Impact of Xpert® Carba-R-based screening for carbapenem-resistant organisms on infection-related mortality in hematopoietic stem cell transplant recipients.

Background: The emergence of carbapenem-resistant organisms (CROs) poses a major challenge to clinical infection control in hospitals. Patients undergoing hematopoietic stem cell transplants (HSCTs) infected with CROs are at high risk of mortality. Proactive screening of HSCT patients for CRO colonization may enable early and accurate preemptive anti-CRO therapy, reduce the probability of secondary infections, and contribute to infection prevention and control measures. However, screening CRO colonization with stool/rectal swab culture and sensitivity has a low positivity rate with a long turnaround time, which limits the effectiveness of the interventions. A more rapid and accurate method to detect CRO colonization is urgently needed. Xpert Carba-R assay provides a rapid and accurate detection of carbapenemase types, enabling targeted anti-infective therapy selection based on the identified resistance mechanism. Methods: We conducted a historically controlled prospective study at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between August 2021 and July 2022. The study population comprised adult HSCT patients (≥18 years old) who received preemptive anti-CRO therapy based on rectal culture and Xpert Carba-R screening during this period. A total of 381 patients who underwent HSCT from August 2020 to July 2022 were included in the study, and CRO colonization screening was performed on admission and weekly thereafter. In the historic control group from August 2020 to July 2021, HSCT patients were screened only by rectal swab traditional CRO culture, and CRO colonization was determined if the rectal culture was positive. In the study group from August 2021 to July 2022, two rectal swab specimens were collected from HSCT patients for both CRO traditional culture (RS-culture) and Xpert Carba-R testing (RS-Carba-R). CRO colonization was determined if either of the screening methods was positive. CRO-active antibiotics were immediately provided on the first febrile episode of neutropenia (FN) in CRO-colonized patients. Clinical outcome data for the CRO monthly colonization rate and anti-infection efficiency were collected and contrasted between the two groups. Results: In the historic group, 47 out of 197 patients (23.9%) were identified as colonized with CRO, detected only by RS-culture. In the study group, 41 out of 184 patients (22.3%) were identified as colonized with CRO, detected by either RS-culture or RS-Carba-R; among them, Escherichia coli was the most common CP-CRO strain, and the most prevalent carbapenemase type was NDM. This indicated a slightly lower annual detection rate of CRO gut colonization in the study group compared to the historic group, but no significant difference was observed (22.3% vs. 23.9%, p = 0.715). The incidence of CRO-related bloodstream infections (CRO-BSI) was significantly lower in the study group compared to the historic group (4.8% vs. 25.5%, p = 0.012), and the CRO-related mortality in colonized patients decreased from 19.4% in the historic group to 2.4% in the study group (p = 0.046). The monthly detection rate of CRO gut colonization by RS-culture in the historic group remained steady, with no significant fluctuation (19.7% in the first month and 18.8% in the last month). In contrast, the monthly detection rate of CRO gut colonization by either RS-culture or RS-Carba-R in the study group was higher in the first month compared to the historic group (21.2% in August 2021 vs. 18.8% in July 2021). However, a gradual decline in the monthly detection rates of CRO gut colonization by RS-culture and/or RS-Carba-R was observed in the study group, dropping from 21.2% in the first month to 2.9% in the last month. The univariate and multivariate analyses indicated that the study group had a shorter length of hospitalization (OR = 0.94, 95% CI 0.88-0.99, p = 0.038) and CRO-related mortality (OR = 0.12, 95% CI 0.01-0.75, p = 0.021) than the historic group. Conclusions: Our study showed a positive effect of more rapid CRO colonization screening using rectal swabs with Xpert Carba-R and culture, which can guide potent CRO preemptive therapy for subsequent infections based on the detected carbapenemase mechanism, thereby reducing mortality and the spread of CRO infection in HSCT patients. Clinical Trial Registration: chictr.org, identifier ChiCTR2100041976.