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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 20,601 KTRs who received their first KT from 2011 to 2016. Three-quarters of KTRs started CMV prophylaxis (86.9% of high-, 83.6% of intermediate-, and 31.7% of low-risk KTRs). Median time to prophylaxis discontinuation was 121, 90, and 90 days for high-, intermediate-, and low-risk KTRs, respectively. Factors associated with receiving CMV prophylaxis were highrisk 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 liver disease, or had 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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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 NRUTI (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls., Methods: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection., Results: We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment., Conclusions: In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.)., (Copyright © 2024 Massachusetts Medical Society.)

Objective: To evaluate postoperative outcomes among patients undergoing colon surgery who receive perioperative prophylaxis with ertapenem compared to other antibiotic regimens., Design and Setting: Multicenter retrospective cohort study among adults undergoing colon surgery in seven hospitals across three health systems from 1/1/2010 to 9/1/2015., Methods: Generalized linear mixed logistic regression models were applied to assess differential odds of select outcomes among patients who received perioperative prophylaxis with ertapenem compared to other regimens. Postoperative outcomes of interest included surgical site infection (SSI), Clostridioides difficile infection (CDI) and clinical culture positivity for carbapenem-resistant Enterobacteraciae (CRE). Inverse probability weights were applied to account for differing covariate distributions across ertapenem and non-ertapenem groups., Results: A total of 2,109 patients were included for analysis. The odds of postoperative SSI was 1.56 times higher among individuals who received ertapenem than among those receiving other perioperative antimicrobial prophylaxis regimens in our cohort (46 [3.5%] vs 20 [2.5%]; IPW-weighted OR 1.56, [95% CI, 1.08-2.26], P = .02). No statistically significant differences in odds of postoperative CDI (24 [1.8%] vs 16 [2.0%]; IPW-weighted OR 1.07 [95% CI, .68-1.68], P = .78) were observed between patients who received ertapenem prophylaxis compared to other regimens. Clinical CRE culture positivity was rare in both groups (.2%-.5%) and did not differ statistically., Conclusions: Ertapenem use for perioperative prophylaxis was associated with increased odds of SSI among patients undergoing colon surgery in our study population, though no differences in CDI or clinical CRE culture positivity were identified. Further study and replication of these findings are needed.

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.

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., Competing Interests: D.L.S. receives honoraria for AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMd, as well as consulting fees from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron, and Springer Publishing. C.M.D. received honoraria from Gilead Sciences for serving on a grant review committee. V.S. received research grant support from Eli Lilly and Company and consulting fees from DiaSorin SpA. M.P. received grant support from Merck, Hologic, Moderna, Shire/Takeda, and Pfizer, as well as provided consultation to/serves on the advisory board for Rebiotix, Takeda, and Union Therapeutics. C.B.S. has received grants paid to her institution from GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics. G.H. is a recipient of research grants from Allovir, Karius, and AstraZeneca. G.H. serves on the scientific advisory boards of Karius and AstraZeneca and has received honoraria from MDOutlook and MAD-ID/ID Connect. J.H. is a recipient of grants paid to his institution from Pfizer, Janssen, and Scynexis. The other authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-rhee a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-rhee an interview with the author., (© 2020 by the American Association for the Study of Liver Diseases.)

Background: Staphylococcus lugdunensis is a coagulase-negative staphylococcus with similar virulence characteristics as Staphylococcus aureus. Whether S. lugdunensis causes infective endocarditis (IE) in a similar proportion of cases as S. aureus (reported to be 12.6% in a definitive multicenter prospective study) is unclear., Methods: We conducted a retrospective cohort study of adult patients with at least one blood culture positive for S. lugdunensis at our institution from January 2006 to December 2014. We examined microbiology data, ascertained disease severity and determined the proportion of patients with definite or possible IE based on the 2000 Modified Duke Criteria. Because coagulase-negative staphylococci were routinely identified to the species level at our institution from 2012 onwards, we determined the proportion of patients with definite or possible IE before and after implementation of routine speciation. We also compared our results with reported proportions of IE among patients with S. lugdunensis bacteremia (SLB) in other institutions by conducting a systematic review of the scientific literature. Nonparametric bootstrapping methods were performed to determine 95% confidence intervals (CI) for proportions of IE in patients with SLB., Results: Seventy-four patients with SLB were identified, of whom 64% (47/74) had sepsis by SIRS criteria, and 18% (13/74) had severe illness by Pittsburgh bacteremia score (PBS). Kaplan-Meier survival analysis showed that one-year survival among patients with severe illness was worse than patients with non-severe illness (p = 0.02). Fifteen percent (11/74) of patients had definite or possible IE (95% CI 6.8-23.0%). The proportion of SLB patients with definite or possible IE was 15.8% (6/38, 95% CI 5.3-28.9%) prior to routine speciation and 13.9% (5/36, 95% CI 2.8-27.8%) after routine speciation (p = 0.71). Among patients with at least two positive blood cultures for S. lugdunensis, 25% (10/40, 95% CI 12.5-40.0%) had IE. Systematic review of the literature yielded eight relevant retrospective studies. Of studies that included patients with one or more positive blood cultures for S. lugdunensis, the proportion of IE ranged from 6.3% to 27.0%., Conclusion: The proportion of definite or possible IE among patients with SLB is similar to the proportion of IE among patients with S. aureus bacteremia. The proportions of IE among patients with SLB at other institutions fall within the 95% CI yielded by bootstrapping. Our findings suggest that growth of S. lugdunensis in two separate blood cultures should prompt consideration of workup for IE., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Cytomegalovirus (CMV), human herpes virus (HHV)-6, and HHV-7 are ubiquitous β-herpesviruses that can cause opportunistic infection and disease in kidney transplant recipients. Active CMV infection and disease are associated with acute allograft failure and death, and HHV-6 and HHV-7 replication are associated with CMV disease. CMV prevention strategies are used commonly after kidney transplantation, and include prophylaxis with antiviral medications and preemptive treatment upon the detection of asymptomatic viral replication in blood. Both approaches decrease CMV disease and allograft rejection, but CMV prophylaxis is preferred for high-risk patients because it is easy to administer and may be more effective in real-world settings. CMV disease commonly occurs even with current preventive strategies, whereas HHV-6 and HHV-7 diseases are rare. The clinical manifestations of CMV, HHV-6, and HHV-7 are nonspecific, and laboratory confirmation is essential to establishing diagnoses. Although nucleic acid testing has supplanted other diagnostic modalities given its high sensitivity and specificity, histopathologic examination sometimes is necessary to identify disease definitively. Ganciclovir and valganciclovir are the treatments of choice for CMV and HHV-6, and foscarnet can be used to treat HHV-7. Treatment duration should be informed by the initial severity of disease, and subsequent clinical and virologic responses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: Although some studies have examined the epidemiology of bloodstream infections after liver transplantation, they were based in single centers and did not identify bloodstream infections treated in other hospitals., Methods: We retrospectively examined a cohort of 7912 adult liver transplant recipients from 24 transplant centers using 2004 to 2012 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 3 State Inpatient Databases, and identified bloodstream infections, inpatient death, and cumulative 1-year hospital costs. Multilevel Cox regression analyses were used to determine factors associated with bloodstream infections and death., Results: Bloodstream infections were identified in 29% (n = 2326) of liver transplant recipients, with a range of 19% to 40% across transplant centers. Only 63% of bloodstream infections occurring more than 100 days posttransplant were identified at the original transplant center. Bloodstream infections were associated with posttransplant laparotomy (adjusted hazard ratio [aHR], 1.52), prior liver transplant (aHR, 1.42), increasing age (aHR, 1.07/decade), and some comorbidities. Death was associated with bloodstream infections with and without septic shock (aHR, 10.96 and 3.71, respectively), transplant failure or rejection (aHR, 1.41), posttransplant laparotomy (aHR, 1.40), prior solid-organ transplant (aHR, 1.48), increasing age (aHR, 1.15/decade), and hepatitis C cirrhosis (aHR, 1.20). The risk of bloodstream infections and death varied across transplant centers. Median 1-year cumulative hospital costs were higher for patients who developed bloodstream infections within 1 year of transplant compared with patients who were bloodstream infection-free (US $229 806 vs US $111 313; P < 0.001)., Conclusions: Bloodstream infections are common and costly complications after liver transplantation that are associated with a markedly increased risk of death. The incidence and risk of developing bloodstream infections may vary across transplant centers.

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.