Clostridium difficile infection (CDI) is a significant cause of morbidity, mortality, and increased health care costs in the U.S. Discharges for which CDI was listed as any diagnosis doubled from 31/100,000 population in 1996 to 61/100,000 in 2003. Recent data suggest a conservative estimate for the annual U.S. cost for CDI management around $3.2 billion dollars. Little is known about the morbidity and mortality of CDI in complex chronic care patients such as persons with spinal cord injury and disorder (SCI/D). Individuals with SCI/D are at high risk for these infections compared to the general population due to their underlying health impairment, frequent hospitalization or contact with the health care system, frequent/chronic use of invasive medical devices such as urinary catheters, development of pressure ulcers, and frequent use of antibiotics. C. difficile colonization has been reported to be 18% in SCI patients admitted to an acute rehabilitation unit. However, little is known about the burden or long-term impact of CDI nor on the most effective treatment strategies in persons with SCI/D.
The goals of this study were to: 1) characterize the burden and magnitude of CDI in Veterans with SCI/D, assess whether the rate of CDI is increasing, and examine risk factors associated with development of CDI; 2) assess the impact of CDI in Veterans with SCI/D on health care outcomes including mortality and LOS; 3) describe medical management strategies utilized for CDI and compare the effectiveness of the common antibiotic treatment on outcomes including treatment failure and 30-day case fatality. Secondary objective: validate the use of laboratory-confirmed test data for defining CDI cases, failure of treatment, recurrence of CDI, and treatment received.
This was a retrospective, longitudinal analysis of 9 years (FY2002-FY2010) of national VA medical encounter, pharmacy, and microbiology laboratory data to assess morbidity, mortality, utilization, and treatment of CDI in Veterans with SCI/D. This study utilized several national VA databases including Medical SAS datasets, VA Emerging Pathogens Initiative (EPI) Database, CDW, DSS NDE for laboratory and pharmacy data, the VA Spinal Cord Dysfunction Registry, and the VA Vital Status File. A medical record review on 180 inpatients with positive C. difficile tests compared to 150 non-cases at risk due to antibiotic exposure was conducted for validation purposes. Classifications of CDI cases, settings, mode of acquisition and severity were defined by CDI surveillance recommendations published by McDonald et al., 2007 and clinical practice guidelines for CDI published by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Bed days of care (BDOC) and person-days (PDs) were used as denominators to calculate incidence. PDs was based on BDOC, including only days the individual was "at risk" for infection. For both CDI and non-CDI cases, the first 48 hour (2 days) after admission were excluded from PDs. For those that developed CDI, PDs up to 8 weeks after initial CDI were removed since individuals were not at risk during this time. The severity of illness definition for severe-complicated illness was modified to accommodate typical low blood pressure in SCI/D patients; hypotension was defined for patients with paraplegia as systolic/diastolic <100/70 mm Hg and tetraplegia <90/60 mm Hg.
Over 17,000 Veterans with SCI/D from 104 VA facilities in our cohort received health care in VA during the study time period FY2002-FY2010; with 2,427 CDI cases among them (2,104 healthcare facility-onset, healthcare facility-associated (HO-HCFA); 126 community-onset, healthcare facility-associated (CO-HCFA); 197 community-associated (CA) CDI (including indeterminate cases)). Approximately 22% of these cases were recurrences. Concomitant fluoroquinolone use was found to be a risk factor for recurrence of CDI. In contrast, concomitant tetracycline use and history of a cerebrovascular accident were protective for recurrence. Length of stay greater than 90 days from the initial CDI episode was also a risk factor for recurrence among those with HO-HCFA CDI. Eighty-five percent of HO-HCFA CDI (n=1788), occurred in acute care; excluding recurrences (n=1409), the overall incidence rate of new cases was 9.3/10,000 BDOC and 10.5/10,000 PDs. The rate of new cases has decreased over time from a peak of 13.5/10,000 PDs in FY2005 to 7.9/10,000 PDs in FY2010. Differences in rates were seen in age, region of the country, and SCI/D characteristics. Antibiotic exposure was the largest risk factor for CDI, followed by PPI and/or H2 blocker exposure, and 30-day history of invasive respiratory procedure were associated with risk of developing CDI. Compared to those without new HO-HCFA CDI, the 30-day mortality and median LOS was significantly higher for those with new HO-HCFA CDI (16.8% vs 9.7%, p<0.0001; 81 days vs 7 days, p<0.0001). The majority of new HO-HCFA CDI cases were treated with metronidazole (80.7%) and/or vancomycin (46.3%); other treatments included bacitracin, rifampin, rifaximin, nitazoxanide, cholestyramine and colestipol (0.1%, 2.2%, 0.1%, 0.1%, 3.3%, 2.7%). Those cases treated with metronidazole were more likely to result in failure of treatment (48.9% vs 15.1%, p<0.0001) but were similar in recurrence of CDI (20.5% vs 15.4%, p=0.06) and 30-day case fatality (6.3% vs 6.3%, p=0.96). Treatment results did not vary by severity of CDI. For our secondary objective, we verified our laboratory-based definition based on a medical record review and showed that 99.4% of selected cases truly had CDI and 90.3% of those designated as non-CDI cases were truly non-CDI cases.
The incidence rate of CDI has decreased over time in Veterans with SCI/D, however, the CDI rate is higher than the general Veteran population and antibiotic use is the largest risk factor. In addition, the concurrent use of antibiotics after initial CDI onset and its impact on recurrence suggests that strategies are needed to reduce unnecessary antibiotic use including education of providers and implementing other antimicrobial stewardship strategies. This study provides baseline data on risks and incidence of CDI in this population that may be used to plan prevention strategies, improve ongoing initiatives that promote prevention of CDI, and improve the ongoing rehabilitation management of Veterans with SCI/D.
- Evans CT, Fitzpatrick M, Ramanathan S, Kralovic SM, Burns SP, Goldstein B, Smith B, Gerding DN, Johnson S. Healthcare facility-onset, healthcare facility-associated Clostridioides difficile infection in Veterans with spinal cord injury and disorder. The journal of spinal cord medicine. 2019 Oct 30; 1-11.
- Evans CT, Johnson S. Prevention of Clostridium difficile Infection With Probiotics. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015 May 15; 60 Suppl 2:S122-8.
- Evans CT, Safdar N. Current Trends in the Epidemiology and Outcomes of Clostridium difficile Infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015 May 15; 60 Suppl 2:S66-71.
- Balbale SN, Johnson S, Burns SP, Kralovic SM, Goldstein B, Gerding DN, Evans CT. Community-associated Clostridium difficile infection among veterans with spinal cord injury and disorder. Infection control and hospital epidemiology. 2014 May 1; 35(5):577-80.
- Ramanathan S, Johnson S, Burns SP, Kralovic SM, Goldstein B, Smith B, Gerding DN, Evans CT. Recurrence of Clostridium difficile infection among veterans with spinal cord injury and disorder. American journal of infection control. 2014 Feb 1; 42(2):168-73.
- Evans (Mayfield) CT, Suda KJ. Improving Infection Prevention and Management in Veterans with Spinal Cord Injury/Disorder. Paper presented at: Paralyzed Veterans of America Summit; 2015 Sep 2; Jacksonville, FL.
- Ramanathan S, Evans (Mayfield) CT. Prevalence and predictors for recurrence of Clostridium difficile infection in Veterans with spinal cord injury /disorder. Poster session presented at: Paralyzed Veterans of America Summit; 2015 Sep 1; Jacksonville, FL.
- Evans (Mayfield) C, Guihan M, LaVela SL, Weaver FM. SCI Quality Enhancement Research Initiative (QUERI): Building and Implementing. Presented at: Academy of Spinal Cord Injury Professionals Annual Meeting; 2013 Sep 2; Las Vegas, NV.
- Evans (Mayfield) C. Clostridium difficile infection in Veterans with spinal cord injury and disorder. Paper presented at: VA Center for Comprehensive Access and Delivery Research and Evaluation Annual Meeting; 2013 Aug 7; Iowa City, IA.
- Evans (Mayfield) C. Clostridium difficile infection in Veterans with spinal cord injury and disorder. Paper presented at: VA Salt Lake City Informatics, Decision Enhancement, and Surveillance Center Meeting; 2013 Jul 10; Salt Lake City, UT.
- Evans (Mayfield) C, Johnson S, Burns SP, Poggensee L, Smith BM, Goldstein B, Kralovic S, Gerding DN. Outcomes of Clostridium difficile infection (CDI) in veterans with spinal cord injury/disorder (SCI/D). Poster session presented at: ID Week: A Joint Meeting of IDSA, SHEA, HIVMA, and PIDS; 2012 Oct 17; San Diego, CA.
- Evans (Mayfield) C, Johnson S, Burns SP, Poggensee L, Smith BM, Goldstein B, Kralovic S, Gerding DN. Clostridium Difficile Infection (CDI) in Spinal Cord Injury/Disorder (SCI/D) Patients: Trends Over Time and Risk Factors. Poster session presented at: Anaerobe Society of the Americas Biennial Congress; 2012 Jun 30; San Jose, CA.
Brain and Spinal Cord Injuries and Disorders, Infectious Diseases