bluuebunny/crossref_metadata_2025 huggingface dataset:
2803. Is Maternal Plasma Zika Virus Load Associated with Birth Outcomes and Maternal Disease Severity?
Authors: Pellerin Sarah , Funk Anna Louise , Tressières Benoit , Guyomard Stéphanie , Najioullah Fatiha , Poveda Jean-Dominique , Guerbois-Galla Mathilde , Fontanet Arnaud , Hoen Bruno
Published: October 2019

Background

Adverse fetal outcomes and infant birth defects may develop following Zika virus (ZIKV) infection during pregnancy, especially if this occurs in the first trimester. The aim of this study was to assess the relationship between plasma ZIKV load at the time of acute symptoms and (1) the rate and severity of birth defects in neonates born to mothers who had presented with ZIKV infection during pregnancy, and (2) clinical severity of maternal ZIKV infection.

Methods

Within a cohort of pregnant women living in the French territories in the Americas and exposed to ZIKV during the 2016 outbreak, we analyzed the data of women who developed a symptomatic infection confirmed by a positive plasma ZIKV RT–PCR, using the RealStar Zika virus RT–PCR Kit (Altona Diagnostics, Hamburg, Germany). Plasma ZIKV load quantification was based on the number of cycle times (CT) at which ZIKV RNA was detected (lower CTs indicating a higher viral load). Variables indicating clinical severity of infection included the number of symptoms experienced and the severity of rash. Birth defects possibly linked to ZIKV infection were defined as microcephaly, brain imaging abnormalities, and central nervous system dysfunction. Multivariable logistic regression was used to examine whether potentially ZIKV-related abnormalities were linked to changes in CT, and multivariable linear regression was used to identify clinical correlates with CT value.

Results

Of the 277 live-born neonates who were born to mothers who met the selection criteria, 15 (5.4%) had abnormalities possibly linked to ZIKV infection. The median (IQR) ZIKV RT–PCR CT values were similar, with 31.4 (29.3–33.2) and 31.8 (30.0–33.0), in women delivering normal neonates and those delivering neonates with defects, respectively (OR: 1.04, P = 0.685). Plasma ZIKV load was lower with every day since first symptom onset, and higher with each additional symptom experienced, as indicated by changes in CT of 0.3 (95% CI: 0.2 ‒ 0.5, P < .001) and −0.3 (95% CI: −0.5 ‒ −0.1, P = 0.002) for each unit, respectively.

Conclusion

No relationship was observed between plasma ZIKV load and abnormal pregnancy outcomes but higher plasma ZIKV load was associated with a more recent and severe maternal ZIKV infection.

Disclosures

All authors: No reported disclosures.
2806. Follow-up of Children with Confirmed Perinatal Zika Virus Exposure: The First 2-year experience in the Costa Rican Tertiary Pediatric Hospital
Authors: Brenes-Chacon Helena , Avila-Aguero Maria L , Camacho-Badilla Kattia , Naranjo-Zuniga Gabriela , Benavides Adriana , Soriano-Fallas Alejandra
Published: October 2019

Background

Costa Rica (CR) has local transmission of Zika Virus (ZIKV) Infection since February 2016. Perinatal exposure (PE) and infection (PI) cases have been documented. Following a national protocol, reporting and follow-up of patients is mandatory. 2018 data of CR reported 272 women with confirmed ZIKV infection during pregnancy. Even though neurological sequelae are described in PI, including microcephaly, affected patients can develop symptoms within months after birth with development, language, and behavior alterations.

Methods

Retrospective descriptive study of patients born from August 1, 2016 until July 31, 2018, with laboratory confirmed PE. Follow-up was performed at referral hospital.

Results

101 patients were enrolled (37% of all national confirmed perinatal ZIKV exposure during study period). Median age of first evaluation was 5 months (range: 0.6–21). 86/101 (86%) were classified as adequate term infants. 34/101 (33.7%) mothers got infected at first trimester, 55 (54.4%) at second, and 11 (10.8%) at third trimester. No data available in one. 8/101 (8%) patients had microcephaly at birth, with only 3/101 (3%) with persistence at follow-up, and 3/101 (3%) developed it later (after 9 months). 3/101 (3%) had confirmed congenital ZIKV syndrome (laboratory confirmation in symptomatic children), and 2 (2%) congenital ZIKV infection (laboratory confirmation in asymptomatic child). 6/101 (6%) had tone abnormalities and global development delay. 9 (9%) had central nervous system (CNS) ultrasound abnormalities, and 3 (3%) developed seizures. 2 (2%) had visual abnormalities, 1 (1%) had hearing impairment, 4 (4%) developed eating abnormalities, 6 (6%) developed language delay, and 4 (4%) had hyperactive behavior. All findings were divided according to maternal trimester of infection.

Conclusion

PI is a health problem in CR. Microcephaly at is infrequent, with international data showing it affects less than 1% of newborns. Most motor and development delay were documented in patients infected early during pregnancy, but specific language and behavior abnormalities also affected patients with later PE. Mortality was not documented, but significant CNS abnormalities were evident in congenital ZIKV syndrome patients.

Disclosures

All authors: No reported disclosures.
175. There Was a Fungus Among Us: A Cohort of Fungal Infectious Endocarditis Cases in East Tennessee
Authors: Morelli Morgan K , Lorson William , Shorman Mahmoud
Published: October 2019

Background

Fungal infective endocarditis (IE) represents less than 2% of all IE cases, but it carries a mortality rate as high as 50%. While cases of IE are on the rise in recent years due to the increased prevalence of persons who inject drugs (PWID), there are few published studies of fungus as the cause. Candida species is the most likely fungal pathogen in IE. Known risk factors include prosthetic heart valves, healthcare-associated infections, and injection drug use. Since fungi are a rare culprit in endocarditis, there is little information on incidence, treatment recommendations, and outcomes.

Methods

A retrospective cohort of patients with Candida IE was analyzed between October 2013 and September 2018 at a university hospital in East Tennessee. Demographic, microbiologic, substance use status, mortality, and echocardiographic data were collected.

Results

Nine patients with Candida IE met inclusion criteria. Mean age was 37, 67% were males. Risk factors included PWID, oral opioid abuse, previous valve surgery and autoimmune disease. 5 (55%) were caused by Candida albicans, 3 (33.3%) Candida paraipsalosis, and 1 (11%) grew both Candida tropicalis and albicans. Valves involved: 4 (66.7%) native tricuspid, 2 (22%) native aortic. 2 (22%) had native mitral, 1 (11%) had both tricuspid and mitral valve involvement. Echinocandins were used in 5 (55%) and 2 (22%) underwent surgery. There was 1 (11%) in-hospital mortality and 2 (22%) within 1 year of discharge (Table 1).

Conclusion

Fungal IE is a rare disease with high mortality and increasing incidence, especially in PWID. High index of suspicion is required for early diagnosis. Treatment is traditionally a combination of surgery and antifungal therapy. Although, medical treatment alone can be successful in patients who are not surgical candidates, such as in PWID.

Disclosures

All authors: No reported disclosures.
176. Streptococcus intermedius: A Study of 107 Isolates
Authors: Pandya Dhyanesh , Kannangara Don
Published: October 2019

Background

Streptococcus anginosus (SA), Streptococcus constellatus (SC), and Streptococcus intermedius (SI) constitute the S. anginosus group (SAG). The majority of SI reports are single or few cases and small series. In a 2017 study of 263 cases of SAG only 36 (13.7%) were identified as SI, responsible for pyogenic nonbacteremic infections. Another study (2001) found 14 SI out of 122 SAG isolates of which 12 were from abscesses. In some reports, SI was only identified after molecular sequencing as original culture reports were negative. We present results of the analysis of 335 SAG isolates during a 3-year period with much higher numbers of SI (107) 32%, and bacteremia (17) 16% than previously reported. SI isolates exceeded S. constellatus (77) 23% with SA being the majority (45%)151. Our study disclosed previously unreported sites of infection and differences in the type of bacteremia (monomicrobial vs. polymicrobial).

Methods

We reviewed the charts of 1321 Streptococcal isolates which included 335 SAG with 107 SI during the last 3 years, in patients admitted to our network hospitals. Age, sex, clinical findings, lab reports, procedures, imaging, and susceptibilities were analyzed.

Results

Age range was one month to 90 years with 167 males and 166 females. There were 335 SAG isolates, SA 151(67M/84F), SI 107(56M/51F) and SC 77 (47M/30F). 70% of SI patients were in the 40–80 age group. There were 17 SI bacteremias (all monomicrobial) compared with 26 SA (17%), with 14 (54%) polymicrobial and 11 SC with 5 polymicrobial l (46%). 16 isolates were from empyema fluid, 11 related to IVDU, 9 liver abscesses, 6 perforated bowel, 3 peritonsillar abscesses, 3 breast abscesses, 3 mandibular osteomyelitis, 3 neck infections, 3 myositis, 3 pancreas associated, 1 each of mandibular sialadenitis, epidural abscess, cranial osteomyelitis, brain abscess, vertebral osteomyelitis and remainder soft-tissue infections in extremities or face. Some were related to poor oral hygiene or dental procedures. One abdominal wall infection was from a toothpick puncture. Twenty-five were polymicrobial infections. There were 4 deaths, three attributable to SI infection. All isolates tested (32) were susceptible to penicillin (MIC 0.008–0.125 μg/mL), ceftriaxone (MIC = 0.032–0.125 μg/mL) and vancomycin (MIC 0.38–1.0 μg/mL).

Conclusion

SI appears to be underreported. All SI bacteremias in the study were monomicrobial in contrast to 54% SA and 45% SC blood cultures with multiple organisms. The most common isolation site was empyema fluid. Almost all isolates appeared to originate from oral or gastrointestinal flora. Several of the sites encountered have not been reported previously. All isolates tested were susceptible to penicillin, ceftriaxone, and vancomycin.

Disclosures

All authors: No reported disclosures.
614. Metabolic Interventions for the Resensitization of Daptomycin-Resistant (DAP-R) Streptococcus mitis-oralis Strains to DAP In vitro and Ex Vivo in a Simulated Model of Experimental Endocarditis (IE)
Authors: Somerville Greg , Powers Robert , Rose, Warren , Miro Jose , Bayer Arnold , Mishra Nagendra
Published: October 2019

Background

Streptococcus mitis-oralis is a leading cause of IE. Treatment of this pathogen is limited by frequent high-level β-lactam resistance and the propensity to develop high-level DAP-R during DAP exposure. The current study elucidated key metabolic perturbations associated with high-level DAP-R in prototype S. mitis-oralis strain 351, following in vitro selection of DAP-R by 10-day serial passage in sub-inhibitory DAP. Furthermore, to test translatability of such metabolic changes (see below), the synergistic activity of combinations of DAP plus a strategic metabolic inhibitor (i.e., fosfomycin) vs. DAP or fosfomycin alone was assessed, using DAP-R S. mitis-oralis strain 351-D10 (MIC >256 µg/mL) in vitro and in an ex vivo IE model.

Methods

MICs. E test Growth Curve: Optical density (OD600) determined spectrophotometrically at 0–8 hours glyceraldehyde-3-phosphatedehydrogenase (GAPDH) activity. Kit from BioVision®. Metabolomics: one-dimensional 1H NMR-MS and two-dimensional 1H-13C HSQC in vitro time-kill assay: Using sub-MIC/MIC drug concentrations (initial inoculum ~1 × 105 CFU/mL) for 0, 2, 4, 6, and 8 hours. Ex vivo IE model: Simulated endocardial vegetations (SEVs) quantitatively cultured at 0, 4, 8, 24, 32, 48, and 72 hours with DAP or fosfomycin alone or in combination.

Results

NMR metabolomics analysis identified a number of metabolite differences in the 351 D10 DAP-R vs. 351 DAP-S strain (Figure 1). These data are consistent with a significant reduction in GAPDH activity (a glycolytic enzyme) in 351-D10 vs. 351 strain. Based on these metabolic changes, fosfomycin (a phosphoenolpyruvate analog) was chosen as a strategic metabolic inhibitor to attempt to “resensitize” our DAP-R S. mitis-oralis strain to DAP. The combination of DAP + fosfomycin demonstrated synergistic killing of the DAP-R strain vs. DAP or fosfomycin alone in the in vitro time-killing assays. Moreover, the DAP-R strain was synergistically cleared from SEVs by DAP + fosfomycin in the ex vivo IE model.

Conclusion

Taken together, these data indicate there are unique metabolome signatures associated with the DAP-R phenotype in S. mitis-oralis. In addition, these data provide support for further studying the use of strategic S. mitis-oralis metabolic inhibitors in additional strain-sets to resensitize DAP-R strains to DAP, using in vitro, ex vivo and in vivo models.

Disclosures

All authors: No reported disclosures.
2206. Patterns of Care and Outcomes in Elderly Patients Hospitalized with Community-acquired Pneumonia in the United States
Authors: Rastogi Radhika , Deshpande Abhishek , Le Phuc , Yu Pei-Chun , Imrey Peter , Hashmi Ardeshir , Rothberg Michael
Published: October 2019

Background

Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in the elderly. Few studies compare the elderly (>65) and very elderly (≥85 years). We aimed to describe characteristics and patterns of care for very elderly patients hospitalized with CAP.

Methods

We conducted a retrospective cohort study using administrative data from 2010 to 2015 of about 660 US hospitals in the Premier database. Adults aged ≥65 years hospitalized with CAP, identified by either a principal ICD-9 code of pneumonia or a principal diagnosis of sepsis or respiratory failure coupled with a secondary code for pneumonia, were included. We compared demographics, insurance status, comorbidities, presentation characteristics and treatments among three age groups: 65–74, 75–84, and ≥ 85 years.

Results

The final sample included 488,382 patients aged ≥65 years, a third of whom were ≥85 years. Geriatricians cared for <1% of patients during hospitalization, regardless of patient age. Compared with those aged 65–74 years, the patients ≥85 were more likely to be female, of white race, have Medicare insurance, and a principal diagnosis of aspiration pneumonia (17.1% vs. 7%) (Table 1). The oldest group had higher rates of cardiac comorbidities, chronic kidney disease and dementia, but lower rates of diabetes, obesity, pulmonary disease, and smoking. On presentation, more of the very elderly had concomitant urinary tract infections. They were less likely to receive opiates and benzodiazepines, but more likely to receive foley catheters and antipsychotic medications. Antibiotics given in the first 2 days were similar across the groups. Fewer very elderly patients were admitted to the ICU or got ventilation compared with younger groups. More of the very elderly were discharged to hospice and fewer were discharged home. Compared with younger ages, the very elderly had similar lengths of stay but lower costs, and higher in-hospital mortality and 30-day readmission.

Conclusion

The very elderly represent a unique population with distinct clinical characteristics and outcomes from younger elderly patients. They have different co-morbidities and appear to receive less aggressive treatment with lower costs and higher mortality despite similar lengths of stay.

Disclosures

All authors: No reported disclosures.
2207. Narrowing Antibiotic Spectrum of Activity for Trauma-Associated Pneumonia Through the Use of a Disease-Specific Antibiogram
Authors: Ting Michelle , Radosevich John , Weinberg Jordan , Nailor Michael D
Published: October 2019

Background

Organism susceptibilities for trauma-associated pneumonia (TAP) differ from those in other groups of patients, including the critically ill. The purpose of this study was to identify common organisms and their susceptibilities in the respiratory isolates of trauma patients diagnosed with pneumonia within the first 7 days of hospital admission, and to create a disease-state antibiogram specific to TAP to guide empiric antibiotic therapy in this patient population.

Methods

This study was an IRB-approved, retrospective chart review of adult trauma patients with pneumonia admitted between September 1, 2015 and August 31, 2018 were evaluated. Patients included were diagnosed with and treated for pneumonia, with respiratory cultures drawn within the first 7 days of admission; both culture-positive and culture-negative patients were included. Subgroup antibiograms were made for a diagnosis made on days 1–3, 4–5, and 6–7.

Results

There were 131 patients included with a median age of 45; 85% were male, and 31% were illicit drug users. The majority of patients (63%) had ventilator-associated pneumonia, and most respiratory samples (77%) were obtained via bronchiolar lavage. Cultures were positive in 109 patients and negative in 22. There were 144 total isolates; 54% were Gram-negative bacteria. The most common Gram-negative pathogens were Haemophilus influenzae (16%) and Klebsiella pneumoniae (15%). The most common Gram-positive pathogen was Staphylococcus aureus; 9% of all patients grew methicillin-resistant S. aureus. With culture-negative patients counted as susceptible, ceftriaxone monotherapy and ceftriaxone + vancomycin susceptibility were 85% and 94% of patients, respectively. Susceptibilities to cefazolin, ampicillin/sulbactam, cefepime, piperacillin/tazobactam, and levofloxacin were 49%, 69%, 91%, 90%, and 92%, respectively. Illicit drug use and day of pneumonia diagnosis did not appreciably affect antibiotic susceptibilities.

Conclusion

For TAP diagnosed within the first 7 days of hospital admission, ceftriaxone monotherapy is adequate as empiric therapy, including in ventilated patients. The addition of vancomycin can be considered in patients with MRSA risk factors or who are critically ill.

Disclosures

All authors: No reported disclosures.
181. Antimicrobial Susceptibility Trends and Risk Factors for Antibiotic Resistance in Pseudomonas aeruginosa Bacteremia: A 10-Year Experience at a Korean Tertiary Hospital
Authors: Suk Kang Jin , Moon Chisook , Jun Mun Seok
Published: October 2019

Background

Bacteremia due to Pseudomonas aeruginosa is associated with high mortality and inappropriate initial antimicrobial therapy leads to worse outcomes. We aimed to analyze clinical characteristics of P. aeruginosa bacteremia and risk factors for antibiotic resistance and investigate their antimicrobial susceptibility trends.

Methods

We retrospectively reviewed the medical records of patients with P. aeruginosa bacteremia admitted to a tertiary hospital between January 2009 and March 2019.

Results

A total of 242 patients were identified and the median age was 70 years [interquartile range (IQR) 57.6–75.4]. Hepatobiliary tract (28.5%) was most common primary site of infection, followed by respiratory tract (20.2%) and urinary tract (15.7%). Out of 197 (81.4%) patients treated with susceptible antibiotics and the median duration of active antibiotic therapy was 10 days (IQR 4–15.5). The percentages of susceptible P. aeruginosa to amikacin, aztreonam, cefepime, ceftazidime, ciprofloxacin, colistin, gentamicin, imipenem, meropenem, piperacillin–tazobactam, and ticarcillin-clavulanate were 90.1%, 57.9%, 77.3%, 74.8%, 74.4%, 99.2%, 91.3%, 76.0%, 76.0%, 69.4%, and 51.2%. There were 24.8% carbapenem-resistant P. aeruginosa (CRPA), 36.4% multidrug-resistant P. aeruginosa (MDRPA), and 15.3% extensively drug-resistant P. aeruginosa (XDRPA). Susceptible P. aeruginosa to gentamycin and ticarcillin-clavulanate were significantly decreased in 2014–2019 than that in 2009–2013 (both; P < 0.001). Resistance rates to carbapenems and fluoroquinolones tended to increase over time. CRPA, MDRPA, and XDRPA were significantly associated with delayed active therapy (>48 h) (all; P < 0.001). Independent risk factors for CRPA were urinary tract infection (adjusted odds ratio [aOR], 3.4; 95% confidence interval [CI], 1.5–7.8), underlying hematologic malignancy (aOR, 3.0; 95% CI, 1.1–8.3) and cerebrovascular accident (aOR, 2.6; 95% CI, 1.1–5.9), hospital-acquired infection (aOR, 2.5; 95% CI, 1.0–6.1), and co-colonization with multidrug-resistant organisms (aOR, 2.2; 95% CI, 1.1–4.4).

Conclusion

The identification of risk factors for antibiotic resistance and analysis of antibiotics susceptibility are useful for early initiation of appropriate antibiotics in patients with P. aeruginosa bacteremia.

Disclosures

All authors: No reported disclosures.
196. Impact of BioFire FilmArray® Blood Culture Identification on the Management of Staphylococcus aureus Bacteremia
Authors: Nguyen Kiet , McKamey Lacie , Green Sarah
Published: October 2019

Background

Staphylococcus aureus bacteremia (SAB) is associated with 30-day mortality rates that are as high as 20 to 40%. In order to reduce mortality and treatment failures, SAB management should include prompt infectious diseases (ID) consult, repeat blood cultures, source control, intravenous antibiotics for the entirety of treatment, and optimal treatment duration. The objective of this study was to determine the impact of BioFire FilmArray® Blood Culture Identification (BCID) on the implementation of these standard of care measures in the management of SAB across a large health system.

Methods

This study was an IRB approved, retrospective chart review evaluating the impact of rapid diagnostics on the management of SAB before and after implementation of BCID. The composite endpoint consisted of mortality at 30 days, persistent SAB (≥7 days), and recurrence of S. aureus infection within 30 days. Patients were included if they were ≥18 years old and at least one blood culture was positive with S. aureus. The pre-BCID period was between September 1, 2016 and March 31, 2017. The post-BCID period was between April 1, 2017 and July 31, 2018. Fisher’s exact test, student’s t-test, and descriptive statistics were used in the analysis.

Results

A total of 200 patients met eligibility (pre-BCID, n = 102; post-BCID, n = 98). The composite endpoint was met in 34% of patients in the pre-BCID group and 29% in the post-BCID group (P = 0.45). Mortality at 30 days (17% vs. 17%, P = 1.00), persistent SAB (16% vs. 13%, P = 0.69), and rates of recurrence within 30 days (4% vs. 1%, P = 0.37) were similar between groups. ID consult increased after BCID implementation (83% vs. 92%, P = 0.001). More patients in the post-BCID received appropriate durations of antibiotics (75% vs. 86%, P = 0.04) and had decreased time, in hours, to definitive therapy (7 ± 17 vs. 1 ± 5, P ≤ 0.05).

Conclusion

The management of SAB after implementation of BCID did not show a decrease in the primary outcome but did show an improved time to appropriate therapy. A larger study is needed to determine whether improved time to appropriate therapy translates to an improvement in patient outcomes.

Disclosures

All authors: No reported disclosures.
225. Bloodstream Infections in Adult Allogeneic Stem Cell Transplant Recipients with Acute Gastrointestinal Graft-vs. -Host Disease within the First 180 Days Post-Transplantation
Authors: Modi Anita R , Rybicki Lisa A , Majhail Navneet , Mossad Sherif B
Published: October 2019

Background

Infections are the most common cause of non-relapse mortality in adult allogeneic stem cell transplant (allo SCT) recipients. Acute gastrointestinal graft-vs.-host disease (GI GVHD) often leads to friable mucosa and interventions increasing infectious risk. We describe the relationships between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI) at our institution.

Methods

We reviewed 441 adults who underwent allo SCT from 2011 to 2017 and were diagnosed with GI GVHD, non-GI GVHD, or no GVHD based on the Modified Glucksberg Scale within the first 100 days of transplant. The maximum grades of GI GVHD and non-GI GVHD were used in the analysis. A BSI episode constituted a blood culture positive for bacteria or fungi and antibiotic treatment. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method.

Results

Overall BSI incidence by day 180 was 32%; Gram-negative bacilli were the predominant organisms. Adjusting for grade of non-GI GVHD, patients with acute grade 4 GI GVHD had higher risk of BSI as compared with patients with no GI GVHD (HR 3.02, P < 0.001), while those with grade 3 GI GVHD had similar risk (HR 1.01, P = 0.98). Patients with grade 1 or 2 GI GVHD demonstrated lower BSI risk compared with those with no GI GVHD (HR 0.48, P = 0.015; HR 0.44, P = 0.08, respectively). Results were similar after adjusting for patient- and transplant-related risk factors for BSI. Grade of GI GVHD had no association with non-BSI risk. Patients who developed BSI or non-BSI had significantly higher overall mortality risk compared with those without infectious complications (HR 2.52, P < 0.001 for BSI; HR 1.60, P = 0.001 for non-BSI).

Conclusion

Acute grade 4 GI GVHD may reliably indicate higher BSI and overall mortality risk in this population. Understanding the relationships between acute GI GVHD and BSI can guide future treatment strategies for adult allo SCT recipients.

Disclosures

All authors: No reported disclosures.
239. Epidemiologic Analysis of a Worldwide Collection of Escherichia coli ST131 Using the 1928D Core Genome (cg) Multilocus Sequence Type (MLST) Reveals Country Specific and Globally Disseminated Clades
Authors: Deshpande Lalitagauri M , Davis Andrew P , Fredrik Dyrkell F , Amellos Dimitrios , Castanheira Mariana
Published: October 2019

Background

Increasing antimicrobial resistance (R) among Escherichia coli (EC) isolates can be associated with the expansion of the pandemic sequence type (ST) 131 that harbors virulence factors and causes more severe infections when compared with other antimicrobial-R EC. We evaluated the core genome MLST (cgMLST) profiles and R genes using the bioinformatics tool 1928D to evaluate the epidemiology of a global ST131 EC collection and unrelated STs.

Methods

A total of 259 EC clinical isolates belonging to ST131 (n = 206), ST131-single loci variant (SLV; n = 25), and 28 non-ST131 isolates collected from 27 countries during 2016–2018 were selected. Whole-genome sequencing FASTQ files were uploaded to the 1928D pipeline to generate MLST, cgMLST and R gene prediction. cgMLST assignment was based on comparing >2,500 genes.

Results

Among 231 ST131 and SLV EC isolates, 7 clades were identified (3 major [178 isolates]; Table) applying cgMLST allele distance (ad) of ≤50 as a cutoff. A total of 21 isolates were not assigned to clades (>50 ad from ST131 and SLV). Based on >95% concordance, 11 alleles differentiated clades II and III from clade I, while 6 alleles separated clades I and III from clade II. Isolates in clades I to IV were ciprofloxacin R (MIC, ≥4 mg/L); clades I and III predominantly carried blaCTX-M-15 (39/43 and 61/66), blaOXA-1 (35/43 and 43/66), and aac(6’)-Ib-cr (39/43, 45/66) while clade II carried blaCTX-M-14-like and rarely aac(6’)Ib-cr (3/69). The most ad between the 7 ST131 clades was 216, while unrelated STs showed variable ad among isolates within that ST. Isolates bellowing to ST1193 were closely related genetically (ad of 30), but other STs had more variability among isolates (ST167, ad 552; ST38, ad 150; and ST69, ad 179).

Conclusion

1928D is a robust platform for epidemiological analysis of isolates, providing additional granularity when compared with MLST. Clades II and III were closely related, but carried different blaCTX-M genes, while clades I and III were not as closely related, but both carried blaCTX-M-15, blaOXA-1, and aac(6’)Ib-cr. These findings suggest that these clades might have acquired R genes at different points in their genetic evolution. A threshold of ≤50 (cgMLST distance) was useful for classifying isolates into clades.

Disclosures

All authors: No reported disclosures.
242. Comprehensive Pathogen Detection for Pediatric Febrile Neutropenia by Metagenomic Next-Generation Sequencing
Authors: Horiba Kazuhiro , Torii Yuka , Hara Yuichiro , Shimada Mayuko , Suzuki Takako , Takeuchi Suguru , Okumura Toshihiko , Kawada Jun-ichi , Muramatsu Hideki , Takahashi Yoshiyuki , Ogi Tomoo , Ito Yoshinori
Published: October 2019

Background

Febrile neutropenia (FN) is a common complication in patients with solid tumors and hematologic malignancies. Identification of the causative microorganisms would contribute to optimization of antimicrobial treatment and thus improve the outcome of FN. However, causative microorganisms are detected in only 10% to 20% of FN patients. Next-generation sequencing (NGS) allows us to comprehensively analyze all microorganisms present in a clinical sample. In this study, we aimed to utilize NGS for the detection of microbial pathogens in infectious diseases and elucidate the infection source in FN.

Methods

FN is defined by two characteristics: (1) neutrophils count < 500/µL, and (2) fever ≥38.0°C. From 2016 to 2018, 112 plasma/serum samples of pediatric FN patients (11 positive blood cultures) were analyzed. Serum samples from 10 neutropenic patients without fever were also analyzed as controls. Shotgun sequencing method was applied for these samples. The metagenomic analyses were performed through the pipeline PATHDET, which has been newly established in our laboratory. Diagnosis based on NGS results was made based on the following criteria: (1) number of reads from all pathogens per million reads (PR) >650, (2) a specific pathogen’s reads per million reads (RPM) >200, and (3) diversity index >3.0. The NGS results were compared with those from blood culture.

Results

Sequencing reads of bacteria isolated through blood culture were identified by NGS in all 11 plasma/serum samples leading to the diagnosis of FN. The causative pathogens were diagnosed by NGS using the above criteria in 11 patients. However, the results were consistent with those of blood culture in only 4 samples. Of 101 cases with negative blood culture results, the causative pathogens were detected in 17 cases: Acinetobacter soli (2 cases), Burkholderia cepacian (1 case), Klebsiella variicola (1 case), and Roseomonas sp. (1 case) were identified at the species level. In addition, 7 cases (e.g., Acinetobacter) were identified at the genus level, and 5 cases (e.g., Enterobacteriaceae) were identified at the family level.

Conclusion

Metagenomic NGS technique has great potential for detecting causative pathogens with greater efficiency than the conventional methods.

Disclosures

All authors: No reported disclosures.
246. Carbapenem-resistant Klebsiella (CRK) Bloodstream Infections (BSIs) Are Caused by Bacterial Populations That Are Genotypically and Phenotypically Diverse
Authors: Nguyen Minh-Hong , Chen Liang , Cheng Shaoji , Squires Kevin , Hao Binghua , Shields Ryan K , Kreiswirth Barry , Clancy Cornelius J
Published: October 2019

Background

The majority of bacterial BSIs are believed to stem from a single, clonal organism. We hypothesized that most CRK BSIs are caused by genetically diverse, clonal strains that exhibit different phenotypes.

Methods

Blood cultures (BCs) that were positive for CRK from each of 10 patients (patients) were streaked onto agar plates, and 100 individual colonies were chosen for Illumina whole-genome sequencing. Strains from 3 patients were tested for in vitro phenotypes and virulence in mice.

Results

Patients had BSIs due to ST258 K. pneumoniae (Kp; 6), non-ST258 Kp (3), and K. michiganensis (Km; 1). 5 patients were infected with strains that differed by core genome single nucleotide polymorphism phylogeny (2–5 unique genotypes/patient) [figure]. 6 patients were infected with strains that differed by gene or plasmid content, and/or gene deletions [table]. Differences in individual patients encompassed antibiotic resistance and putative virulence genes (including mixtures of blaKPC+ and blaKPC– strains, and various capsular (CPS) and porin mutant strains). In total, BSIs in 8 of 10 patients were caused by a genotypically diverse population. In each of 3 patients, genotypically diverse ST258 Kp strains demonstrated significant differences in antibiotic susceptibility, CPS content, mucoviscosity, adherence, resistance to serum killing, and mortality rates and tissue burdens during BSIs of mice. ST258 strains from a pt with and without a KPC-bearing IncFIA plasmid differed in β-lactam susceptibility, but were equally virulent. Progressive loss of CPS in ST258 strains from another patient enhanced serum killing and adherence, and attenuated virulence. Using PCR markers to test 96 colonies per positive BC bottle, we demonstrated that strains selected by the clinical micro lab accounted for 2% to 98% of a population in different patients.

Conclusion

CRK causing BSIs in most patients demonstrated remarkable genotypic diversity, which impacted antibiotic susceptibility, virulence and other phenotypes. Differences were not recognized during hospitalization since clinical labs select single, morphologically distinct colonies for evaluation. Studies are needed to understand the clinical implications of our findings, diversity during other BSIs, and whether clinical lab practices need revision.

Disclosures

All authors: No reported disclosures.
261. A Retrospective Evaluation of Coccidioidomycosis Skin Testing in Patients with Pulmonary Coccidioidomycosis in an Endemic Region
Authors: Mafi Neema , Girardo Marlene , Blair Janis E
Published: October 2019

Background

Making the decision to stop antifungal therapy in patients with coccidioidomycosis can be challenging in patients with risk factors for relapsed infection. Spherulin-based coccidioidal skin testing was re-introduced to the market in 2014 and approved for the detection of delayed-type hypersensitivity in patients with a history of pulmonary coccidioidomycosis

Methods

We searched electronically for patients who had a spherulin skin test placed in our institution from January 1, 2015 through March 1, 2017, and then included patients age 18 years and older who met the definition for confirmed or probable pulmonary coccidioidomycosis. A retrospective chart review was conducted, and included details of clinical illness, antifungal treatment, serology, and chest imaging

Results

From January 1, 2015 to August 31, 2017, 172 patients with coccidioidomycosis had a spherulin skin test placed. We included for further study the 129 patients who had primary pulmonary coccidioidomycosis, followed for a median of 18 months (range 0–50 months); 56 (43.4/%) were male, 108 (85.7/%) Caucasian, median age was 55 years (range18–89).19/12914.7%)) were smokers, 14/129 (10.9%) were diabetic, 2 patients had HIV (1.6%) and 15/129 (11.6) we immunocompromised without HIV. 116/129(89.9%) % received antifungal treatment. Median time from illness to skin test was 13.5 months (range 0–78). Eighty-nine of 129 patients (69%) had a positive skin test, 40 (31%) had a negative test. Antifungal treatment was subsequently discontinued in 75/89 (84%), and one patient (1.2%) with a positive test, experienced relapsed infection. Among 30/40 with negative CST, antifungals were discontinued and none relapsed.

Conclusion

The presence of delayed-type hypersensitivity to coccidioidomycosis, manifested by a positive spherulin skin test, was associated with discontinuation of antifungal therapy, and a low percentage of relapsed infection.

Disclosures

All authors: No reported disclosures.
270. T2MR: A New Tool for Anti-Fungal Stewardship
Authors: Jariwala Ripal , Zeitler Kristen , Montero Jose
Published: October 2019

Background

Candidemia is associated with mortality rates between 30 and 50%. T2 magnetic resonance assay (T2MR) is a costly, rapid diagnostic technology that can detect the five most common Candida species in blood with a sensitivity of 91% and specificity of 99.4%. The clinical role of this tool remains unclear but this study shares our clinical experience with T2MR.

Methods

We conducted a retrospective chart review of patients with T2MR testing performed from April 25, 2017 through April 25, 2018. T2MR ordering was restricted to Infectious Diseases pharmacists and physicians without specific ordering criteria. Variables cataloged included the time between order and result in the medical chart, T2MR result, anti-fungal therapy and duration. Descriptive statistics were reported on collected variables.

Results

Sixty-eight unique patients had T2MR ordered at least once during the study time period. The median age was 62.5 years (interquartile range (IQR), 22–92) and 42 patients (62%) were male. The median time between order and result appearing in the medical chart was 6.21 hours (IQR, 3.55–40.93). Out of 72 tests performed, 4 were positive (2 for C. parapsilosis and 2 for C. krusei/glabrata). Only 1 of 4 T2MR positive patients had concurrent candidemia while 1 patient had suspected fungal endophthalmitis, 1 patient was managed for a fistula, and 1 patient had cutaneous candidiasis. Of the negative tests, 1 patient had a false negative T2MR result despite blood cultures growing C. glabrata. There was only 1 invalid test in our sample. Thirty-six patients were initiated or maintained on anti-fungal therapy at the time of the T2MR test, with micafungin being the most commonly prescribed anti-fungal agent. Negative T2MR patients had a median anti-fungal therapy duration of 2 days (IQR, 0–16). Sixteen patients (44%) had their anti-fungal therapy discontinued within 1 day of the negative T2MR result. There were no patients with a negative T2MR result who subsequently developed candidemia within 30 days after T2MR testing.

Conclusion

Our study showcases the benefit seen with T2MR in curtailing unnecessary anti-fungal exposure. Study limitations include a small cohort and evaluation at a single center. There is an opportunity for this technology to be utilized in anti-fungal stewardship.

Disclosures

All authors: No reported disclosures.
275. Delayed Diagnosis of Histoplasmosis in Pediatric Patients due to Atypical Clinical Presentations
Authors: Gonzalez Saldaña Napoleon , Xochihua Diaz Luis , Palacios Reyes Deborah , Zuyino Mondragon Salinas Izveidy
Published: October 2019

Background

Histoplasmosis is a systemic mycosis with a wide range of clinical manifestations which represents a diagnostic challenge. It affects immunocompromised patients but also, previously healthy individuals that are exposed to a large inoculum of Histoplasma. The aim of our study was to describe the clinical presentation, epidemiologic features, laboratory/imaging findings and outcome of pediatric patients with histoplasmosis.

Methods

a retrospective study including patients diagnosed as Histoplasmosis according to ICD-10 at a tertiary care center in Mexico City during 2009 to 2019. Clinical, epidemiological and laboratory/imaging data were gathered from each patient’s clinical file.

Results

5 patients with diagnosis of histoplasmosis were included; 2 patients were classified as proven with histopathologic confirmation, 2 patients as probable and 1 patient as possible according to the EORTC/MSG. The mean age of presentation was 7 years, 3/5 patients were male and 3/5 reported exposure to bats. Diagnosis was delayed by an average time of 6 months due to the variability of clinical presentations (progressive disseminated histoplasmosis, spinal histoplasmosis, cerebral histoplasmosis, intestinal histoplasmosis and mild acute pulmonary histoplasmosis). For the diagnosis, 1/5 had positive ELISA, 1/5 positive immunodiffusion (M band), 1/5 positive EIA in cerebrospinal fluid and 2/5 with histopathology findings that matched histoplasmosis. Pulmonary imaging with interstitial infiltrates in 4/5 and evidence of cavitation in one patient. Hemophagocytic syndrome was a complication in 1/5 and medullary syndrome was developed in the patient with spinal histoplasmosis which resolved with treatment. Liposomal amphotericin B was the treatment in 4/5, followed by itraconazole as the maintenance therapy.

Conclusion

This study shows variable clinical presentations of Histoplasmosis which resulted in an important delay in diagnosis. This study highlights the importance of diagnostic suspicion in both healthy children and immunocompromised patients, always taking into account epidemiological risks such as exposure to bats.

Disclosures

All authors: No reported disclosures.
278. CNS Blastomycosis: A Descriptive Analysis and Review of Diagnosis and Treatment
Authors: Majdick Kathryn , Kaye Keaton , Shorman Mahmoud
Published: October 2019

Background

Blastomycosis is a systemic infection, well known to regions of the Southeastern and Ohio River Basin in the United States. Inhalation of the dimorphic fungus most often causes pulmonary manifestations. Hematogenous dissemination can affect various organs in immunocompromised hosts. Central Nervous System (CNS) involvement is a rare manifestation of Blastomycosis infection, accounting for 5%–10% of extrapulmonary involvement. It is important to diagnosis early and treat due to the increased morbidity in high-risk patients.

Methods

Our study retrospectively reviewed cases from a Tertiary Care Facility in East Tennessee from 2011 to 2018 with the diagnosis of CNS Blastomycosis. Data collection included demographics, risk factors, varied clinical presentation, methods of diagnosis, treatment plans and outcomes.

Results

Total of 8 CNS Blastomycosis cases were identified. Detailed demographics are presented in Table 1. The average age was 52 years, 7 (87.5%) were male. 6 (75%) were classified as immunocompromised. 6 of the 8 cases were tested for HIV, all of which were negative. MRI brain imaging was utilized in 7 (87.5%) cases, which demonstrated lesion enhancements, Table 2 and Images 1 and 2. CSF was collected in 6 (75%) patients. 5 patients (62%) presented with neurological complaints. All patients received Liposomal Amphotericin B (LAmpB), followed by a prolonged course of azoles. 5 (62%) developed acute renal insufficiency after starting Amphotericin B. 2 (25%) died.

Conclusion

CNS Blastomycosis is a rare diagnosis with increased morbidity and mortality. Obtaining brain imaging in addition to lumbar puncture can help in timely diagnosis of CNS Blastomycosis. Treatment involves lipid formulation of Amphotericin B followed by oral azole therapy, preferably voriconazole. Renal insufficiency was a common finding after this treatment. A high level of suspicion is crucial for recognition of CNS Blastomycosis in endemic regions of the Southeastern and Ohio River Basin.

Disclosures

All authors: No reported disclosures.
287. Exploring the Natural History and Clinical Outcomes of Hepatitis B Core Antibody Positive Hemodialysis Patients in a Large Metropolitan Tertiary Care Hospital System with a Focus on Occult Hepatitis B
Authors: Vahia Amit T , Chitturi Chandrika , Rizzo Olivia , Lwin Nihn , Soman Sandeep , Yee Jerry , Soi Vivek , Uduman Junior , Alangaden George J
Published: October 2019

Background

Occult Hepatitis B (OHB) is defined as hepatitis B core antibody (HBcAb) positivity in the absence of surface antibody (HBsAb) or surface antigen (HBsAg) positivity. The reported incidence ranges from 0.3% to 58% in the hemodialysis (HD) population. Our study is among the first in the United States to examine the natural history of OHB patients (patients). This work is of interest in HD patients to estimate Hepatitis B transmission risk.

Methods

We performed a retrospective analysis of 352 Hep B cAb positive HD patients between 2010 and 2017 in the Henry Ford Health System and Greenfield Dialysis Centers in SE Michigan. This system contains 5 hospitals including a 900-bed tertiary referral center in Detroit, serving a high-risk, medically complex population. Our primary outcomes were the development of HBsAb positivity, considered protective, or development of HBsAg positivity or new Hepatitis B viremia, considered adverse events. Univariate and multivariate logistic regression analysis was performed to study pertinent risk factors for the clinical outcomes comparing OHB and Non-OHB patients. Statistical analysis was performed using SAS 9.4.

Results

Of the 352 HBcAb patients studied, 98 (27%) were OHB patients. Each group shared similar baseline demographics apart from OHB patients having higher ALT and a greater proportion of drug use and Hepatitis C (Hep C) compared with non-OHB patients (Table 1). There were 15 adverse events in the non-OHB group, including 10 viremias. Only 1 adverse event was seen in the OHB group, a patient who developed viremia of 19 copies/mL (Table 2). Conversely, OHB status was a statistically significant predictor of protective HBsAb development in follow-up (P < 0.01), occurring at a 7-fold increased rate compared with non-OHB patients. Univariate analysis showed that a history of liver disease, Hep C, and drug use predicted HBsAb development (Table 3). When studying adverse outcomes, history of liver disease raises the risk of adverse events in unadjusted models (P < 0.05) (Table 4).

Conclusion

OHB patients in our center tend to develop protective HBsAb titers over time rather than develop viremia or antigenemia in contrast to non-OHB patients. Our study finds that OHB confers minimal risk of potential transmission of Hepatitis B among HD patients.

Disclosures

All authors: No reported disclosures.
295. South Carolina Hepatitis C Telehealth Initiative (SCHTI): Increasing Access to HCV Care
Authors: Derrick Caroline , Chastain Cody A , Meissner Eric G , Love Bryan , Wagner Tyler , Harrison Adrena , Crawford Kimberly , Ahuja Divya
Published: October 2019

Background

Lack of access to specialists is often a deterrent to comprehensive health care, especially in rural areas. Chronic Hepatitis C (CHC) affects 1% of the US population, and with the availability of highly efficacious treatment, it is imperative innovative steps are taken to screen and treat these patients. The South Carolina Hepatitis C Telehealth Initiative (SCHTI) is designed to provide Infectious Diseases (ID) consultation to rural providers caring for HCV-infected individuals across the Southeast. SCHTI is an interdisciplinary collaboration incorporating physicians, pharmacists, nurses and case managers from USC, MUSC, and Vanderbilt University.

Methods

SCHTI tele-consultation sessions were initiated in 2016, are held weekly, and provide a short didactic followed by discussion of patient cases with real-time feedback to the presenting providers. In addition, the program provides 1-hour continuing education certification for physicians, pharmacists and nurses. The South Carolina Department of Health and Human Services has approved SCHTI as an alternative to in-office expert consultation.

Results

From July 2016 through December 2018, 63 sessions were conducted, with 43 unique providers presenting cases and over 160 clinical attendees. Participating providers include Infectious Diseases, Family Medicine and Internal Medicine, amongst others. 259 cases have been reviewed, with a mean of 4.11 cases/session. Genotype 1a predominated and 44% of cases had advanced liver fibrosis. An increasing number of cases are young patients outside the high-prevalence birth cohort, and these individuals have a history of intravenous drug use. Overall, 13% of HCV cases were co-infected with HIV.

Conclusion

SCHTI provides multidisciplinary HCV teleconsultation to providers across the Southeast and is improving access to specialists and high-quality health care for patients across rural areas within the Southeast. Future outcomes to be assessed include sustained virologic response rates, relapse rates and impact on hepatic and extra hepatic morbidity and mortality from CHC.

Disclosures

All authors: No reported disclosures.