Bring it on again: antimicrobial stewardship in transplant infectious diseases: updates and new challenges.

Advancement in solid organ transplantation and hematopoietic stem cell transplant continues to improve the health outcomes of patients and widens the number of eligible patients who can benefit from the medical progress. Preserving the effectiveness of antimicrobials remains crucial, as otherwise transplant surgeries would be unsafe due to surgical site infections, and the risk of sepsis with neutropenia would preclude stem cell transplant. In this review, we provide updates on three previously discussed stewardship challenges: febrile neutropenia, Clostridioides difficile infection, and asymptomatic bacteriuria. We also offer insight into four new stewardship challenges: the applicability of the "shorter is better" paradigm shift to antimicrobial duration; antibiotic allergy delabeling and desensitization; colonization with multidrug-resistant gram-negative organisms; and management of cytomegalovirus infections. Specifically, data are accumulating for "shorter is better" and antibiotic allergy delabeling in transplant patients, following successes in the general population. Unique to transplant patients are the impact of multidrug-resistant organism colonization on clinical decision-making of antibiotic prophylaxis in transplant procedure and the need for antiviral stewardship in cytomegalovirus. We highlighted the expansion of antimicrobial stewardship interventions as potential solutions for these challenges, as well as gaps in knowledge and opportunities for further research.

HIV transmission through living donor kidney transplant: An 11-year follow-up on the recipient and donor.

HIV transmission via solid organ transplant is a rare but serious complication. Here, we describe long-term outcomes in a case of living donor-derived transmission of HIV in a kidney transplant recipient. After 11 years since transplant surgery, the donor shows no evidence of abnormal renal function, while the recipient continues to have a functioning graft. HIV is well controlled in both individuals. This single case report highlights the possibility of acceptable long-term outcomes in living kidney donors with HIV as well as in donor-derived HIV transmission to kidney transplant recipients.

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS-CoV-2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS-CoV-2 infection who underwent antibody testing with a single commercially available anti-nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty-six (51%) had positive anti-nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti-nucleocapsid antibodies, and transplant-related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID-19 may be less likely to form SARS-CoV-2 antibodies.

Psychosocial Factors and the Care Cascade for Hepatitis C Treatment Colocated at a Syringe Service Program.

BACKGROUND: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) is highly effective. However, people who inject drugs face significant barriers to DAA access. METHODS: We describe a program that colocates HCV management within a syringe service program in New York City. We performed a retrospective chart review of all patients with confirmed HCV viremia. RESULTS: From 2015 to 2018, 102 patients with viremia completed intake. Fifty-eight patients started DAAs. Nine patients discontinued treatment or were lost to follow-up before completion; 1 is continuing DAA treatment. Of 48 patients who completed therapy, sustained virologic response (SVR) was achieved in 43 (89.6%). Age and established mental health treatment at intake were associated with SVR. Regular cocaine use was negatively associated with SVR in univariate analysis, but this association was not significant after adjustment for age. Of 30 patients completing DAA therapy with active illicit opioid use at intake, 14 (46.4%) engaged in opioid use disorder (OUD) treatment during therapy, and 9 remained in OUD treatment after completion of DAA treatment. CONCLUSIONS: Loss to follow-up is a challenge for people who inject drugs, but among those who completed treatment, SVR was achieved at a high rate. Mental health treatment may facilitate HCV cure. Conversely, HCV therapy may facilitate engagement in OUD treatment and other services.

Cytomegalovirus Infection in Allogeneic Hematopoietic Cell Transplantation Managed by the Preemptive Approach: Estimating the Impact on Healthcare Resource Utilization and Outcomes.

We quantified cytomegalovirus (CMV) antiviral use and hospital length of stay (LOS) associated with CMV infection in a contemporary cohort of conventional (CONV) and CD34-selected (T cell-depleted) hematopoietic cell transplantation (HCT) recipients managed by preemptive therapy (PET) in a single US center. Adults who received first allogeneic HCT at Memorial Sloan Kettering Cancer Center from June 2010 through December 2014 were analyzed. Days on PET, number of readmissions, and readmission LOS by day 180 post-HCT were summarized. Estimated unit value (EUV) was defined as the expected number of PET days for a cohort of 100 HCT with characteristics as the analyzed cohort. Standardized incidence ratio was calculated as the ratio of observed outcomes of patients with CMV viremia over the outcomes of patients without CMV viremia. Of 318 patients, 88 received CONV and 230 CD34-selected HCT. Rates of CMV viremia were 26.3% for CONV and 41.9% for CD34-selected (P = .003). Among patients with viremia 68.2% CONV and 97.9% CD34-selected received PET. EUV for PET was 852 days and 2821 days for CONV and CD34-selected, respectively. The standardized incidence ratios for number of readmission and readmission LOS were 1.7 (95% confidence interval [CI], 1.4 to 2.1) and 1.2 (95% CI, 1.1 to 1.3), respectively, for CONV HCT and 1.7 (95% CI, 1.3 to 2.1) and 1.6 (95% CI, 1.5 to 1.7), respectively, for CD34-selected HCT. Overall survival was similar between patients with and without CMV viremia by HCT type. CMV end-organ disease was associated with lower overall survival only in CD34-selected HCT (P = .0007). CMV infection managed by PET requires substantial antiviral use and is associated with longer readmission LOS more, particularly among CD34-selected HCT.

Co-Infections by Double-Stranded DNA Viruses after Ex Vivo T Cell-Depleted, CD34+ Selected Hematopoietic Cell Transplantation.

Recipients of ex vivo T cell-depleted (TCD) hematopoietic cell transplantation (HCT) are at risk of infection by double-stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV). Healthcare utilization in the first 6 months post-HCT was compared between patients with dsDNA viremia versus no viremia. This was an observational study of adult patients with acute leukemia and myelodysplastic syndrome who received CD34+ selected, peripheral blood HCT at Memorial Sloan Kettering Cancer Center from March 2012 through December 2014. Patients were prospectively monitored by quantitative PCR assays for CMV, ADV, HHV6, and EBV in whole blood or plasma. The cumulative incidence of viremia(s) at day +180, EOD at 1 year, and OS at 1 year were estimated by the Kaplan-Meier method and compared by the log-rank test among patient with and without viremia/EOD. Standardized incidence ratios were used to compare overall length of hospital stay (LOS), number of readmissions after HCT, and length of readmissions through day +180. Of 156 patients, 96 (62%) were CMV recipient seropositive. Forty-two patients received grafts from matched related (27%), 86 from matched unrelated (55%), and 28 from mismatched (18%) donors. Overall, 132 patients (85%) had ≥1 viremia and 52 (33%) ≥2 viremias by day +180. The cumulative incidences for CMV, HHV6, ADV, and EBV viremia were 44%, 61%, 7%, and 16%, respectively, with median times of onset 28 days (interquartile range [IQR], 25 to 33), 33 days (IQR, 25 to 47), 60 days (IQR, 19 to 84), and 79 days (IQR, 54 to 106) post-HCT, respectively. Twenty-eight patients (18%) developed EOD by dsDNA viruses at 1 year post-HCT. Treatment for CMV accounted for 91% total antiviral treatment-days. Compared with patients with no viremia, patients with CMV viremia, HHV6 viremia, or ≥2 viremias experienced longer LOS (P <.001) and a higher number of readmissions (P <.001) by day +180. OS rate at 1 year was 79% and was similar between patients with or without dsDNA viremias. EOD was associated with lower 1-year OS rates (63.4%) versus without EOD (81.1%) (P = .02). Of 33 patients who died, 10 died due to infection, and 7 of these infection-related deaths were due to dsDNA viruses. Viremia by dsDNA viruses occurred in 85% of TCD HCT recipients by day +100 and 33% of patients experienced ≥2 viremias by day +180. CMV accounted for most antiviral use. CMV, HHV6, or ≥2 viremias were associated with more readmissions and longer LOS. One year OS rate was 78%. EOD by dsDNA viruses was associated with decreased 1-year OS. Infections by dsDNA viruses pose a substantial burden after TCD HCT.

Understanding and preventing wrong-patient electronic orders: a randomized controlled trial.

OBJECTIVE: To evaluate systems for estimating and preventing wrong-patient electronic orders in computerized physician order entry systems with a two-phase study. MATERIALS AND METHODS: In phase 1, from May to August 2010, the effectiveness of a 'retract-and-reorder' measurement tool was assessed that identified orders placed on a patient, promptly retracted, and then reordered by the same provider on a different patient as a marker for wrong-patient electronic orders. This tool was then used to estimate the frequency of wrong-patient electronic orders in four hospitals in 2009. In phase 2, from December 2010 to June 2011, a three-armed randomized controlled trial was conducted to evaluate the efficacy of two distinct interventions aimed at preventing these errors by reverifying patient identification: an 'ID-verify alert', and an 'ID-reentry function'. RESULTS: The retract-and-reorder measurement tool effectively identified 170 of 223 events as wrong-patient electronic orders, resulting in a positive predictive value of 76.2% (95% CI 70.6% to 81.9%). Using this tool it was estimated that 5246 electronic orders were placed on wrong patients in 2009. In phase 2, 901 776 ordering sessions among 4028 providers were examined. Compared with control, the ID-verify alert reduced the odds of a retract-and-reorder event (OR 0.84, 95% CI 0.72 to 0.98), but the ID-reentry function reduced the odds by a larger magnitude (OR 0.60, 95% CI 0.50 to 0.71). DISCUSSION AND CONCLUSION: Wrong-patient electronic orders occur frequently with computerized provider order entry systems, and electronic interventions can reduce the risk of these errors occurring.