Is yearly interferon gamma release assay latent tuberculosis infection screening warranted among patients with rheumatological diseases on disease-modifying drugs in non-endemic settings?

OBJECTIVE: Patients living with rheumatologic diseases on disease-modifying antirheumatic drugs (DMARD) are at an increased risk of developing tuberculosis (TB). Current guidelines recommend screening for latent tuberculosis infection (LTBI) before initiating DMARD. However, data is lacking on the value of yearly screening for LTBI. METHODS: A retrospective chart review was conducted on adult patients (≥ 18 years) with rheumatologic disease on DMARD followed longitudinally in the outpatient rheumatology clinics between 2017-2021. Collected data included patient demographics, rheumatologic diagnosis, medications, TB-related risk factors, interferon gamma release assay (IGRA) results, LTBI diagnosis and treatment. Descriptive statistics were performed. RESULTS: Among 339 patients, 81 (23.9%) were male, 259 (76.4%) were white, and 93 (27.5%) were Latinx. Inflammatory arthritis (84.1%) was the most common rheumatic diagnosis. Common DMARD were JAK inhibitors (19.2%), TNF-alpha inhibitors (18.9%), and IL-17 A inhibitors (18.0%). Only 2 patients at baseline had positive IGRA, and both had a history of treated LTBI. Positive IGRA tests were recorded in 1 (0.7%), 3 (1.8%), 3 (1.3%), and 3 (1.1%) in the years 2018, 2019, 2020, and 2021, respectively. Four patients converted from negative to positive during serial yearly IGRA testing. After reviewing the IGRA test and TB risk factors, only one patient was considered newly diagnosed with LTBI, requiring 4 months of rifampin. CONCLUSION: In a non-endemic area, serial IGRA testing of low-risk patients on DMARD yielded very low rate of newly diagnosed LTBI. A targeted LTBI screening based on TB-related risk factors should be performed prior to IGRA testing rather than universal yearly screening in a non-endemic setting.

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

Atypical pneumonia testing in transplant recipients.

BACKGROUND: The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. METHODS: A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T-cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre-defined criteria. A cost analysis of diagnostic testing was performed. RESULTS: Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1-year post-transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. CONCLUSION: The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings.

The cascade of care in testing and treatment of latent tuberculosis infection in liver transplant candidates.

BACKGROUND: Testing and treatment for latent tuberculosis infection (LTBI) can mitigate risk of active tuberculosis (TB) post-liver transplant (LT). Testing and treatment completion rates have been reported low in this population. Our study aims to quantify the proportion of LT candidates who completed LTBI care cascade in our center. METHODS: A retrospective chart review was conducted on LT candidates from 2012 to 2021. Primary outcome was the proportion of patients who completed each cascade stage. Secondary outcome was an analysis of factors associated with positive and indeterminate LTBI testing. RESULTS: Of the 273 LT candidates, 265 (97.1%) were referred to transplant infectious disease (TID), 264 (96.7%) had orders for interferon-gamma release assay (IGRA), 262 (96%) underwent TID evaluation, and 259 (94.9%) completed IGRA. Twenty had LTBI, and 18 were treatment naïve and recommended for treatment. Of the 18, 15 (83.3%) agreed to therapy, 14 (77.8%) initiated treatment, and 12 (66.7%) completed treatment. No posttransplant TB reactivation occurred. Patients born in Asia, previous incarceration, past military service, and granuloma findings on chest imaging were likely to have positive IGRA (p < .05). Older age and travel to TB-endemic countries were likely to have indeterminate IGRA (p < .05). Indeterminate IGRAs were more common in QuantiFERON (QTF)-Gold Plus TB (15.3%) versus QTF-Gold TB (9.3%, p < .001). CONCLUSIONS: High rates of LTBI testing and treatment initiation and completion can be attributed to a standardized process that includes TID evaluation. Future studies in larger cohort are needed to better understand factors that can optimize the completion rates of LTBI treatment in LT candidates.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

Increased Detection of Mycobacterium tuberculosis Disease Using a Tissue-Based Laboratory-Developed Polymerase Chain Reaction Assay Compared to Standard Diagnostics.

Standard diagnostics for Mycobacterium tuberculosis (MTB) including acid-fast bacilli (AFB) smear and culture, and Xpert™ MTB/RIF real-time Polymerase Chain Reaction (RT-PCR; Xpert) have variable sensitivity and/or long turnaround times. We describe the clinical performance of a laboratory-developed tissue-based MTB PCR compared with AFB culture and Xpert using a composite reference standard (CRS). Over an 8-year period, MTB PCR was performed on pulmonary, pleural, or lymph node specimens for 36 patients. Of these, 11 met criteria for confirmed/probable MTB using CRS. MTB PCR was positive in 100% (11/11), AFB cultures were positive in 73% (8/11), and Xpert in 0% (0/4). MTB PCR was negative in 25 cases of "No MTB" (100% specific). The MTB PCR assay resulted faster than positive AFB culture (mean time 4.3 versus 21.2 days). Tissue-based MTB PCR was associated with increased and rapid detection of MTB, improving clinical sensitivity in strongly suspected MTB cases.

Incidence and associated risk factors for invasive fungal infections and other serious infections in patients on ibrutinib.

BACKGROUND: Ibrutinib is a small molecule tyrosine kinase inhibitor that blocks the activity of B cells and other immune effectors and is used in a variety of hematologic malignancies. There have been numerous reports of increased frequency of serious infections including invasive fungal infections (IFI) in patients on ibrutinib. METHODS: Demographic and clinical features of all patients receiving ibrutinib at a single tertiary care center were collected from electronic medical records. Univariate and multivariate statistical analyses were performed to find out the factors associated with infection. RESULTS: A total of 244 patients received ibrutinib for hematologic malignancies, of which 44 (18.0%) experienced ≥ 1 serious infection including 5 (2.0%) with IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis), 39 (16.0%) with bacterial infections and 8 (3.3%) with viral infections. Ten patients (4.1%) experienced multiple infections or co-infections while on ibrutinib and 10 (4.1%) expired or were transferred to hospice as a result of infection. In multivariate analysis risk factors that were less common in uninfected versus infected patients included advanced age (73 years vs. 77 years), Eastern Cooperative Oncologic Grade (ECOG) performance score ≥ 2 (6.5% vs. 31.8%) and concurrent use of steroids (4.5% vs. 20.5%) or other cytotoxic agents (0% vs. 4.6%). CONCLUSIONS: There was a high rate of serious infection but relatively few IFI in patients receiving ibrutinib. Most patients who developed serious infections while on ibrutinib had additional predisposing risk factors including concurrent use of steroids or other cytotoxic agents, advanced age and frailty.

Letermovir treatment of cytomegalovirus infection or disease in solid organ and hematopoietic cell transplant recipients.

BACKGROUND: Few options are available for cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients. METHODS: Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected. RESULTS: Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. Forty-five of 47 (94%) were treated with other agents prior to LET, and 57% had a history of prior CMV disease. Seventy-seven percent were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load < 1000 international units (IU)/ml at LET initiation, two experienced >1 log rise in viral load by week 12, and no deaths were attributed to CMV. Ten patients had viral load > 1000 IU/ml at LET initiation, and six of 10 (60%) had a CMV viral load < 1000 IU/ml at completion of therapy or last known value. LET was discontinued in two patients for an adverse event. CONCLUSIONS: Patients treated with LET with viral load < 1000 IU/ml had good virologic outcomes. Outcomes were mixed when LET was initiated at higher viral loads. Further studies on combination therapy or alternative LET dosing are needed.

A retrospective matched cohort single-center study evaluating outcomes of COVID-19 and the impact of immunomodulation on COVID-19-related cytokine release syndrome in solid organ transplant recipients.

This retrospective matched cohort study describes 30 solid organ transplant (SOT) patients with Coronavirus Disease 2019 (COVID-19) matched 1:2 to 60 non-SOT patients (control group) based on age, body mass index (BMI), and comorbidities (hypertension and diabetes mellitus with hemoglobin A1c > 8.0%). The SOT group had a higher proportion of cardiovascular disease (P < .05). During the index hospitalization, there were no significant differences with regard to disease severity or critical care needs (mechanical intubation, vasopressors, and renal replacement therapy). At 28 days, 4 (13%) patients died in the SOT group and 8 (13%) patients died in the control group (P = 1.0). Nineteen patients received tocilizumab in the SOT group compared to 29 patients in the control group. Among these patients, interleukin-6 (IL-6) and soluble interleukin-2 receptor (sIL2R) levels increased after tocilizumab and interleukin-10 (IL-10) levels decreased after tocilizumab. Overall, SOT patients had comparable mortality to non-SOT patients, although numerically more SOT patients received tocilizumab (63% vs 48%) and steroids (37% vs 20%). Larger, multi-center studies are needed to ascertain these findings. Lastly, the complex cytokine release syndrome in COVID-19 remains an area of intense research and the analysis of key interleukin levels (IL-6, IL-10, and sIL2R) in this study contributes to the understanding of this process.

Clinicopathologic Features of Tissue Granulomas in Transplant Recipients: A Single Center Study in a Nontuberculosis Endemic Region.

CONTEXT.­: There is a paucity of literature about tissue granulomas in transplant patients. OBJECTIVE.­: To characterize the clinicopathologic features of granulomas in this population and develop a clinically judicious approach to their evaluation. DESIGN.­: We performed chart reviews of solid organ and allogeneic hematopoietic stem cell transplant recipients at Yale New Haven Hospital to identify patients with granulomas on biopsy obtained pathologic specimens. Pretransplant and posttransplant specimens were included. Data points included demographics, clinical presentation, epidemiologic risk factors, biopsy indication, location and timing, immunosuppression, histopathology, microbiology, and associated clinical diagnosis. Granuloma-related readmissions and mortality were recorded at 1, 3, and 12 months. RESULTS.­: Biopsy proven granulomas were identified in 56 of 2139 (2.6%) patients. Of 56, 16 (29%) were infectious. Common infectious etiologies were bartonellosis (n = 3) and cytomegalovirus hepatitis (n = 3). Tuberculosis was not identified. Clinical symptoms prompted tissue biopsy in 27 of 56 (48.2%) cases while biopsies were obtained for evaluation of incidental findings or routine disease surveillance in 29 of 56 (51.8%). Presence of symptoms was significantly associated with infectious etiologies; 11 of 27 (40.7%) symptomatic patients compared with 5 of 29 (17.2%) asymptomatic patients had infectious causes. One death from granulomatous cryptogenic organizing pneumonia occurred. In pretransplant asymptomatic patients, no episodes of symptomatic disease occurred posttransplantation. CONCLUSIONS.­: Granulomas were uncommon in a large transplant population; most were noninfectious but presence of symptoms was associated with infectious etiologies. Granulomas discovered pretransplant without clear infectious etiology likely do not require prolonged surveillance after transplantation. Symptomatology and epidemiologic risks factors should guide extent of microbiologic evaluation.

Added Diagnostic Utility of Clinical Metagenomics for the Diagnosis of Pneumonia in Immunocompromised Adults.

BACKGROUND: In the evaluation of community-acquired pneumonia, 30% to 60% of cases remain undiagnosed, despite extensive conventional microbiologic testing (CMT). Clinical metagenomics (CM) is an unbiased pathogen detection method that can increase diagnostic yield. RESEARCH QUESTION: Does adding clinical metagenomics to conventional microbiologic testing improve the diagnostic yield for pneumonia in immunocompromised adults? STUDY DESIGN AND METHODS: We performed a noninterventional prospective study of immunocompromised adults with pneumonia who underwent bronchoscopy and BAL over 2 years. CMT was performed per standard of care. A commercial CM test was performed on residual BAL fluid. Final microbiologic diagnoses were based on CMT vs CMT + CM. Final clinical diagnoses for CMT and CMT + CM were made based on laboratory results in conjunction with clinical and radiologic findings. Hypothetical impact of CMT + CM on management and antimicrobial stewardship was also assessed. RESULTS: A total of 30 immunocompromised adult patients (31 episodes of pneumonia) were included. Final microbiologic diagnoses were made in 11 cases (35%) with the use of CMT and in 18 cases (58%) with the use of CMT + CM. Bacterial pneumonia was diagnosed in five cases (16%) by CMT and in 13 cases (42%) by CMT + CM; fungal pneumonia was diagnosed in six cases (19%) by CMT and in seven cases (23%) by CMT + CM, and viral pneumonia was diagnosed in two cases (6%) by CMT and in five cases (16%) by CMT + CM. The hypothetical impact of CMT + CM on management was deemed probable in one case, possible in eight cases, and unlikely in two cases, whereas the impact on antimicrobial stewardship was possible in 13 cases and unlikely in seven cases. Final clinical diagnoses were made in 20 of 31 cases (65%) based on CMT and in 23 of 31 cases (74%) based on CMT + CM. INTERPRETATION: CMT + CM increased diagnostic yield in immunocompromised adults with pneumonia from 35% to 58%, mostly by the detection of additional bacterial causes but was less useful for fungal pneumonia.

Unilateral leg pain caused by cryptococcal myositis: An unusual presentation of disseminated cryptococcosis in a kidney transplant recipient.

Cryptococcal disease is a rare but often serious infection in solid organ transplant recipients, commonly presenting as meningitis and pneumonia but can rarely cause myositis. We report the case of a 43-year-old female kidney transplant recipient with two previous graft failures requiring re-transplantations who presented with a 1-month duration of worsening unilateral leg pain, swelling, and shortness of breath. Blood cultures isolated Cryptococcus neoformans. A calf biopsy was performed and histopathology revealed myonecrosis with yeast forms consistent with Cryptococcus spp. Liposomal amphotericin B (LamB) was administered. Her course was complicated by hypoxemic respiratory failure with development of ground glass opacities on chest imaging. Work-up revealed bacterial and C neoformans pneumonia and probable Pneumocystis jirovecii pneumonia (PJP) She received trimethoprim-sulfamethoxazole and LamB and was discharged on fluconazole. Shortly thereafter she was re-admitted with confusion, septic shock, and multi-organ failure. Work-up revealed PJP with subsequent development of cryptococcal meningitis. Despite aggressive management, she expired. Disseminated cryptococcal infection may manifest as myositis. Presence of cryptococcal infection is a marker of severe net state of immunosuppression (IS), hence, presence of other opportunistic infections is likely. Early recognition of cryptococcal infection, institution of targeted therapy, and IS reduction are important to improve overall survival.

Emerging Microbiology Diagnostics for Transplant Infections: On the Cusp of a Paradigm Shift.

In light of the heightened risk for infection associated with solid organ and hematopoietic stem cell transplantation, rapid and accurate microbiology diagnostics are essential to the practice of transplant clinicians, including infectious diseases specialists. In the last decade, diagnostic microbiology has seen a shift toward culture-independent techniques including single-target and multiplexed molecular testing, mass-spectrometry, and magnetic resonance-based methods which have together greatly expanded the array of pathogens identified, increased processing speed and throughput, allowed for detection of resistance determinants, and ultimately improved the outcomes of infected transplant recipients. More recently, a newer generation of diagnostics with immense potential has emerged, including multiplexed molecular panels directly applicable to blood and blood culture specimens, next-generation metagenomics, and gas chromatography mass spectrometry. Though these methods have some recognized drawbacks, many have already demonstrated improved sensitivity and a positive impact on clinical outcomes in transplant and immunocompromised patients.

Gomori Methenamine Silver Stain on Bronchoalveolar Lavage Fluid Is Poorly Sensitive for Diagnosis of Pneumocystis jiroveci Pneumonia in HIV-Negative Immunocompromised Patients and May Lead to Missed or Delayed Diagnoses.

CONTEXT.­: Direct visualization of Pneumocystis jiroveci organisms, using Gomori methenamine silver (GMS) staining in bronchoalveolar lavage fluid (BAL), is a historical gold standard that has been widely used for the diagnosis of P jiroveci pneumonia (PJP). However, the stain may be less sensitive in human immunodeficiency virus (HIV)-negative immunocompromised patients owing to a lower burden of organisms. OBJECTIVES.­: To assess the sensitivity of the GMS stain on BAL fluid for the diagnosis of PJP in HIV-negative immunocompromised patients as compared to HIV-positive patients. DESIGN.­: We conducted a retrospective review from 2012 to 2018 to identify immunocompromised patients (≥18 years old) who underwent bronchoscopy with BAL GMS staining for the diagnosis of PJP. To assess for sensitivity, we sought to identify BAL GMS-positive cases and BAL GMS-negative cases of PJP. The BAL GMS-negative cases were categorized into proven and probable PJP. RESULTS.­: We identified 45 adult immunocompromised patients with proven and probable PJP, including 24 HIV-negative (11 BAL GMS-positive and 13 BAL GMS-negative) and 21 HIV-positive cases (all were BAL GMS-positive). The sensitivity of BAL GMS for the diagnosis of PJP in HIV-negative immunocompromised patients was 11 of 24 (46%) versus 21 of 21 (100%) in HIV-positive patients (CD4: median, 10 cells/mL; range, 3-300 cells/mL). Delayed or missed diagnoses were seen in 3 cases of BAL GMS-negative PJP. Re-examination of BAL GMS slides showed rare P jiroveci cysts in 1 case. CONCLUSIONS.­: BAL GMS has poor sensitivity for PJP in HIV-negative immunocompromised patients. Using BAL GMS as a sole method for PJP may result in missed or delayed diagnoses in this population.

An assessment of transesophageal echocardiography studies rated as rarely appropriate tests for infective endocarditis at an academic medical center.

PURPOSE: Endocardial involvement documented by echocardiography is a major criterion of the modified Duke criteria (MDC) for infective endocarditis (IE). Though transesophageal echocardiography (TEE) is sensitive in the diagnosis of IE, it can be inappropriately used. METHODS: This retrospective study included all patients who underwent TEE due to bacteremia, fever, and/or endocarditis in a single, tertiary academic medical center in 2013. Data collected from electronic medical charts were as follows: demographics, history, physical examination, blood cultures, and transthoracic (TTE) and TEE findings. Cases were categorized based on appropriate use criteria (AUC) and MDC. An infectious disease (ID) specialist reviewed cases with rarely appropriate TEE use. RESULTS: In the 194 patients included, 147 (75.8%) were rated as appropriate, 36 (18.6%) rarely appropriate, and 11 (5.6%) uncertain. Of the 36 with rarely appropriate TEEs, using MDC 31 (86%) were rejected and 5 (14%) were possible for IE. Retrospective chart review by an ID specialist determined that 10 of these patients warranted TEE due to compelling issues, including immunosuppression or complicated infection. CONCLUSIONS: In this retrospective cohort, almost one fifth of cases were rated as rarely appropriate. However, a review of these cases showed that TEE was often pursued when the clinical situation involved immunosuppression or complex infectious process. There remains room for improvement to our screening process for TEE and a need to implement a nuanced educational plan to better precisely identify appropriate cases for TEE usage.

Heart or lung transplant outcomes in HIV-infected recipients.

BACKGROUND: Limited published data exist on outcomes related to heart and/or lung transplantation in human immunodeficiency virus (HIV)-infected individuals. METHODS: We conducted a multicenter retrospective study of heart and lung transplantation in HIV-infected patients and describe key transplant- and HIV-related outcomes. RESULTS: We identified 29 HIV-infected thoracic transplant recipients (21 heart, 7 lung, and 1 heart and/or lung) across 14 transplant centers from 2000 through 2016. Compared with an International Society for Heart and Lung Transplantation registry cohort, we demonstrated similar 1-, 3-, and 5-year patient and allograft survivals for each organ type with a median follow up of 1,064 (range, 184-3,745) days for heart and 1,540 (range, 116-3,206) days for lung recipients. At 1 year, significant rejection rates were high (62%) for heart transplant recipients (HTRs). Risk factors for rejection were inconclusive, likely because of small numbers, but may be related to cautious early immunosuppression and infrequent use of induction therapy. Pulmonary bacterial infections were high (86%) for lung transplant recipients (LTRs). Median CD4 counts changed from baseline to 1 year from 399 to 411 cells/µl for HTRs and 638 to 280 cells/µl for LTRs. Acquired immunodeficiency syndrome-related events, including infections and malignancies, were rare. Rates of severe renal dysfunction suggest a need to modify nephrotoxic anti-retrovirals and/or immunosuppressants. CONCLUSIONS: HIV-infected HTRs and LTRs have similar survival rates to their HIV-uninfected counterparts. Although optimal immunosuppression is not defined, it should be at least as aggressive as that for HIV-uninfected recipients. Such data may help pave the way for the use of hearts and lungs from HIV-infected donors in HIV-infected recipients through HIV Organ Policy Equity Act protocols.

The impact of a multimodal approach to vancomycin discontinuation in hematopoietic stem cell transplant recipients (HSCT) with febrile neutropenia (FN).

BACKGROUND: Current guidelines recommend adding vancomycin to empiric treatment of FN in patients who meet specific criteria. After 48 hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. Based on these recommendations, a vancomycin stewardship team defined criteria for discontinuation of vancomycin at 48 hours and increased surveillance of vancomycin usage through a multimodal approach. The purpose of this retrospective analysis is to assess the impact of this multimodal approach on the discontinuation of empiric vancomycin at 48 hours in FN. METHODS: This retrospective analysis included a pre- and post-intervention cohort of 200 HSCT recipients with FN from 2015 to 2018. Criteria for continued vancomycin use beyond 48 hours included culture-documented resistant Gram-positive infection, positive Methicillin-Resistant S aureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability with concern for sepsis. The following patient characteristics were collected: previous MRSA infection, MRSA nasal swab collection and results, culture results, duration of vancomycin use, rationale for continuation of vancomycin beyond 48 hours, and re-initiation of vancomycin. RESULTS: In the post-intervention cohort, vancomycin discontinuation at 48 hours increased from 31% (95% CI 21.94-40.05) to 70% (95% CI 61.02-78.97; P < 0.0001). An additional 23% of vancomycin orders were discontinued at 72 hours. Off criteria vancomycin use decreased from 33% in pre to 1% in the post-implementation cohort. CONCLUSION: Establishing define criteria for vancomycin use in FN patients with a multimodal approach of physicians from hematology and infectious diseases, clinical pharmacists and the antibiotic stewardship team significantly improved vancomycin discontinuation.

Successful treatment of primary donor-derived human herpesvirus-8 infection and hepatic Kaposi Sarcoma in an adult liver transplant recipient.

Kaposi sarcoma (KS) may rarely occur in transplant recipients through primary human herpesvirus-8 (HHV-8) infection from a seropositive donor. This report describes a patient who developed hepatic KS after receiving a split liver transplant from an HHV-8-positive donor. The recipient was treated with liposomal doxorubicin after reduction in immunosuppression led to acute cellular rejection. This treatment achieved regression of KS while preserving allograft function, demonstrating a successful therapeutic strategy for this malignancy.

Diagnosing Ring-Enhancing Lesions in the Brain of a Patient With AIDS Without Brain Biopsy: A Case of Central Nervous System Histoplasmoma.

We report a case of a Puerto Rican male with advanced AIDS who presented with multiple falls and pancytopenia. Magnetic resonance imaging (MRI) of the brain, as initial workup, revealed 2 ring-enhancing brain lesions. Initial cerebrospinal fluid analysis revealed minimal cells, mildly elevated protein, and no organism seen on gram stain. Due to prohibitive thrombocytopenia, brain biopsy was deferred. He had neither clinical nor radiographic improvement despite empiric therapy for both toxoplasmosis and bacterial abscesses. Indicated by pancytopenia, bone marrow (BM) aspiration was performed. Culture of BM aspirate grew Histoplasma capsulatum. Urine histoplasma antigen was markedly elevated. He was treated with liposomal amphotericin B (LamB) for progressive disseminated histoplasmosis with probable central nervous system involvement. Cerebrospinal fluid histoplasma antigen obtained after 2 months of LamB was detected. After prolonged course of LamB, he took itraconazole. Brain MRI at 7-month follow-up revealed significant improvement from baseline study.