Vancomycin-resistant
(VRE) is now one of the leading causes of nosocomial infections in the United States. Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of VRE ...colonization and infection. VRE has emerged as a major cause of bacteremia in this population, raising important clinical questions regarding the role and impact of VRE colonization and infection in HSCT outcomes as well as the optimal means of prevention and treatment. We review here the published literature and scientific advances addressing these thorny issues and provide a rational framework for their approach.
The recognition of the role of complement and Janus kinase (JAK)-dependent cytokines in the pathogenesis of inflammatory and immune-mediated disorders has revolutionized the treatment of a myriad of ...rheumatological and inflammatory diseases. C5 inhibitors and Janus kinase inhibitors have emerged as attractive therapeutic options. Because of the blockage of immune pathways, these targeted therapies carry an increased risk of infection. This article reviews the mechanism of action and the approved and off-label indications of the agents with most clinical experience within this drug classes. It discusses the associated risks of infection, proposing screening, prevention, and risk mitigation strategies.
The risk of toxoplasmosis in high‐risk cardiac transplant recipients is well recognized prompting universal donor and candidate screening with administration of targeted post‐transplant ...chemoprophylaxis in high‐risk (D+/R−) cardiac transplant patients. In contrast, until recently, there have been neither well‐defined recommendations nor consensus regarding toxoplasmosis preventive strategies among non‐cardiac solid organ transplant recipients. We report 3 cases of post‐transplant toxoplasmosis in non‐cardiac transplant recipients (one lung and two liver); all 3 infections presumed to be donor‐derived. Not surprisingly, pre‐transplant Toxoplasma serology was negative in all the patients. None of the patients were on trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis at the time of diagnosis of toxoplasmosis. The median time from transplant to onset of infection was 90 days (range: 30‐120 days). Clinical presentations included cerebral (n = 1) and disseminated infections (n = 2). Two of the 3 patients, both with disseminated infection died (mortality ~ 67%).
Purpose of Review:
Dimorphic endemic fungi exist as mold and yeast forms at room and body temperature within the host, respectively. Primary infection can arise from new environmental exposure and ...less frequently through organ transplantation. Reactivation of latent infection can occur when immunosuppression is introduced or intensified. Transplant and immunocompromised hosts (ICH) represent important populations at risk for complicated and disseminated forms of endemic mycoses (EM). Diagnosis is challenging as immunosuppression contributes to insidious clinical presentations resulting in diagnostic and treatment delays. Herein, we present updated diagnosis and prevention strategies for EM in the potential organ donor, transplant candidate and recipient, and ICH.
Recent Findings:
Several EM have previously been considered as restricted to a limited geographical area; however, factors such as global warming, changing precipitation patterns, and increased travel are actively expanding the geographical distribution of endemic fungi. Serological testing, often used in the immunocompetent host, has significant limitations in transplant recipients and ICH. Fungal molecular methods have emerged as an important complementary diagnostic strategy for EM but would benefit from greater standardization and wider availability. High clinical suspicion and a multipronged diagnostic approach are recommended for timely diagnosis and prevention of complications.
Summary:
In ICH, combining diagnostic methods increases diagnostic yield for EM. Immunosuppression-specific risk assessment, laboratory monitoring, and targeted antifungal prophylaxis are pivotal to reduce EM burden. The use of molecular methods for early diagnosis and the role of newer azoles and immunomodulation in the management of EM require further investigation.
Chagas disease (CD) is the third most common parasitic infection globally and can cause cardiac and gastrointestinal complications. Around 300,000 carriers of CD live in the U.S., with about 3000 of ...those in Colorado. We described our experience in diagnosing CD at a Colorado teaching hospital to revise screening eligibility criteria. From 2006 to 2020, we reviewed Trypanosoma cruzi (TC) IgG serology results for 1156 patients in our institution. We identified 23 patients (1.99%) who had a positive test. A total of 14/23 (60%) of positive serologies never had confirmatory testing, and 7 of them were lost to follow up. Confirmatory testing, performed in 9 patients, resulted in being positive in 3. One additional case of CD was identified by positive tissue pathology. All four confirmed cases were among patients born in Latin America. While most of the testing for CD at our institution is part of the pretransplant screening, no confirmed cases of CD derived from this strategy. Exposure risk in this population is not always documented, and initial positive results from screening are not always confirmed. The lack of standardized screening protocols for CD in our institution contributes to underdiagnosis locally and in health systems nationwide. Given a large number of individuals in the U.S. with chronic CD, improved screening is warranted.
Left ventricular assisted devices (LVADs) have revolutionized the treatment of advanced heart failure, providing meaningful increases in survival, functional capacity, and quality of life. There are ...two categories of LVADs patients: (1) bridge-to-transplant and (2) destination therapy. Advanced heart failure and destination LVADs often carry a poor prognosis. The overall 1-year mortality rate remains as high as 30%. LVAD-specific infections, LVAD-related infections, and non-LVAD-related infections represent important emerging clinical problems in this setting. With an incidence ranging from 30 to 50%, these lead to high rates of hospitalization, morbidity, and mortality. Bacteremias caused by anaerobic pathogens in patients with LVAD are underreported. Herein, we describe the microbiological findings, treatment, and clinical outcome of four patients with LVADs and advanced heart failure with anaerobic bacteremias. Fusobacterium species was the most frequent etiological agent. Most patients had a relatively favorable short-term outcome with survival rates of 100% at 30 days and of 50% at 90 days. However, due to other multiple long-term complications, overall mortality remains at 50% during the first year and increases to 75% beyond the first year. Anaerobic bacteremia sources included the oral cavity from odontogenic infections and aspiration pneumonia. Anaerobic bacteremia constitutes an unfavorable mortality prognostic factor in patients with destination LVADs. We recommend implementing preventive strategies with a comprehensive dental care evaluation in patients with LVADs and advanced heart failure.
Eculizumab inhibits complement effector functions and has significantly impacted the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. However, the risks of ...potentially life-threatening infections, notably with Neisseria spp. in addition to its cost, are major challenges in clinical practice. In this review, we characterize and summarize the infectious complications reported with the use of eculizumab in the context of its typical and expanding indications.
Use of eculizumab is rapidly extending to the fields of transplantation and neurology. Eculizumab has been primarily associated with an increased risk of meningococcal infections. Immunization against its commonest serotypes (ABCWY) is now possible with the advent of the meningococcal B vaccine. A combined ABCWY vaccine is underway. Preventive strategies against breakthrough Neisseria infections should also include chemoprophylaxis. Less is known about the association of eculizumab with other infections as recently reported. Surrogate markers of complement blockade, notably CH50, and eculizumab efficacy may help in the risk assessment of infection.
Eculizumab has opened new horizons in the treatment of complement-mediated disorders. Prophylactic and immunization strategies against the risk of Nesseria spp. infections are sound and feasible. The use of eculizumab is expanding beyond complement-mediated diseases to transplantation and neurological disorders. Further research is needed to better define and stratify the risk of infection and prevention strategies in patients with the latter indications.
Abstract
Background
Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) ...to identify infectious etiologies of FN and its impact on antimicrobial management.
Methods
This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results.
Results
Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes 12.7%), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases.
Clinical Trials Registration
NCT02912117
Conclusion
KT shows promise in the diagnosis and treatment optimization of FN.
Microbial cell-free DNA sequencing using the Karius test (KT) detects organisms not identified by conventional microbiological tests. KT can be useful in the etiologic diagnosis of infection of febrile neutropenia and may facilitate prompt and optimal antimicrobial therapy.
In 2022, the largest global outbreak of mpox to date emerged. In the immunocompetent host, mpox generally presents as a self-limiting illness. However, immunosuppression, such as that seen with ...advanced HIV, has been associated with significant morbidity and mortality related to mpox infection. To evaluate the impact of immunosuppression related to solid organ transplantation on clinical features and outcomes of mpox we established a multicenter case registry. Eleven cases from 7 participating centers in the USA were submitted. All cases occurred in males. The majority were kidney transplant recipients (91%, n = 10). Median duration of symptoms at presentation was 6 days (range, 3-14 days). Rates of hospitalization were high (73%, n = 8) with a median length of stay of 4.5 days (range, 1-10 days). Mpox in solid organ transplant recipients was associated with a high burden of skin lesions and systemic symptoms. Fever, fatigue, pharyngitis, and proctitis were commonly reported. Other clinical features included headache, myalgia, epididymo-orchitis, urinary retention, hematemesis, pneumonitis, and circulatory shock. All patients received treatment with tecovirimat. There was 1 mpox-related death in the cohort. Infection was reported to have resolved at 30-day follow-up in all other cases.
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