Corrigendum: Real-World Treatment Patterns of Antiviral Prophylaxis for Cytomegalovirus Among Adult Kidney Transplant Recipients: A Linked USRDS-Medicare Database Study.

[This corrects the article DOI: 10.3389/ti.2022.10528.][This corrects the article DOI: 10.3389/ti.2023.12367.].

Real-World Treatment Patterns of Antiviral Prophylaxis for Cytomegalovirus Among Adult Kidney Transplant Recipients: A Linked USRDS-Medicare Database Study.

Limited data exist on cytomegalovirus (CMV) antiviral treatment patterns among kidney transplant recipients (KTRs). Using United States Renal Database System registry data and Medicare claims (1 January 2011-31 December 2017), we examined CMV antiviral use in 22,878 KTRs who received their first KT from 2011 to 2016. Three-quarters of KTRs started CMV prophylaxis (85.8% of high-, 82.4% of intermediate-, and 32.1% of low-risk KTRs). Median time to prophylaxis discontinuation was 98, 65, and 61 days for high-, intermediate-, and low-risk KTRs, respectively. Factors associated with receiving CMV prophylaxis were high-risk status, diabetes, receipt of a well-functioning kidney graft, greater time on dialysis before KT, panel reactive antibodies ≥80%, and use of antithymocyte globulin, alemtuzumab, and tacrolimus. KTRs were more likely to discontinue CMV prophylaxis if they developed leukopenia/neutropenia, had cardiovascular disease, or received their kidney from a deceased donor. These findings suggest that adherence to the recommended duration of CMV-prophylaxis for high and intermediate-risk patients is suboptimal, and CMV prophylaxis is overused in low-risk patients.

Could cell-free DNA and host biomarkers assist in antimicrobial stewardship with organ transplant recipients?

BACKGROUND: Antimicrobial stewardship in solid organ transplant (SOT) recipients is important to prevent antimicrobial-associated complications, but traditional stewardship principles are challenging to implement for SOT patients. Newer methodologies to optimize stewardship efforts are needed. METHODS: PubMed was searched using the keywords "cell free DNA," "metagenomic sequencing," "host biomarker," "antimicrobial stewardship," and "SOT." RESULTS: Metagenomic sequencing of cell free DNA has the potential to be a stewardship tool for SOT recipients. Various studies have shown its use for antimicrobial de-escalation and duration shortening. Host gene expression profiles can differentiate between infectious and noninfectious syndromes and may assist in stewardship efforts. However, information in immunocompromised hosts is conflicting. CONCLUSION: Microbial cell free DNA sequencing and host gene expression profiling show promise as stewardship tools in SOT recipients. Future studies on antimicrobial stewardship in SOT recipients should focus on their clinical use and feasibility.

Computing antimicrobial use/antimicrobial resistance ratios: A novel way to assess inpatient antimicrobial utilization using current National Healthcare Safety Network metrics.

BACKGROUND: Current methods for benchmarking inpatient antimicrobial use (AU) could benefit from combining AU with antimicrobial resistance (AR) information to provide metrics benchmarked to microbiological data; this may yield more instructive and better risk-adjusted measurements than AU and AR in isolation. METHODS: In this retrospective single-center study, we computed facility-wide AU/AR ratios from 2019 to 2020 for specific antimicrobial agents and corresponding AR events, and compared median monthly AU/AR ratios between March 2019 through December 2019 (pre-COVID period) and March 2020 through December 2020 (COVID period). Aggregate AU was expressed as a ratio to aggregate AR events for antimicrobials that typically have activity against the AR organism and are frequently used to treat the AR organism in clinical practice. We also computed AU/AR ratios in our surgical intensive care unit in the pre-COVID period. RESULTS: High-median facility-wide monthly AU/AR ratios were observed for intravenous vancomycin/methicillin-resistant Staphylococcus aureus, with 130.0 in the pre-COVID period and 121.3 in the COVID period (p =.520). Decreases in facility-wide median monthly AU/AR ratios were observed between periods for meropenem/ESBL Enterobacterales (20.9 vs. 7.9, p < .001), linezolid/vancomycin-resistant Enterococcus (48.5 vs. 15.8, p =.004), and daptomycin/vancomycin-resistant Enterococcus (32.2 vs. 4.8, p = .002). Increases in facility-wide median monthly AU/AR ratios were observed between periods for ceftazidime-avibactam/carbapenem-resistant Enterobacterales (0.0 vs. 3.2, p = .020) and ceftazidime-avibactam/multidrug-resistant Pseudomonas aeruginosa (0.0 vs. 4.0, p = .017). The AU/AR ratio for intravenous vancomycin/methicillin-resistant S. aureus in the surgical intensive care unit was 191.5 in the pre-COVID period. CONCLUSIONS: AU/AR ratios may be used to supplement current AU and AR metrics. Future directions should include the development of more AU metrics benchmarked to microbiological information. AU metrics more specific to transplant infectious diseases should be developed.

Comparative incidence and outcomes of COVID-19 in kidney or kidney-pancreas transplant recipients versus kidney or kidney-pancreas waitlisted patients: A single-center study.

BACKGROUND: COVID-19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes. METHODS: In this retrospective cohort study, we assembled kidney or kidney-pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney-pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory-confirmed COVID-19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network. RESULTS: COVID-19 was identified in 62 of 887 kidney or kidney-pancreas transplant recipients and 20 of 434 kidney or kidney-pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID-19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116). CONCLUSIONS: Our study provides single-center data and an informatics approach that can be used to inform the design of multicenter studies.

I want to go home: should we abandon open surgery for treatment of rectal prolapse? Consideration of discharge destination following surgery for rectal prolapse.

AIM: Despite the financial and value-based implications associated with higher levels of care at discharge, few studies have evaluated modifiable treatment factors that may optimize postacute care. The aim of this work was to assess the association between operative approach and disposition to a higher level of care and other outcomes following surgery for rectal prolapse. METHOD: Using a retrospective cohort study design, the database of the National Surgical Quality Improvement Program was used to identify patients with rectal prolapse who underwent perineal repair or open or laparoscopic rectopexy with or without resection between 2012 and 2017. Discharge destination and 30-day postoperative outcomes were compared using propensity score mathcing and weighting. Nomograms generated using multivariable regression calculated the risk of requiring higher levels of care upon discharge and morbidity. RESULTS: Propensity-score analysis included 3000 patients [1500 in the perineal group, 580 in the open abdominal group and 920 in the minimally invasive (MIS) group]. Patients who received open abdominal surgery were more likely to require elevation of care at destination compared with those who received perineal surgery (OR 1.65, 95% CI 1.22-1.24) and MIS abdominal surgery (OR 1.80, 95% CI 1.18-2.76). Similar effects were seen for overall morbidity. Increased age, higher American Society of Anesthesiologists class, congestive heart failure, dependent functional status and open surgery were independent predictors of discharge to higher level of care (c-statistic = 0.79). CONCLUSION: Open surgery compared with MIS and perineal surgery was associated with higher levels of discharge disposition following rectal prolapse surgery. Future research should continue to identify modifiable treatment factors that reduce poor postoperative outcomes among patients with rectal prolapse.

Electronic Measurement of a Clinical Quality Measure for Inpatient Hypoglycemic Events: A Multicenter Validation Study.

BACKGROUND: Hypoglycemia related to antidiabetic drugs (ADDs) is important iatrogenic harm in hospitalized patients. Electronic identification of ADD-related hypoglycemia may be an efficient, reliable method to inform quality improvement. OBJECTIVE: Develop electronic queries of electronic health records for facility-wide and unit-specific inpatient hypoglycemia event rates and validate query findings with manual chart review. METHODS: Electronic queries were created to associate blood glucose (BG) values with ADD administration and inpatient location in 3 tertiary care hospitals with Patient-Centered Outcomes Research Network (PCORnet) databases. Queries were based on National Quality Forum criteria with hypoglycemia thresholds <40 and <54 mg/dL, and validated using a stratified random sample of 321 BG events. Sensitivity and specificity were calculated with manual chart review as the reference standard. RESULTS: The sensitivity and specificity of queries for hypoglycemia events were 97.3% [95% confidence interval (CI), 90.5%-99.7%] and 100.0% (95% CI, 92.6%-100.0%), respectively for BG <40 mg/dL, and 97.7% (95% CI, 93.3%-99.5%) and 100.0% (95% CI, 95.3%-100.0%), respectively for <54 mg/dL. The sensitivity and specificity of the query for identifying ADD days were 91.8% (95% CI, 89.2%-94.0%) and 99.0% (95% CI, 97.5%-99.7%). Of 48 events missed by the queries, 37 (77.1%) were due to incomplete identification of insulin administered by infusion. Facility-wide hypoglycemia rates were 0.4%-0.8% (BG <40 mg/dL) and 1.9%-3.0% (BG <54 mg/dL); rates varied by patient care unit. CONCLUSIONS: Electronic queries can accurately identify inpatient hypoglycemia. Implementation in non-PCORnet-participating facilities should be assessed, with particular attention to patient location and insulin infusions.

Comparative Epidemiology and Outcomes of Human Immunodeficiency virus (HIV), Non-HIV Non-transplant, and Solid Organ Transplant Associated Cryptococcosis: A Population-Based Study.

In this population-based study in the contemporary era in the United States, the proportion of human immunodeficiency virus (HIV)-negative patients with cryptococcosis approaches that in HIV-infected patients. Cryptococcosis is associated with higher mortality rates in HIV-negative patients (including organ transplant recipients).

Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation.

BACKGROUND: Urinary tract infections (UTIs) are common following kidney transplantation (KT); however, the influence of recurrent post-KT UTI (R-UTI) is not well-characterized. METHODS: We compared graft outcomes, patient outcomes and multidrug-resistance rates between patients with no UTI, nonrecurrent UTI (NR-UTI) (urine sample containing >105 bacterial colony-forming units/mL) and R-UTI (≥2 UTIs in any 6-month period or ≥3 UTIs in any 12-month period) post-KT in a retrospective cohort study (1999-2014) at Barnes-Jewish Hospital (St Louis, MO). All adult KT recipients were included and those experiencing mortality within 30 days of KT were excluded. RESULTS: Of 2469 recipients included, 1835 (74.3%) had no UTI, 465 (18.8%) had NR-UTI and 169 (6.8%) had R-UTI. R-UTI was associated with poorer graft survival compared with NR-UTI [hazard ratio (HR) 1.45; 95% confidence interval (CI) 1.23-1.83; P < 0.001) and no UTI (HR 2.11; 95% CI 2.02-3.80; P < 0.001). This relationship persisted after adjusting for confounding factors in Cox regression (HR 2.01; 95% CI 1.53-2.66; P < 0.001). There was no difference in patient survival between no UTI and NR-UTI (HR 1.21; 95% CI 0.91-1.63; P = 0.181); however, R-UTI was associated with poorer patient survival compared with nonrecurrent cases (HR 1.87; 95% CI 1.21-2.89; P = 0.005). R-UTI were more likely to be caused by multidrug-resistant Gram-negative organisms (risk ratio 1.49; 95% CI 1.31-1.70; P < 0.001). CONCLUSIONS: R-UTIs were associated with poorer graft and patient outcomes, as well as increased multidrug-resistance compared with nonrecurrent cases.

Pseudozyma and other non-Candida opportunistic yeast bloodstream infections in a large stem cell transplant center.

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.

Pharmacoepidemiology of cytomegalovirus prophylaxis in a large retrospective cohort of kidney transplant recipients with Medicare Part D coverage.

We assembled a cohort of 21 117 kidney transplant patients from July 2006 to June 2011 with Medicare Part D coverage using US Renal Database System data to determine real-world use of cytomegalovirus (CMV) prophylaxis. CMV prophylaxis was defined as filled prescriptions for daily oral valganciclovir (≤900 mg), ganciclovir (≤3 g), or valacyclovir (6-8 g) within 28 d of transplant. Multilevel logistic regression analyses were performed to determine factors associated with CMV prophylaxis. CMV prophylaxis (97% valganciclovir) was identified in 61% of kidney transplant recipients (median duration, 64 d); 71% of seronegative recipients of kidneys from seropositive donors (D+/R-); 63% of R+ patients; 60% of patients with unknown serostatus; and 34% of D-/R- patients. Variability in usage of prophylaxis among transplant centers was greater than variability within transplant centers. One in four transplant centers prescribed CMV prophylaxis to >60% of their D-/R- patients. CMV donor/recipient serostatus, lymphocyte-depleting agents for induction and mycophenolate for maintenance were associated with CMV prophylaxis. CMV prophylaxis was commonly used among kidney transplant recipients. Routine prescription of CMV prophylaxis to D-/R- patients may have occurred in some transplant centers. Limiting unnecessary use of CMV prophylaxis may decrease healthcare costs and drug-related harms.

Delayed-onset cytomegalovirus disease coded during hospital readmission in a multicenter, retrospective cohort of liver transplant recipients.

Delayed-onset cytomegalovirus (CMV) disease can occur among liver transplant recipients after CMV prophylaxis is stopped. We hypothesized that delayed-onset CMV disease (>100 days after transplant) occurs more commonly than early-onset CMV disease and is associated with clinical sepsis and death. Using 2004-2010 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 4 Healthcare Cost and Utilization Project state inpatient databases, we assembled a large and more representative cohort of 7229 adult liver transplant recipients from 26 transplant centers, and we identified demographics, comorbidities, CMV disease, and clinical sepsis coded during readmission and inpatient death. Multivariate analysis was performed with Cox proportional hazards models. Delayed-onset CMV disease occurred in 4.3% (n = 309), whereas early-onset CMV disease occurred in 2% (n = 142). Delayed-onset CMV disease was associated with previous transplant failure or rejection [adjusted hazard ratio (aHR), 1.4; 95% confidence interval (CI), 1.1-1.7]. Clinical sepsis > 100 days after transplant was associated with previous CMV disease (aHR, 1.3; 95% CI; 1.0-1.7), previous transplant failure or rejection (aHR, 2.1; 95% CI; 1.8-2.4), female sex (aHR, 1.3; 95% CI; 1.1-1.5), and several comorbidities. Death > 100 days after transplant was associated with delayed-onset CMV disease (aHR, 2.0; 95% CI; 1.6-2.6), transplant failure or rejection (aHR, 4.3; 95% CI; 3.4-5.5), increasing age by decade (aHR, 1.1; 95% CI; 1.0-1.2), and some comorbidities. In conclusion, delayed-onset CMV disease is more common than early-onset CMV disease among liver transplant recipients. Previous CMV disease may be a risk factor for clinical sepsis > 100 days after transplant, and delayed-onset CMV disease may be a risk factor for death > 100 days after transplant.

Comparative antimicrobial use in coronavirus disease 2019 (COVID-19) and non-COVID-19 inpatients from 2019 to 2020: A multicenter ecological study.

OBJECTIVE: We sought to determine whether increased antimicrobial use (AU) at the onset of the coronavirus disease 2019 (COVID-19) pandemic was driven by greater AU in COVID-19 patients only, or whether AU also increased in non-COVID-19 patients. DESIGN: In this retrospective observational ecological study from 2019 to 2020, we stratified inpatients by COVID-19 status and determined relative percentage differences in median monthly AU in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (March-December 2020) and the pre-COVID-19 period (March-December 2019). We also determined relative percentage differences in median monthly AU in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period. Statistical significance was assessed using Wilcoxon signed-rank tests. SETTING: The study was conducted in 3 acute-care hospitals in Chicago, Illinois. PATIENTS: Hospitalized patients. RESULTS: Facility-wide AU for broad-spectrum antibacterial agents predominantly used for hospital-onset infections was significantly greater in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (with relative increases of 73%, 66%, and 91% for hospitals A, B, and C, respectively), and during the pre-COVID-19 period (with relative increases of 52%, 64%, and 66% for hospitals A, B, and C, respectively). In contrast, facility-wide AU for all antibacterial agents was significantly lower in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period (with relative decreases of 8%, 7%, and 8% in hospitals A, B, and C, respectively). CONCLUSIONS: AU for broad-spectrum antimicrobials was greater in COVID-19 patients compared to non-COVID-19 patients at the onset of the pandemic. AU for all antibacterial agents in non-COVID-19 patients decreased in the COVID-19 period compared to the pre-COVID-19 period.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

Hospital-acquired coronavirus disease 2019 (COVID-19) among patients of two acute-care hospitals: Implications for surveillance.

OBJECTIVES: We quantified hospital-acquired coronavirus disease 2019 (COVID-19) during the early phases of the pandemic, and we evaluated solely temporal determinations of hospital acquisition. DESIGN: Retrospective observational study during early phases of the COVID-19 pandemic, March 1-November 30, 2020. We identified laboratory-detected severe acute respiratory coronavirus virus 2 (SARS-CoV-2) from 30 days before admission through discharge. All cases detected after hospital day 5 were categorized by chart review as community or unlikely hospital-acquired cases, or possible or probable hospital-acquired cases. SETTING: The study was conducted in 2 acute-care hospitals in Chicago, Illinois. PATIENTS: The study included all hospitalized patients including an inpatient rehabilitation unit. INTERVENTIONS: Each hospital implemented infection-control precautions soon after identifying COVID-19 cases, including patient and staff cohort protocols, universal masking, and restricted visitation policies. RESULTS: Among 2,667 patients with SARS-CoV-2, detection before hospital day 6 was most common (n = 2,612; 98%); detection during hospital days 6-14 was uncommon (n = 43; 1.6%); and detection after hospital day 14 was rare (n = 16; 0.6%). By chart review, most cases after day 5 were categorized as community acquired, usually because SARS-CoV-2 had been detected at a prior healthcare facility (68% of cases on days 6-14 and 53% of cases after day 14). The incidence rates of possible and probable hospital-acquired cases per 10,000 patient days were similar for ICU- and non-ICU patients at hospital A (1.2 vs 1.3 difference, 0.1; 95% CI, -2.8 to 3.0) and hospital B (2.8 vs 1.2 difference, 1.6; 95% CI, -0.1 to 4.0). CONCLUSIONS: Most patients were protected by early and sustained application of infection-control precautions modified to reduce SARS-CoV-2 transmission. Using solely temporal criteria to discriminate hospital versus community acquisition would have misclassified many "late onset" SARS-CoV-2-positive cases.

Can Donor-Derived Cell-Free DNA Detect Graft-Versus-Host Disease in Solid Organ Transplantation: A Case Report.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease.

Methicillin-resistant Staphylococcus aureus USA300 clone as a cause of Lemierre's syndrome.

We describe a case of a young woman who had methicillin-resistant Staphylococcus aureus USA300 clone (MRSA-USA300)-associated Lemierre's syndrome and secondary necrotizing pneumonia and cerebral infarcts. We also review 11 cases of S. aureus-associated Lemierre's syndrome reported in the literature from 1965 to 2010. Recognition of S. aureus as an emergent cause of Lemierre's syndrome informs the initial empirical antibiotic choice for this life-threatening condition and may positively impact patient outcomes.