When you need to dive in the deep end-Transplanting SARS-CoV-2 PCR+ recipients.

There is an ongoing need to understand whether transplantation during acute Coronavirus disease 2019 (COVID-19) can be performed safely, especially when urgent transplant is required. We collected retrospective data of all consecutive non-lung transplant recipients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) on the day of planned deceased donor organ implantation. Data were collected from two large transplant centers from 01/01/2022 to 02/01/2023. Demographics, details regarding COVID-19 infection, waitlist priority, and details regarding transplantation were obtained. A descriptive analysis was performed. A total of 12 patients were identified: 7 renal, 4 liver, and 1 heart transplant recipient. All 12 patients were vaccinated for COVID-19. Ten were asymptomatic outpatients found positive on admission and transplanted immediately. Two were in-patients with mild COVID-19 symptoms and were reactivated on the waitlist following 3 days of remdesivir when no progression to severe COVID-19 occurred. Most patients (10/12) received remdesivir posttransplant. No complications attributed to COVID-19 were noted nor were any secondary family or healthcare worker infections observed. All recipients were managed with special isolation precautions befitting their potentially infectious state. Standard induction therapy was used in all recipients. After a median follow up period of 143 days (interquartile range: 96-201 days), 3 episodes of rejection were documented, 2/7 renal recipients experienced delayed graft function, and 2/4 liver recipients required renal replacement therapy. Graft and patient survival were 100%. Transplantation can safely proceed in select, minimally symptomatic, non-lung recipients with a positive SARS-CoV-2 PCR at the time of transplant.

Prolonged severe acute respiratory syndrome coronavirus 2 persistence, attenuated immunologic response, and viral evolution in a solid organ transplant patient.

Unlike immunocompetent hosts, the duration of viral persistence after infection with severe acute respiratory syndrome coronavirus 2 can be prolonged in immunosuppressed patients. Here, we present a case of viral persistence for over 19 weeks in a patient with a history of solid organ transplant and explore the clinical, virologic, and immunologic course. Our patient still demonstrated viral persistence at 138 days with low polymerase chain reaction cycle threshold values and evidence of continuing viral sequence evolution indicative of ongoing virus replication. These findings have important implications for infection prevention and control recommendations in immunosuppressed patients. Immune response, including neutralizing antibody titers, T cell activity, and cytokine levels, peaked around days 44-72 after diagnosis. Anti-S trimer antibodies were low at all time points, and T cell response was attenuated by day 119. As immune response waned and viral load increased, increased genetic diversity emerged, suggesting a mechanism for the development of viral variants.

Baloxavir treatment of oseltamivir-resistant influenza A/H1pdm09 in two immunocompromised patients.

Few treatment options are available for oseltamivir-resistant influenza. It has been proposed that baloxavir can be effective in this setting due to its distinct mechanism of action but clinical experience is lacking for immunocompromised patients. We report two such cases treated with baloxavir after failure of oseltamivir and detection of oseltamivir resistance mutations. Baloxavir/zanamivir combination therapy was effective in one patient, but persistent viral shedding was noted with baloxavir monotherapy in the other patient.

The solid organ transplant recipient with SARS-CoV-2 infection.

PURPOSE OF REVIEW: The COVID-19 pandemic is a major challenge to global health, particularly among vulnerable populations. Here, we describe the emerging epidemiology and relevant data on treatment options for COVID-19. We discuss the implications of current knowledge for solid organ transplant (SOT) recipients. RECENT FINDINGS: Risk factors and outcomes of COVID-19 among SOT recipients remain uncertain, but recent data suggest similar outcomes to the general population. Case reports of donor-derived SARS-CoV-2 infection are emerging. Few studies on treatment of COVID-19 among SOT recipients are available, and therefore, general recommendations are similar to the general population. Vaccine efficacy in the SOT population is uncertain. SUMMARY: COVID-19 remains a significant threat to SOT recipients and studies on treatment and prevention specific to this population are urgently needed. Although vaccines represent the greatest hope to control this pandemic, their efficacy in this immunocompromised population is uncertain.

Reduced Mortality of Staphylococcus aureus Bacteremia in a Retrospective Cohort Study of 2139 Patients: 2007-2015.

BACKGROUND: Understanding the changing epidemiology of Staphylococcus aureus bacteremia, as well as the variables associated with poor outcomes, can yield insight into potential interventions. METHODS: This study was a retrospective, observational cohort study of adult patients at an academic medical center in New York City who had S. aureus bloodstream infections between 1 January 2007 and 31 December 2015. Participants were divided into 3 periods: group 1 (2007-2009), group 2 (2010-2012), and group 3 (2013-2015) for trend analysis. All clinical strains were genotyped (spa.). The main outcome was 30-day all-cause mortality. RESULTS: There were 1264 episodes of methicillin-susceptible S. aureus (MSSA) and 875 episodes of methicillin-resistant S. aureus (MRSA) bacteremia, with a rising proportion due to MSSA (55% group 1; 59% group 2; 63% group 3; P = .03.) There were no significant changes in average age, gender, Charlson score, and distribution of strain genotypes. Mortality in MRSA infection was unchanged (25% group 1; 25% group 2; 26% group 3), while mortality in MSSA infection significantly declined (18% group 1; 18% group 2; 13% group 3). The average time to antistaphylococcal therapy (AST) in MSSA infection declined during the study (3.7 days group 1; 3.5 group 2; 2.2 group 3). In multivariate analysis, AST within 7 days of initial positive MSSA culture was associated with survival. CONCLUSIONS: Mortality in MSSA bloodstream infection is declining, associated with a decrease in time to targeted therapy. These results emphasize the potential for rapid diagnostics and early optimization of treatment to impact outcomes in MSSA bacteremia.

Tocilizumab for severe COVID-19 in solid organ transplant recipients: a matched cohort study.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.

COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.

Clinical Significance of Human Herpesvirus 6 Positivity on the FilmArray Meningitis/Encephalitis Panel.

A review of 15 patients who tested positive for human herpesvirus 6 (HHV-6) on the FilmArray Meningitis/Encephalitis panel revealed that the majority were unlikely to have HHV-6 encephalitis. Criteria to assist interpretation of HHV-6 positive results are presented.

Genomic Surveillance Reveals Diversity of Multidrug-Resistant Organism Colonization and Infection: A Prospective Cohort Study in Liver Transplant Recipients.

Background: Multidrug-resistant organisms (MDROs) are an important cause of morbidity and mortality after solid organ transplantation. We aimed to characterize MDRO colonization dynamics and infection in liver transplant (LT) recipients through innovative use of active surveillance and whole-genome sequencing (WGS). Methods: We prospectively enrolled consecutive adult patients undergoing LT from March 2014 to March 2016. Fecal samples were collected at multiple timepoints from time of enrollment to 12 months posttransplant. Samples were screened for carbapenem-resistant Enterobacteriaceae (CRE), Enterobacteriaceae resistant to third-generation cephalosporins (Ceph-RE), and vancomycin-resistant enterococci. We performed WGS of CRE and selected Ceph-RE isolates. We also collected clinical data including demographics, transplant characteristics, and infection data. Results: We collected 998 stool samples and 119 rectal swabs from 128 patients. MDRO colonization was detected in 86 (67%) patients at least once and was significantly associated with subsequent MDRO infection (0 vs 19.8%, P = .002). Child-Turcotte-Pugh score at LT and duration of post-LT hospitalization were independent predictors of both MDRO colonization and infection. Temporal dynamics differed between MDROs with respect to onset of colonization, clearance, and infections. We detected an unexpected diversity of CRE colonizing isolates and previously unrecognized transmission that spanned Ceph-RE and CRE phenotypes, as well as a cluster of mcr-1-producing isolates. Conclusions: Active surveillance and WGS showed that MDRO colonization is a highly dynamic and complex process after LT. Understanding that complexity is crucial for informing decisions regarding MDRO infection control, use of therapeutic decolonization, and empiric treatment regimens.

Outcomes for potential kidney transplant recipients offered public health service increased risk kidneys: A single-center experience.

BACKGROUND: Discard rate of Public Health Service Increased Risk (PHS-IR) organs is high despite the absence of worse kidney transplant outcomes. METHODS: We conducted a retrospective, single-center study of PHS-IR kidney offers made to kidney transplant-only potential recipients from 6/2004 to 5/2015. Overall mortality and transplant outcomes between potential recipients were stratified by response to PHS-IR kidney offers. Cox regression and Kaplan-Meier analyses of mortality and allograft failure were performed. RESULTS: A total of 2423 potential recipients were offered a PHS-IR kidney, with 1502 transplanted, with or without a PHS-IR kidney. Predictors of accepting a PHS-IR kidney included higher Estimated Post Transplant Survival (EPTS) score, prior kidney transplant, and lower educational achievement on multivariable analysis (P = 0.025, P = 0.004, P = 0.023). A positive response to a PHS-IR kidney was associated with lower risk of mortality (3.63% vs 11.6%; aHR 0.467, P = 0.0008). PHS-IR kidney recipients had decreased risk of allograft loss compared to non-PHS-IR recipients (P = 0.007), though mortality outcomes were not significantly different based on PHS-IR status (P = 0.38). No transmission of HIV, HBV, or HCV occurred from PHS-IR kidney donors in this cohort. CONCLUSIONS: Efforts must be made to increase awareness of the beneficial outcomes of PHS-IR organs to maximize appropriate donor allocation.

Sino-Orbital Fungal Infection by Tilletiopsis minor, a Rare Human Pathogen, Diagnosed by Internal Transcribed Spacer Sequencing.

Orbital infection can be caused by numerous pathogens, and accurate diagnosis informs appropriate therapy. The authors report a case of a 78-year-old man with well-controlled diabetes mellitus and recurrent sino-orbital infection following multiple surgical procedures with negative microbiologic results. This case presented a diagnostic and treatment challenge and was aided by the use of internal transcribed spacer sequencing for pathogen identification. The fungal pathogen, Tilletiopsis minor, has not previously been described as a human pathogen in the sinus and orbit. This report describes a novel orbital pathogen and highlights the importance of diagnostic diligence and utilizing internal transcribed spacer sequencing in the workup of atypical orbital infection.

Epidemiological and biological determinants of Staphylococcus aureus clinical infection in New York State maximum security prisons.

BACKGROUND: Large outbreaks of Staphylococcus aureus (SA) infections have occurred in correctional facilities across the country. We aimed to define the epidemiological and microbiological determinants of SA infection in prisons to facilitate development of prevention strategies for this underserved population. METHODS: We conducted a case-control study of SA infection at 2 New York State maximum security prisons. SA-infected inmates were matched with 3 uninfected controls. Subjects had cultures taken from sites of infection and colonization (nose and throat) and were interviewed via structured questionnaire. SA isolates were characterized by spa typing. Bivariate and multivariable analyses were conducted using conditional logistic regression. RESULTS: Between March 2011 and January 2013, 82 cases were enrolled and matched with 246 controls. On bivariate analysis, the use of oral and topical antibiotics over the preceding 6 months was strongly associated with clinical infection (OR, 2.52; P < .001 and 4.38, P < .001, respectively). Inmates with clinical infection had 3.16 times the odds of being diabetic compared with inmates who did not have clinical infection (P < .001). Concurrent nasal and/or oropharyngeal colonization was also associated with an increased odds of infection (OR, 1.46; P = .002). Among colonized inmates, cases were significantly more likely to carry the SA clone spa t008 (usually representing the epidemic strain USA300) compared to controls (OR, 2.52; P = .01). CONCLUSIONS: Several inmate characteristics were strongly associated with SA infection in the prison setting. Although many of these factors were likely present prior to incarceration, they may help medical staff identify prisoners for targeted prevention strategies.

Obesity as a Determinant of Staphylococcus aureus Colonization Among Inmates in Maximum-Security Prisons in New York State.

Obesity increases a person's susceptibility to a variety of infections, including Staphylococcus aureus infections, which is an important cause of morbidity in correctional settings. Using a cross-sectional design, we assessed the association between obesity and S. aureus colonization, a risk factor for subsequent infection, in New York State maximum-security prisons (2011-2013). Anterior nares and oropharyngeal cultures were collected. Structured interviews and medical records were used to collect demographic, behavioral, and medical data. Body mass index (BMI; weight (kg)/height (m(2))) was categorized as 18.5-24.9, 25-29.9, 30-34.9, or ≥35. The association between BMI and S. aureus colonization was assessed using log-binomial regression. Thirty-eight percent of 638 female inmates and 26% of 794 male inmates had a BMI of 30 or higher. More than 40% of inmates were colonized. Female inmates with a BMI of 25-29.9 (prevalence ratio (PR) = 1.37, 95% confidence interval (CI): 1.06, 1.76), 30-34.9 (PR = 1.52, 95% CI: 1.17, 1.98), or ≥35 (PR = 1.49, 95% CI: 1.13, 1.96) had a higher likelihood of colonization than did those with a BMI of 18.5-24.9 after we controlled for age, educational level, smoking status, diabetes status, and presence of human immunodeficiency virus. Colonization was higher among male inmates with a BMI of 30-34.9 (PR = 1.27, 95% CI: 1.01, 1.61). Our findings demonstrate an association between BMI and S. aureus colonization among female prisoners. Potential contributory biologic and behavioral factors should be explored.

Infectious Disease Prophylaxis During and After Immunosuppressive Therapy.

Immune-mediated renal diseases are a diverse group of disorders caused by antibody, complement, or cell-mediated autosensitization. Although these diseases predispose to infection on their own, a growing array of traditional and newer, more targeted immunosuppressant medications are used to treat these diseases. By understanding their mechanisms of action and the infections associated with suppression of each arm of the immune system, nephrologists can better anticipate these risks and effectively prevent and recognize opportunistic infections. Focusing specifically on nonkidney transplant recipients, this review discusses the infections that can be associated with each of the commonly used immunosuppressants by nephrologists and suggest interventions to prevent infectious complications in patients with immune-mediated renal disease.

Emergence of sequence type 398 as a community- and healthcare-associated methicillin-susceptible staphylococcus aureus in northern Manhattan.

The methicillin-susceptible Staphylococcus aureus (MSSA) clone sequence type (ST) 398 has increasingly been identified as a pathogen in diverse geographic settings, yet its epidemiology remains incompletely understood. In this case-control study of MSSA infections, we identified ST398 MSSA as both a major community- and hospital-associated MSSA pathogen in the Dominican neighborhood of northern Manhattan.

Molecular characterization of methicillin-susceptible Staphylococcus aureus clinical isolates in the United States, 2004 to 2010.

While much is known about the geographic distribution of different clonal types of methicillin-resistant Staphylococcus aureus (MRSA), few studies have assessed the molecular epidemiology of methicillin-susceptible S. aureus (MSSA), despite its continued clinical importance. In each U.S. Census region, reference laboratories collected successive MSSA isolates from patients with invasive or superficial staphylococcal infections for use in the Tigecycline Evaluation and Surveillance Trial. All isolates from the periods of 2004 to 2005 and 2009 to 2010 underwent antimicrobial susceptibility testing and characterization of their staphylococcal protein A (spa) type. Of the 708 isolates analyzed, 274 spa types were identified and divided into 15 genetic clusters. The most common clones were spa t002 (n = 63, 8.9%) and t008 (n = 56, 7.9%). While the distribution of the predominant spa types did not differ by U.S. Census region or time period, spa t008 was nearly twice as common in community skin and soft tissue infections than in nosocomial bloodstream infections (11.1% versus 5.6%, respectively; P = 0.008). Despite such differences, both community and nosocomial settings had diverse staphylococcal clonal types representing all major spa clusters. In contrast to those of MRSA, MSSA infectious isolates show wide genetic diversity without clear geographical or temporal clustering. Notably, the prevalent MSSA strains (spa t002 and spa t008) are analogous to the predominant MRSA clones, further demonstrating the importance of both lineages.

CYTOMEGALOVIRUS RETINITIS WITH BELATACEPT IMMUNOSUPPRESSION.

PURPOSE: To report two cases of cytomegalovirus (CMV) retinitis in renal transplant patients after conversion to belatacept immunosuppression. METHODS: Case report. RESULTS: Case A was a 41-year-old African American man with no ocular history, chronic hepatitis B infection on entecavir, status-post living relative renal transplant for end-stage renal disease secondary to IgA nephropathy presented with a chief complaint of "blurry vision" in his right eye. Fundoscopic examination of the right eye revealed perivascular retinitis of the superior arcade extending temporally and a lesion nasal to the optic disk. The patient was diagnosed with CMV retinitis with macular involvement. Case B was a 52-year-old woman with an ocular history significant for bilateral vein occlusions treated with laser, and a medical history of hypertension, hyperlipidemia, and end-stage renal disease secondary to hypoplastic kidney status-post deceased donor renal transplant presented with one week of blurred vision in the right eye. Fundoscopic examination of the right eye revealed macular star configuration of exudates, as well as subretinal fibrosis temporal to the macula. Fundoscopic examination of the left eye showed Grade 4 vitreous haze and multiple areas of retinal whitening and hemorrhage, consistent with CMV retinitis infection. The patient was diagnosed with bilateral CMV retinitis, with macular involvement in the right eye. CONCLUSION: Renal transplant patients converted to belatacept immunosuppression may be at an increased risk for herpes virus infection, and thus herpes virus retinitis. Although the degree of risk remains uncharacterized, patients on belatacept therapy who are at the high risk of CMV infection (i.e., donor-positive/recipient-negative patients) should be counseled on the presenting signs and symptoms of CMV retinitis. In these cases, clinicians should also consider regular monitoring of serum CMV titers or continuation of antiviral prophylaxis.

Cycle Thresholds Among Solid Organ Transplant Recipients Testing Positive for SARS-CoV-2.

BACKGROUND: The optimal duration of transmission-based precautions among immunocompromised patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. METHODS: Retrospective review of patients with solid organ transplant with positive SARS-CoV-2 polymerase chain reaction result from nasopharyngeal specimens admitted to the hospital between March 13, 2020 and May 15, 2020. RESULTS: Twenty-one percent of solid organ transplant recipients with positive SARS-CoV-2 polymerase chain reaction detected ≥20 d after symptom onset (or after first positive test among asymptomatic individuals) had a low cycle threshold (ie, high viral load). The majority of these patients were asymptomatic or symptomatically improved. CONCLUSIONS: Solid organ transplant recipients may have prolonged high viral burden of SARS-CoV-2. Further data are needed to understand whether cycle threshold data can help inform strategies for prevention of healthcare-associated transmission of SARS-CoV-2 and for appropriate discontinuation of transmission-based precautions.

What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak.

BACKGROUND: Tocilizumab, an interleukin-6 receptor blocker, has been used in the inflammatory phase of COVID-19, but its impact independent of corticosteroids remains unclear in patients with severe disease. METHODS: In this retrospective analysis of patients with COVID-19 admitted between March 2 and April 14, 2020 to a large academic medical center in New York City, we describe outcomes associated with tocilizumab 400 mg (without methylprednisolone) compared to a propensity-matched control. The primary endpoints were change in a 7-point ordinal scale of oxygenation and ventilator free survival, both at days 14 and 28. Secondary endpoints include incidence of bacterial superinfections and gastrointestinal perforation. Primary outcomes were evaluated using t-test. RESULTS: We identified 33 patients who received tocilizumab and matched 74 controls based on demographics and health measures upon admission. After adjusting for illness severity and baseline ordinal scale, we failed to find evidence of an improvement in hypoxemia based on an ordinal scale at hospital day 14 in the tocilizumab group (OR 2.2; 95% CI, 0.7-6.5; p = 0.157) or day 28 (OR 1.1; 95% CI, 0.4-3.6; p = 0.82). There also was no evidence of an improvement in ventilator-free survival at day 14 (OR 0.8; 95% CI, 0.18-3.5; p = 0.75) or day 28 (OR 1.1; 95% CI, 0.1-1.8; p = 0.23). There was no increase in secondary bacterial infection rates in the tocilizumab group compared to controls (OR 0.37; 95% CI, 0.09-1.53; p = 0.168). CONCLUSIONS: There was no evidence to support an improvement in hypoxemia or ventilator-free survival with use of tocilizumab 400 mg in the absence of corticosteroids. No increase in secondary bacterial infections was observed in the group receiving tocilizumab.

Supervised Machine Learning Approach to Identify Early Predictors of Poor Outcome in Patients with COVID-19 Presenting to a Large Quaternary Care Hospital in New York City.

BACKGROUND: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. METHODS: We performed a nested case-control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. RESULTS: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (<4 days, 41%; 4-8 days, 31%; >8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for <4, 4-8, and >8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1; requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL; and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. CONCLUSION: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.