Friday, December 23, 2016 Written by Dr. Erminia Casari is Director at the Microbiology Laboratory of Humanitas Hospital in Milan, Italy and Professor of Microbiology at the Specializing School of Microbiology and Virology at University of Pavia

Cost-effective Management of Clostridium difficile Infection—the Humanitas Experience

Clostridium difficile infection (CDI) is increasingly recognized as one of the most important healthcare associated infections throughout Europe, Canada and the United States.[1] The increasing incidence and severity has been attributed to the emergence of the hypervirulent strains PCR ribotypes 027 and 078 and the prevalence of CDI has risen from 3% to 13% [2, 3]. With the increasing infection rates from C. difficile, many recent studies have focused on the economic burden imposed by the management of CDI – notably, extended hospitalization, laboratory costs, and medical costs.[4]

For Humanitas, a revolutionary turning point in CDI infection management occurred with the implementation of rapid molecular diagnostics using the Xpert C. difficile test. Patient length of stay (LOS) has decreased, as has the need for repeat testing. The time to accurate CDI diagnosis is much faster, and antimicrobial stewardship has substantially improved.

Humanitas is a consortium of three private hospitals known in Italy as “Istituto di Ricovero e Cura a Carattere Scientifico” (IRCCS). It is a centre for healthcare service excellence, recognized by the Ministry of Health and the regional government of Lombardy. These accolades, however, have not provided immunity from the increasing prevalence of CDI. Between 2010 and 2011, CDI rates at Humanitas rose from 8% to 12% --rates comparable for acute hospitals in Italy [5].

Prior to the implementation of the Xpert C. difficile test in December 2011, patients suspected of CDI stayed in isolation on average 18 and 25 days in 2010 and 2011 respectively. The enzyme immunoassay (EIA) toxin A/B testing used as a standalone testing algorithm is rapid, yet provided unreliable and inconclusive CDI diagnosis. Delays in accurate diagnosis meant that tests were being repeated-- at times on 10 separate samples per patient [Fig1 – EIA toxin A/B workflow]. Delays were further compounded by a lack of standardization of stool samples tested. Additionally, there were delays in commencement of antibiotic treatment for presumed-negative, now-positive patients.

Humanitas had already successfully implemented the Xpert MTB/RIF test on the GeneXpert system for routine molecular testing for Mycobacteria tuberculosis. The introduction of the Xpert C. difficile test now enabled rapid and highly sensitive molecular diagnosis for CDI. Adopting ESCMID guidelines[6] for PCR-based diagnostic CDI testing enabled improved infection surveillance management practices, important for the Humanitas hospital group.

Introduction of molecular CDI diagnosis with Xpert C. difficile improved the patient management workflow for CDI. A comparison of the former EIA testing workflow and newer Xpert C. difficile workflow can be seen in Figures 1 and 2. The accuracy and high sensitivity of the Xpert C. difficile test meant that cases unresolved by the reduced performance of EIA testing were now resolved. Patients identified as CDI-positive were also able to commence appropriate antibiotics treatment sooner rather than later. Introduction of the Xpert C. difficile test has also reduce the number of endoscopy test requests, which is now only required in severe cases. Clinicians have grown confident in the performance of Xpert C. difficile, such that patients testing negative are removed from isolation within a day thereby freeing up beds for patients testing positive.

The accuracy of front-end PCR diagnosis enables starting appropriate treatment earlier. It also allows infection resolution to be monitored using only clinical symptoms, as opposed to unreliable EIA testing, a practice common in most Italian hospitals. Freedom from diagnostic testing on the back end of the patient management process has reduced the average patient stay in isolation. The average isolation LOS is now 13 days, a decrease of 5 and 12 days respectively, compared with 2010 and 2011 LOS.

While the Xpert C. difficile test is associated with increased test costs, the reduction in repeat testing and the resulting improvement in patient management practices has not only justified the investment but shown a reduction in overall hospital costs [Figure 3].

Testing with Xpert C. difficile resulted in approximately a 4-fold reduction in testing numbers compared to EIA. The increased diagnostic cost is offset by a reduction in antibiotic treatment and decontamination costs [Figure 4] and average isolation days [Figure 5].

Overall the Humanitas Hospital has seen improvement in patient management and savings in hospitalization costs despite the additional cost of PCR testing as compared with EIA testing for CDI.

Author information:
Dr. Erminia Casari is Director at the Microbiology Laboratory of Humanitas Hospital in Milan, Italy and Professor of Microbiology at the Specializing School of Microbiology and Virology at University of Pavia. She has published in multiple journals, on diagnostic microbiology and infectious diseases.

To listen to Dr Casari’s recorded webinar on “Clostridium difficile: Improvements in Patient Management - Use of Standalone Rapid Molecular Test in Acute Hospital Setting” click on: http://www.cepheidimpact.com/workshop-series.php.

References

  1. Kuijper EJ, Coignard B, Tüll P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect. 2006;12 Suppl 6:2-18.
  2. Goorhuis A, Bakker D, Corver J, et al. Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis 2008; 47:1162–70.
  3. Rupnik M,Widmer A, Zimmermann O, Eckert C, Barbut F. Clostridium difficile toxinotype V, ribotype 078, in animals and humans. J Clin Microbiol 2008; 46:2146.
  4. GHANTOJI SS, SAIL K, LAIRSON DR, DUPONT HL, GAREY KW. Economic healthcare costs of Clostridium difficile infection: a systematic review. J Hosp Infect 2010; 74: 309-318.
  5. SANSONE S, ASCHBACHER R, STAFFLER M, BOMBONATO M, GIRARDI F, LARCHER C, WIEDERMANN CJ. Nosocomial diarrhea in adult medical patients: the role of Clostridium difficile in a North Italian acute care teaching hospital. J Prev Med Hyg 2009, 50: 117-120.
  6. M. J. T. Crobach, O. M. Dekkers, M. H. Wilcox, E. J. Kuijper. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): Data review and recommendations for diagnosing Clostridium difficile-infection (CDI).Clin Microbiol Infect 2009; 15: 1053–1066