Hidden consequences: Uncovering belimumab's role in the development of Pneumocystis jirovecii pneumonia in a lupus patient.

INTRODUCTION: Pneumocystis jirovecii is an opportunistic fungal organism that can cause fatal pneumonia in immunocompromised individuals. It is a disease associated with CD4+ T cell depletion or high-dose steroids. However, there is increasing evidence that B cell dysfunction may also play a role in this illness. CASE REPORT: A 33-year-old female with SLE, who was maintained on belimumab and low-dose prednisone (2.5 mg daily), presented with progressive cough and shortness of breath. She had been on monthly belimumab and prednisone 2.5 mg daily for 19 months, and her CD4 count was >200/uL, but her CD19+ B cell was <1% due to the belimumab. She developed a persistent cough and progressive dyspnea that did not respond to empiric antibiotic therapy for pneumonia. She went to the hospital for acute worsening of her dyspnea and cough. An extensive workup was performed, including a VATS procedure and surgical biopsy, which gave a definitive diagnosis of PJP. The patient was treated and discharged on trimethoprim-sulfamethoxazole. She made a complete recovery. DISCUSSION: Our report demonstrates the first confirmed case of pneumocystis jirovecii pneumonia in a patient with B cell depletion due to chronic maintenance therapy with belimumab. Our patient's diagnosis of PJP was unexpected, given her normal CD4+ count and the use of such a low dose of prednisone. We attribute her susceptibility to PJP infection to her profound B cell depletion in response to her belimumab therapy, supporting previous research indicating the importance of CD4+ T cells and B cells in the protective immune response against PJP. This case may help shape future clinical guidelines concerning PJP prophylaxis, particularly in SLE patients with deficient B lymphocytic activity and B cell depletion.

Passive transfer of SARS-CoV-2 antibodies with platelet transfusions.

BACKGROUND: Although over 5000 platelet transfusions occur daily in the United States, the presence of SARS-CoV-2 antibodies in platelet units is not commonly evaluated for. The effects of platelet transfusions with SARS-CoV-2 antibodies remain largely unknown. We evaluated single-donor (apheresis) platelet units for SARS-CoV-2 antibodies and determined if platelet transfusions passively transferred antibodies to seronegative recipients. STUDY DESIGN AND METHODS: We conducted a retrospective analysis as part of a quality assurance initiative during February to March 2021 at a tertiary referral academic center in suburban New York. Platelet units and platelet recipients were evaluated for the presence of SARS-CoV-2 antibodies using the DiaSorin LIASON SARS-CoV-2 S1/S2 IgG assay. There were 47 platelet recipients eligible for study inclusion. The primary outcome was the presence of SARS-CoV-2 spike protein IgG antibodies in the recipient's blood after platelet transfusion. RESULTS: Twenty-three patients received platelets with SARS-CoV-2 spike protein IgG antibodies; 13 recipients had detection of SARS-COV-2 antibodies (56.5%), and 10 recipients did not. The median antibody titer in the platelet units given to the group with passive antibodies detected was significantly higher compared to the median antibody titer in the platelet units given to the group without antibodies detected (median [interquartile range]: 306 AU/ml [132, 400] vs. 96.1 AU/ml [30.6, 186], p = .027). CONCLUSIONS: Our study demonstrated a significant rate of passive transfer of SARS-CoV-2 spike protein IgG antibodies through platelet transfusions. Considering the volume of daily platelet transfusions, this is something all clinicians should be aware of.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).

Impact of Respiratory Viral Panel Polymerase Chain Reaction Assay Turnaround Time on Length of Stay and Antibiotic Use in Patients With Respiratory Viral Illnesses.

Background: Respiratory viral illnesses account for many hospitalizations and inappropriate antibiotic use. Respiratory viral panels by polymerase chain reaction (RVP-PCR) provide a reliable means of diagnosis. In 2015, the RVP-PCR assay at our institution was switched from respiratory viral panel (RVP) to rapid respiratory panel (rapid RP), which has a faster turnaround time (24 hours vs 12 hours, respectively). The purpose of this study was to evaluate the effect of RVP-PCR tests on duration of antibiotic use and length of stay (LOS) in hospitalized patients. Methods: We performed a retrospective chart review of patients who had a RVP-PCR ordered within a 1-year time period before and after the assay switch. Patients who were pregnant, had received antibiotics within 30 days prior to admission, were not discharged, or had not completed antibiotics by end of study period were excluded. Results: Data were obtained from a total of 140 patients (70 in each group). Of these, 25 (35.7%) in the RVP group and 28 (40.0%) in the rapid RP group had a positive result. The median LOS was 4.5 days (IQR, 3-9 days) in the RVP group and 5 days (IQR, 3-9 days) in the rapid RP group (P = .78). The median duration of antibiotic use was 4 days (IQR, 2-7 days) in the RVP group and 5 days (IQR, 1-7 days) in the rapid RP group (P = .8). Conclusion: Despite faster turnaround time, there was no significant difference in duration of antibiotic use, or LOS between the RVP and rapid RP groups.

The clinical impact of early detection of ESBL-producing Enterobacterales with PCR-based blood culture assays.

BACKGROUND: Starting January 4, 2021, our health system core microbiology laboratory changed blood culture identification (BCID) platforms to ePlex BCID from BioFire BCID1 with the additional capability to detect the blaCTX-M-Type gene of ESBL-producing organisms. Clinical outcomes of ESBL bloodstream infections (BSI) after implementing ePlex BCID were unknown. METHODS: Patients with ESBL BSI were compared pre and postimplementation of ePlex BCID in this 11-hospital retrospective analysis (BioFire BCID1 in 2019 vs ePlex BCID in 2021). The primary outcome was time from the Gram stain result to escalation to a carbapenem. Secondary outcomes included in-hospital mortality, 30-day readmission rate, length of stay (LOS), and the duration of antimicrobial therapy. RESULTS: A total of 275 patients were analyzed. The median time of Gram stain result to escalation to carbapenem was reduced from 44.5 hours with BioFire BCID1 to 7.9 hours with ePlex BCID (P < .001). There were no significant differences in mortality, 30-day readmission, or LOS. The duration of antimicrobial therapy for ESBL BSI was lower in the ePlex BCID group (from 14.4 days to 12.7 days, P = .014). CONCLUSIONS: Timely detection of the blaCTX-M-Type gene by BCID provides valuable information for the early initiation of appropriate and effective antimicrobial therapy. Although it was not associated with lower mortality, 30-day readmission, or LOS, it may have benefits such as decreasing antimicrobial exposure to patients.

Barriers to Implementing Registered Nurse-Driven Clinical Decision Support for Antibiotic Stewardship: Retrospective Case Study.

BACKGROUND: Up to 50% of antibiotic prescriptions for upper respiratory infections (URIs) are inappropriate. Clinical decision support (CDS) systems to mitigate unnecessary antibiotic prescriptions have been implemented into electronic health records, but their use by providers has been limited. OBJECTIVE: As a delegation protocol, we adapted a validated electronic health record-integrated clinical prediction rule (iCPR) CDS-based intervention for registered nurses (RNs), consisting of triage to identify patients with low-acuity URI followed by CDS-guided RN visits. It was implemented in February 2022 as a randomized controlled stepped-wedge trial in 43 primary and urgent care practices within 4 academic health systems in New York, Wisconsin, and Utah. While issues were pragmatically addressed as they arose, a systematic assessment of the barriers to implementation is needed to better understand and address these barriers. METHODS: We performed a retrospective case study, collecting quantitative and qualitative data regarding clinical workflows and triage-template use from expert interviews, study surveys, routine check-ins with practice personnel, and chart reviews over the first year of implementation of the iCPR intervention. Guided by the updated CFIR (Consolidated Framework for Implementation Research), we characterized the initial barriers to implementing a URI iCPR intervention for RNs in ambulatory care. CFIR constructs were coded as missing, neutral, weak, or strong implementation factors. RESULTS: Barriers were identified within all implementation domains. The strongest barriers were found in the outer setting, with those factors trickling down to impact the inner setting. Local conditions driven by COVID-19 served as one of the strongest barriers, impacting attitudes among practice staff and ultimately contributing to a work infrastructure characterized by staff changes, RN shortages and turnover, and competing responsibilities. Policies and laws regarding scope of practice of RNs varied by state and institutional application of those laws, with some allowing more clinical autonomy for RNs. This necessitated different study procedures at each study site to meet practice requirements, increasing innovation complexity. Similarly, institutional policies led to varying levels of compatibility with existing triage, rooming, and documentation workflows. These workflow conflicts were compounded by limited available resources, as well as an implementation climate of optional participation, few participation incentives, and thus low relative priority compared to other clinical duties. CONCLUSIONS: Both between and within health care systems, significant variability existed in workflows for patient intake and triage. Even in a relatively straightforward clinical workflow, workflow and cultural differences appreciably impacted intervention adoption. Takeaways from this study can be applied to other RN delegation protocol implementations of new and innovative CDS tools within existing workflows to support integration and improve uptake. When implementing a system-wide clinical care intervention, considerations must be made for variability in culture and workflows at the state, health system, practice, and individual levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04255303; https://clinicaltrials.gov/ct2/show/NCT04255303.

Suspected Primary Adrenal Lymphoma (PAL) Associated With Hemophagocytic Lymphohistiocytosis (HLH).

Adrenal incidentalomas, masses noted on imaging performed for other purposes, are common, with 10% to 15% presenting as bilateral adrenal masses. These cases can be challenging as the differential diagnosis is broad, including metastatic disease, primary adrenal lymphoma (PAL), or infection, and often requiring a biopsy if initial biochemical workup is unrevealing. We present here a relevant case description, laboratory and radiologic imaging studies, and discussion of literature. A 62-year-old Korean woman presented with altered mental status and fevers. She was found to have bilateral adrenal incidentalomas and retained acupuncture needles. Adrenal workup did not show biochemical evidence of hormonal excess. Infectious workup was unrevealing, as was a metal/toxin workup due to retained acupuncture needles. Fevers and episodes of hypotension persisted which prevented the patient from obtaining an adrenal biopsy. Bone marrow biopsy was obtained for pancytopenia and revealed B-cell lymphoma with large cell morphology and few histiocytes with hemophagocytosis, raising concern for lymphoma-induced hemophagocytic lymphohistiocytosis (HLH). PAL associated with HLH was highly suspected in our patient, given the large (7 cm) bilateral adrenal masses and bone marrow biopsy findings of lymphoma. The patient was treated for diffuse large B-cell lymphoma, with clinical improvement. PAL is a rare but aggressive lymphoma with few reported cases. It should be considered in the differential for both unilateral and bilateral adrenal masses. An early diagnosis is crucial as the main treatment is chemotherapy rather than surgery and it confers a significant survival benefit.

Hospital-Acquired Bloodstream Infections in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection (Coronavirus Disease 2019): Association With Immunosuppressive Therapies.

BACKGROUND: Immunosuppressive therapies proposed for Coronavirus disease 2019 (COVID-19) management may predispose to secondary infections. We evaluated the association of immunosuppressive therapies with bloodstream-infections (BSIs) in hospitalized COVID-19 patients. METHODS: This was an institutional review board-approved retrospective, multicenter, cohort study of adults hospitalized with COVID-19 over a 5-month period. We obtained clinical, microbiologic and laboratory data from electronic medical records. Propensity-score-matching helped create balanced exposure groups. Demographic characteristics were compared across outcome groups (BSI/no BSI) using two-sample t-test and Chi-Square test for continuous and categorical variables respectively, while immunosuppressive therapy use was compared using McNemar's test. Conditional logistic regression helped assess the association between immunosuppressive therapies and BSIs. RESULTS: 13,007 patients were originally included, with propensity-score-matching producing a sample of 6,520 patients. 3.74% and 3.97% were diagnosed with clinically significant BSIs in the original and propensity-score-matched populations respectively. COVID-19 patients with BSIs had significantly longer hospitalizations, higher intensive care unit admission and mortality rates compared to those without BSIs. On univariable analysis, combinations of corticosteroids/anakinra [odds-ratio (OR) 2.00, 95% confidence intervals (C.I.) 1.05-3.80, P value.0342] and corticosteroids/tocilizumab [OR 2.13, 95% C.I. 1.16-3.94, P value .0155] were significantly associated with BSIs. On multivariable analysis (adjusting for confounders), combination corticosteroids/tocilizumab were significantly associated with any BSI [OR 1.97, 95% C.I. 1.04-3.73, P value.0386] and with bacterial BSIs [OR 2.13, 95% C.I. 1.12-4.05, p-value 0.0217]. CONCLUSIONS: Combination immunosuppressive therapies were significantly associated with BSI occurrence in COVID-19 patients; their use warrants increased BSI surveillance. Further studies are needed to establish their causative role.

Design, development, and deployment of an indication- and kidney function-based decision support tool to optimize treatment and reduce medication dosing errors.

Delivering clinical decision support (CDS) at the point of care has long been considered a major advantage of computerized physician order entry (CPOE). Despite the widespread implementation of CPOE, medication ordering errors and associated adverse events still occur at an unacceptable level. Previous attempts at indication- and kidney function-based dosing have mostly employed intrusive CDS, including interruptive alerts with poor usability. This descriptive work describes the design, development, and deployment of the Adult Dosing Methodology (ADM) module, a novel CDS tool that provides indication- and kidney-based dosing at the time of order entry. Inclusion of several antimicrobials in the initial set of medications allowed for the additional goal of optimizing therapy duration for appropriate antimicrobial stewardship. The CDS aims to decrease order entry errors and burden on providers by offering automatic dose and frequency recommendations, integration within the native electronic health record, and reasonable knowledge maintenance requirements. Following implementation, early utilization demonstrated high acceptance of automated recommendations, with up to 96% of provided automated recommendations accepted by users.

A case of Listeria monocytogenes meningitis complicated by Hydrocephalus and Intraventricular hemorrhage: A review of treatment options and outcomes.

Listeria monocytogenes is a gram-positive bacillus known to cause various human infections including central nervous system infections. The most common central nervous system manifestations are meningitis and rhomboencephalitis, however rare complications including hydrocephalus and intracerebral hemorrhage can occur and are associated with increased mortality and incidence of lasting neurologic sequelae. The mortality ranges from 17 % to greater than 30 % in patients with neurological involvement [[1], [2], [3]]. Various case reports have studied the differing treatment approaches and outcomes of patients who experienced these complications, and there is still no consensus on optimal treatment approaches. In this paper, we report a case of Listeria meningitis complicated by both acute hydrocephalus and intracerebral hemorrhage and analyze the factors that led to a favorable outcome by reviewing the existing literature.

Adult onset immunoglobulin A vasculitis (Henoch-Schonlein purpura) with alveolar hemorrhage.

S. pyogenes is the cause of many important human diseases, ranging from mild superficial skin infections to life-threatening systemic diseases. The post streptococcal syndromes are immune mediated phenomena including Immunoglobulin A Vasculitis (Henoch-Schönlein purpura). HSP is more common in children and usually self limited but it can cause skin, joint, renal, gastrointestinal and rarely respiratory involvement. We present a case with Streptococcus pyogenes pneumonia that presented with respiratory failure, pulmonary hemorrhage, extensive rash and renal failure.

Can Procalcitonin Be Used as a Reliable Marker for Infectious Fever in Patients with Intracranial Hemorrhage?

OBJECTIVE: To determine whether procalcitonin (PCT) levels are different in infected versus noninfected febrile patients with intracranial hemorrhage (ICH). METHODS: This prospective observational study included 104 patients with ICH and fever >38.3°C admitted to the intensive care unit of a tertiary care hospital. PCT was measured on day 1 (PCT 1) of fever and 48-72 hours later (PCT 2). Patients were determined to have an infection (pneumonia, urinary tract infection, or bacteremia) based on cultures, imaging, and clinical impression of treating clinicians. RESULTS: Analysis of variance indicated significant mean differences in patients with no, probable, and definite infection (F2,103 = 3.12, P = 0.048) between PCT 1 and PCT 2 (F2,72 = 4.64, P = 0.013). Patients with probable infection had the highest PCT 1 (mean = 0.47, SD = 0.93), and patients with definite infection had higher PCT 2 (mean = 0.62, SD = 0.85). Additional analyses of univariable mean differences showed mean PCT 1 that was significantly higher in the probable infection group compared with the no infection group. Mean PCT was significantly higher at both time points in the definite infection group compared with the no infection group. There were no significant differences between the probable and definite infection groups. CONCLUSIONS: PCT levels were higher in patients with ICH and infections and may be a useful marker to differentiate between infectious and noninfectious etiologies of fevers in these patients. Further studies, including randomized controlled trials, will help in establishing the utility of this marker in optimal management of febrile patients with ICH.

Acremonium pneumonia in an AIDS patient.

Acremonium is a saprophytic fungus mostly causing superficial skin, nail, or ocular infections after traumatic inoculation. However, it is being recently recognized as one of the opportunistic infections in immunocompromised patients including neutropenia, malignancies, chronic granulomatous disease (CGD) and transplant recipients. To our knowledge there have been no reported cases of Acremonium infection, related to HIV or AIDS. We present a case of Acremonium pneumonia in a patient with no past medical history who was found to have AIDS.

Infections in alcoholic liver disease.

Alcoholic individuals are at increased risk of infection in general, in part because of immune defects. In addition, associated situations, such as depressed mental status, increase risk to specific syndromes such as lung abscess related to depressed consciousness and aspiration. Social factors related to hygiene and living situations are also linked to specific microorganisms, such as Mycobacteria tuberculosis, Bartonella quintana, Vibrio vulnificus, and Capnocytophaga canimorus..