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2670. Clostridioides difficile Infection (CDI) in Solid-Organ (SOT) and Hematopoietic Stem Cell Transplant (HCT) Recipients: A Prospective Multinational Study

Abstract Background CDI is an important cause of morbidity and mortality in SOT and HCT patients (pts). In retrospective single-center analyses, severe disease and relapse were common. We undertook a multicenter prospective observational study to evaluate outcomes of CDI among both SOT and HCT patients. Methods Adults with a first episode of CDI, defined as 3 liquid stools/24 h with the detection of C. difficile toxin in stool, within the first 2 years of SOT or HCT were recruited from 12 centers internationally in the INSIGHT network. At enrollment, demographics, comorbidities, medication histories and outcomes were collected prospectively over 90 days to assess clinical cure, recurrences and complications and to define baseline risk factors for clinical cure and recurrent CDI. Results 132 patients (81 SOT, 51 HCT (32 allogeneic)) were enrolled: median age 56 years, 62.1% were males, 97% were hospitalized. 80.3% were diagnosed by DNA assay. CDI occurred a median of 20 days post transplant (IQR: 6–133). 108 patients were on PPIs. 98.5% were on antibiotics before CDI. 1st line treatment regimen was oral vancomycin in 66 patients (40 SOT, 26 HCT), metronidazole in 48 patients (27 SOT, 21 HCT), both drugs in 14 (10 SOT, 4 HCT), fidaxomicin (3) and linezolid (1). Rejection within 60 days before CDI was uncommon (6.2% SOT) as was GVHD (27.5%). 110 patients (83%, 95% CI: 46–89)) (65 SOT, 45 HCT) had clinical cure; 18% (95% CI: 11–27) had recurrent CDI, 2 were admitted to the ICU due to CDI, 11 (8.3%) died (2 HCT related to CDI). Among baselines variables, only first-line regimen was associated with a higher rate of clinical cure (P = 0.003), most notably for SOT. Factors that did not have a statistically significant negative impact on clinical cure included sex, age > 60, race, country, transplant type, steroids, diabetes, CMV viremia/disease, WBC > 15,000, creatinine > 1.5 mg/dL, or specific antibiotic given prior to CDI. Higher recurrence rates were associated with metronidazole-only regimen (OR: 4.6, 95% CI: 1.6–12.8; P = 0.004) and a history of CMV after transplant (OR: 5.2, 95% CI: 1.7–15.7; P = 0.003). Conclusion Despite their immunosuppressed state, recurrence, ICU admission and mortality occurred in a minority of SOT and HCT with CDI. Initial use of metronidazole and CMV viremia/disease were associated with higher recurrence rates. Disclosures All authors: No reported disclosures.


Tufts Medical Center, Boston, Massachusetts
Session: 274. Transplant ID: C. diff Saturday, October 5, 2019: 12:15 PM Background: CDI is an important cause of morbidity and mortality in SOT and HCT patients (pts). In retrospective single-center analyses, severe disease and relapse were common. We undertook a multicenter prospective observational study to evaluate outcomes of CDI among both SOT and HCT patients.
Methods: Adults with a first episode of CDI, defined as 3 liquid stools/24 h with the detection of C. difficile toxin in stool, within the first 2 years of SOT or HCT were recruited from 12 centers internationally in the INSIGHT network. At enrollment, demographics, comorbidities, medication histories and outcomes were collected prospectively over 90 days to assess clinical cure, recurrences and complications and to define baseline risk factors for clinical cure and recurrent CDI.
Conclusion: Despite their immunosuppressed state, recurrence, ICU admission and mortality occurred in a minority of SOT and HCT with CDI. Initial use of metronidazole and CMV viremia/disease were associated with higher recurrence rates.
Disclosures. All authors: No reported disclosures.  (CDI) is a leading cause of morbidity and mortality in a hospitalized patient. The incidence and severity of nosocomial CDI have increased significantly since the year 2000. Solid-organ transplant recipients (SOT) are at high risk for CDI for multiple reasons including impaired defense mechanisms from immunosuppression, perioperative antibiotic use, and organ failure. For the past decade, there has been the advance modality of diagnosis and treatments for CDI including early detection of toxin, novel antibiotics, and fecal microbiota transplantation. With the innovative measurements and the effort of antibiotic stewardship, the recent study show improvement of mortality in hospitalized CDI; however, there is still lack of such evidence among SOT patients. Therefore, it would be beneficial to scrutinize the prevalence and outcomes of CDI among SOTs with the most current available nationwide database.

Outcomes of Clostridium difficile Infection in Solid-Organ
Methods: Our study utilized the 2015 and 2016 National Inpatient Sample (NIS). It is the largest publicly available all-payer inpatient healthcare database in the United States, yielding national estimates of hospital inpatient stays. Patients with history or undergoing SOT transplant procedure who were hospitalized in 2015 and 2016 NIS database were included in our study. We included heart, lung, liver, intestinal, kidney, pancreas, or at least one of these organs transplanted in our definiton of SOT. History of organ tranplants and CDI were extracted by using ICD-9-CM and ICD-10-CM from discharged diagnosis. Baseline characteristic include age, gender, race, median household income were collected. Confounding includes comorbidities which were calculated into charlson comorbidity index (CCI) and discharge diagnosis of pneumonia and urinary tract infection. Primary outcomes include in-patient mortality, hospital length of stay and total hospital charges. Secondary outcomes include transplant failure or rejection, colectomy and disposition of patients. Multivariable logistic regression was used for the adjusted analysis of the primary and secondary outcomes include all confounders and significant covariates. All reported CIs were two-sided 95% intervals, and tests were done at the two-sided 5% significance level. Stata v14.2 (Stata Corp, College Station, Texas) was utilized for all analyses.
Conclusion: Our study found that CDI associated with significant overall worse outcomes among hospitalized solid-organ transplant patients. Multicenter prospective study is considered as a future direction to evaluate the impact to healthcare. Despite the improvement of overall mortality of CDI in general population in the United States from prior study, CDI in SOTs remains problematic. More attention is needed in this particular field.