<span class="paragraphSection"><strong>Objectives:</strong> The incidence of <span style="font-style:italic;">Clostridium difficile</span> infection (CDI) in adults with malignancy is 7%–14% compared with 1%–2% in the general hospitalized population. Despite the increased incidence of CDI in this population, a major concern is the propensity of CDI to recur, leading to delays in therapy impacting outcomes. We conducted a retrospective case–control study to identify risk factors for recurrent CDI (rCDI) and to determine the impact of rCDI on adult patients with a haematological malignancy.<strong>Methods:</strong> Adult haematology patients with CDI from June 2010 to December 2014 were divided into two groups: rCDI and non-rCDI. Multivariable models using logistic regression were constructed to identify risk factors for rCDI.<strong>Results:</strong> A total of 100 patients in our study yielded a 41% recurrence rate. CDI impacted chemotherapy significantly more in the rCDI group (53.7% versus 11.9%, <span style="font-style:italic;">P</span> <0.001), primarily due to interruptions in established treatment plans (46.3% versus 10.3%, <span style="font-style:italic;">P</span> <0.001). Risk factors for rCDI identified at index included salvage lymphoma chemotherapy (OR 9.64, 95% CI 1.02–91.15, <span style="font-style:italic;">P</span> = 0.048) and severe CDI (OR 4.82, 95% CI 1.31–17.66, <span style="font-style:italic;">P</span> = 0.018). Longitudinal risk factors included exposure to fluoroquinolones (OR 3.96, 95% CI 1.04–15.15, <span style="font-style:italic;">P</span> = 0.044), ceftriaxone (OR 18.93, 95% CI 1.27–281.95, <span style="font-style:italic;">P</span> = 0.033) and piperacillin/tazobactam (OR 10.4, 95% CI 1.81–59.64, <span style="font-style:italic;">P</span> = 0.009).<strong>Conclusions:</strong> Haematology patients exhibit a higher rate of rCDI than general hospitalized patients. Utilization of this multivariable model to guide index CDI therapy at index may help to decrease the rCDI and prevent delays or interruptions in chemotherapy.</span>
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