI: 10.1111/j.1399‐0012.2009.01035.x © 2009 John Wiley & Sons A/S.Abstract:  The purpose of this study was to evaluate risk factors, protective factors, and outcomes associated with Clostridium difficile‐associated disease (CDAD) in allogeneic hematopoietic stem‐cell transplant (HSCT) recipients. A case–control study was performed with 37 CDAD cases and 67 controls. In the multivariable logistic regression analysis, receipt of a third or fourth generation cephalosporin was associated with increased risk of CDAD (OR = 4.6, 95% CI 1.6–13.1). Receipt of growth factors was associated with decreased risk of CDAD (OR=0.1, 95% CI 0.02–0.3). Cases were more likely to develop a blood stream infection after CDAD than were controls at any point before discharge (p < 0.001). CDAD cases were more likely than controls to develop new onset graft‐vs.‐host disease (GVHD) (p < 0.001), new onset severe GVHD (p < 0.001), or new onset gut GVHD (p = 0.007) after CDAD/discharge. Severe CDAD was a risk factor for death at 180 d in multivariable Cox proportional hazards regression (HR=2.6, 95% CI 1.1–6.2). CDAD is a significant cause of morbidity and mortality in allogeneic HSCT patients, but modifiable risk factors exist. Further study is needed to determine the best methods of decreasing patients’ risk of CDAD.

Objective.: To compare incidence of hospital-onset Clostridium difficile infection (CDI) measured by the use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis codes with rates measured by the use of electronically available C. difficile toxin assay results.Methods.: Cases of hospital-onset CDI were identified at 5 US hospitals during the period from July 2000 through June 2006 with the use of 2 surveillance definitions: positive toxin assay results (gold standard) and secondary ICD-9-CM discharge diagnosis codes for CDI. The x² test was used to compare incidence, linear regression models were used to analyze trends, and the test of equality was used to compare slopes.Results.: Of 8,670 cases of hospital-onset CDI, 38% were identified by the use of both toxin assay results and the ICD-9-CM code, 16% by the use of toxin assay results alone, and 45% by the use of the ICD-9-CM code alone. Nearly half (47%) of cases of CDI identified by the use of a secondary diagnosis code alone were community-onset CDI according to the results of the toxin assay. The rate of hospital-onset CDI found by use of ICD-9-CM codes was significantly higher than the rate found by use of toxin assay results overall (P<.001), as well as individually at 3 of the 5 hospitals (P<.001 for all). The agreement between toxin assay results and the presence of a secondary ICD-9-CM diagnosis code for CDI was moderate, with an overall k value of 0.509 and hospital-specific k values of 0.489–0.570. Overall, the annual increase in CDI incidence was significantly greater for rates determined by the use of ICD-9-CM codes than for rates determined by the use of toxin assay results (P = .006).Conclusions.: Although the ICD-9-CM code for CDI seems to be adequate for measuring the overall CDI burden, use of the ICD-9-CM discharge diagnosis code for CDI, without present-on-admission code assignment, is not an acceptable surrogate for surveillance for hospital-onset CDI.

Objective.: To describe a pseudo-outbreak ofClostridium difficileinfection (CDI) caused by a faulty toxin assay lot and to determine the effect of sensitivity, specificity, and repeated testing forC. difficileon perceived CDI burden, positive predictive value, and false-positive results.Design.: Outbreak investigation and criterion standard.Patients.: Patients hospitalized at a tertiary care hospital who had at least 1 toxin assay for detection ofC. difficileperformed during the period from July 1, 2004, through June 30, 2006.Methods.: The run control chart method and thex²test were used to compare CDI rates and the proportion of positive test results before, during, and after the pseudo-outbreak. The effect of repeated testing was evaluated by using 3 hypothetical models with a sample of 10,000 patients and various assay sensitivity and specificity estimates.Results.: In November of 2005, the CDI rate at the hospital increased from 1.5 to 2.6 cases per 1,000 patient-days (P< .01), and the proportion of positive test results increased from 13.6% to 22.1% (P< .01). An investigation revealed a pseudo-outbreak caused by a faulty toxin assay lot. A decrease of only 1.2% in the specificity of the toxin assay would result in a 32% increase in perceived incidence of CDI at this institution. When calculated by use of the manufacturer's stated specificity and sensitivity and this institution's testing practices, the positive predictive value of the test decreased from 80.6% to 4.1% for patients who received 3 tests.Conclusion.: Specificity is as important as sensitivity when testing for CDI. False-positive CDI cases can drain hospital resources and adversely affect patients. Repeated testing forC. difficileshould be performed with caution.

Clostridium difficile infection is an important health care-associated infection. The incidence and severity of C. difficile infection are increasing. Recent C. difficile infection outbreaks with high proportions of severe outcomes have been linked to an emerging, hypervirulent strain of C. difficile. Recently recognized risk factors of C. difficile infection include fluoroquinolone exposure and gastric acid suppression. Effective prevention measures for C. difficile infection include contact precautions and antimicrobial stewardship. Awareness of C. difficile infection is critical to provide appropriate clinical care.

Objective.: To evaluate the impact of cases of community-onset, healthcare facility (HCF)-associated Clostridium difficile infection (CDI) on the incidence and outbreak detection of CDI.Design.: A retrospective multicenter cohort study.Setting.: Five university-affiliated, acute care HCFs in the United States.Methods.: We collected data (including results of C. difficile toxin assays of stool samples) on all of the adult patients admitted to the 5 hospitals during the period from July I, 2000, through June 30, 2006. CDI cases were classified as HCF-onset if they were diagnosed more than 48 hours after admission or as community-onset, HCF-associated if they were diagnosed within 48 hours after admission and if the patient had recently been discharged from the HCF. Four surveillance definitions were compared: cases of HCF-onset CDI only (hereafter referred to as HCF-onset CDI) and cases of HCF-onset and community-onset, HCF-associated CDI diagnosed within 30, 60, and 90 days after the last discharge from the study hospital (hereafter referred to as 30-day, 60-day, and 90-day CDI, respectively). Monthly CDI rates were compared. Control charts were used to identify potential CDI outbreaks.Results.: The rate of 30-day CDI was significantly higher than the rate of HCF-onset CDI at 2 HCFs (P < .01 ). The rates of 30-day CDI were not statistically significantly different from the rates of 60-day or 90-day CDI at any HCF. The correlations between each HCF's monthly rates of HCF-onset CDI and 30-day CDI were almost perfect (ρ range, 0.94-0.99; P < .001). Overall, 12 time points had a CDI rate that was more than 3 standard deviations above the mean, including 11 time points identified using the definition for HCF-onset CDI and 9 time points identified using the definition for 30-day CDI, with discordant results at 4 time points (k = 0.794; P < .001).Conclusions.: Tracking cases of both community-onset and HCF-onset, HCF-associated CDI captures significantly more CDI cases, but surveillance of HCF-onset, HCF-associated CDI alone is sufficient to detect an outbreak.

Clostridium difficileis well recognized as the most common infectious cause of healthcare-associated diarrhea. Since 2000, this pathogen has demonstrated an increased propensity to cause more frequent and virulent illness that is often refractory to treatment. An analysis by the Centers for Disease Control and Prevention revealed that, in the United States, the number of patients discharged from hospitals who received theInternational Classification of Diseases, Ninth Revisiondischarge diagnosis code forC. difficileinfection (CDI) more than doubled from 2000 to 2003. Unpublished data indicate that this trend has continued and that more than 250,000 US hospitalizations were associated with CDI in 2005. A previously uncommon hypervirulent strain ofC. difficileis thought to contribute, in part, to the dramatic increase in the incidence and severity of the infection. Although the economic impact of the disease is believed to be profound and is expected to increase, data on the costs associated with CDI are scarce. To more completely assess its economic burden, we performed a review of available literature that reported costs associated with the infection.