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Item Cryptococcal Meningitis in Young, Immunocompetent Patients: A Single-Center Retrospective Case Series and Review of the Literature(Oxford University Press, 2023-08-11) Stack, Matthew; Hiles, Jon; Valinetz, Ethan; Gupta, Samir K.; Butt, Saira; Schneider, Jack G.; Medicine, School of MedicineBackground: Cryptococcal meningitis is an uncommon but serious infection with high mortality and morbidity. Classically described in immunocompromised patients, including those with solid organ transplants or HIV/AIDS, cryptococcosis has also been reported in young and otherwise healthy patients, albeit rarely. Methods: We retrospectively searched for all cases of cryptococcal meningitis in young (≤50 years) and previously healthy patients with no known immunocompromising conditions from January 2015 to January 2022 at Indiana University Health (IU Health). Additionally, a PubMed literature review was performed with the keywords "cryptococcal meningitis" and "immunocompetent" from January 1988 to January 2022. Clinical courses, including outcomes and treatment regimens, were evaluated. Results: We identified 4 local cases of cryptococcal meningitis in otherwise healthy patients age ≤50 years. Three cases were due to Cryptococcus neoformans, with 1 experiencing a postinfectious inflammatory response syndrome (PIIRS). The PubMed search identified 51 additional cases, with 32 (63%) being caused by Cryptococcus neoformans and 8 (17%) by Cryptococcus gattii. Of the 51 cases, only 2 resulted in death directly due to cryptococcosis. Fifteen (29%) had PIIRS, with steroid treatment documented in 11 of 15. Antifungal induction regimens and duration were varied but predominately consisted of amphotericin and flucytosine, with a mean induction duration of 5.0 weeks. Conclusions: Cryptococcal meningitis in young, previously healthy patients is likely under-recognized. PIIRS (akin to immune reconstitution inflammatory syndrome observed in HIV/AIDS) with prolonged recovery should be of concern. Determining risk factors for cryptococcosis in these patients remains elusive.Item Direct antimicrobial susceptibility testing of positive blood cultures: A comparison of the accelerate Pheno™ and VITEK® 2 systems(Elsevier, 2019) Schneider, Jack G.; Wood, James B.; Smith, Nathan W.; Emery, Christopher L.; Davis, Thomas E.; Manaloor, John J.; Bocian, Brittany; Schmitt, Bryan H.; Medicine, School of MedicineObjectives To compare the performance and time-to-result (TTR) for antimicrobial susceptibility testing (AST) of positive blood cultures (PBC) using the Accelerate Pheno™ system (AXDX) and both a direct VITEK® 2 card inoculation workflow (DV2) and traditional FDA-approved VITEK® 2 workflow using subcultured isolates (V2). Methods Patient samples with monomicrobial Gram-negative rod bacteremia were tested on AXDX and DV2 in tandem, and compared to V2 AST results. Categorical agreement (CA) errors were adjudicated using broth microdilution. Instrumentation times and AST TTR were compared. Results AXDX and DV2 had a CA of 91.5% and 97.4%, respectively, compared to V2. Post-adjudication, AXDX, DV2, and V2 had CA of 94.7%, 95.7% and 96.5%, respectively. Instrument run times were 6.6 h, 9.4 h, and 9.2 h, and AST TTR were 8.9 h, 12.9 h and 35.5 h, respectively. Conclusions AXDX and DV2 AST is fast and reliable, which may have significant antimicrobial stewardship implications.Item Identifying Risk Factors That Distinguish Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection From Common Upper Respiratory Infections in Children(2021) Schneider, Jack G.; Relich, Ryan F.; Datta, Dibyadyuti; Bond, Caitlin; Goings, Michael; Hall, Dylan; Lei, Guang-Sheng; Kedra, Jennifer; John, Chandy C.; Medicine, School of MedicineBackground Demographic and clinical risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children presenting with respiratory viral symptoms are not well defined. An understanding of risk factors for SARS-CoV-2 infection can help prioritize testing. Methodology We evaluated potential demographic and clinical factors in children who had respiratory viral symptoms and were tested by polymerase chain reaction (PCR) for SARS-CoV-2 and other respiratory viral infections. Results Among the 263 symptomatic children tested for routine seasonal respiratory viruses by PCR, 18 (6.8%) tested positive for SARS-CoV-2. Overall, 22.2% of SARS-CoV-2-infected children and 37.1% of SARS-CoV-2-uninfected children had infection with one or more non-SARS-CoV-2 pathogens (p = 0.31). Higher proportions of children with compared to without SARS-CoV-2 infection were male (77.8 vs. 51.8%, p = 0.05), Hispanic (44.4% vs. 9.8%, p < 0.001), or had the symptoms of fatigue (22.2% vs. 2.5%, p = 0.003) or anosmia/ageusia (11.1% vs. 0%, p = 0.004). History of hypoxic-ischemic encephalopathy (HIE) and obesity were more common in children with versus without SARS-CoV-2 infection (11.1% vs. 1.2%, p = 0.04, and 11.1% vs. 0%, p = 0.004, respectively). In a multivariate analysis, Hispanic ethnicity, symptoms of fatigue or anosmia/ageusia, and presence of obesity (as noted on physical examination) or HIE were independently associated with SARS-CoV-2 infection. Numbers in each category were small, and these preliminary associations require confirmation in future studies. Conclusions In this area of the United States, infection with other viruses did not rule out infection with SARS-CoV-2. Additionally, children with respiratory viral symptoms who were of Hispanic ethnicity, had symptoms of weakness/fatigue, or had obesity or HIE were at an increased risk for SARS-CoV-2 infection. Future studies should assess if these factors are associated with risk in populations in other areas of the United States.Item Outcomes in children with vesicoureteral reflux receiving antibiotic prophylaxis(Cambridge University Press, 2025-02-12) Tompkins, Madeline G.; Kussin, Michelle; Christenson, John C.; Boyd, LaKeisha; Tat, Kiet; Schneider, Jack G.; Han, Rachel T.; Pediatrics, School of MedicineAntibiotic prophylaxis in children with vesicoureteral reflux (VUR) remains controversial. We reviewed patients diagnosed with VUR after an index urinary tract infection (UTI) who subsequently received antibiotic prophylaxis. Recurrent UTIs in patients with and without urologic anomalies occurred in 57% and 33%, respectively. Multidrug-resistant organisms accounted for 25% of first UTI recurrences.Item P-1606. Utilizing Diagnostic Stewardship to Help Increase the Yield and Clinical Value of Broad Range PCR Testing at a Tertiary Children’s Hospital(Oxford University Press, 2025-01-29) Fortna, Sarah; Alali, Muayad; Prabhudas-Strycker, Kirsten; Mellencamp, Kagan A.; Boyd, LaKeisha; Goings, Michael; Khan, Haseeba; Fahey, Mackenzie; Samaro, Matthew; Schneider, Jack G.; Graduate Medical Education, School of MedicineBackground: Broad range PCR testing (BR-PCR) in various clinical samples has the ability to provide timely diagnoses that cannot always be made through conventional testing (CT), yet its diagnostic yield and clinical impact have been variable, especially by specimen type. As such, we developed an ID-physician led diagnostic stewardship approval protocol to help optimize test usage. Methods: We conducted a single-center, retrospective pre/post study to assess the impact of an ID-led diagnostic stewardship approval protocol for BR-PCR testing. All clinical specimen types obtained for BR-PCR at Riley Hospital for Children were evaluated between 10/1/2019 to 4/30/2022 (pre-intervention) and 5/1/2022-12/31/2023 (post-intervention). Clinical relevancy of BR-PCR results was determined after review from two ID physician experts and compared between the two time periods, along with clinical impact and overall cost savings. Results: A total of 931 BR-PCR tests were sent from 238 specimens collected from 175 patients in the pre-intervention period, while 208 BR-PCR tests were sent from 65 specimens collected from 65 patients in the post-intervention period. Clinical relevancy of results was determined to be 30.7% and 56.9% for pre-and post-intervention periods, respectively (p< 0.001). 23.1% of post intervention results led to a change in clinical management, compared to 12.6% in the pre-intervention period (p=0.035). Bronchial lavage (BAL) was the most common specimen type with 52.9% of results being clinically relevant post-intervention, compared to 29.6% in the pre-intervention period; p=0.068). Results that led to a clinical change in management were also slightly higher but non-significant for BALs post-intervention (11.8% vs 9.9% pre intervention; p=0.816). Overall cost savings post-intervention was estimated to be $200,000. Conclusion: Use of an ID-physician led diagnostic stewardship approval protocol led to an overall improvement in clinical utility for BR-PCR testing at our institution and was influenced by specimen type. Prospective, multi-center studies are needed to determine which specimen types, diagnoses, and potential diagnostic stewardship measures will help increase the yield and clinical value of BR-PCR testing.Item P-1749. Implementation of an Automatic 36-hour Stop Order on Empiric Meropenem Usage(Oxford University Press, 2025-01-29) Parker, Connor; Schneider, Jack G.; Boyd, LaKeisha; Kussin, Michelle L.; Graduate Medical Education, School of MedicineBackground: Implementation of automatic stop orders (ASOs) for empiric antimicrobials have reduced antimicrobial use without negatively impacting patient outcomes. Given a recent increase in empiric meropenem use at our tertiary referral pediatric hospital, a 36-hour meropenem ASO option was implemented in the EMR for patients with sepsis requiring empiric antibiotics active against ESBL-producing organisms. We sought to evaluate the impact this initiative had on meropenem use and safety outcomes. Methods: A 36-hour ASO for meropenem was implemented on October 12th, 2022. We conducted a single-center, retrospective pre/post evaluation of order set implementation of all patients admitted to Riley Hospital for Children and treated with meropenem between 9/01/2019–9/01/2021 (pre-intervention) and 10/13/2022–10/13/2023 (post-intervention). The primary outcome was meropenem utilization, as measured by the number of meropenem days and doses per admission. Secondary outcomes included total hospital and ICU mean length of stay (LOS), mortality within 30 days of meropenem exposure, and 30-day readmission rate. Results: 309 admissions during which meropenem was administered were included. Demographics between pre-ASO (147 patients; n = 193 admissions) and post-ASO (88 patients; n = 116 admissions) groups were similar. There was no difference in the number of meropenem days (pre and post-ASO: median = 4; p = 0.88) or the number of meropenem doses (pre-ASO: 11 vs. post-ASO: 10; p = 0.63). Secondary safety outcomes including death within 30 days of meropenem administration (8.7% vs. 8.7%; p = 0.99), hospital LOS (18 vs 15.5 days; p = 0.42), ICU admission, and 30-day readmission rate were not significantly different. The new ASO was utilized in 23.3% of admissions in the post-implementation period. Conclusion: Use of the new ASO was not widely adopted, making evaluation of impact difficult. No significant difference in meropenem use nor clinical outcomes were identified after implementation, which has informed the next Plan-Do-Study-Act (PDSA) cycle for quality improvement at our center, likely with a focus on EMR modifications and education.Item Speckled-egg staining appearance of cryptococcal osteomyelitis in an immunocompetent patient(Elsevier, 2025-01-28) Stack, Matthew Alexander; Lavik, John-Paul; Schneider, Jack G.; Cross, Brynne E.; Pathology and Laboratory Medicine, School of MedicineIntroduction: Cryptococcal infections are typically thought of as occurring in immunocompromised patients, such as patients with HIV/AIDS, solid organ transplant recipients, or patients with rheumatologic diseases that require immunomodulatory therapy. Moreover, Cryptococcus spp. classically appear as variably-sized yeasts with narrow-based budding surrounded by a thick polysaccharide capsule. However, cryptococcal infections are being increasingly reported in atypical hosts, at times with non-characteristic histochemical staining appearances. Herein, we report a case of cryptococcal osteomyelitis in an otherwise immunocompetent individual that had a "speckled-egg" staining appearance on direct-smear Gram stain. Case: The patient is an otherwise healthy 89-year-old male with a past medical history notable only for hypertension who presented with progressive left-sided neck pain that became worse despite lidocaine trigger point injections; imaging was obtained and revealed a C1-C2 prevertebral abscess, C2-C4 osteomyelitis, and a small C2-C4 abscess. An aspiration biopsy from one of the cervical abscesses grew Cryptococcus neoformans. Despite prompt initiation of liposomal amphotericin B as soon as the organism was suspected, the patient's mentation declined with associated progression of weakness in his upper and lower extremities. The patient was ultimately transitioned to comfort care. Conclusions: Unconventional presentations of cryptococcal disease are becoming increasingly recognized in seemingly immunocompetent patients. Our case was unique given that it occurred in a patient who appeared to be immunocompetent and the Gram stain showed a speckled-egg staining pattern that alone was not distinctive for cryptococcal yeasts. Despite the patient's lack of any classic comorbidities associated with invasive cryptococcal disease, his advanced age was likely a risk factor.Item Susceptibility Provision Enhances Effective De-escalation (SPEED): utilizing rapid phenotypic susceptibility testing in Gram-negative bloodstream infections and its potential clinical impact(Oxford Academic, 2019-01-01) Schneider, Jack G.; Wood, James B.; Schmitt, Bryan H.; Emery, Christopher L.; Davis, Thomas E.; Smith, Nathan W.; Blevins, Sarah; Hiles, Jon; Desai, Armisha; Wrin, Justin; Bocian, Brittany; Manaloor, John J.; Medicine, School of MedicineAbstract Objectives We evaluated the performance and time to result for pathogen identification (ID) and antimicrobial susceptibility testing (AST) of the Accelerate Pheno™ system (AXDX) compared with standard of care (SOC) methods. We also assessed the hypothetical improvement in antibiotic utilization if AXDX had been implemented. Methods Clinical samples from patients with monomicrobial Gram-negative bacteraemia were tested and compared between AXDX and the SOC methods of the VERIGENE® and Bruker MALDI Biotyper® systems for ID and the VITEK® 2 system for AST. Additionally, charts were reviewed to calculate theoretical times to antibiotic de-escalation, escalation and active and optimal therapy Results ID mean time was 21 h for MALDI-TOF MS, 4.4 h for VERIGENE® and 3.7 h for AXDX. AST mean time was 35 h for VITEK® 2 and 9.0 h for AXDX. For ID, positive percentage agreement was 95.9% and negative percentage agreement was 99.9%. For AST, essential agreement was 94.5% and categorical agreement was 93.5%. If AXDX results had been available to inform patient care, 25% of patients could have been put on active therapy sooner, while 78% of patients who had therapy optimized during hospitalization could have had therapy optimized sooner. Additionally, AXDX could have reduced time to de-escalation (16 versus 31 h) and escalation (19 versus 31 h) compared with SOC. Conclusions By providing fast and reliable ID and AST results, AXDX has the potential to improve antimicrobial utilization and enhance antimicrobial stewardship.Item The Association Between COVID-19 and Febrile Seizure: A Retrospective Case-Control Study(Wolters Kluwer, 2023) Hanlon, Sean M.; Sim, Don; Schneider, Jack G.; Yang, Ziyi; Thompson, Sean M.; Emergency Medicine, School of MedicineBackground/objective: Throughout the pandemic, febrile seizures have resulted from infection secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The objective of this study is to determine if there is an increased association between COVID-19 and febrile seizures as compared with other causes of febrile seizures. Methods: This was a retrospective case control study. Data were collected from the National Institute of Health (NIH) supported National COVID Cohort Collaborative (N3C). Patients from 6 to 60 months who were tested for COVID-19 were included; cases were defined as COVID-19-positive patients whereas controls were defined as COVID-19-negative patients. Febrile seizures diagnosed within 48 hours of the COVID-19 test were considered to be associated with the test result. Patients were subjected to a stratified gender and date matching design followed by a logistic regression controlling for age and race. Results: During the study period, 27,692 patients were included. Of those, 6923 patients were COVID-19-positive, among which 189 had febrile seizures (2.7%). After logistic regression, the likelihood of having febrile seizures concurrently with COVID-19 as compared with other causes was 0.96 ( P = 0.949; confidence interval, 0.81, 1.14). Conclusions: There were 2.7% of the patients with COVID-19 that were diagnosed with a febrile seizure. However, when subjected to a matched case control design with logistic regression controlling for confounding variables, there does not appear to be an increased risk of febrile seizures secondary to COVID-19 as compared with other causes.