bluuebunny/crossref_metadata_2025_split huggingface dataset:
793. Diagnostic Accuracy of Single vs. Multiple Gene Xpert for Discontinuation of Airborne Infection Isolation in Suspected Pulmonary Tuberculosis Patients at a US Safety-Net Hospital
Authors: Seth Bhavna , Bernardo John , Sulis Carol 
Published: November 2018

Abstract

Background
Patients suspected to have pulmonary tuberculosis (PTB) undergo serial sputum analysis under airborne infection isolation (AII). The US FDA approved the Cepheid GeneXpert-MTB-Rif® to support removing patients from AII. The FDA requires that “either one or two” separate sputum specimens be examined. To clarify this statement, the National Tuberculosis Controllers’ Association and the Association of Public Health Laboratories published guidelines that recommend that two sputum specimens be used and recommend that each institution examine their own data to determine whether one specimen is sufficient. Most patients in low prevalence settings do not have PTB yet are tested several times; an optimal testing strategy will reduce unnecessary isolation and related expenses. We sought to determine the diagnostic accuracy of a single vs. two sputum samples for Xpert MTB/RIF in discharging suspected PTB patients from AII.

Methods
Retrospective review of patients admitted between September 2016 to January 2018 was undertaken to identify sensitivity, specificity, positive and negative predictive values, for MTB gene Xpert in comparison to Mycobacterial culture as the gold standard. We further analyzed whether a larger number of such tests improved diagnostic yield for PTB.

Results
One hundred seventy-one patients, 17.5% of whom were HIV+, mostly of non-US origins (64%), provided 312 samples for Xpert MTB/RIF, of which 26 were Xpert-positive. These 26 samples came from 15 patients, 14 of whom were diagnosed using the first sample tested with Xpert MTB/RIF. Sensitivity and specificity of the first sample tested with Xpert MTB/RIF were more than those for the first two samples considered together or for all tested samples. Of these 15 positive cases, 13 were confirmed on sputum culture; 10 were positive from the first, one from the second, and two from the third sputum samples cultured.

Conclusion
Patients suspected to have PTB at our facility can be rapidly and accurately discharged from AII after testing a single sputum sample for MTB/RIF Xpert.

Disclosures
All authors: No reported disclosures.
796. Treatment of Latent Tuberculosis Infection in a Refugee Population
Authors: Herchline Thomas , Trent Ashley 
Published: November 2018

Abstract

Background
As tuberculosis (TB) rates decline in the United States, many new cases are among individuals who migrated from countries with a high incidence of TB. Public Health – Dayton & Montgomery County screens incoming refugees for active and latent TB. The objective of this study was to estimate the number of active cases of TB prevented through screening and treatment of LTBI.

Methods
Data were collected through retrospective chart review of refugee seen between July 1, 2011 and June 30, 2015. Refugees younger than 5 years old were excluded. New cases of active TB identified from July 1, 2011 through August 31, 2017 were reviewed for cases in refugees. The number of expected new, active TB cases was 100–150 per 100,000 person-years of follow-up (McBride, MJA 2012).

Results
A total of 607 charts were reviewed: 373 were males, 234 females. Ages ranged from 6 to 77 years, average 27.4 years. The leading countries of origin were Kenya (79), Iraq (68), Rwanda (59), Ethiopia (55), and Nepal (52). There were three cases of active TB diagnosed on initial evaluation; there were no cases of active TB diagnosed in 2,341 person-years of follow-up. Among refugees, 23.1% had positive T-Spots; highest in the 36–45 age group (35.0%) and refugees from South to East Asia (29.6%). LTBI was diagnosed in 21.1% of refugees; highest in the 46–55 age group (33.3%) and refugees from South to East Asia (27.8%). The majority of subjects with LTBI completed treatment (78.9%). Treatment completion was highest among the 13–17 age group (100.0%), males (81.4%), and refugees from South to East Asia (92.9%); lowest in the &gt;56 age group (40.0%) and European region (50.0%).

Conclusion
Based on published data, an estimated 2.3–3.5 active cases of TB were prevented through this program. Treatment completion rates were higher than reported for non-refugee populations. Results indicate the program is effective at screening for and preventing development of active TB.

Disclosures
All authors: No reported disclosures.
993. Combining Key Residues of the Russian and US Live-Attenuated Influenza Viruses for a More Attenuated Virus
Authors: Smith Andrew , Rodriguez-Garcia Laura , El Ghouayel Maya , Martinez-Sobrido Luis , Dewhurst Stephen 
Published: November 2018

Abstract

Background
The Live Attenuated Influenza Virus (LAIV) used in the United States is based on the cold-passaged A/AnnArbor/6/60 strain (AA). An alternative LAIV (Len), developed from the cold-passaged A/Leningrad/134/17/57 strain, has also been used in some countries outside the United States. Recent concerns with the efficacy and safety of the current US LAIV warrant the development of an improved LAIV.

Methods
We used in vitro minireplicon and multicycle viral growth assays to analyze the combined effects of polymerase mutations from LAIV (AA) and LAIV (Len) on the phenotype of PR8. Mini-replicon assays were performed in HEK-293T cells with firefly luciferase under the control of the influenza virus NP promoter; we controlled for cell density with a constitutively active Renilla luciferase. Multicycle growth curve experiments were performed at 33°C, 37°C, and 39°C in MDCK cells with an m.o.i. of 0.001. Mean values for triplicate infections at 12, 24, 48, and 72 hours were plotted as TCID50/mL.

Results
Control experiments showed replication of PR8 (AA) and PR8 (Len) in MDCK cells was significantly decreased as compared with WT PR8 at 37°C and 39°C at 24–48 hour time points, but not at 33C (the temperature of nasal passages). We found that polymerase activity was up to 3 logs more temperature-sensitive (ts) at 37°C and 39°C with the combined Len and AA mutations using the mini-replicon assay. In the growth curve experiments, the combined Len and AA mutations conferred up to a 4-log decrease in replication levels at 37°C as compared with PR8 (Len) and an even greater decrease compared with PR8 (AA).

Conclusion
Our findings suggest combining the AA and Len LAIV polymerase mutations decreases LAIV replication at body temperature (37°C), as compared with either LAIV alone. This could be useful in developing an improved LAIV that is safer in vulnerable hosts (e.g., children under the age of 2 who may be vulnerable to wheezing), while also permitting dose escalation that might result in greater efficacy.
Minireplicon assay.

Polymerase activity of combination mutants.

Multicycle replication kinetics of combination mutants (red) against PR8 Len (black) at 33C (solid), 37C (dashed) and 39C (dotted).

Disclosures
All authors: No reported disclosures.
1005. HIV-Associated Bloodstream Infection (BSI): Trends Over 7 Years
Authors: Hooshmand Babak , Witherell Rebeca , Riederer Kathleen , Johnson Leonard , Khatib Riad 
Published: November 2018

Abstract

Background
Patients with HIV are known to be at risk for bacteremia. Whether the type of organisms changed over time is uncertain. We present a review of bacteremia in HIV-patients during 2010–2016.

Methods
We reviewed blood culture (BC) results (January 1, 2010–December 31, 2016), selected patients with BSI, defined their HIV status, the place of onset (community onset [CO]: 0–3 days after admission; hospital onset [HO]: ≥4 days), patient demographics, the source and organism distribution and compared patients with and without HIV.

Results
We encountered 5,179 BSI episodes, 93 were among 73 HIV-patients (table). HIV patients were younger, and more likely to be African Americans. Majority of cases were community onset (79.1% and 74.5% in cases with/without HIV, respectively). The three most common organisms in HIV patients were Staphylococcus aureus (SA), Escherichia coli (EC) and Streptococcus pneumoniae (SPN) and in non-HIV patients SA, EC, and Klebsiella pneumoniae (KP). While the rate of SA (25.3%–22.0%), SPN (2%–3%), and KP (10.2%–8.4%) remained stable during the study period, EC rate increased (18.5–25.7; P = 0.002). HIV patients were more likely to have the respiratory tract as the source of BSI.

Conclusion
HIV-patients remain at higher risk for SPN and to have a respiratory source of BSI but the top causes of BSI in patients with and without HIV are SA and EC. Whether the higher rate of SPN among HIV patients is related to poor compliance with vaccination or suboptimal immune status is uncertain. Further studies are needed to compare pneumococcal vaccination compliance rate in patients with or without HIV.
African Americans; vascular; Soft tissue/bone; urinary tract; respiratory.

Disclosures
All authors: No reported disclosures.
1011. Sepsis and Secondary Hemophagocytic Lymphohistiocytosis
Authors: Fazal Farhan , Wig Naveet , Soneja Manish , Mitra Dipendra K , Panda Sk , Satpathy Gita , Vikram Naval Kishore , Pandey R M , Chaturvedi P K 
Published: November 2018

Abstract

Background
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition diagnosed by HLH 2004 criteria. This criterion has common clinical and laboratory features with sepsis and tropical fevers, but there is marked difference in management and outcome of these two entities. The study is conducted to know whether there is any difference in the clinico-laboratory features, management, and outcome of sepsis with or without secondary HLH.

Methods
This is a prospective observational study where patients presenting with sepsis and bicytopenia are included. The patients underwent relevant investigations according to 2004 HLH diagnostic criteria. The patients are divided into sepsis with or without HLH. The underlying etiology, treatment, and outcome of the two groups are analysed.

Results
Fifty sepsis patients are included in the study, out of which 28 fulfilled the HLH diagnostic criteria which comprised of 18 men and 10 women. The etiology were bacterial (three enteric fever, three tuberculosis, two scrub typhus, one Staphylococcal aureus), viral (one dengue fever, two HIV, two encephalitis), fungal (one aspergillosis, one mucormycosis, two others), parasites (three malaria, one leishmania) malignancy (two hodgkin lymphoma, one non-Hodgkins lymphoma), and unknown etiology in six patients, with &gt;1 etiology in three patients (Figure 2). The percentage of each criterion fulfilled in both groups is given in Figure 1, showing an increased occurrence of splenomegaly, low NK cell activity, hypertriglyceridemia in HLH patients. Steroids along with supportive treatment was given to 53% and etoposide was added in 7%. Treatment for underlying etiology alone without immunosuppressive treatment was given in 39%. The mortality in those with HLH vs. without HLH was 42% and 31%, respectively. The median duration of hospital stay was 18 and 36 days in HLH and without HLH group, respectively.

Conclusion
HLH should be suspected in sepsis patients with bicytopenia specially in tropical fevers. There is increased mortality if the sepsis patients fulfil HLH criteria. Early diagnosis and management is of paramount importance.

Disclosures
All authors: No reported disclosures.
1028. Synergizing Infectious Diseases and Substance Use Treatment to Improve the Outcomes of Endocarditis in People Who Inject Drugs at a Large Academic Hospital
Authors: Meisner Jessica , Koenig Helen , Tebas Pablo 
Published: November 2018

Abstract

Background
Philadelphia is at the epicenter of the urban opioid epidemic: currently more than 70,000 individuals use heroin and in the year 2017 there were 1,200 overdose deaths. Endocarditis in patients with opioid use disorder (OUD) requires long hospitalizations for IV antibiotic use that delays the initiation of rehabilitation and opioid replacement therapy. We decided to implement an integrative approach to both problems. During the first step (this study), we evaluated the current care and identified areas that could be improved and in a second step developed an intervention with the goal to improve long-term outcomes.

Methods
We conducted a retrospective chart review of patients admitted to the Hospital of University of Pennsylvania with infective endocarditis (IE) and OUD from July 2016 to June 2017. Patients were identified via ICD-10 codes for infective endocarditis and substance use.

Results
Among the 669 admissions for patients with a diagnosis of OUD, 37 had IE (33 unique patients). Seventy-three percent of those required valve replacement surgery. Mean length of stay was 32 days (IQR 16, 49), 10% left against medical advice. The overall readmission rate was 55%. The most common valves involved were tricuspid with 20 (54%) and 10 aortic (27%). On discharge, only 6 (18%) of the patients were discharged on Medication Assisted Treatment (MAT), 14 (38%) were discharged with prescriptions for narcotics, and zero for naloxone. HIV testing was not performed on 7 (21%) patients and 1 patient was HIV positive. Twenty-three (70%) patients were antibody positive for HCV, seven (21%) were antibody negative, three (9%) were not tested. S. aureus was the causal pathogen in 25 (76%) cases, with seven (19%) being methicillin resistant.

Conclusion
The lack of a systematic approach to management of patients with OUD admitted for endocarditis represents a missed opportunity to improve the care and outcomes of patients with OUD in regards to withdrawal, relapse prevention and harm reduction. We designed, implemented, and started to evauate an intervention to initiate MAT in conjuction with the managament of the infectious diseases complications and a standardized approach to screening these patients for HIV, hepatitis B/C and offering PrEP, HIV therapy, and/or HCV therapy where appropriate.

Disclosures
All authors: No reported disclosures.
1039. Surveillance Blood Cultures Associated With Decreased Mortality in Gram-Negative Bacteremia
Authors: Maskarinec Stacey A , Van Duin David , Ruffin Felicia , Fowler Jr Vance G , Thaden Joshua T 
Published: November 2018

Abstract

Background
Prior studies have suggested that surveillance blood cultures (SBCs) may not be indicated in the setting of Gram-negative bacteremia (GNB). However, it is unclear how particular microbial species influence the need for SBCs in GNB.

Methods
We conducted a prospective cohort study of inpatients at Duke with Staphylococcus aureus bacteremia (SAB) and GNB from 2002–2015. Patients who died &lt;24 hours from the first positive blood culture were excluded. Patients provided written informed consent. SBCs were defined as a blood culture drawn from 24 hours to 7 days from initial positive blood culture. Persistent bacteremia was defined as a positive SBC with the same organism. Statistical testing included Fishers exact and chi-square tests.

Results
There were 2856 episodes of bacteremia over the study period (SAB: 1,147 [40%]; GNB: 1,709 [60%]). SBCs were drawn in 87% (1,003/1,147) of SAB patients and 64% (1,097/1,709) of GNB patients. SBC rates varied by GNB species (P &lt; 0.001), being more commonly drawn for those patients with Pseudomonas bacteremia (128/159 [80%]) than those with Escherichia bacteremia (377/592 [62%]). In GNB, acquisition of SBCs, regardless of positivity, was associated with decreased in-hospital mortality (177/1,173 [15%] vs. 109/536 [20%]; P = 0.008). The in-hospital mortality benefit associated with SBCs varied with GNB species, including Pseudomonas (30/128 [23%] vs. 14/31 [45%]; P = 0.02) and Escherichia (33/377 [9%] vs. 37/215 [17%]; P = 0.003). In-hospital mortality in those with SAB was also lower when SBCs were drawn (143/1003 [14%] vs. 46/144 [32%]; P = 0.0001) (figure). In GNB, positive SBCs, relative to negative SBCs, was associated with increased in-hospital mortality (44/217 [20%] vs. 133/956 [14%]; P = 0.02). Persistent bacteremia occurred in 49% (494/1003) of SAB patients and 20% (217/1097) of GNB patients with SBCs. Persistent bacteremia risk differed by GNB species (P = 0.004), and was highest among those with Stenotrophomonas maltophilia (9/19 [47%]) or Serratia (24/76 [31%]).

Conclusion
Acquisition of SBCs in patients with GNB was associated with decreased mortality, and this was driven in part by species-specific differences.

Disclosures
D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee. V. G. Fowler Jr., Merck, Cerexa/Actavis, Pfizer, Advanced Liquid Logis, NIH, MedImmune, Basilea, Karius, Contrafect, Regneron, Genentech, Affinergy, Locus, Medical Surface, Inc., Achaogen, Astellas, Arsanis, Bayer, Cubist, Debiopharm, Durata, Grifols, Medicines Co, Novartis: Collaborator, Consultant and Scientific Advisor, Consulting fee, Research grant and Research support.
1040. Comparative Characteristics of Patients With Pseudomonas Bacteremia Receiving Intravenous Only vs. Intravenous Followed by Oral Therapy
Authors: Vu Trung , Yang Linda , Hopkins Teri , Frei Christopher R , Cadena Jose , Walter Elizabeth 
Published: November 2018

Abstract

Background
There have been few studies on treatment approaches to Pseudomonas bacteremia and transition from intravenous (IV) to oral (PO) therapy. The objective of this study was to determine whether IV to PO switch therapy was associated with worse 30-day mortality than IV only therapy for patients with Pseudomonas bacteremia.

Methods
This was a retrospective cohort study comparing patients with ciprofloxacin-susceptible Pseudomonas bacteremia treated with IV only to those transitioned from IV to PO switch therapy. We evaluated 153 consecutive patients from January 2008 to October 2017; of those, 119 (78%) had ciprofloxacin-susceptible Pseudomonas. We excluded 68 patients due to polymicrobial bacteremia, &lt;3 days, or &gt;21 days of therapy. This left 54 patients for evaluation, 29 of whom received IV only, and 25 with IV to PO switch therapy.

Results
Median patient age was 66 years for both groups. IV only therapy was associated with Hispanic ethnicity (48% vs. 28%, P = 0.0271, hospital-acquired infection (52% vs. 13%, P = 0.0035), Pitt bacteremia score (median [interquartile range] of 3 [2–3] vs. 1 [0–2], P = 0.0007), duration of IV therapy (median [interquartile range] of 11 [7–14] vs. 4 [2–6], P &lt; 0.0001), and 30-day mortality (31% vs. 0%, P = 0.0023). The IV only group was more likely to have an associated diagnosis of pneumonia (44% vs. 16%, P = 0.0264) and less likely to have an associated diagnosis of urinary tract infection (17% vs. 60%, P = 0.0021). In a multivariate analysis, with IV only vs. IV to PO switch therapy as the independent variable, mortality as the dependent variable, and pneumonia and UTI as covariates, IV only was independently associated with mortality (P = 0.0006).

Conclusion
Patients on IV only therapy were more likely to die at 30 days than those on IV to PO switch therapy, when accounting for differences in diagnosis of pneumonia and UTI, suggesting clinician recognition of increased severity of illness in the IV only group.

Disclosures
All authors: No reported disclosures.
1047. Global Surveillance: Susceptibility of Ceftolozane–Tazobactam Against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa Isolates Collected From Bloodstream Infections in the United States From 2015 to 2017
Authors: Arends S J Ryan , Shortridge Dee , Castanheira Mariana , Streit Jennifer M , Flamm Robert K 
Published: November 2018

Abstract

Background
Ceftolozane–tazobactam (C-T) is an antibacterial combination of a novel antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicines Agency in 2015 to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors Gram-negative (GN) isolates resistant to C-T worldwide. In the current study, isolates were collected from patients hospitalized with bloodstream infections (BSIs) from 2015 to 2017 within the United States.

Methods
A total of 3,377 prevalence-based BSI GN isolates, including Escherichia coli (EC; 1,422), Klebsiella pneumoniae (KPN, 630), and Pseudomonas aeruginosa (PSA; 344), were collected during 2015 to 2017 from 32 PACTS hospitals in the United States. Isolates were tested for C-T susceptibility by CLSI broth microdilution method in a central monitoring laboratory (JMI Laboratories). Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MEM), and piperacillin–tazobactam (TZP). Antibiotic-resistant phenotypes analyzed (CLSI, 2018) for EC and KPN included carbapenem-R (CR) and non-CR extended-spectrum β-lactamase (ESBL); as well as CAZ-nonsusceptible (CAZ-NS), MEM-NS, and COL-NS PSA.

Results
Of the 3,377 BSI GN isolates, 3,219 (95.3%) had a C-T MIC ≤ 4 mg/L. The three most prevalent GN species isolated from BSIs were EC (42.1%), KPN (18.7%), and PSA (10.2%). The %S of C-T and comparators for the top three pathogens are shown in the table. C-T showed activity against these isolates with %S of ≥96.0% against all three species. Of the comparators tested, AMK and COL also had high %S against these isolates.

Conclusion
C-T demonstrated activity against the most prevalent contemporary GN isolates from BSIs in the US. C-T was the only beta-lactam that had ≥96%S against all three species: EC, KPN, and PSA. For PSA, C-T maintained activity (&gt;90%S) against isolates resistant to CAZ, TZP, and MEM. These data suggest that C-T may be a useful treatment for GN BSI.

Disclosures
S. J. R. Arends, Merck: Research Contractor, Research support. D. Shortridge, Merck: Research Contractor, Research support. M. Castanheira, Merck: Research Contractor, Research support. J. M. Streit, Merck: Research Contractor, Research support. R. K. Flamm, Merck: Research Contractor, Research support.