Infections following chimeric antigen receptor T cell therapy: 2018-2022.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is an emerging therapeutic modality for relapsed and refractory hematological malignancies. Infectious complications following CAR T-cell therapy are not well defined. METHODS: This is a retrospective analysis of data on patients who received CAR T-cell therapy between April 2018 and December 2022 at the Karmanos Cancer Center, Detroit. Patients' data were collected up to their last known clinic or inpatient follow-up visit. An infectious episode was defined as any microbiologically proven or clinically documented infection. RESULTS: Seventy-six patients received therapy with FDA-approved CAR T-cell products. Thirty-three patients (43.4%) had at least one infectious episode. There were 61 infectious episodes during a median follow-up of 184 (96-340) days. Median duration for the onset of infection was 59 (22-209) days. Bacterial and viral infections occurred in 42.6% and 41% of the infectious episodes, respectively. COVID-19 was the most common infectious complication (14.8%). Time-to-event analysis showed that most infections occurred within the first 100 days. Empirical antibiotic use during Cytokine Release Syndrome/Immune effector Cell-Associated Neurotoxicity Syndrome (CRS/ICANS) in the absence of documented bacterial infection was reported in 85.7% of patients. Clostridioides difficile accounted for 11.5% of all infectious episodes. Five of six patients with C. difficile infection had CRS/ICANS and received antibiotics. CONCLUSION: COVID-19 and C. difficile infection were the most common infections following CAR T-cell therapy. Most infections occurred within the first 100 days. Empiric antibiotic use and C. difficile infection were common in patients with CRS/ICANS, in the absence of documented bacterial infection, thus providing an excellent opportunity for antimicrobial stewardship in this population.

Establishing best practices in measles, mumps, and rubella serologic screening for kidney transplant candidates.

Optimizing immunity against vaccine-preventable diseases improves outcomes in kidney transplant (KT) patients (Arora et al, World J Transplant, 2019, 9:1; Sester et al, Transplant Rev, 2008, 22:274; Fishman, N Engl J Med, 2007, 357:2601). The American Society for Transplantation (AST) Clinical Practice Guidelines advises that serologic screening for measles, mumps, and rubella (MMR) be conducted for all KT candidates, since live-attenuated vaccines are contraindicated post-transplantation (Malinis et al, Clin Transplant, 2019, 33:e13548). Our team at Mayo Clinic Florida (MCF) conducted a quality improvement (QI) initiative to establish a best MMR screening and immunizations clinical practice in KT candidates using a Plan-Do-Study-Act (PDSA) model. By retrospective chart review of all KT candidates evaluated at our institution from January 1, 2016 to December 31, 2017, baseline data determining the rate of MMR serologic screening was established. PDSA cycles were implemented to adopt protocol-driven testing for MMR serologies, immunization documentation, and vaccination in cases of seronegativity to any of the three MMR viruses in all pre-KT candidates. Two PDSA cycles were completed in 4 months. The study population totaled 447 patients (baseline n = 283, PDSA 1 n = 61, PDSA 2 n = 103). Baseline data showed that 83% (n = 235) of pre-KT candidates received infectious disease consultation (IDC). Complete MMR (all three viruses) serological screening in KT candidates improved from baseline 3.9%-87.4% post-PDSA cycle 2 (P < .001). Necessary immunizations per AST guidelines were ordered in only 41.1% (n = 23) of the control cohort vs 100% (n = 12) and 96.9% (n = 31) of PDSA cycles 1 and 2, respectively (P < .001). The data reflect significant practice improvements in MMR screening and immunization rates among KT candidates by using protocol-driven orders combined with our pre-existing IDCs.

Predominant Intractable Nausea in the Diagnosis of Bulbar Myasthenia Gravis: A Case Study and Review of Literature.

Gastrointestinal (GI)-predominant myasthenia gravis (MG) is rare and presents a complex clinical scenario. We report the case of a 73-year-old female with dysphagia and intractable nausea found to have bulbar MG. Her symptoms persisted despite conventional MG management with plasma exchange therapy and anticholinergics. We review existing literature and discuss the clinical manifestations, diagnosis, and treatment of bulbar MG. This case highlights the need for novel MG treatment modalities in patients like ours with anomalous, GI-predominant MG who might not respond to conventional management.

Three-tier stratification for CNS COVID-19 to help decide which patients should undergo lumbar puncture with CSF analysis: a case report and literature review.

The COVID-19 pandemic continues to overwhelm global healthcare systems. While the disease primarily causes pulmonary complications, reports of central nervous system (CNS) involvement have recently emerged ranging from encephalopathy to stroke. This raises a practical dilemma for clinicians as to when to pursue neuroimaging and lumbar tap with cerebrospinal fluid (CSF) analysis in COVID-19 patients with neurological symptoms. We present a case of an encephalopathic patient infected with SARS-CoV-2 with no pulmonary symptoms. We propose a three-tier risk stratification for CNS COVID-19 aiming to help clinicians to decide which patients should undergo CSF analysis. The neurological examination remains an integral component of screening and evaluating patients for COVID-19 considering the range of emerging CNS complications.

Value of Broad Range 16S Ribosomal RNA Gene PCR / Sequencing (Br-PCR) of CSF in the Diagnosis of Bacterial Meningitis.

Bacterial meningitis is a life-threatening condition that requires quick and definitive diagnosis. Bacterial cultures from cerebrospinal fluid (CSF) return with a negative result as treatment with antimicrobials are sometimes started before sampling of CSF can be obtained which makes isolating the causative bacteria challenging. The value of Broad Range 16S Ribosomal RNA Gene Polymerase Chain Reaction / Sequencing of CSF (Br-PCR) can address this problem by amplifying and identifying any bacterial DNA present in a clinical sample. A 65-year-old female presented with rapid onset of high fevers, headache, chills and right hip pain. She had blood cultures drawn, unremarkable CSF analysis in the emergency department, and was discharged home. Ten hours later, she developed vomiting and altered mental status, returned to hospital and started on antimicrobials for gram negative bacteremia and emergently intubated with repeat lumbar puncture showed evidence of bacterial meningitis with pleocytosis and elevated opening pressures. Empiric antimicrobial therapy was started. All subsequent CSF microbiological stains, cultures, and molecular analyses were negative. The blood cultures grew Haemophilus influenzae and H. influenzae meningitis was presumed to be the cause. Therefore, Br-PCR on CSF was sent which detected Haemophilus species DNA. She received a 3-week course of ceftriaxone. After rehabilitation, she returned home without any significant neurological deficits. No relapse of meningitis at 4 months was noted. The application for Br-PCR in the setting of suspected bacterial meningitis with negative stains and cultures could improve a diagnostic algorithm for bacterial meningitis.

16S rRNA Gene PCR/Sequencing of Cerebrospinal Fluid in the Diagnosis of Post-operative Meningitis.

INTRODUCTION: Post-operative meningitis (POM) is a life-threatening complication of neurosurgery. Diagnosis is often difficult due to pre-existing inflammation and antecedent antimicrobial use. Bacterial cerebrospinal fluid (CSF) cultures may reveal no growth, but empiric antibiotics are typically given due to the high morbidity and mortality associated with POM. 16S rRNA gene PCR/sequencing is a molecular methodology that can identify the presence of bacteria regardless of viability for culture. CASE PRESENTATION: A patient presented with a rapid onset of fever associated with headache, neck pain, nausea and altered mental status 11 days after undergoing laser interstitial thermal therapy for treatment of recurrent astrocytoma at another hospital. Based on clinical presentation and imaging, POM was suspected, and empiric antibacterial therapy was started. Microbiological stains and cultures of CSF were negative. Due to persistent fevers, 16S rRNA gene PCR/sequencing was done on CSF; it detected a member of the order Enterobacteriales most closely resembling Serratia species. All antimicrobials were stopped except for cefepime, which was given for 2 weeks. The patient's mental status fully recovered. CONCLUSION: The application of 16S rRNA gene PCR/sequencing in the setting of POM is of value by improving the quality of patient care and decreasing costs by antimicrobial de-escalation. Further studies regarding the positive and negative predictive values of this test are required.

Delayed COVID respiratory failure: what every front line healthcare worker needs to know.

The pandemic of COVID-19 has presented several diagnostic challenges in both recognition of acute disease and also the temporal presentation of disease convalescence with return to normal activity. We present a case of delayed clinical progression of COVID-19 associated respiratory failure on day 25 after initial symptom onset and, notably, after initial full resolution of symptoms and negative RT-PCR nasopharyngeal testing. The patient's delayed presentation of exertional dyspnea and the utilization of specific characteristics of chest radiography in confirmation with laboratory cytokine measurement allowed for clinical re-categorization of the patient's status to active COVID-19 clinical disease and changed acute management. COVID-19 positive patients should be advised to continue to monitor for respiratory deterioration for a greatly extended period of time, even if RT-PCR testing is negative and initial clinical symptoms have resolved. Frontline healthcare workers, including first responders and primary care providers, also need to be aware to monitor for and recognize this delayed presentation.