bluuebunny/crossref_metadata_2025 huggingface dataset:
2306. Impact of Cytomegalovirus Disease on New-Onset Dementia: Population-Based-Matched Case–Control Cohort Study
Authors: Hwa Lee Kyoung , Eun Kwon Da , Do Han Kyung , Hoon Han Sang , Goo Song Young
Published: October 2019

Background

The association of human cytomegalovirus (CMV) with dementia is still controversial. Previous studies suggested that serostatus of latent CMV infection assessed by serum CMV IgG could play a role in development of neurodegeneration with cognitive impairment. This study is aimed to evaluate the relation of CMV tissue invasive diseases to vascular dementia and Alzheimer’s dementia.

Methods

The ICD-10 codes from the National Health Insurance Database covering 50 million people were used to collect the patient group (n = 687) aged ≥ 40 years with CMV tissue invasive end-organ diseases and control group (n = 3,435) matched by non-CMV infection, age and sex with 1:5 ratio. The subjects were retrieved for enrolled patients during 2010–2014 with wash-out period for 6 years, and followed until December 2016.

Results

Multivariate regression model adjusted by age and sex showed a significantly higher incidence rate of dementia (odds ratio [OR], 2.10 and 95% confidence intervals [CI], 1.45–3.05) in patients with CMV disease. According to the type of dementia, the risk of vascular dementia in patient group (OR, 3.31 and 95% CI, 1.30–8.41) was higher than Alzheimer’s dementia (OR, 1.74 and 95% CI, 1.09–2.78). In the age subgroup analysis adjusted by sex, patients aged 40–59 years with CMV disease had a higher risk of dementia than those aged ≥ 60 years (OR, 12.3 [95% CI, 3.2–47.6] vs. 1.8 [95% CI, 1.2–2.7], P = 0.010).

Conclusion

CMV disease independently increased the risk of vascular dementia as well as Alzheimer’s dementia.

Disclosures

All authors: No reported disclosures.
2309. Could Mean Platelet Volume Predict Platelet Count Recovery in Dengue Virus Infection?
Authors: Sanz Ana M , Martinez Diana M , Valencia Andrea , Flórez Liliana , Tovar Diego , Parra-Lara Luis Gabriel , Rosso Fernando
Published: October 2019

Background

Dengue fever, a major public health problem throughout tropical and subtropical regions, has often unpredictable clinical evolution and outcomes. Thrombocytopenia is a common laboratory finding in dengue fever and severe dengue during the dengue critical phase. To the best of our knowledge, there is no clinical data about patient and disease factors that could predict in a short time the platelet recovery. Mean platelet volume (MPV), a measurement of platelet size, has a strong inverse correlation with platelet count and could indirectly reflect bone marrow activity. The aim of this study was to describe the behavior of MPV during the platelet count nadir and recovery.

Methods

An observational prospective study was conducted. We included patients with confirmed dengue virus infection with SD BIOLINE Dengue Duo kit (Abbott, Santa Clara, USA; former Alere Inc., Waltham, USA) attended at Fundación Valle del Lili, Cali - Colombia. Blood count was analyzed by xn-3000 system impedance method (Sysmex, Kobe, Japan). Laboratory and clinical data were recollected from clinical charts and clinical laboratory database. Platelet count (PC) and MPV were measured repeatedly during clinical management. Time was measured from the first blood count. A non-parametric analysis with a cubic smoothing spline was performed for platelet count and MPV.

Results

A total of 54 patients were analyzed from April 2016 to January 2016. 50% of patients had at least three blood counts. The median of the lowest PC was 112,500/L (IQR = 67,000–148,500), and the median of the highest MPV was 11. 25 fL (IQR = 10. 42–12. 15). MPV increased from the first blood count until day six, while platelets presented slight fluctuations. On the sixth day after first blood count, MPV presented a high peak that suggests an inverse relationship with a platelets decrease (Figure 1).

Conclusion

MPV increased with thrombocytopenia during the critical period and its decline precedes platelet count recovery. MPV could be useful to predict the platelet count recovery.

Disclosures

All authors: No reported disclosures.
2311. Bacteremia Is Not Commonly Detected in Ebola Virus Disease
Authors: Matson Matthew J , Massaquoi Moses , Sprecher Armand , Giuliani Ruggero , Edwards Jeffrey K , Dekker John P , Ricotta Emily , Feldmann Friederike , Feldmann Heinz , Munster Vincent J , Chertow Daniel S
Published: October 2019

Background

Rates of bacteremia in Ebola virus disease (EVD) are not currently known. Given the potential for secondary bacterial infection during acute EVD, current treatment guidelines recommend empiric use of broad-spectrum antibiotics. We sought to determine rates of bacteremia among patients evaluated for EVD at the ELWA-3 Ebola Treatment Unit in Monrovia, Liberia during the 2013–16 West Africa epidemic.

Methods

Deidentified blood samples and matched clinical data from 235 Ebola virus (EBOV)-positive patients and 102 EBOV-negative patients were evaluated under a University of Liberia Pacific Institute for Research and Evaluation IRB-approved protocol. 0.2 mL aliquots of frozen whole blood samples collected at triage, prior to the administration of antibiotics, were inoculated into BD BACTEC Peds Plus bottles and incubated under aerobic conditions in a BD BACTEC FX40 for 5 days in the National Institute of Allergy and Infectious Disease Biosafety Level 4 laboratory in Hamilton, MT. Positive samples were sub-cultured on nonselective sheep blood agar and chocolate agar and pure colonies were selected for identification by 16S sequencing and by matrix assisted laser desorption ionization time-of-flight mass spectrometry.

Results

No difference in rates of bacteremia was detected among EBOV-positive vs. EBOV-negative patients – 3.8% and 3.9%, respectively. Predominant isolates included Staphylococcus epidermidis and other coagulase-negative staphylococci, thought consistent with contaminants. Pathogenic species included Staphylococcus aureus and possibly Paenibacillus spp.

Conclusion

These data suggest that bacteremia does not commonly complicate EVD. However, as both prolonged sample storage and low culture volume may negatively affect sensitivity, additional molecular analyses are needed to support this conclusion.

The Intramural Research Program of the National Institutes of Health supported this work.

Disclosures

All authors: No reported disclosures.
2312. Mortality of Severe Dengue Patients Admitted to Intensive Care Units over 15 Years: Have We Improved?
Authors: Rosso Fernando , Parra-Lara Luis Gabriel , Sanz Ana M , Ospina-Tascon Gustavo A , Granados Marcela
Published: October 2019

Background

Dengue mortality can be preventable in endemic regions. However, access to intensive care units (ICU) and continuous monitoring strategies are limited in developing countries. In 2010, WHO dengue clinical practice guidelines (CPG) were implemented in the Americas region which strengthened hospital healthcare management and prioritized early ICU admission in severe dengue cases. We hypothesized that early access to the ICU might decrease the mortality of patients with dengue. This study aimed to describe trends in dengue cases and mortality in the ICU for 15 years in Cali, Colombia.

Methods

An observational retrospective study about dengue cases treated in adult ICU was conducted, in the Fundación Valle del Lili. We included cases between 2001 to 2015 years. Clinical data were collected from the ICU database and medical charts. A Cochran-Armitage test for trend was used to assess the presence of an association between fatal cases and total cases in dengue patients at ICU during the study period, and to evaluate differences in the mortality cases before and after the implementation of the dengue CPG.

Results

A total of 49,962 episodes of attention in ICU were analyzed, and 70 cases with severe dengue and dengue shock attended in ICU were included. The median age was 42 years (IQR = 24–60), eight cases were older than 65 years, and 54% were male. Five fatal cases were reported during this period. The fatal cases had a length of stay in ICU of 2 days (IQR = 1–4) vs. 2 days (IQR = 1–3) for nonfatal cases. Overall mortality for dengue cases in the ICU was 7.14%. The highest mortality was presented in 2007 with 33.33% (1/3), and after 2010 there were no fatal cases. Dengue mortality showed a decreasing linear variation over time in the ICU (p = 0.047); also there was a statistically significant difference over time in adults mortality before and after of implementation of dengue CPG (P = 0.029).

Conclusion

Dengue mortality cases in the ICU have decreased in the last 15 years, which is related to early admission to the ICU and continuous clinical monitoring.

Disclosures

All authors: No reported disclosures.
2318. Prevalence of Influenza-like Illness in Sheltered Homeless Populations: A Cross-Sectional Study in Seattle, WA
Authors: Rogers Julia H , Brandstetter Elisabeth , Wolf Caitlin , Logue Jennifer , Kim Ashley E , Newman Kira L , Sugg Nancy , Gerard April M , Weis Braia , Fay Noah , Newman Jennifer , Cathey Jeffery , Englund Janet A , Boeckh Michael , Chu Helen Y
Published: October 2019

Background

Individuals experiencing homelessness are at an increased risk of respiratory illness due to high prevalence of underlying chronic conditions, inadequate ventilation and crowding in shelters, and difficulty accessing health services. Few studies have investigated the prevalence and transmission of viral respiratory infections within shelters. We sought to determine the prevalence and risk factors for influenza-like illness (ILI) at two homeless shelters in Seattle, WA.

Methods

Between January and April 2019, we conducted a cross-sectional study of adults experiencing homelessness who identified their primary residence as one of the two shelters in Seattle. Participants voluntarily enrolled if they self-reported at least two symptoms of acute respiratory illness in the past week. Demographic, clinical, and behavioral data were ascertained via questionnaire, and a mid-nasal swab was collected. ILI was defined as fever with cough or sore throat. Chronic lung disease was defined as chronic obstructive pulmonary disease, asthma, and/or chronic bronchitis.

Results

Among the 480 participants enrolled in the study, 204 (42.5%) reported ILI symptoms. Of those enrolled, 144 (30.0%) had chronic lung disease. The prevalence of ILI was higher among individuals with chronic lung disease (53.5% vs. 42.5%, P = 0.001). A total of 422 (87.9%) had health insurance; the prevalence of ILI was lower among those with health insurance (42.4% vs. 57.8%, P = 0.66). 216 (45.0%) of participants received flu vaccine; the prevalence of ILI was similar among those who received the vaccine than those that did not (42.6% vs. 42.4%, P = 1.00). 129 (30.6%) of those with health insurance sought care for their reported symptoms; ILI was more prevalent in those that sought care than those that did not throughout the observation period (33.8% vs. 21.7%, P = 0.002). Of those with ILI that sought care, 46 (54.8%, P = 0.42) received antivirals or antibiotics. Laboratory results for the corresponding mid-nasal swabs are pending.

Conclusion

A large proportion of our study population self-reported ILI and chronic lung disease. Despite high insurance coverage, a low proportion of homeless enrolled sought care for their symptoms or received treatment.

Disclosures

All authors: No reported disclosures.
2323. Clinical Characteristics and Disease Burden of Epstein–Barr Virus and Four β-Herpes Viruses Infections in Children Visiting Emergency Room
Authors: Hattori Fumihiko , Kawamura Yoshiki , Miura Hiroki , Kozawa Kei , Ihira Masaru , Yoshikawa Tetsushi
Published: October 2019

Background

It is well known that most of infants and young children with primary EBV and CMV infection are inapparent, and primary HHV-6B and HHV-7 infection cause exanthema subitum (ES). However, the precise incidence of apparent infection of these viruses remains unclear. Therefore, we sought to elucidate clinical features and disease burdens of these viral infections in febrile children visiting emergency room (ER).

Methods

Between June 2015 and December 2017, febrile children under 5 years old, who visited ER and received hematological examination, were enrolled in this study. Detection of serum viral DNAs using real-time PCR and measurement of antibody titers in acute-phase serum were carried out. Clinical information was collected from the medical records.

Results

In total of the 905 cases, EBV, CMV, HHV-6B and HHV-7 were detected in 18 cases (2%), 12 cases (1.3%), 104 cases (11.5%) and 23 cases (2.5%), respectively. No HHV-6A DNA was detected. Primary infection rates among EBV, CMV, HHV-6B and HHV-7-infected patients accounted for 44%, 25%, 91% and 57%, respectively. Admission rates of the primary-infected patients were 88% of EBV, 68% of CMV, 66% of HHV-6B and 42% of HHV-7, respectively. Five of the 8 cases (62.5%) of primary EBV-infected patients demonstrated typical clinical course of infectious mononucleosis (IM); however, no IM patient was seen in 9 patients with viral reactivation. No IM case was observed in CMV-infected patients, regardless of primary infection or reactivation. Clinical characteristics were compared between patients with primary HHV-6B and HHV-7 infections because of similarity of clinical features. Average age (1.5 vs. 2.8 years old; P < 0.001), duration of fever (4.5 vs. 2.9 days; P < 0.001), the highest body temperature (40.2 vs. 39.6°C; P < 0.001), and the frequency of typical skin rash (ES) (87% vs. 54%; P < 0.001) were statistically different between the two viral infections. The main reason for admission due to primary HHV-6B and HHV-7 infection was complex-type febrile seizure (58.7 vs. 66.7%; P = 0.705).

Conclusion

The clinical features and disease burden of the 5 human herpesviruses infections were elucidated in the febrile children visiting ER.

Disclosures

All authors: No reported disclosures.
2335. Newborn Dried Blood Spot for Retrospective Diagnosis of Congenital Cytomegalovirus (CMV) Infection: It’s Time for Universal Screening!
Authors: Medoro Alexandra K , Shimamura Masako , Malhotra M D S , Findlen Ursula M , Hounam Gina , Hanlon Cory T , Kaptsan Irina , Adunka Oliver , J. Sanchez Pablo
Published: October 2019

Background

The diagnosis of congenital cytomegalovirus (cCMV) infection requires that CMV be detected in a body fluid before 3 weeks of age. After 3 weeks, a diagnosis of cCMV infection is difficult since one cannot differentiate between prenatal, natal, and postnatal CMV acquisition. Infants who refer on the newborn hearing screen often are diagnosed with hearing loss after 3 weeks of age. Our objective was to describe the use of the newborn dried blood spot (DBS) for detection of CMV DNA in infants who are evaluated for sensorineural hearing loss (SNHL).

Methods

Retrospective review of the electronic health records of infants who were referred to the Neonatal Infectious Disease (NEO-ID) Clinic at Nationwide Children’s Hospital, Columbus, OH since 2015 for evaluation of SNHL. Demographic, clinical, laboratory, and radiographic data were reviewed. With maternal informed consent, the newborn DBS was obtained from the Ohio Department of Health for detection of CMV DNA by polymerase chain reaction (PCR) testing as previously described (Boppana et al. JAMA, 2010).

Results

Eighteen infants (gestational age [mean ± SD], 38 ± 4 weeks; birth weight, 3,094 ± 705 g) with SNHL were referred by Otolaryngology for evaluation of possible cCMV infection; 17 (94%) had referred on the newborn hearing screen. The 18 infants were first tested for CMV at 151 ± 124 days of age (mean ±SD; range, 21–521 days), and 3 (17%) had a positive CMV DBS. Fourteen (78%) of the 18 infants had a positive serum CMV IgG antibody while 5 (63%) of 8 infants had CMV DNA detected in urine by PCR. Of the 3 infants with a positive CMV DBS, 2 were tested for CMV DNA PCR in urine and both were positive. Of the 3 infants, 1 had a negative serum CMV IgG antibody test at 174 days of age but the urine CMV PCR test was positive. In comparison, of 54 infants with cCMV infection confirmed by a positive urine CMV PCR in the first 3 weeks of age, 37 (68%) had a positive CMV DBS.

Conclusion

DBS testing for CMV DNA by PCR testing identified a small minority of infants with SNHL and thus confirming congenital infection. However, the overall sensitivity of CMV DBS testing in our cohort was 68%, suggesting that some infants with SNHL due to congenital CMV infection are missed.

Disclosures

All authors: No reported disclosures.
2356. Increased Clinical Specificity with Ultrasensitive Detection of Clostridioides difficile Toxins: Reduction of Overdiagnosis Compared with Nucleic Acid Amplification Tests
Authors: Sandlund Johanna , Estis Joel , Katzenbach Phoebe , Nolan Niamh , Hinson Kirstie , Herres Jennifer , Pero Troy , Peterson Gwyn , Schumaker Jeung-Mi , Stevig Craig , Warren Rhonda , West Tsubasa , Chow Siu-Kei
Published: October 2019

Background

Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections, resulting in significant morbidity, mortality, and economic burden. Diagnosis of CDI relies on the assessment of clinical presentation and laboratory tests. We have evaluated the clinical performance of ultrasensitive Single Molecule Counting technology for detection of C. difficile toxins A and B.

Methods

Stool specimens from 298 patients with suspected CDI were tested with nucleic acid amplification test (NAAT; BD MAX™ Cdiff assay or Xpert® C. difficile assay) and Singulex Clarity® C. difficile toxins A/B assay. Specimens with discordant results were tested with cell cytotoxicity neutralization assay (CCNA), and results were correlated with disease severity and outcome.

Results

There were 64 NAAT-positive and 234 NAAT-negative samples. Of the 32 NAAT+/Clarity− and 4 NAAT-/Clarity+ samples, there were 26 CCNA− and 4 CCNA- samples, respectively. CDI relapse or overall death was more common in NAAT+/toxin+ patients than in NAAT+/toxin− and NAAT−/toxin− patients, and NAAT+/toxin+ patients were 3.7 times more likely to experience relapse or death (Figure 1). The clinical specificity of Clarity and NAAT was 97.4% and 89.0%, respectively, and overdiagnosis was over three times more common in NAAT+/toxin− than in NAAT+/toxin+ patients (Figure 2). Negative percent agreement between NAAT and Clarity was 98.3%, and positive percent agreement increased from 50.0% to effective 84.2% and 94.1% after CCNA testing and clinical assessment.

Conclusion

The Clarity assay was superior to NAATs in diagnosis of CDI, by reducing overdiagnosis and thereby increasing clinical specificity, and presence of toxins was associated with disease severity and outcome.

Disclosures

All authors: No reported disclosures.
130. Clinical Presentation and Molecular Epidemiology Characterization of Invasive GBS Infection in Nara, Japan from 2007 to 2016
Authors: Hirai Nobuyasu , Kasahara Kei , Ogawa Yoshihiko , Suzuki Yuki , Hishiya Naokuni , Nakano Ryuichi , Yano Hisakazu , Yoshikawa Masahide , Mikasa Keiichi
Published: October 2019

Background

Streptococcus agalactiae (GBS), a leading cause of neonatal infections, also occurs as an invasive infection in elderly people. The aim of this study was to evaluate the clinical aspect of invasive infections and the phenotypic and genetic diversity of GBS isolates to develop better antibiotics treatment and curb the increasing rate of antibiotic resistance in Nara, Japan.

Methods

GBS strains sequentially collected from blood and cerebrospinal fluid cultures between 2007 and 2016 were identified and evaluated for capsular types, multilocus sequence typing (MLST), antibiotic susceptibility, resistant gene, and pulsed-field gel electrophoresis (PFGE). Clinical characteristics were retrospectively collected.

Results

A total of 42 GBS isolates (12 from children and 30 from adults) were collected. In adults, common underlying conditions were malignancy and diabetes, and primary bacteremia was the most common source of infection. In children, 6 were early-onset diseases, 4 were late-onset diseases, and 2 were school children. Overall, the mortality rate was 0% in children and 17% in adults. The serotypes and main clonal complex are summarized in Table 1. Minimum inhibitory concentrations of the antibiotics were also determined (Table 2). The serotypes and resistant genes are shown in Table 3. PFGE revealed serotypes V and VI belonging to ST1, and serotype III belonging to ST335 were highly identical.

Conclusion

In clinical aspects, neonates with early-onset diseases experienced certain disorders during the perinatal period. In adults, serotype Ib, which tends to exhibit levofloxacin resistance, was the most common, followed by serotypes V and VI belonging to ST1; however, they were not observed in children. Contrastingly, serotype III belonging to ST335, which tends to exhibit macrolide resistance, was mainly observed in children. Quinolone among adults and macrolide among the younger generation are widely used as oral antibiotics in Japan. A tendency to use antibiotics affects bacterial flora and induces selectivity of specific clones, thereby causing diseases in the local community. Continuous surveillance is warranted in local areas for appropriate antibiotics treatment and prevent increasing antibiotic-resistant isolates.

Disclosures

All authors: No reported disclosures.
131. Duration of Therapy for the Treatment of Gram-Negative Bloodstream Infections
Authors: Shulder Stephanie , O’Connell Matthew , Agedal Kaitlyn J , Conn Kelly M , Pillinger Kelly E
Published: October 2019

Background

While current guidelines suggest a total treatment duration of 7 to 14 days for gram-negative bloodstream infections (GN-BSI), there is mounting evidence to suggest that shorter durations may be sufficient. This study compared the treatment outcomes of patients who received short duration therapy (6–10 days) with those who received long durations (11–15 days).

Methods

This was a retrospective study of adult patients who grew an aerobic gram-negative organism from a blood culture while admitted at Strong Memorial Hospital between May 2016 and May 2018. The primary outcome was a composite of mortality and relapsed GN-BSI with the same organism within 90 days of index culture. Secondary outcomes included clinical resolution at end of therapy (EOT), length of stay (LOS), 30-day readmission rate, Clostridoides difficile infection (CDI), development of recurrent GN-BSI resistant to prior antibiotic therapy, and development of multi-drug-resistant (MDR) GN-BSI within 90 days. Appropriate therapy was defined as an antibiotic with confirmed in vitro susceptibility that was either parenteral or a highly bioavailable oral antibiotic (fluoroquinolones or sulfamethoxazole–trimethoprim).

Results

Of 600 patients screened, 116 were included in the long duration group and 34 patients in the short-duration group. The majority of patients had a urinary source of infection (59.3%). The primary composite outcome occurred in 11.8% of the short duration group compared with 10.3% in the long (P > 0.999). There was no difference in clinical resolution at EOT, LOS, or rates of CDI, MDR GN-BSI, recurrent GN-BSI resistant to prior therapy, or 30-day readmission. Patients in the long duration group were discharged with longer appropriate outpatient courses (8 days vs. 0.5 days, P < 0.001), which remained significant when including lower bioavailability agents (e.g., oral β lactams) (8 days vs. 5 days, P < 0.001).

Conclusion

There was no difference in clinical outcomes between the long and short duration therapy for treatment of GN-BSI. This study may support shorter treatment durations for uncomplicated GN-BSI, but should be interpreted cautiously given the smaller sample size.

Disclosures

All authors: No reported disclosures.
132. Epidemiology, Antimicrobial Resistance and Predictors of Typhoidal and Non-Typhoidal Salmonella Bacteremia in Victoria, Australia
Authors: Griffin David W J , Tramontana Adrian R , Jaksic Sasha , Wong Jenny S J
Published: October 2019

Background

Salmonella species are major contributors to the global burden of foodborne disease. While typhoidal salmonella (TS) is typically associated with travel in high-income settings, non-typhoidal salmonella (NTS) is more commonly associated with locally acquired diarrhoeal disease. We aimed to assess the epidemiology, antimicrobial resistance (AMR) patterns, and clinical markers of Salmonella bloodstream infections (BSI) in Victoria, Australia.

Methods

We conducted a retrospective audit of blood culture results over a 5.5-year period at a large, private pathology provider, in Victoria, Australia. All Salmonella isolates detected in blood between January 2013 and June 2018 were included. Epidemiological, microbiological, AMR and clinical data were extracted from the pathology record and collated for analysis.

Results

Of 27,546 positive blood cultures, 262 were positive for Salmonella spp. (rate 9.51 per 1,000 positive cultures) in 187 episodes. 113 (60%) were NTS (47.8% S. Typhimurium, 9.7% S. Enteritidis), while 74 (40%) were TS (59% S. Typhi, 41% S. Paratyphi). Patients with TS were younger (median age 29 vs. 65, P < 0.0001), more likely to have traveled [OR 125 (95% CI 28.47, 549], but fewer had a positive stool [OR 0.21 (95% CI 0.08–0.58)] than those with NTS. NTS was associated with a higher median CRP (149 vs. 83, P < 0.001) and more frequently associated with an abnormal white cell count (39% vs. 18%, P = 0.003). Quinolone non-susceptibility was stable with time, and occurred more frequently in TS than NTS (71 vs. 23%, P < 0.0001). Non-susceptibility to Azithromycin was also common in TS (42%), and increasing with time (P = 0.02). Non-susceptibility to ≥1 antibiotic occurred in 54 (73%) of TS, while 24 (32%) had non-susceptibility ≥2. Ceftriaxone resistance occurred infrequently in both NTS and TS (2 vs. 0%, P = 0.5).

Conclusion

Salmonella is an uncommon cause of BSI in our setting, with similar proportions of TS and NTS. Typhoidal isolates were more likely to be associated with travel, and antimicrobial resistance. Despite this, ceftriaxone remains a reliable option for first-line therapy for both TS and NTS. Quinolone resistance remains common, while Azithromycin resistance has increased with time in TS.

Disclosures

All authors: No reported disclosures.
2400. Are Multiple Clostridioides difficile Infections in Pediatric Oncology Patients Related to Recurrence of the Same Isolate or Re-infections with Different isolates?
Authors: Barbar Ruba , Hakim Hana , Hayden Randall , Hayden Randall , Garner Cherilyn D , Brazelton de Cardenas Jessica B , Carroll Karen C , Bourdas Dimitrios , Kimberly. Carroll Shawna
Published: October 2019

Background

Pediatric oncology and hematopoietic stem cell transplant patients (POTP) are at increased risk for Clostridioides difficile infection (CDI) and recurrence. It is unknown whether recurrent CDI is related to the same C. difficile strain as the initial CDI. We describe genomic relatedness of C. difficile strains in patients with multiple CDI using whole-genome sequencing (WGS).

Methods

This was a retrospective cohort study of CDI in POTP in 2016. CDI cases were identified by electronic medical record search for positive C. difficile toxin PCR tests. Patients with multiple CDI episodes were identified. CDI episodes were classified as incident, duplicate or recurrent using National Healthcare Safety Network (NHSN) definitions. Retrieved residual stool specimens were cultured anaerobically, toxin-producing C. difficile isolates were determined using a cell culture cytotoxicity assay with neutralization and WGS was performed followed by core genome MLST (cgMLST). Variability of the isolates was summarized by strain type (ST), and a minimum spanning tree was constructed, defining genomically related isolates as those with <7 allele difference.

Results

Eighteen patients had 51 positive C. difficile samples. CDI were classified as incident in 31 (61%) episodes, recurrent in 18 (36%), and duplicate in 2 (3%). Isolates from 47 (92%) samples were sequenced, identifying 14 different strain types (ST) in 41 (87%) isolates. Of the 31 incident CDI, 13 (42%) episodes occurred 8 weeks or more after the initial incident CDI. Among those 13 incident CDI, 7 (54%) had prior CDI due to a related isolate. Of the 18 recurrent CDIs, 10 (55%) were due to an isolate related to the previous incident CDI and 5 (28%) were due to an isolate unrelated to the incident CDI. The relatedness of the remaining 3 recurrent episodes could not be evaluated because no isolate was available for sequence analysis.

Conclusion

CDI classification of incident vs. recurrent infection using NHSN definition might be not applicable in POTP. WGS showed that more than half of CDI episodes classified as incident were actually a recurrence of a previous C. difficile strain. Similarly, some CDI episodes classified as recurrent were actually re-infection with a different stain.

Disclosures

Randall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board
2415. Oral Vancomycin for Secondary Prophylaxis of Clostridium difficile Infections among High-risk Patients
Authors: Lew Alison , Rao Krishna , Tribble Alison , Klein Kristin , Ateya Mohammad , Nagel Jerod
Published: October 2019

Background

Clostridium difficile infection (CDI) is associated with high rates of recurrence, and major risk factors for recurrence include prior CDI episode(s) and antibiotic exposure. Prior studies concluded a reduction in CDI recurrence using oral vancomycin for prophylaxis (ppx), but were limited by prescriber bias and inclusion of all hospitalized adult patients with prior CDI and receipt of systemic antibiotics. We sought to determine whether or not oral vancomycin prophylaxis reduced CDI recurrence in high-risk patients.

Methods

This retrospective cohort study included patients > 2 years of age who had at least 2 episodes of CDI within the last year prior to broad-spectrum antibiotic exposure. The ppx cohort included patients who received oral vancomycin for > 50% of the duration of broad-spectrum antibiotic therapy, and the no ppx cohort included patients who received no oral vancomycin while on broad-spectrum antibiotics. Cohorts were compared via a univariate analysis. A Kaplan–Meier analysis was used to evaluate the time-to-event for development of CDI.

Results

Of 108 patients who met inclusion criteria, 88 patients were included in the no ppx cohort and 20 patients in the ppx cohort. The primary outcome of CDI incidence was numerically lower in the ppx cohort [13 (14.8%) vs. 2 (10%), p = 0.733]. Secondary outcomes within 12 weeks of broad-spectrum antibiotic initiation were similar between cohorts. The mean time from broad-spectrum antibiotic initiation to CDI recurrence was longer among the ppx cohort, suggesting a delay in time to CDI recurrence (29 + 25.9 vs. 57.5 + 26.1 days, p = 0.171). This delay led to a lower incidence of hospital acquired (HA) CDI in the ppx cohort [4 (30.8%) vs. 0 (0%), P > 0.99]. The Kaplan–Meier analysis (Figure 1) demonstrated no significant difference in time-to-event of CDI, p = 0.70.

Conclusion

The use of oral vancomycin for secondary ppx of CDI was not shown to have a statistically significant difference in CDI recurrence compared with no ppx in this study. However, this may be due to the low sample size in the ppx cohort and low CDI event rates. The trend toward a delay in CDI recurrence and reduction in HA-CDI with the use of oral vancomycin is hypothesis generating. Further controlled studies are warranted to confirm the role of oral vancomycin for secondary ppx of CDI.

Disclosures

All authors: No reported disclosures.
137. Impact of Rapid Susceptibility Testing on Outcomes in Patients with Bacteremia
Authors: Megherea Oxana , Patel Ruchi , Lake Patrick , Bicking Keri , Sebti Rani
Published: October 2019

Background

Early organism identification via rapid diagnostics has been shown to reduce time to effective antimicrobial therapy and improve patient outcomes in patients with bacteremia, but antimicrobial susceptibility testing is still required to optimize therapy. The objective of this study was to determine the impact of an institution-specific rapid susceptibility testing method on outcomes in patients with bacteremia.

Methods

This was a retrospective pre- and post-intervention study of 100 adult patients with bacteremia. Patients were excluded if they had polymicrobial infection, fungemia, blood cultures collected at outside hospitals, or if they expired prior to susceptibility results. Patients were identified through a report containing positive blood cultures from October 2017 to February 2018 (pre-intervention [PrI]) and October 2018 to February 2019 (post-intervention [PoI]). The primary endpoint was the rate of clinical failure (a composite of 28-day mortality or bacteremia persisting greater than 6 days). Secondary endpoints included microbiologic outcomes, time to effective and optimal therapy, length of stay (LOS) and therapy adjustments.

Results

Baseline characteristics were similar between groups; a third of the patients were immunosuppressed (Table 1). The most common sources of infection were urinary and intra-abdominal, and the most common organisms identified were E.coli and Klebsiella spp. No significant difference in the rate of clinical failure was identified between PrI and PoI (24% vs. 18%, P = 0.6242) (Table 2). In the PoI, the time to identification, susceptibility results, and effective therapy was significantly shorter with similar time to optimal therapy and LOS. In the PoI, antimicrobial stewardship program (ASP) interventions were made significantly sooner after susceptibility results.

Conclusion

In this small, retrospective, single-center study, the implementation of a rapid susceptibility testing method was associated with reduced time to susceptibility results and more rapid interventions by the ASP, but no difference in the rate of clinical failure or time to optimal therapy was identified.

Disclosures

All authors: No reported disclosures.
2451. Hospital-acquired Legionella Pneumonia Outbreak at an Academic Medical Center. A Case–control Study of Risk Factors
Authors: Kessler Michael , Osman Fay , Pop-Vicas Aurora E , Safdar Nasia
Published: October 2019

Background

An outbreak of hospital-acquired Legionella pneumonia, associated with potable water contamination, occurred at our university hospital in November of 2018, despite a longstanding copper-silver ionization system. We conducted a case–control study to examine risk factors for Legionella pneumonia.

Methods

We matched controls to cases by dates of admission, hospital ward, and admitting service, in a 4:1 ratio. We reviewed patient charts for potential risk factors and exposures, and summarized demographic information using descriptive analyses. Univariate and multiple logistic regression analyses were also performed. We used pulsed-field gel electrophoresis for molecular typing of isolates from patient respiratory samples and hospital water samples.

Results

We identified 13 cases of nosocomial legionella pneumonia over a one-month period (Figure 1), with 8 males, 5 females, and a mean age of 63 years. The average time to diagnosis was 19 days following admission. Six patients were transplant recipients – two had solid organ, and six had bone marrow transplant. Urinary Legionella antigen was positive in all cases. Table 1 shows predictors for Legionella pneumonia in univariate analyses. Current smoking (OR = 7.5, 95% CI [1.11 – 50.84], p = 0.03], pre-admission steroid prescription (OR = 6.5, 95% CI [1.65 – 26.20], p = 0.008], documentation of shower (OR = 6.2, 95% CI [1.54 – 25.82], p = 0.01], and number of showers prior to hyper-chlorination (OR = 1.45, 95% CI [1.03 – 2.04], p = 0.03] were significant risk factors on univariate analysis. The multiple regression model was also significant (P < 0.001) with all of the above-identified predictors (Table 2). Molecular typing found Legionella strains from patient respiratory samples and water samples to be identical. Multiple interventions, including restriction of showering, hyper-chlorination, and optimization of water flow through the copper-silver ionization system were implemented, and were successful in mitigating the outbreak.

Conclusion

We found showering to be a modifiable risk factor for Legionella pneumonia in this outbreak. Interventions to reduce this risk might include point of use filters in showers in high-risk populations.

Disclosures

All authors: No reported disclosures.
2462. Public Health Response to Contain the First Outbreak of New Delhi Metallo-β-Lactamase-Producing Klebsiella pneumoniae in Minnesota
Authors: VonBank Brittany , O’Malley Sean , Snippes Vagnone Paula , Ellen Bennett Mary , Hale Tammy , Walters Jacy , Lynfield Ruth
Published: October 2019

Background

Carbapenem-resistant Enterobacteriaceae (CRE) producing the New Delhi-metallo-β-lactamase (NDM) carbapenemase are uncommon in the United States but are a serious threat for untreatable antibiotic-resistant infections. In Minnesota (MN), NDM-CRE is typically associated with receipt of healthcare abroad. We describe the public health response to contain the first outbreak of NDM-CRE in MN.

Methods

CRE is reportable, with isolate submission to the MN Department of Health (MDH) for MALDI-TOF identification, phenotypic carbapenemase production testing, and PCR for carbapenemase genes. On December 24, 2018, MDH identified a case of NDM-K. pneumoniae in a long-term care facility (LTCF) without travel. MDH initiated an investigation. We defined a case as having NDM-K. pneumoniae matching the outbreak PFGE pattern from a clinical or surveillance culture. Cases were identified through surveillance, point prevalence survey (PPS) rectal swab colonization testing, and PFGE at MDH. MDH collected a healthcare exposure history for all cases. A containment response occurred in any facility where a case received healthcare in the 30 days prior.

Results

Nine cases of clonal NDM-K. pneumoniae with specimen collection dates between December 24, 2018 and March 26, 2019 were identified; 8 were residents of LTCF A and 1 was a roommate in LTCF B of a former LTCF A resident. PPS testing of 260 healthcare contacts occurred in 6 facilities, including LTCF A, LTCF B, and 4 acute care hospitals (ACH) that accepted LTCF A transfers; 7/9 cases were identified through PPS and 2/9 cases were identified through CRE surveillance. One case from LTCF A was identified in an ACH, but PPS did not identify transmission in ACHs. MDH conducted on-site infection control assessments in 2 LTCFs, identified numerous infection control (IC) lapses at LTCF A, and provided telephone IC consultation to 4 ACHs.

Conclusion

Surveillance and PPS uncovered an outbreak of NDM CRE in 2 LTCFs. Patient transfers led to a regional public health response lasting several months that included IC consultation and additional PPS. Intervention to coordinate containment responses among interconnected healthcare facilities is critical to containing the spread of novel resistance mechanisms in the United States.

Disclosures

All authors: No reported disclosures.
2471. Review of Methicillin-Resistant Staphylococcus aureus, Clostridium difficile and Acquired Bloodstream Infections Across all United Kingdom Intensive Care Units following Implementation of a Statutory National Infection Control Campaign.
Authors: Batra Rahul , Edgeworth Jonathan , Wulff Jerome , Harrison David
Published: October 2019

Background

Methicillin-Resistant Staphylococcus aureus (MRSA) and C. difficile infection have reduced across the UK National Health Service in the last decade following implementation of an infection control campaign. The national impact on hospital-acquired infections in the ICU however has not been comprehensively documented.

Methods

Data on MRSA, C. difficile, vancomycin-resistant Enterococcus (VRE) and ICU-acquired bloodstream infection (UABSIs) were analyzed from 1,189,142 consecutive patients from 2007 to 2016 recorded prospectively and standardized by highly trained assessors. Initial coverage was 139 ICUs increasing to 275 ICUs representing 100% of general, adult UK ICUs.

Results

ICU MRSA and C. difficile admissions and acquisitions per 1000 patients decreased between 2007 and 2012 (MRSA admissions 38.8 to 13.1; acquisitions 25.4 to 4.1; C. difficile admissions 10.6 to 4.2; acquisitions 11.1 to 3.5), whereas VRE admissions and acquisitions increased from 1.9 to 5.3 and 1.5 to 5.9, respectively. There were 13,114 UABSIs in 1.8% patients staying >48 hours. UABSIs fell from 7.3 (95% CI 6.9–7.6) to 1.6 (95% CI 1.5–1.7)/1,000 bed-days between 2007 and 2012. Adjusting for patient admission and ICU factors the IRR was 0.21 (95% CI 0.19–0.23, P < 0.001) from 2007 to 2016. Reductions in UABSIs were seen for all main organisms excluding VRE with greatest reductions for MRSA (97%), Pseudomonas aeruginosa (80%), S. aureus (77%) and Candida spp. (71%) but lower reductions for E. coli (54%) and Klebsiella (42%).

Conclusion

Large decreases in ICU-acquired infections occurred across the UK ICU network between 2007 and 2012 linked with the first few years of the national infection control campaign, but rates have been static since. Further reductions in ICU will likely require a new intervention framework.

Disclosures

All authors: No reported disclosures.
2495. Pharmacokinetics of Cabotegravir (CAB) and Rilpivirine (RPV) Long-Acting (LA) Injectables in HIV-infected Individuals through 48 Weeks in the FLAIR and ATLAS Phase 3 Studies
Authors: Patel Parul , Ford Susan L , Crauwels Herta , Han Kelong , Rossenu Stefaan , Neyens Martine , Griffith Sandy , Hudson Krischan J , Margolis David , Baker Mark , Williams Peter , Spreen William
Published: October 2019

Background

Monthly injectable CAB LA + RPV LA was noninferior to daily oral 3-drug antiretroviral therapy in HIV-1 virologically suppressed adults. CAB and RPV pharmacokinetics (PK) were assessed during the 48 Week maintenance period of the ATLAS and FLAIR Phase 3 studies.

Methods

Patients received oral CAB 30 mg + RPV 25 mg once daily for 4 weeks to assess individual tolerability prior to intramuscular (IM) injections of CAB LA 600 mg + RPV LA 900 mg followed by CAB LA 400 mg + RPV LA 600 mg every 4 weeks. Plasma CAB and RPV concentrations were measured pre-and post-dose at select visits using validated analytical methods.

Results

Baseline demographics for the pooled randomized ATLAS and FLAIR population (n = 591, LA arms) were: median age 38 years, 27% female, 18% African American, median BMI 25 kg/m2 (range: 15 – 51). CAB and RPV plasma concentrations at select visits are summarized in the table. After initial IM doses, mean CAB and RPV troughs were well above their respective in vitro PA-IC90 values (CAB, 0.166 μg/mL; RPV 12 ng/mL). At Week 48, mean CAB troughs were 17x PA-IC90 and between oral CAB 10–30 mg exposures. Similarly, mean RPV troughs were 7x PA-IC90 and remained within the exposure range following oral RPV 25 mg once daily. 80% of RPV steady-state was achieved by Week 48 and 100% for CAB by Week 44. Initial CAB concentrations in females and those with BMI ≥30 kg/m2 were lower due to slower absorption but this difference resolved by Week 48. For RPV, there was no absorption difference by gender or BMI.

Conclusion

CAB and RPV PK were consistent between studies achieving therapeutic concentrations within the first dosing interval that steadily increased over time through Week 48, for both males and females and irrespective of BMI. CAB LA + RPV LA provided compatible PK profiles following monthly IM dosing in a diverse patient population through 48 weeks.

Disclosures

All authors: No reported disclosures.
2510. Systematic Literature Review of Multiclass Resistance in Heavily Treatment Experienced Persons with HIV
Authors: Mauskopf Josephine , Fernandez Maria M , Ghosn Jade , Sax Paul , Priest Julie , Garris Cindy , Clark Andrew
Published: October 2019

Background

Because of progress in antiretroviral therapy (ART), fewer people with HIV experience virologic failure with multiclass resistance. We sought to estimate the prevalence of multiclass resistance since the introduction of INSTI-based regimens using a systematic literature review.

Methods

A systematic literature search using PubMed, Embase, and the Cochrane Library was conducted of articles published since 2008, the year when INSTI-based regimens for treatment-experienced people with HIV became widely used. Bibliographies of existing literature reviews, websites of European and International organizations reporting data on HIV and AIDS, and abstracts presented from 2016–2018 at conferences were searched to identify additional relevant studies. Using predefined criteria, two reviewers independently reviewed studies reporting multiclass (three-class or greater) resistance in persons with HIV infection who are treatment experienced and were either perinatally infected or infected as adults. Studies from Western Europe, Australia, Canada and the United States (US) using any type of resistance definitions and resistance tests were included.

Results

A total of 441 unique articles were identified, 343 were excluded during level 1 screening and 98 articles were included for full-text review. A total of 34 articles (11 US studies, 3 from Canada, 1 from Australia, and 19 from Western European countries.) met the inclusion criteria and were included in data extraction analysis. Over the past decade, a modest decrease in the prevalence of three-class (NNRTI, NRTI, PI) resistance was observed in studies from the United States and Canada, ranging from 8.3% in 2009 to 6.7% in 2014 (Figure 1). Western European countries and Australia showed similar trends. The prevalence of 4-class resistance (including INSTIs) with virologic failure in the current treatment era is low, less than 2% (Figure 2).

Conclusion

The prevalence of multiclass resistance has decreased over the past decade, with three-class resistance continuing to decline and four-class resistance rare. Although the population with treatment failure and no viable options for a suppressive regimen is currently small, this group of people with HIV are in urgent need of novel treatment options.

Disclosures

All authors: No reported disclosures.