bluuebunny/crossref_metadata_2025_split huggingface dataset:
674. Variations in Agreement and Epidemiological Cutoff Value (ECV) between Fosfomycin (FOF) Agar Dilution and Broth Microdilution Using Standard- and High-Inoculum Protocols for Klebsiella pneumoniae (KP)
Authors: Krueger Amanda R , Anderson Jadyn C , Smith Elizabeth C , Bixby Morgan L , Brigman Hunter V , Hirsch Elizabeth B 
Published: January 2021

Abstract

Background
FOF has been used in the treatment of multidrug-resistant (MDR) KP infections despite established susceptibility breakpoints. At present, agar dilution (AD) is considered the reference method for FOF while broth microdilution (BMD) is specifically recommended against despite its convenience over AD. We therefore sought to assess FOF activity against KP, along with essential and categorical agreement between AD and BMD methods to determine if BMD could be used as a reliable testing method.

Methods
Minimal inhibitory concentration (MIC) values were determined for a convenience collection of 69 KP isolates (59.4% MDR) from three US institutions. MIC testing was conducted in duplicate on separate days using AD and BMD methods; essential and categorical agreement were calculated using AD as the reference method. Fourteen isolates were also analyzed using high-inoculum AD (105.3-5.9 CFU/mL) similar to the BMD method. MIC values were categorized using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria for Escherichia coli (≤ 64 mg/L, susceptible). ECVs were determined according to CLSI methodology.

Results
MIC values varied between methods, withMIC50/MIC90 values being 32/256 mg/L for AD and 128/256 mg/L for BMD. Using E. coli criteria, susceptible/intermediate/resistant rates were 82.6/2.9/14.5% (AD) and 44.9/21.7/33.3% (BMD). Essential agreement was 44.9% and categorical agreement was 60.8%. When using high-inoculum AD, MIC values were on average three-fold higher compared to standard-inoculum AD, with 10 of the 14 (71.4%) isolates brought into essential agreement with BMD. Calculated ECVs were 128 mg/L for standard-inoculum AD and 1024 mg/L for BMD.

Conclusion
Our collection of KP displayed high MIC values to FOF, in addition to substantial discrepancies between AD and BMD methods. Essential agreement increased with the use of high-inoculum AD testing, which better correlated with BMD results. ECV for BMD was three dilutions higher than that for standard-AD ECV. Based on these results, we recommend further investigation of BMD for FOF testing using a larger isolate collection, along with optimization of currently recommended testing methods. In light of these results, KP-specific breakpoints should also be examined.

Disclosures
Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)
676. New PLST Locus for Sequence-based Typing of Candida glabrata Clinical Isolates
Authors: Edlind Tom , Katiyar Santosh 
Published: January 2021

Abstract

Background
Healthcare-associated infections (HAI) with the opportunistic yeast Candida glabrata have become increasingly common in the fluconazole era, and may be endogenous or nosocomial in origin. Effective intervention requires distinguishing between these sources, which in turn requires epidemiological analysis in conjunction with isolate typing. Multiple approaches to C. glabrata typing have been described, ranging from length-based microsatellite and PFGE analyses to sequence-based MLST and WGS; however, issues of cost and technical complexity preclude their routine use in clinical labs. Polymorphic locus sequence typing (PLST) addresses these issues by employing conventional PCR and Sanger sequencing of selected tandem repeat loci that exhibit high rates of both SNPs and insertion/deletion. In our previous study, PLST loci CgMT-J and CgMT-M resolved 104 isolates into 10 phylogenetic clusters and 20 to 24 alleles (Katiyar et al., 2016, J. Clin. Microbiol. 54:1042). Within clusters N and P, isolates from 4 patients each (sets DSY and KM) who received treatment at the same healthcare facilities shared alleles. While consistent with nosocomial transmission, these alleles were also shared by epidemiologically unrelated strains.

Methods
CgMT-J/CgMT-M were identified by bioinformatic analysis of the only two, closely related C. glabrata genome sequences available at the time. Since current GenBank databases include sequences for 16 strains, including 4 epidemiologically related pairs, we bioinformatically searched for new loci exhibiting greater strain resolution.

Results
Locus CgMT-C represents an intergenic region on chromosome C that includes multiple tandem repeats and has no detectable homolog in other yeast. Phylogenetic analysis of database sequences resolved all 12 unrelated strains. In the laboratory, the CgMT-C locus was readily amplified and sequenced directly from C. glabrata colony lysates, including those prepared from chromogenic agars. Most importantly, CgMT-C analysis confirmed identities of the cluster N and P isolates from DSY and KM patients, and resolved them from all unrelated strains.

Conclusion
CgMT-C PLST represents a powerful new tool for C. glabrata epidemiology and infection control.

Disclosures
Tom Edlind, PhD, MicrobiType LLC (Employee, Scientific Research Study Investigator)
678. Polymorphic Locus Sequence Typing for Pseudomonas aeruginosa Outbreak Detection and Investigation
Authors: Edlind Tom 
Published: January 2021

Abstract

Background
Pseudomonas aeruginosa is a common agent of healthcare-associated infection (HAI), which can be challenging to treat due to intrinsic or acquired antibiotic resistance. In contrast to most HAI, the source of P. aeruginosa infection is typically environmental; e.g., from the faucets, drains, and showers in patient rooms. To unambiguously identify the source, strain typing of patient and environmental isolates is required. Typing methods include sequence-based MLST and WGS which resolve strains based on relatively rare SNPs, and length-based MLVA which resolves strains based on relatively frequent insertions/deletions within tandem repeats. These and other methods previously applied to P. aeruginosa have one or more limitations relating to cost, technical complexity, reproducibility, and turnaround time that preclude their routine use. Polymorphic locus sequence typing (PLST) is a hybrid approach that employs sequence analysis of the one or two most phylogenetically informative tandem repeat-containing loci within the genome of a microbial species. Strain resolution equals or exceeds MLST and MLVA and approaches that of WGS. Here, the identification and evaluation of candidate PLST loci for P. aeruginosa epidemiology are described.

Methods
Tandem repeats were bioinformatically identified in representative genome sequences, and screened by BLASTN queries of GenBank genome databases followed by clustal alignments and phylogenetic analysis. Candidate loci were amplified from heat-treated colony lysates and Sanger sequenced.

Results
PLST locus PaMT1 (Mbp 2.568-2.569 in the PA01 genome) resolved 99 alleles from 144 epidemiologically unrelated isolates with GenBank genome sequences, yielding diversity index = 0.991. Nineteen sets of isolates shared healthcare facility and PaMT1 allele, consistent with nosocomial transmission. Examples, confirmed by WGS-SNP analysis, include isolates from 8 VAP patients, 2 sets of cancer patient isolates, and a pair of isolates from patient and hospital sewage. In the laboratory, locus PaMT1 was readily amplified and sequenced from colony lysates, yielding typing data with 1-2 day turnaround.

Conclusion
PaMT1 PLST provides an affordable, user-friendly, and timely tool for P. aeruginosa outbreak detection and investigaton.

Disclosures
Tom Edlind, PhD, MicrobiType LLC (Employee, Scientific Research Study Investigator)
683. Molecular Detection of Enterovirus D68 among Children with Acute Respiratory Tract Infection in Ghana
Authors: Appiah-Kubi Joyce 
Published: January 2021

Abstract

Background
Acute respiratory tract infections of viral origin remain a leading cause of morbidity, mortality and economic loss regardless of age or gender. A small number of acute respiratory tract infection cases caused by enterovirus D68 (EV-D68) have been reported regularly to Centers for Disease Control and Prevention since 1987 by countries in North America, Europe and Asia. However, in 2014 and 2015, the number of reported confirmed EV-D68 infections was much greater than in previous years. The National Influenza Centre (NIC), Ghana carries out surveillance of respiratory infections, focusing on those caused by influenza virus; however, there is inadequate information on other viruses causing respiratory infections in Ghana, including EV-D68.

Objectives
To investigate the association of EV-D68 with Severe Acute Respiratory Infections (SARI) and Influenza-Like Illness (ILI) in Ghana.

Methods
This was a retrospective cross-sectional study which involved archived human respiratory specimens stored at -80ºC at the NIC from 2014 to 2015. Using a random sampling method, oropharyngeal and nasopharyngeal swabs from patients with SARI and ILI that were negative by real-time PCR for human influenza viruses were screened for EV-D68 using real-time reverse transcription-polymerase chain reaction (rRT-PCR).

Results
Enterovirus D68 was detected in 4 (2.2%) out 182 SARI samples tested. EV-D68 was detected in children younger than 5 years (4-100% of positives) and was not detected in children older than 5 years. Enterovirus D68 was detected more frequently in SARI cases (3%) than in ILI cases (1.2%).

Conclusion
This study has shown for the first time the presence of EV-D68 in acute respiratory infection in Ghana. The results confirmed minimal EV-D68 circulation in the Ghanaian population.

Disclosures
All Authors: No reported disclosures
686. Elevations in TNFα and IL-18 are Associated with Increased Risk of Probable Cytomegalovirus Tissue Invasive Disease in Solid Organ Transplant Recipients
Authors: Karaba Andrew H , Figueroa Alexis , Ray Stuart C , Avery Robin K , Avery Robin K , Cox Andrea L 
Published: January 2021

Abstract

Background
Human cytomegalovirus (CMV) continues to cause significant morbidity and mortality in solid organ transplant (SOT) recipients despite prophylaxis. Tissue invasive CMV disease (TI-CMV) can lead to end-organ damage and graft loss. Diagnosing TI-CMV can be challenging as CMV viral load in the blood does not always correlate with episodes of TI-CMV and therefore definitive diagnosis often requires an invasive procedure such as bronchoscopy or colonoscopy. The purpose of this study was to determine if proinflammatory cytokines, including IL-18, are elevated in SOT recipients with probably TI-CMV as a way to identify patients at risk for this severe form of CMV disease.

Methods
The electronic medical record was searched for adult SOT recipients who were tested for CMV via blood qPCR during an 11-month period.Twenty-nine SOT recipients were identified that had episodes of CMV DNAemia without other concomitant infections during this time period. Patients were divided into those that had probable TI-CMV and those with CMV DNAemia alone, by chart review. Inflammatory cytokines (IFNγ, TNFα, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-18, and IL-1RA) were measured in residual plasma from these patients using a commercially available multiplex assay for at least two time points during the study period. Wilcoxon-Rank-Sum, logistic regression, and principal component analysis was performed comparing patients with and without probable TI-CMV.

Results
Patients with probable TI-CMV had significantly higher IL-18, TNFα, and IL-1β than patients with CMV DNAemia alone (p &lt; 0.001, &lt; 0.001, and &lt; 0.05 respectively). When adjusting for transplant type and CMV recipient serostatus, elevations in TNFα (OR 1.43, 95% CI 1.07-1.92) and IL-18 (OR 2.00, 95% CI 1.06-3.75) were associated with increased odds of having probable TI-CMV. In principal component analysis the combination of CMV viral load, IL-18, TNFa, and IL-1β accounted for 80% of the variance in the data.

Conclusion
TNFα and IL-18 in combination with CMV viral load may be useful in predicting likelihood of TI-CMV. This is important in situations where tissue biopsies are not feasible, and adds to our diagnostic capability for TI-CMV in SOT recipients.

Disclosures
Stuart C. Ray, MD, miDiagnostics, Inc. (Board Member, Research Grant or Support) Robin K. Avery, MD, Aicuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)Chimerix (Scientific Research Study Investigator)Merck (Grant/Research Support, Scientific Research Study Investigator)Oxford Immunotec (Scientific Research Study Investigator)Qiagen (Scientific Research Study Investigator)Takeda/Shire (Scientific Research Study Investigator)
688. Marginal Structure Models to Estimate the Effect of Cytomegalovirus Infection on Hospitalization Among Children Undergoing Allogeneic Hematopoietic Cell Transplantation
Authors: Li Yun , Oganisian Arman , Boge Craig L K , Hayes Molly , Newman Alexander , Fisher Brian T , Fisher Brian T 
Published: January 2021

Abstract

Background
Children receiving an allogeneic hematopoietic cell transplant (HCT) are at risk for cytomegalovirus (CMV) infection in the post-transplant period, necessitating routine surveillance for CMV. Some patients will not have CMV detected while others will have intermittent or persistent CMV detection. Prior analyses assessing the association of CMV infection on hospitalization in the post-transplant period have been limited by methods that did not consider the time-varying nature of the exposure (CMV reactivation) and its confounders or aim to obtain causal effect estimates. We aimed to assess the causal effect of CMV reactivation on hospitalization using a causal modeling approach.
The Effect of CMV Infection on Hospitalization Using Generalized Estimating Equations and Marginal Structural Models

Methods
A cohort of allogeneic HCT patients transplanted at Children’s Hospital of Philadelphia January 2004–April 2017 was assembled and followed for 100 days after transplant. Eligible patients included those under CMV surveillance, defined as having ≥2 CMV whole blood polymerase chain reaction tests in the first month after HCT. All information was abstracted from medical charts. The association of CMV reactivation on the rate of hospitalization was estimated using traditional generalized estimating equations and repeated using a marginal structural model that accounted for time-varying exposure, confounders and non-random drop-out and obtained effects with causal interpretations.

Results
The study cohort included 340 pediatric allogeneic HCT recipients under CMV surveillance testing. 46.5% were female and the median age was 9 (range: 0 to 26). The CMV infection rate was 33.9%, with a median time to CMV detection of 23.5 days (range: 4-100). CMV infection was common in Donor+/Recipient+ (58.9%) and Donor-/Recipient+ (34.6%) patients. A traditional model estimates an additional week of CMV infection was associated with a 22% increase in average weekly hospitalization (Incidence rate ratio: 1.22, 95%: 1.12 -1.34). A marginal structure model estimates an additional week of CMV infection is associated with 3% increase in average weekly hospitalization incidence (Incidence rate ratio: 1.03, 95%: 0.91-1.16).

Conclusion
Our research showed the effect of CMV on hospitalization diminished after properly considering the time-varying nature of the CMV infection status and its confounders.

Disclosures
Brian T. Fisher, DO, MPH, MSCE, Astellas (Advisor or Review Panel member)Merck (Grant/Research Support)Pfizer (Grant/Research Support)
690. Oka-Strain Varicella-Zoster Virus Meningitis in a Healthy Adolescent
Authors: Nadimpalli Sruti S , Gershon Anne 
Published: January 2021

Abstract

Background
Routine vaccination with varicella-zoster (VZV) vaccine has resulted in significant declines in the incidence of VZV cases, hospitalizations, and deaths across pediatric age. This vaccine is safe and effective and adverse events are monitored closely.

Methods
We describe a case of vOka meningoencephalitis in a twelve-year-old vaccinated boy who presented with altered mental status and a vesicular facial rash.

Results
A twelve-year-old healthy, fully-vaccinated boy presented to urgent care clnic with left-sided frontotemporal headache, left-sided eye pain, and photosensitivity. Over several days, a left-sided facial rash progressed to include papular and vesicular lesions over the cheek, as well as over the left side of the chin and at the midline of the lower lip. He was somnolent, sleeping 18- 20 hours a day. The child was evaluated by a pediatric neurologist who noted a left-sided ptosis and left lateral rectus palsy; he was admitted for further workup. Cerebrospinal fluid (CSF) analysis showed WBC of 33 cells/ml3 with 92% lymphocytes; glucose of 44mg/dL (serum glucose 84mg/dL), and protein of 50mg/dL (range: 15-45). Nasopharyngeal multiplex polymerase chain reaction (PCR) (BioFire Diagnostics, Salt Lake City, Utah) was positive for rhinovirus/enterovirus. Testing of facial vesicles for varicella-zoster virus (VZV) and herpes simplex virus (HSV) was negative by DFA and culture, and enteroviral throat and rectal PCRs were negative. However, CSF PCR for VZV was found to be positive. In light of this finding, the viral isolate was sent to Dr. Anne Gershon’s research lab at Columbia University Medical Center for typing and was determined to be vOka. Quantitative and functional immune studies were performed, and were normal. The patient initially received 7 days of intravenous acyclovir, during which time his rash resolved and mental status returned to baseline. He completed a total of 14 days of acyclovir and has had no recurrences.

Conclusion
This case represents only the tenth case of Oka-strain meningitis in an immunocompetent child reported to date, and one of very few cases in immunocompetent adolescents. While rare, vOka meningitis is an entity of which primary care pediatricians and infectious diseases specialists should be aware, even in older children.

Disclosures
All Authors: No reported disclosures
695. Infective endocarditis in people who inject drugs (PWID) at UK Medical Center
Authors: Cari Evelyn Villacorta , Henderson John T , Burgess Donna R , Porterfield J Zachary , Leedy Nicole , Thornton Alice 
Published: January 2021

Abstract

Background
The Intravenous Drug Use (IVDU) epidemic has been developing into a public health crisis in the last twenty years. As a result, the incidence of severe bacterial infections such as infective endocarditis (IE) has been rising dramatically.

Methods
Cross-sectional study, we reviewed records of all admissions to University of Kentucky hospitals with IVDU associated ICD9/10 codes who received an Infectious Diseases consult during 2018 and focused on the cases with a diagnosis of IE. We describe associated epidemiologic, clinical, and microbiological features

Results
We include 391 patients in this cohort, among those 157 patients were for IE. Patients had a median age of 34 years old (range: 20 - 62); 81 (51.5%) were female, and five (6.1%) were pregnant and 153 (97.4%) identified as white. A previous episode of infective endocarditis was reported in 55 (35%) cases. The most common illicit substances used were heroin 68 (43.3%) and methamphetamine 65 (41.45%). Tobacco abuse was reported in 134 (86.4%) cases. Fever reported in 93 (59.8%) cases, shortness of air in 43 (28.0%) cases, and chest pain in 44 (28.6%) cases were the most common symptoms. Hepatitis C antibody was positive in 115/149 (73.2%) and 3/143 (1.9%) were HIV positive. Right-sided IE was more frequent, the tricuspid valve was involved in 94 (59.8%) patients. Gram-positive pathogens were isolated in 139 (88.5%) patients, Staphylococcus aureus was isolated in 102 (64.9%) patients, of which 67 (65.7%) were methicillin resistant. Gram-negative pathogens were isolated in 18 (11.2%) patients. Eighty-eight (56.4%) patients had an addiction medicine consult during their admission, (22.9%) patients left against medical advice and 20 (12.7%) patients needed to be readmitted within 30 days after discharge. Overall mortality was 12.7% and was significantly associated with infection by gram-negative pathogens (RR: 2.5; CI 95% 1.05 – 6.25, p=0.037).

Conclusion
Infectious endocarditis is a frequent complication in PWID which carries a high risk of mortality and often involves the tricuspid valve. The most common pathogen isolated was S. aureus, isolation of gram-negative pathogens was associated with increased mortality.

Disclosures
All Authors: No reported disclosures
703. Do Patients with Drug Use-Associated Infective Endocarditis Receive Differential Care?
Authors: Ceniceros Ashley , Felson Uriel , Fox Aaron 
Published: January 2021

Abstract

Background
Outpatient parenteral antimicrobial therapy (OPAT) is the preferred modality for long term intravenous antibiotics for infections such as infective endocarditis (IE). People with drug use-associated (DUA) infections achieve similar outcomes as those with non-DUA-infections when treated using OPAT. The study objective was to compare OPAT use between cohorts of patients with DUA-IE and non-DUA-IE.

Methods
This retrospective cohort study compared OPAT use for DUA-IE vs. non-DUA-IE in adults hospitalized between 1/1/15 and 9/1/19 at three Bronx, NY hospitals. We used multivariable logistic regression to assess the association between DUA-IE and discharge with OPAT, adjusting for clinically significant covariates that were decided a priori. Additional models excluded patients with unstable housing and those who left against medical advice (AMA).
Figure 1: Flow chart of inclusion and exclusion criteria

Results
The cohort included 457 patients (346 non-DUA-IE, 111 DUA-IE). Compared to those with non-DUA-IE, DUA-IE patients were younger (mean age 54.9 years), more commonly male (65.8%), Hispanic (44.1%), Medicaid insured (40.5%), and undomiciled (9%). In models adjusting for age, sex, race/ethnicity, insurance, year of admission, length of stay, socioeconomic status, Charlson Comorbidity Index, MICU admissions, and infectious disease consults, DUA-IE patients had significantly lower odds of being discharged with OPAT than non-DUA-IE patients (aOR 0.16, 95% CI 0.08, 0.34). Odds of being discharged with OPAT remained lower for DUA-IE patients after excluding unstably housed patients (aOR 0.17, 95% CI 0.09, 0.38) and patients who left AMA (aOR 0.23, 95% CI 0.11, 0.47).
Table 1: Non-DUA-IE and DUA-IE Patient Characteristics

Table 2: Unadjusted and Adjusted Odds Ratios for Discharge with OPAT

Table 3: Odds Ratios for Discharge with OPAT Among Patients Stably Housed and Retained in Care

Conclusion
Patients with DUA-IE were discharged with OPAT significantly less than those with non-DUA-IE, and patients having unstable housing or leaving AMA did not account for these differences. These data do not elucidate whether differential treatment was clinically appropriate, but other studies have demonstrated safety and effectiveness of OPAT in DUA-infections. Understanding whether addressable clinician-related factors, including their attitudes toward people who use drugs, contribute to differential treatment is an important next step in this research.

Disclosures
All Authors: No reported disclosures