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Objective: To describe clinical syndromes, opportunities for antimicrobial optimization, and acceptance of recommendations made by an immunocompromised antimicrobial stewardship program performing in-person prospective audit and feedback (IPPAF) on inpatient oncology services., Design: Retrospective cohort study., Setting: Three inpatient oncology services including patients with solid tumor malignancies in an academic cancer center., Patients: Hospitalized adults with oncologic malignancies receive antimicrobials for any indication., Methods: We reviewed all patients receiving antimicrobials on inpatient oncology services who were included in IPPAF and prospectively documented clinical syndromes represented, most common recommendations, and acceptance rate. We also examined the standardized antimicrobial administration ratio (SAAR) for oncology units over the study period., Results: Over 34 weeks, we performed 154 interventions for 138 patients. Metastatic malignancy was common (52%) and 90-day mortality was high (43%). Diagnostic uncertainty was common (33/154, 21%), as were cases of intra-abdominal pathology (30/154, 19%), pneumonia (25/154, 16%), and urinary tract infection (12/154, 8%). The most common recommendations were changes in duration (63/154, 41%) and stopping antimicrobials for syndromes determined to be noninfectious (29/154, 19%). Acceptance of interventions was high (77% overall) and several SAARs on the primary oncology unit significantly decreased after starting IPPAF., Conclusions: We identified numerous opportunities for antimicrobial optimization among solid tumor malignancy patients. Most clinical syndromes were ones also encountered frequently in non-oncology populations, but several were unique and represented opportunities for targeted education., Competing Interests: None., (© The Author(s) 2024.)

Background: In the United States, universal screening for human T-lymphotropic virus (HTLV) in deceased organ donors was discontinued in 2009. Since then, the transplant guideline suggests considering targeted screening. However, the outcomes of this change in HTLV screening have not been evaluated., Methods: Using the Organ Procurement and Transplantation Network database between 2010 and 2022, we analyzed the HTLV antibody screening frequency and seroprevalence in potential deceased organ donors and their correlations with HTLV infection risks, including race and high-risk behaviors for blood-borne pathogen infection. Although targeted screening has not been established for HTLV, we hypothesized that screening rates should correlate with the proportions of donors with infection risk if screening is targeted. We also evaluated the organ utilization of HTLV-seropositive donors., Results: Of 130 284 potential organ donors, 22 032 (16.9%) were tested for HTLV antibody. The proportion of donors tested for HTLV varied between Organ Procurement Organizations (median [interquartile range], 3.8% [1.0%-23.2%]; range, 0.2%-99.4%) and was not correlated to HTLV infection risks. There were 48 seropositive donors (0.22%), and at least 1 organ from 42 of these donors (87.5%) was transplanted. The number of organs recovered and transplanted per donor was significantly lower in HTLV-seropositive than in HTLV-negative donors (recovered, 2 [2-3] versus 3 [3-5], P  < 0.001; transplanted, 2 [1-3] versus 3 [2-4], P  < 0.001). However, HTLV-1 infection was not attributed as the cause of nonrecovery except for only 1 HTLV-seropositive donor., Conclusions: HTLV screening practices varied across the United States. Our findings suggest that targeted screening was not performed after the elimination of universal screening., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV)., Methods: We report the results of a phase I/II, double-blind, placebo-controlled randomized dose-escalation trial of cidofovir in KTRs with biopsy-confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow-up through day 49., Results: The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log 10 reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group)., Conclusions: These preliminary results indicate that low-dose cidofovir was safe and tolerated but had no significant BKPyV-specific antiviral effect in KTRs with BKPyVAN., (© 2024 The Author(s). Transplant Infectious Disease published by Wiley Periodicals LLC.)

Purpose of Review: We aim to review the rationale, methods, and experiences with diagnostic stewardship targeted at urinary tract infection (UTI) and related urinary syndromes., Recent Findings: In the last 18 months, several articles have demonstrated the impact of diagnostic stewardship interventions at limiting inappropriate diagnosis of UTIs or inappropriate antibiotic-prescribing, targeting the urinary tract. Antimicrobial stewardship programs may create and implement interventions at the point of urine test ordering, urine test resulting, or at the point of prescribing antibiotics after results have returned. Specific design and implementation of stewardship interventions depends on context. To maximize their impact, interventions should be accompanied by education and garner buy-in from providers., Summary: Diagnostic stewardship can decrease unnecessary antibiotics and inappropriate diagnosis of UTI with multifaceted interventions most likely to be effective. Remaining questions include how to reduce ASB treatment in new populations, such as those with immune compromise, and persistent unknowns regarding UTI diagnosis and diagnostics., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Repeating nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reactions (PCRs) within 14 days may increase healthcare costs and inform anti-MRSA antibiotic therapy without known benefit. Within an inpatient admission, our retrospective, single-center evaluation found that conversion from negative to positive on repeat nasal MRSA PCR screen was uncommon (2%)., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

Immunocompromised (IC) patients are high risk for complications due to a high rate of antibiotic exposure. Antimicrobial stewardship interventions targeted to IC patients can be challenging due to limited data in this population and a high risk of severe infection-related outcomes. Here, the authors review immunocompromised antimicrobial stewardship barriers, metrics, and opportunities for antimicrobial use and testing optimization. Last, the authors highlight future steps in the field., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Acceptable post-transplant outcomes were reported in kidney transplant recipients from donors with coronavirus disease 2019 (COVID-19); however, there are no comparative studies with well-matched controls., Methods: This multicenter, prospective observational study, which included three transplant centers in the United States, enrolled 61 kidney recipients from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected deceased donors. Using optimal matching methods, we matched every recipient to three comparators receiving kidneys from SARS-CoV-2-negative deceased donors with otherwise highly similar characteristics in the same transplant centers to compare 6-month eGFR., Results: Among recipients of SARS-CoV-2-infected donor kidneys, one recipient died with a functional graft within 6 months. Mean 6-month eGFR was not significantly different between SARS-CoV-2-infected and noninfected donor groups (55±21 and 57±25 ml/min per 1.73 m 2 , respectively; P = 0.61). Six-month eGFR in recipients from SARS-CoV-2-infected donors who died of reasons other than COVID-19 was not significantly different from those from SARS-CoV-2-negative donors (58±22 and 56±25 ml/min per 1.73 m 2 , respectively; P = 0.51). However, recipients from donors who died of COVID-19 had significantly lower 6-month eGFR than those from SARS-CoV-2-negative donors (46±17 and 58±27 ml/min per 1.73 m 2 , respectively; P = 0.03). No donor-to-recipient SARS-CoV-2 transmission was observed., Conclusions: Six-month eGFR was not significantly different between recipients of kidneys from SARS-CoV-2-infected and noninfected donors. However, those receiving kidneys from donors who died of COVID-19 had significantly lower 6-month eGFR. Donor-to-recipient SARS-CoV-2 transmission was not observed., (Copyright © 2023 by the American Society of Nephrology.)

Solid organ transplant recipients (SOTRs) remain at high risk for infection throughout their post-transplant course. Dosing of immunosuppressive medications, strategies that prevent infection, and choice of empiric antimicrobial treatment could be optimized by a better understanding of an individual patient's risk for infectious complications. Diagnostic tests that qualitatively or quantitatively measure the function of the immune system and/or its response to infection may be useful for individualized management decisions. Numerous studies have identified an association between infectious outcomes after solid organ transplantation (SOT) and the results of a variety of non-pathogen-specific or "pathogen-agnostic" immune monitoring tests. These biomarkers include humoral immune markers, functional or quantitative assessments of cellular immunity, transcriptomic-based diagnostics, and replication of viruses within the human virome, which have been used to predict or diagnose a variety of different infectious diseases complicating SOT. In this narrative review, we discuss several host-derived immune biomarkers that show promise for either predicting or diagnosing infection among SOTRs. However, additional studies are needed to determine the optimal use of immune response testing. Whether immune biomarkers contribute added benefits to current standard clinical care has not yet been determined. Testing must be validated across a range of clinical scenarios, including surveillance to predict infection risk and diagnosis of active infection at various time points post transplant., (© 2023 Wiley Periodicals LLC.)

Background: Cytomegalovirus (CMV) donor-positive/recipient-negative (D+R-) serostatus is independently associated with worse allograft and patient survival across solid organ transplant (SOT) types. We characterized trends in CMV D+R- serostatus among adult SOT recipients performed in the United States., Methods: Donor (D) and recipient (R) CMV serostatus and demographic factors were obtained from the Scientific Registry of Transplant Recipients for persons ≥18 y undergoing a first SOT between January 1, 2000, and December 31, 2020. The proportions of D+R- SOTs over time were assessed using Chi square for trend and modeled through 2040. Factors associated with D/R seropositivity were assessed using logistic models., Results: Among 472 549 SOTs, the average proportion of D+R- SOTs increased significantly among kidney, liver, heart, and lung between 2000 to 2009 and 2010 to 2020: 18.0% to 18.3% ( P  = 0.034), 19.4% to 21.8% ( P  < 0.001), 22.2% to 25.5% ( P  < 0.001), and 23.6% to 27.0% ( P  < 0.001), respectively. The increased proportion over time resulted from a disproportionate increase in R- (34.9% to 37.0% for all organ types, P  < 0.001) and a smaller corresponding change in D+ (60.8% to 60.3%, P  < 0.001)., Conclusions: The proportion of high-risk CMV D+R- SOTs increased significantly across all organs and is projected to continue to increase. These findings inform population-level strategies to mitigate the negative impact of CMV D+R- in SOT., Competing Interests: A.P.L. has received consulting fees, research support, contracted research, or consulting fees from: Amplyx Pharmaceuticals, Novartis, Merck, J&J, NovoNordisc, GSK, NobelPharma, Hologic, and Allovir. The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: A.P.L. has received consulting fees, research support, contracted research, or consulting fees from Amplyx Pharmaceuticals, Novartis, Merck, J&J, NovoNordisc, GSK, NobelPharma, Hologic, and Allovir. H.I. declares no conflicts of interest.

Background: A growing number of studies have demonstrated similar outcomes with shorter courses of antibiotics for bacterial infections. Immunocompromised patients are frequently excluded from these studies despite anticipated benefits associated with shortening antibiotic courses (including lower risks of antibiotic toxicity, Clostridioides difficile infection, drug-resistant pathogens, and microbiome alterations)., Objectives: To critically review the literature that assesses shorter antibiotic courses in immunocompromised patients, specifically among solid organ transplant recipients and neutropenic fever (NF) syndromes among patients on antineoplastic chemotherapy and undergoing haematopoietic cell transplant., Sources: References were identified through searches of PubMed, Embase, MEDLINE, and clinical guidelines documents., Content: Among organ transplant recipients, the majority of studies assessing outcomes associated with shorter antibiotic courses have been retrospective but have demonstrated similar rates of clinically relevant endpoints. Patients with high- and low-risk NF have been well-studied, including enrolment in randomized studies, albeit with heterogeneous patient populations and outcomes assessed. Clinical improvement-guided adoption of shorter courses has been associated with fewer antibiotic days and similar rates of fever recurrence and mortality., Implications: Similar to studies demonstrating efficacy in immunocompetent patients, shorter antibiotic courses should be considered for immunocompromised hosts with presumed bacterial infections. Organ recipients and patients with NF syndromes should be prioritized for study in randomized controlled clinical trials assessing shorter course therapy., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Prolonged antibiotics are associated with toxicity, selection for resistant organisms, and secondary infections such as Clostridioides difficile colitis. Emerging clinical data suggest that short courses of antibiotics can be used for common bacterial infections among immune competent patients, but for many randomized controlled trials (RCTs), immunocompromised patients, including solid organ transplant recipients (SOTRs), have been excluded., Methods: Peer-reviewed publications were identified through PubMed and Embase searches., Results: We review data examining shorter antibiotic courses among immunocompetent and immunocompromised patients and the rationale for use of short antibiotic courses in SOTRs., Conclusion: There are known harms associated with antibiotics and, when studied, existing data do not demonstrate harm associated with shorter courses of antibiotics among SOTRs. Furthermore, several RCTs did include some immune compromised patients and found shorter therapy to result in similar clinical efficacy with diminished adverse effects. Shorter antibiotic durations should be considered in SOTRs, and questions of antibiotic duration among SOTRs should be prioritized for study in clinical trials., (© 2022 Wiley Periodicals LLC.)

Background: BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients., Results and Discussion: Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective., Methods: To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives., Conclusions: These definitions refine established principles of "proven" BKPyV disease and introduce a "probable" disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients., Competing Interests: Potential conflicts of interest. P. B. has received salary, stock options, and support for attending meetings or travel from Roche Diagnostics. D. C. B. has received grants/research support from CareDx (to John Hopkins for research on donor-derived cell-free DNA and relation to BK infection), Natera, Amplyx Pharmaceuticals (to John Hopkins for research on BK), and AlloVir (to John Hopkins for research on BK); consulting fees from CareDx, Medeor, Natera, and Sanofi (use of donor-derived cell-free DNA); honoraria from CareDx (use of donor-derived cell-free DNA), Sanofi (Infections in Transplantation), and Veloxis; and has served on the editorial boards of Transplantation and UpToDate. M. R. H. has received salary and consulting fees from Amplyx Pharmaceuticals and consulting fees from Pfizer, Hybridize Therapeutics, and AlloVir. P. L. has participated in a contract for a clinical trial with AlloVir (planned clinical trial at institution). V. M. receives support as part of the TAVI Forum from Amplyx Pharmaceuticals, Everys Bio, Mikrogen GmbH, Merck, Quest Diagnostics, Roche, SymBio Pharmaceuticals, and Viracor. V. N. has received grants or contracts with AlloVir and is on the advisory board for Hybridize Therapeutics. P. S. R. has a leadership role (president) of the Renal Pathology Society. A. P. L. has received consulting fees and contracts with Amplyx Pharmaceuticals (grant for being site investigator for BKPyV therapy and consulting fees for providing guidance on study design for BKPyV therapies) and has received consulting fees from AlloVir (for providing guidance on study design for immune therapies for viral infectious including BKPyV). All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Among solid organ transplant recipients, donor cytomegalovirus (CMV) seropositive (D+) and recipient seronegative (R-) status are associated with an increased risk of graft loss and mortality after kidney or lung transplantation. Whether a similar relationship exists among liver transplant recipients (LTR) is unknown. We assessed graft loss and mortality among adult LTRs from January 1, 2010, to March 14, 2020, in the Organ Procurement and Transplantation Network database. We used multivariable mixed Cox proportional hazards regression to analyze the association of donor and recipient CMV serostatus group with graft loss and mortality, with donor seronegative (D-) and recipient seronegative (R-) as the reference group. Among 54,078 LTRs, the proportion of D-R-, D- and recipient seropositive (R+), D+R-, and D+R+ was 13.4%, 22.5%, 22%, and 42%, respectively. By unadjusted Kaplan-Meier survival curve estimates, survival by the end of follow-up was 73.3%, 73.5%, 70.1%, and 69.7%, among the D-R-, D-R+, D+R-, and D+R+ groups, respectively. By multivariable Cox regression, the CMV D+R- serogroup, but not other serogroups, was independently associated with increased risks of graft loss (adjusted hazard ratio [aHR], 1.13; 95% confidence interval [CI], 1.05-1.22) and mortality (aHR, 1.13; 95% CI, 1.05-1.22). The magnitude of the association of the CMV D+R- serostatus group with mortality was similar when the Cox regression analysis was restricted to the first year after transplant and beyond the first year after transplant: aHR, 1.13 (95% CI, 1.01-1.27) and aHR, 1.13 (95% CI, 1.02-1.25), respectively. Even in an era of CMV preventive strategies, CMV D+R- serogroup status remains independently associated with increased graft loss and mortality in adult LTRs. Factors in addition to direct CMV-associated short-term mortality are likely, and studies to define the underlying mechanism(s) are warranted., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

We performed multivariable analysis of potential risk factors (including cytomegalovirus [CMV] reactivation) for clinical outcomes by day 28 (death or continued hospitalization, ventilator-free days, intensive care unit (ICU)-free days, hospital-free days) from pooled cohorts of 2 previous prospective studies of CMV-seropositive adults with sepsis. CMV reactivation at any level, >100 IU/mL, >1000 IU/mL, peak viral load, and area under the curve were independently associated with the clinical outcomes. We identified the potential effect size of CMV on outcomes that could be used as end points for future interventional trials of CMV prevention using antiviral prophylaxis in ICU patients with sepsis., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Patients with reported β-lactam antibiotic allergies (BLAs) are more likely to receive broad-spectrum antibiotics and experience adverse outcomes. Data describing antibiotic allergies among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients are limited., Methods: We reviewed records of adult SOT or allogeneic HCT recipients from 1 January 2013 to 31 December 2017 to characterize reported antibiotic allergies at time of transplantation. Inpatient antibiotic use was examined for 100 days posttransplant. Incidence rate ratios (IRRs) comparing antibiotic use in BLA and non-BLA groups were calculated using multivariable negative binomial models for 2 metrics: days of therapy (DOT) per 1000 inpatient days and percentage of antibiotic exposure-days., Results: Among 2153 SOT (65%) and HCT (35%) recipients, 634 (29%) reported any antibiotic allergy and 347 (16%) reported BLAs. Inpatient antibiotics were administered to 2020 (94%) patients during the first 100 days posttransplantation; average antibiotic exposure was 41% of inpatient-days (interquartile range, 16.7%-62.5%). BLA patients had significantly higher DOT for vancomycin (IRR, 1.4 [95% confidence interval {CI}, 1.2-1.7]; P < .001), clindamycin (IRR, 7.6 [95% CI, 2.2-32.4]; P = .001), and aztreonam in HCT (IRR, 9.7 [95% CI, 3.3-35.0]; P < .001), and fluoroquinolones in SOT (IRR, 2.9 [95% CI, 2.1-4.0]; P < .001); these findings were consistent when using percentage of antibiotic exposure-days., Conclusions: Transplant recipients are frequently exposed to antibiotics and have a high prevalence of reported antibiotic allergies. Reported BLA was associated with greater use of β-lactam antibiotic alternatives. Pretransplant antibiotic allergy evaluation may optimize antibiotic use in this population., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Few data support use of 6 over 3 months of antiviral prophylaxis for cytomegalovirus (CMV) disease prevention in donor seropositive/recipient seronegative (D+R-) heart transplant recipients (HTR)., Methods: We retrospectively assessed CMV disease and outcomes in 310 adult HTR between July 5, 2005, and December 30, 2016, at our center. Valganciclovir (VGCV) prophylaxis was given for 3-6 months in the D+R- group. Multivariable models evaluated risk factors for CMV disease in patients who received 3 vs 6 months (±1 month) of prophylaxis, with investigation of inverse probability weighting to correct for confounding variables., Results: The incidence of CMV disease among all patients and the D+R- group was 8.7% (27/310) and 26.5% (22/83), respectively, and included syndrome in 22.2% (6/27) and end-organ involvement in 77.8% (21/27). In a multivariable model, 6 vs 3 months of antiviral prophylaxis was not associated with reduced risk for CMV disease (OR 2.28 [95% CI 0.66, 7.91], P = .19). CMV disease in D+R- HTR was associated with higher rates of hospitalization (87.5% [14/16] vs 6.3% [1/16], P < .001) and for a longer duration than in matched D+R- controls without disease., Conclusions: Cytomegalovirus disease remains a major cause of morbidity in D+R- HTR. In contrast to documented benefit in D+R- lung and kidney recipients, VGCV duration of 6 months was not associated with a lower incidence of CMV disease in D+R- HTR compared to 3-month duration and should be reconsidered in this patient population., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cytomegalovirus (CMV) reactivation has been described in adults with critical illness caused by diverse etiologies, especially severe sepsis, and observational studies have linked CMV reactivation with worse clinical outcomes in this setting. In this study, we review observational clinical data linking development of CMV reactivation with worse outcomes in patients in the intensive care unit, discuss potential biologically plausible mechanisms for a causal association, and summarize results of initial interventional trials that examined the effects of CMV prevention. These data, taken together, highlight the need for a randomized, placebo-controlled efficacy trial (1) to definitively determine whether prevention of CMV reactivation improves clinical outcomes of patients with critical illness and (2) to define the underlying mechanism(s)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

BK polyomavirus (BKPyV) has been associated with hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (HCT), but the natural history of HC and factors associated with the clinical course are incompletely understood. We retrospectively analyzed allogeneic HCT patients transplanted from 2007-2017 who presented after platelet engraftment or after day 28 post-HCT with BKPyV-associated HC (BKPyV-HC), which was defined as a positive urine BKPyV PCR, ≥1 plasma BKPyV viral load result, and macroscopic hematuria (Bedi grade ≥2). Factors associated with resolution of macroscopic hematuria and resolution of all cystitis symptoms within 90 days after HC diagnosis were investigated in multivariable models. In 128 patients with BKPyV-HC, the median times from diagnosis to resolution of all symptoms, macroscopic hematuria, and urinary clots (present in 55% [71/128]) were 24 days (15-44), 17 days (10-30), and 14 days (5-26), respectively. Ninety percent of patients had BKPyV viremia at the onset of HC with a median viral load of 1850 copies/mL (interquartile range, 240-8550). In multivariable models, high plasma viral load (≥10 000 copies/mL) and cytopenias at the beginning of BKPyV-HC were significantly associated with longer macroscopic hematuria and cystitis symptoms. Use of cidofovir was not associated with shorter duration of illness. In conclusion, BKPyV-HC after allogeneic HCT is characterized by prolonged and severe symptoms and requires improved management strategies. High-grade viremia and cytopenias were associated with a longer duration of BKPyV-associated HC. Accurate descriptions of disease and factors associated with prolonged recovery will inform end points of future clinical trials., (© 2020 by The American Society of Hematology.)

Objective: Clostridioides difficile infection (CDI) frequently causes colitis following antibiotic exposure and is a leading cause of gastrointestinal infectious mortality. Infection in the small bowel, C. difficile enteritis (CDE), was previously thought impossible, but case series have challenged this dogma. Clostridioides difficile enteritis prevalence, severity, and potential risk factors are unknown., Methods: We retrospectively analyzed all total colectomy patients over a 20-year period at our institution. C. difficile enteritis was defined by clinical symptoms and positive C. difficile stool testing after colectomy. We compared CDE cases to controls using multivariable analysis to identify potential CDE risk factors., Results: C. difficile enteritis occurred in 44 of 855 (5.1%) patients, a median of 130 days after colectomy. Compared to controls, CDE patients were similar in age, gender, and presence of immunosuppression. The majority (64%) had antibiotics <30 days prior to CDE. In multivariable analysis, CDE risk factors included perioperative acid suppression (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.26-5.04; P = .009), colectomy for inflammatory bowel disease (HR, 2.95; CI, 1.29-6.72; P = .010), colectomy for CDI (HR, 9.95; CI, 2.70-36.63; P ≤ .001), and β-lactam use in the setting of enteral feeds (HR, 17.83; CI, 2.75-115.68; P = .003). C. difficile enteritis presented with severe disease half of the time, with 81.8% requiring hospitalization., Conclusions: C. difficile enteritis is a rare clinical entity that should be considered in postcolectomy patients presenting with CDI symptoms, even years after surgery. Like traditional CDI, likely CDE risk factors include acid suppression and inflammatory bowel disease. Prior antibiotic use in the setting of enteral feeds may amplify CDE risk. C. difficile enteritis often presents as severe disease and frequently requires hospitalization., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Despite many advances in medicine, not all individuals with HIV are able to achieve complete virologic suppression. This retrospective study identifies variables associated with persistent HIV viremia in an academic clinic., Methods: We studied 66 HIV-infected patients with a viral load of >200 copies/mL over 1 year, with controls matched 1:1 via a propensity score utilizing age at diagnosis, era of diagnosis, gender, and initial CD4 count. We collected data on multiple variables including medications, adherence, comorbidities, hospitalizations, and insurance status. Conditional logistic regression was used for unadjusted and adjusted analyses., Results: A total of 66 viremic cases/matched controls were included. Fewer viremic patients were on antiretroviral therapy for all 12 months (45% vs 77%; odds ratio: 0.33, p  = .018) and fewer were of white race (52% vs 70%; odds ratio: 0.49, p  = .053). Hospitalization (11% vs 3%; odds ratio: 10, p  = .028), underinsurance (20% vs 1%; odds ratio: 5.87, p  = .022), and conflicting personal beliefs about their disease (17% vs 3%; odds ratio: 5.5, p  = .027) were more common in viremic patients. Psychiatric illness increased the odds of viremia in patients who had four or more visits (odds ratio: 1.63/6.64 with four/five clinic visits, respectively)., Conclusion: Psychiatric illness is an important contributor to the presence of persistent viremia in HIV-infected patients and deserves further study., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: BK virus nephropathy (BKPyVAN) is a major complication in kidney transplant recipients (KTR) and typically occurs within 1 year of transplant. Guidelines vary in recommendations for BKPyV screening beyond 1 year. A systematic characterization of risk factors and outcomes of late-onset (>1 year) BKPyVAN has not previously been reported., Methods: We retrospectively compared characteristics and outcomes of early- (<1 year) and late-onset BKPyVAN (definitive [biopsy-confirmed] or presumptive [plasma BKPyV >10 000 copies/mL]) in a cohort of 671 KTR and simultaneous kidney-pancreas transplant (SPK) recipients between 2008 and 2013 at a single US transplant center. Proportions were compared using Chi-square or Fisher's exact test with P < .05 considered significant., Results: BKPyVAN was diagnosed in 96 (14.3%) patients (proven 16.7%, presumptive 83.3%): 79 (82.3%) early- and 17 (17.7%) late-onset. The proportion with late-onset BKPyVAN was significantly higher among SPK than KTR (4 of 7 [57.1%] vs 13 of 89 [14.6%], P = .017). Late-onset represented "de novo" infection (no BKPyV detection within the first year) in 14 (82.4%) and progression of earlier lower grade BKPyV reactivation in 3 (17.6%). Clinical outcomes were similar for early- and late-onset BKPyVAN (P > .05 all comparisons). In a pooled analysis of prior studies of BKPyVAN in SPK recipients, 62.9% (17 of 27) were late-onset., Conclusion: A significant proportion of BKPyVAN is late-onset, especially among SPK recipients, and supports a longer duration of BKPyV monitoring for SPK recipients than recommended in some guidelines., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Clostridium difficile infection is a healthcare-associated infection resulting in significant morbidity. Although immunosuppression is associated with Clostridium difficile infection acquisition and adverse outcomes, the epidemiology of Clostridium difficile infection in HIV-infected patients has been little studied in the era of antiretroviral therapy. This study identifies the risk factors for acquisition of Clostridium difficile infection in HIV-infected patients., Methods: A retrospective, propensity score-matched case-control study design was employed, with patients selected from our institution's outpatient HIV clinic. Clostridium difficile infection cases were defined as having positive stool testing plus an appropriate clinical presentation. The propensity score was generated via multiple logistic regression from year of HIV diagnosis, age at first contact, duration of follow-up, gender, and initial CD4 count., Results: The 46 cases included were matched to a total of 180 controls. Prior antibiotic treatment was a significant predictor of Clostridium difficile infection (odds ratio: 13, 95% confidence interval: 3.49-48.8, p  < .001) as was number of hospital admissions in the preceding year (odds ratio: 4.02, confidence interval: 1.81-8.94, p  < .001). Having both proton pump inhibitor use and CD4 count <200 cells/µL significantly increased odds of Clostridium difficile infection in the multivariable model (odds ratio: 15.17, confidence interval: 1.31-175.9, p  = .021)., Conclusion: As in the general population, frequent hospitalizations and exposure to antimicrobials are independent predictors of Clostridium difficile infection acquisition in patients with HIV. Additionally, low CD4 count and proton pump inhibitor use are new potentially modifiable variables that can be targeted for prevention of Clostridium difficile infection in future interventional studies., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.