Conclusion

CDI affects patient mortality and morbidity and increases hospitalization costs. ^{Reference Ghantoji, Sail, Lairson, DuPont and Garey5,Reference Hengel, Schroeder and Jo22} The 2017 estimates for CDI were approximately 462,000 cases of which 235,000 were healthcare-associated making rehospitalizations a significant CDI healthcare cost. ^{Reference Guh, Mu and Winston1} Despite studies investigating CDI-associated readmission rates, a systematic review and meta-analysis have not been performed to calculate estimated rates or investigate prevention strategies. Our study identified an overall rate of 30-day CDI-associated readmission of 7% (95% CI, 5%–8%). These results were consistent between differing study designs, locations, years, and other study characteristics. This study was unable to distinguish between polymerase chain reaction (PCR)-based and other testing for C. difficile infection. PCR testing does not differentiate colonization from infection, and thus, it is quite possible that a portion of CDI readmission cases may have been colonized with C. difficile and admitted for other reasons. A critical review of hospitalization and CDI costs estimated attributable costs for CDI that ranged from $6,774 to $12,212 (2014 USD) for CDI requiring hospital admission. ^{Reference Gabriel and Beriot-Mathiot23} Readmission rates have been shown to affect hospital financial performance in other disease states. ^{Reference Upadhyay, Stephenson and Smith24} In addition to cost containment, readmissions are often considered an easily available measure of quality of care. ^{Reference Fischer, Lingsma, Marang-van de Mheen, Kringos, Klazinga and Steyerberg25} However, distinguishing between planned and unplanned readmissions can be difficult, and accurate data coding can be problematic. This is especially important for CDI in which antibiotics given after hospital discharge can also precipitate dysbiosis of the gut microbiome increasing the risk of CDI. A comprehensive case for economic cost benefits to develop strategies to prevent recurrences was not identified in our review. Nonetheless, in this systematic review, both antimicrobial stewardship strategies in general and the use of therapies known to reduce the likelihood of CDI recurrence (bezlotoxumab) were effective at reducing hospital readmissions. ^{Reference Brumley, Malani, Kabara, Pisani and Collins13,Reference Prabhu, Cornely and Golan19} The interventional studies had above-average readmission rates at baseline. Whether interventions in hospitals with an average rate of 6% would be as effective will require further study. Study quality for identified manuscripts was adequate although we did not personally contact authors for NOS scores but rather judged based on information provided. The 2 nationwide studies were conducted during overlapping periods leaving a small possibility of duplication of patients. Patients in these studies were identified by ICD9/10 codes which may not be entirely reliable. The antimicrobial stewardship bundle included appropriate CDI antimicrobial therapy based on local guidelines, discontinuation of acid suppressive therapy if not indicated, and discontinuation of other unneeded antimicrobials. ^{Reference Brumley, Malani, Kabara, Pisani and Collins13} These data demonstrate that 30-day CDI-associated readmissions are common and modifiable. With a high incidence of disease and the costs of hospitalization, hospital budget holders should invest in strategies that can prevent CDI or recurrent CDI and scale it to invest globally to reduce rates. This would help allocate hospital beds for patients in most need and help allocate resources to CDI patients identified with a high risk of hospital readmission.

In conclusion, this systematic review identified a 6% rate of 30-day CDI-associated hospital readmission. Interventions including antimicrobial stewardship efforts and the use of bezlotoxumab were shown to reduce these rates.