bluuebunny/crossref_metadata_2025_split huggingface dataset:
329. Performance of Next Generation Sequencing in Isolating a Pathogen in Pediatric Osteoarticular Infections
Authors: Ramchandar Nanda , Burns Jessica , Pennock Andrew , Cannavino Christopher R , Farnaes Lauge 
Published: January 2021

Abstract

Background
Osteoarticular infections are often encountered in the pediatric population. Therapy is guided by isolation of a putative organism, however, operative cultures are often negative. Next generation sequencing (NGS) allows for more sensitive sampling of body compartments generally considered sterile. We sought to evaluate the utility of NGS in comparison to culture in detecting a pathogenic organism in acute osteomyelitis and septic arthritis in children.

Methods
This was a single-site study to evaluate the utility of NGS in comparison to culture in detecting a pathogenic organism in acute osteomyelitis and septic arthritis in children. Eligible patients were all patients with osteomyelitis or septic arthritis admitted to Rady Children’s Hospital from July 2019 through July 2020. We excluded any patients with bone or joint surgery within 30 days prior to admission. Operative samples were chosen at the surgeon’s discretion (joint aspirate, synovium, or bone) based on operative findings. We compared NGS testing to standard care culture from the same site.

Results
We enrolled 41 subjects. NGS of the operative samples identified a pathogen in 26 (63.4%) patients versus 18 (43.9%) by culture. Operative culture missed the diagnosis in 10 cases, though PCR identified the organism in 6 of those cases (5 were cases in which Kingella kingae was identified). In 4 subjects, NGS identified a putative organism where standard care testing (either PCR or culture) was negative. NGS was falsely positive in 1 subject and falsely negative for one other subject. Sensitivity was 96.3% (CI 95%, 81.0–99.9%) and Specificity was 92.9% (CI 95%, 66.1–99.8) for NGS versus 64.3% (CI 95%, 44.1–81.4) and 84.6% (CI 95%, 54.6–99.9%) for culture respectively.

Conclusion
In this single site prospective study of pediatric osteoarticular infections, we demonstrate improved sensitivity and specificity of NGS testing when compared to standard culture.

Disclosures
All Authors: No reported disclosures
332. Spinal Infections: Clinical and Microbiological Characteristics in our Urban Referral Health Center
Authors: Ogbebor Osakpolor , Abdulmassih Rasha , Como James D , Bhanot Nitin 
Published: January 2021

Abstract

Background
There has been an increasing trend in spinal infections (SI) in the U.S. over recent years. We sought to characterize the clinical and microbiological characteristics of SI at our hospital.

Methods
We conducted a retrospective review of SI over a 3-year period (2016 - 2019) utilizing ICD codes for data retrieval. Search terms included vertebral osteomyelitis, discitis, and epidural abscess. SPSS was used to compute the data.

Results
Of the initially screened 254 patients, 166 were included for analysis. Pertinent demographics were: mean age 59 years, male (61.4%), obese (44.5%), diabetic (25%), and drug-users (20%). Lumbosacral involvement was most common (69.8%); epidural abscess was present in 51.8% of patients. 15.7% had existing hardware. Overall, 79.5% (132/166) of cases had a positive culture from at least one site: blood 56.6% (94/166), CT-guided 83.5% (56/67), and surgical 51.1% (24/47). Of those patients with negative blood cultures, 22% (16/72) had pathogen recovery by CT-guided methods and 33% (24/72) from surgical specimens. S aureus was the most common pathogen isolated at 53.7% (71/132): MSSA comprised 38.6% (51/132) and MRSA 15.2% (20/132).
The mean CRP (8.46 vs 15.83 mg/dL; P&lt; 0.001), and WBC (9.08 vs 13.18 k/mcL; P&lt; 0.001) were higher in culture-positive as compared to culture-negative cases. Mean ESR and temperature more than 100.4 oF did not differ significantly between these two groups. The 8-week median recurrence rate was 11.4%, of which nearly half had index S aureus bacteremia.
Frequency of organisms isolated

Association of mean inflammatory markers with positive cultures

Conclusion
Our study affirmed that S aureus is the most common cause of SI, of which MSSA was predominant. Epidural abscess was encountered in a substantial fraction of our case population. Leukocytosis and elevated CRP tended to predict culture-positive infection, whereas ESR and fever did not. As recommended in the IDSA Vertebral Osteomyelitis guidelines, blood cultures were obtained in all cases, which yielded positive results in more than half of patients. Pathogen recovery was further improved to nearly 80% with supplemental deep tissue sampling, thus highlighting the opportunity to enhance microbiological diagnosis at our institution.

Disclosures
All Authors: No reported disclosures
336. Neurocysticercosis in a non-endemic region: A large case series from New York City
Authors: Berto Cesar G , Coyle Christina 
Published: January 2021

Abstract

Background
Neurocysticercosis (NCC) is associated with significant morbidity and a variety of clinical presentations We describe our experience with NCC at a New York City hospital.

Methods
A retrospective review of consecutive patients with a confirmed diagnosis of neurocysticercosis who attended to Jacobi Medical Center in New York City was done. Demographic data, symptoms at presentation, and cysticercosis serology were retrieved from the medical records. The cases were classified according to the location of the cysts. Demographic and clinic variables were compared to assess for differences according to the cyst location.

Results
A total of 260 cases of NCC were included. Of these cases, 163 (62.7%) were male, and the median age was 36.7 ± 13.7 years. A total of 245 patients (94.2%) were immigrants from 22 different countries. The most common countries of origin were Mexico (28.8%) and Ecuador (24.2%). Parenchymal NCC alone was seen in 139 patients (53.5%); of these, 31 patients had viable cysts. Forty patients (15.4%) were diagnosed with subarachnoid NCC (SANCC) alone and 19 patients (7.3%) had intraventricular NCC alone. Sixty-two patients (23.8%) had parenchymal and extra parenchymal NCC. Additionally, 24.7% of SANCC cases had concomitant spinal NCC. The median time from immigration to presentation was 9.5 years. SANCC cases had significantly longer time from immigration than parenchymal disease. The most common symptom among patients with only parenchymal NCC was seizures (68.4%). Among patients with only SANCC, 28 patients (70.0%) reported headache. Fifteen patients (37.5%) had intracranial hypertension and 12 required shunt placement. Eight patients (20.0%) of the SANCC group presented as an ischemic event. Cysticercus antigen was measured in 172 patients and was positive in 38 patients (14.6%); all but one with a positive antigen had extra-parenchymal NCC.

Conclusion
This is the largest series of NCC reported in the US and highlights the importance of SANCC disease, a more severe form of NCC. Our data suggests that those with SANCC present with intracranial hypertension and have longer latency than other forms. The NCC recombinant antigen was more likely to be positive in extra-parenchymal disease. This is a complex disease and ID physicians should be aware of the many presentations.

Disclosures
All Authors: No reported disclosures
343. CNS Mold Masquerading as Brain Metastases
Authors: Geneva Ivayla I , She Robert , Mahapatra Rahul 
Published: January 2021

Abstract

Background
Histoplasmosis is known to cause CNS infection with or without disseminated disease and immunosuppression is a risk factor. It can mimic brain tumor and present a diagnostic challenge.

Methods
Case report and literature review using PUBMED.

Results
A 64-year-old white female with myasthenia gravis on mycophenolate mofetil, history of Meniere’s Disease, presented with worsening ataxia and left-sided facial weakness for 4 days. MRI revealed multiple enhancing lesions within the brainstem and supratentorial parenchyma (Figure 1), consistent with metastases but either too small or inaccessible for biopsy. Work up for primary cancer with CT thorax, abdomen-pelvis, transvaginal US, mammogram, bone scan, and CSF cytology were negative. The CSF BioFire PCR and culture were negative. Prednisone taper was started for brain vasogenic edema. Patient presented again two months later with worsening lethargy, vertigo, and recurrent falls. At that time the brain lesions showed continued enlargement on repeat imaging, and stereotactic biopsy was performed. Histopathology showed non-necrotizing granulomas, no evidence of malignancy, but after 12 days a mold was isolated on culture prompting Infectious Diseases consultation. Initial morphologic features were non-diagnostic and empiric voriconazole was initiated. Fungal culture evolved Histoplasma capsulatum and voriconazole was switched to liposomal amphotericin B at 5 mg/kg intravenously every 24 hours. Histoplasma serology was positive at low titer, urine histoplasma antigen was negative. An 8 weeks course of Amphotericin, followed by lifelong suppression with fluconazole, was planned.
Figure 1

Conclusion
The diagnosis of our patient’s brain lesions was challenging as biopsy was not an option initially. An anchoring bias likely existed as the investigations had focused on malignancy, while a more robust evaluation for opportunistic endemic fungi, such as Histoplasma, took place at a later stage. Brain lesions in the immunosuppressed patient can masquerade as malignancy. To ensure timely diagnosis, a multimodal investigational approach should be applied early to include imaging and laboratory evaluation for endemic opportunistic pathogens, as well as biopsy when possible.

Disclosures
All Authors: No reported disclosures
347. Etiologies in a Cohort of Pediatric Patients Who Underwent CSF Metagenomic Next Generation Sequencing
Authors: Wilson-Murphy Molly , Lamb Gabriella S , Gorman Mark P , Ahmed Asim A 
Published: January 2021

Abstract

Background
The differential diagnosis in pediatric patients presenting with concern for CNS infections and/or autoimmune disorders is broad. Despite recent advances in diagnostic modalities, many cases may remain undiagnosed. For example, approximately 50% of pediatric patients with encephalitis do not have an identified etiology. Use of metagenomic next-generation sequencing (mNGS) may improve the diagnostic yield. This study evaluated etiologies in a cohort of pediatric patients who underwent CSF mNGS.

Methods
Retrospective cohort study of all hospitalized patients &lt; 21-years-old who underwent CSF mNGS at a tertiary pediatric hospital from June, 2017 - February, 2020. Final diagnosis was assigned by two independent study physician reviewers (pediatric infectious disease and neurologist) based on documentation including discharge summaries, consult notes, and subsequent clinic notes where available.

Results
Thirty-seven patients (59% female, median age 9 (1–17) years) were identified (21 with encephalitis). Twenty-six (70%) had a definite diagnosis – 10 (27%) infectious, 11 (30%) autoimmune, 5 (14%) other. The most common etiology was anti-MOG antibody associated meningoencephalitis (n=4, 11%). Among infections, Powassan virus encephalitis (n=3, 8%) was most common; other infectious etiologies included EBV, neuroborreliosis, rubella, and Eastern Equine encephalitis. Eight (22%) had a positive result on CSF mNGS; 7 were clinically significant including change in management in 5 of 8 (63%) patients.

Conclusion
In this cohort of pediatric patients who underwent CSF mNGS, an etiology was identified in 70%. Eight patients had a positive result on mNGS which resulted in change in management for the majority of patients. These data suggest that CSF mNGS is high-yield and impacts clinical care. However, given the significant cost of mNGS, future directions include cost analyses to determine when and in whom CSF mNGS should be sent.

Disclosures
Asim A. Ahmed, MD, Karius (Employee)
349. Hardware-Associated Multidrug-resistant Pseudomonas aeruginosa Meningitis Treated with Ceftolozane-Tazobactam
Authors: Li Caitlin , Jones Sarah , Levy Ofer , Dixit Avika 
Published: January 2021

Abstract

Background
Although new treatment options for resistant gram negative rods have been recently developed, data on the use of these novel antibiotics for the treatment of central nervous system (CNS) infections is limited.

Methods
We present the case of a 9-year-old with a complex medical history including cerebral palsy and ventriculoperitoneal shunt dependence who was found to have highly resistant Pseudomonas aeruginosa growing from multiple cerebrospinal fluid (CSF) cultures. Susceptibility testing revealed resistance to multiple classes of antibiotics including carbapenems. Multiple antibiotics were considered for treatment; factors including molecular size, lipophilicity, plasma protein binding, and active transport as well as previously published data were weighed in selecting an antibiotic.

Results
The patient was treated with 28 days of ceftolozane-tazobactam. CSF cultures cleared following externalization of the ventriculoperitoneal shunt to an external ventricular drain. There was no recrudescence of Pseudomonas aeruginosa in the CSF following clearance.

Conclusion
We present the first reported case of ceftolozane-tazobactam used as the sole agent for treatment of resistant gram negative rod infection in the CNS. This agent may be a reasonable choice for other patients requiring treatment of highly resistant infections in this protected space.

Disclosures
Ofer Levy, MD, PhD, Avidea (Other Financial or Material Support, collaboration)Exicure (Other Financial or Material Support, collaboration)Multiple patents (Other Financial or Material Support, I am a named inventor on patents related to vaccine adjuvants)
351. Neurocysticercosis: Clinical Experience in Large Urban Safety Net Hospital in Chicago
Authors: Pendyala Bharath , Lingamaneni Prasanth , DeMarais Patricia , Warrior Lakshmi , Huhn Gregory 
Published: January 2021

Abstract

Background
Neurocysticercosis is a major cause of adult-onset epilepsy and premature death in adults. We aimed to describe the clinical and demographic features in a large patient population in Chicago of which published data is limited.

Methods
A retrospective chart search with ICD9/ICD10 diagnostic code for Neurocysticercosis and neuroimaging suggestive of Neurocysticercosis was performed for clinical encounters in the hospital or affiliated clinics between 2013–2018. After a careful chart review, patients who were clinically diagnosed with Neurocysticercosis were included in the study. A descriptive analysis of the data is presented.

Results
Out of a total of 90 patients all of whom were immigrants, the country of origin was reported in 60% and the majority were from Mexico (83.3%). The mean age at the time of diagnosis was 32.3 years (median 29.5, range &lt; 1 to 67). The most common presenting complaints were seizures (62.1%) and headache (27.6%). The most common type of seizure was generalized (48.8%) followed by focal (36.6%). Approximately a third of patients also had hydrocephalus (33.7%). Many patients had &gt; 1 lesion on neuroimaging (70.7%) out of which the most common type were parenchymal lesions (60.9%) followed by ventricular and subarachnoid. Calcified (45.5%) and cystic lesions (44.2%) were found in about equal number of cases. A minority had both types of lesions (10.4%). Contrast enhancement or edema surrounding the lesion was found in about half (47.2%) of the cases. The number of years since the last visit to an endemic country before diagnosis was reported in 46.6% of cases and the mean was 9.8 years (range 0 to 30) and it was found that per year increase since the last visit increased the chance of having contrast enhancement/edema surrounding the lesion in neuroimaging or requiring treatment with antiparasitic medications. (OR 1.77 (1.08–2.90), P= 0.03).

Conclusion
Our study agrees with previously reported data regarding seizure being the most common presenting complaint, generalized seizures being the most common type. The increasing risk of active lesions with increasing duration since the last visit to an endemic country raises the concern of clinically consequential delay in diagnosis.

Disclosures
All Authors: No reported disclosures
355. Variability in the Current Evaluation and Management of Pediatric Encephalitis: Survey Results from an Emerging Infections Network Survey
Authors: Dehority Walter , Janowski Andrew B , Messacar Kevin , Messacar Kevin , Polgreen Philip M , Beekmann Susan E 
Published: January 2021

Abstract

Background
Childhood encephalitis causes severe morbidity and mortality. Difficulty identifying causative organisms and a lack of effective therapies leads to variability in management. The recent emergence of novel diagnostic tools and the increased recognition of auto-immune encephalitides has the potential to change the approach to this disease. Our objective was to assess the current evaluation and management of childhood encephalitis.

Methods
An 11-question confidential, web-based survey was distributed by the Emerging Infections Network (EIN) of the Infectious Disease Society of America to 370 Pediatric Infectious Disease (ID) physicians between January 29th and February 17th, 2020. Respondents were characterized by practice region, experience since fellowship, place of employment and primary hospital type. Responses were analyzed with SAS, v 9.4.

Results
Responses were obtained from 222 of 370 members (60%) (Table). Of the 222 respondents, 196 (88%) reported caring for children with suspected encephalitis and form the basis for this report. Multi-plex PCR testing of cerebrospinal fluid (CSF) in the initial evaluation of most children with suspected encephalitis was reported by 56% (with 65% of these respondents reporting the use of pathogen-specific confirmatory testing). CSF metagenomic next generation sequencing (mNGS) had been used by 47%, with 74% of all respondents stating they would use this test if likely diagnoses were excluded via standard testing (and 64% of these only using the test if the child was not improving). Variability in the interpretation of negative CSF mNGS results was reported (Fig 1a). Primary involvement of ID physicians in the diagnostic evaluation of auto-immune encephalitis was reported by 33%, yet only 55% of ID physicians reported feeling comfortable diagnosing this condition. Marked variation existed regarding criteria for the use of immunomodulating agents (Fig 1b) and the need for testing for autochthonous tropical viruses in the U.S. (Fig 1c).

Background of 222 Respondents to an Emerging Infections Network Survey Assessing the Evaluation and Management of Pediatric Encephalitis. ID=Infectious Disease; VA=Veterans Affairs; DOD=Department of Defense *Respondents were significantly more likely than non-respondents to have &lt;5 years of ID experience (p=0.04).
Figure 1 Approaches to the Interpretation of CSF mNGS Results, Use of Immunomodulating Agents and Testing for Autochthonous Tropical Viral Pathogens in Children with Encephalitis

Conclusion
Variation exists in the evaluation and management of childhood encephalitis, including the application of new diagnostic modalities and management of autoimmune encephalitides. Updated standardized management guidelines may improve implementation of advances in this realm.

Disclosures
All Authors: No reported disclosures
356. Clinical characteristics of critically ill patients with COVID-19 and invasive pulmonary aspergillosis: a case series from Mexico City
Authors: VALENTE-ACOSTA Benjamin , Moreno-Sanchez Francisco , Espinosa-Aguilar Luis , Hoyo-Ulloa Irma , Mendoza-Aguilar Raquel , Garcia-Guerrero Javier , Ontañon-Zurita Diego , Gomez-Gomez Brenda , Olvera-Guzman Claudia , Cebada-López Margarita , Zuñiga-Mejía Beatriz 
Published: January 2021

Abstract

Background
COVID-19, caused by SARS-CoV-2, has emerged as a global public health emergency and has been the main cause of intensive care admission during the pandemic. Invasive pulmonary aspergillosis (IPA) superinfection has been reported in case series of critically ill patients. Mexico has been widely affected by SARS-CoV-2. We present a case series of COVID-19-associated IPA at a teaching hospital in Mexico City.

Methods
We performed a retrospective analysis of COVID-19 patients admitted to the ABC Medical Center from March 13 to June 1, 2020. Only those with severe or critical COVID-19 were hospitalized. Patients with a diagnosis of putative IPA were analyzed. SARS-CoV-2 was diagnosed by Real-Time PCR from nasopharyngeal swabs. Aspergillus antigen testing in tracheal aspirate and serum was done with Aspergillus-specific galactomannoprotein (GP) ELISA (Euroimmun Medizinische Labordiagnostika).The study was approved by the hospital ethics committee.

Results
Among the 47 admitted patients who required invasive mechanical ventilation (IMV), we identified seven (14.9%) cases of IPA. The mean age was 59.7 ± 17.8 years and five were male. All our patients had comorbidities, but none were under previous immunosuppressive treatment. All had critical COVID-19 pneumonia requiring IMV. All but one patient received corticosteroids, and five patients were treated with tocilizumab before IPA diagnosis. Putative IPA was diagnosed in six cases (86%) by a positive GP in tracheal aspirate, additionally in one of these, the tracheal aspirate culture also grew Aspergillus niger. The remaining one (14%) had a positive serum GP. The median time from COVID-19 to IPA diagnosis was 10 days. There were five bacterial co-infections, three with Pseudomonas aeruginosa, one with Stenotrophomonas maltophilia, and one with Mycobacterium tuberculosis. Six patients were treated with isavuconazole and one voriconazole. As of June 17, 2020, three patients had died, two patients had been discharged, and two were still in the intensive care unit receiving IMV.
Aspergillus niger isolated from a tracheal aspirate of a critically-ill COVID-19 patient

Conclusion
COVID-19-associated IPA had a lower prevalence than previously reported in other series. However, it appears to be linked to high mortality and could be associated with other bacterial coinfections.

Disclosures
All Authors: No reported disclosures