bluuebunny/crossref_metadata_2025 huggingface dataset:
789. Comparison of Interferon-γ Release Assays (IGRAs) for Diagnosis of Latent or Active Tuberculosis in Cancer Patients
Authors: Kulkarni Prathit , Kmeid Joumana , Batista Marjorie , El Chaer Firas , Ariza-Heredia Ella , Graviss Edward A , Mulanovich Victor E , Chemaly Roy F
Published: November 2018

Background

Patients with certain types of cancer are at increased risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (ATB) because of immunosuppression. The purpose of this study was to compare the utility of the two commonly used IGRAs, QuantiFERON-TB Gold® (QFT) and T-spot.TB® (T-spot.TB), for diagnosis of LTBI or ATB in cancer patients.

Methods

We identified patients who had an initial IGRA during 2013 and 2014 at our institution. Along with demographic information, collected clinical data included type of underlying cancer or other condition, reason for testing, diagnosis of ATB following testing, and absolute lymphocyte count (ALC) at the time of testing. IGRA results (positive, negative, borderline, or indeterminate/invalid) were compared between patients who underwent testing with either QFT or T-spot.TB.

Results

A total of 356 patients had 411 QFT tests done, while 737 patients had 853 T-spot.TB tests performed. The most common underlying malignancies in the QFT and T-spot.TB groups were acute myeloid leukemia (30% and 25%, respectively) and solid tumors (28% vs. 30%, respectively). The most common reasons for testing were pre-hematopoietic-cell transplantation (HCT) screening (42% with QFT and 31% with T spot.TB) or suspected pulmonary ATB (34% with QFT and 42% with T spot.TB). In the QFT group, 145/411 (35%) tests were indeterminate, while only 96/853 (11%) tests in the T-spot.TB group were invalid (P <0.001). The median ALC was 650 cells/µL in patients with an indeterminate result in the QFT group and 90 cells/µL in patients with an invalid test in the T-spot.TB group. A total of four patients were diagnosed with ATB at 1 year after testing. Figure 1 provides a flowchart describing IGRA testing results and development of ATB.

Conclusion

The frequency of an inconclusive test result is significantly higher with QFT as compared with T-spot.TB for diagnosis of LTBI or ATB in cancer patients. A low ALC is likely a contributing factor in indeterminate QFT and invalid T spot.TBresults.

Disclosures

E. Ariza-Heredia, Oxford Immunotec: Grant Investigator, Research grant. R. F. Chemaly, Oxford Immunotec: Consultant and Grant Investigator, Research grant.
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

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

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 >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

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

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

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 >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

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

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 <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 < 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

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, <3 days, or >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 < 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

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 (>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.
1048. Beta-Hemolytic Streptococcal Infective Endocarditis: Characteristics and Outcomes From a Large, Multi-National Cohort
Authors: Fernandez-Hidalgo Nuria , Gharamti Amal , Aznar María Luisa , Chu Vivian H , Rizk Hussein , Kanafani Zeina
Published: November 2018

Background

β-Hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with β-hemolytic streptococcal infective endocarditis in a large multi-national cohort, and compare them to patients with oral Viridans IE, a more common cause of IE.

Methods

The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multi-national database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form (CRF) developed by ICE collaborators. Patients with BHS IE were compared with patients with IE due to Oral Viridans Streptococci (OVS).

Results

Among 1336 cases of streptococcal IE, 823 (62%) were caused by OVS and 147 (11%) by BHS. The majority of patients in both groups belonged to the male gender and had similar median age. Among the predisposing conditions, congenital heart disease and native valve predisposition were more commonly associated with OVS IE than with BHS IE (P < 0.005). The presence of endocavitary cardiac device is associated more with BHS IE than with OVS IE (P = 0.026). BHS were more likely to be penicillin-susceptible than OVS (P = 0.001). Clinically, patients with BHS IE are more likely to present acutely (P < 0.005) and with fever (P = 0.024). BHS IE is more likely to be complicated by stroke (P < 0.005) and other systemic embolism (P < 0.005). The overall in-hospital mortality of BHS IE was significantly higher than that of OVS IE (P = 0.001). The independent factors associated with in-hospital mortality for β-hemolytic streptococcal IE were age, per 1-year increment (OR 1.044; CI 1.014–1.075; P = 0.004) and prosthetic valve IE (OR 3.029; CI 1.171–7.837; P = 0.022). The complications associated with a higher in-hospital mortality were CHF (OR 2.513; CI 1.074–5.879; P = 0.034), especially CHF NYHA III or IV (OR 4.136; CI 1.707–10.025; P = 0.002), and stroke (OR 3.198; CI 1.343–7.619; P = 0.009).

Conclusion

Our findings suggest that BHS IE is an aggressive disease characterized by an acute presentation. It is associated with a significant rate of complications and a high rate of in-hospital mortality. This underlines the importance of early surgery to prevent the progression of disease.

Disclosures

All authors: No reported disclosures.
1050. Oral Antibiotics for the Treatment of Gram-Negative Bloodstream Infections: Prescribing Practices and Outcomes at a Large Academic Medical Center
Authors: Claeys Kimberly , Loughry Nora , Chainani Sanjay , Leekha Surbhi , Heil Emily
Published: November 2018

Background

There is limited data to guide the use of oral (PO) antibiotics for the treatment of Gram-negative (GN) bloodstream infection (BSI). The objective of this study was to describe the characteristics and outcomes at a large academic medical center.

Methods

Retrospective observational cohort of adult patients (age ≥18 years) with at least one blood culture positive for aerobic Gram-negative organism(s) treated with antibiotic therapy (IV or oral [PO]) at University of Medical Center from November 2015 to May 2017. Oral antibiotics were described based on bioavailability. The primary outcome of interest was 30-day infection-related readmission. Secondary objectives included evaluation of patient characteristics associated with PO antibiotic use.

Results

During the defined study period 310 patients met inclusion; 113 (36.5%) were switched to PO antibiotic therapy for the treatment of GN BSI within a median of 5 (IQR 3–11) days. Oral antibiotics were initiated at discharge for 50 (44%) of patients switched. Patients switched to PO were less likely to have has a stay in the ICU (24.8% vs. 47.7%, P < 0.0001) and were less likely to have an ID consult (57.5% vs. 71.1%, P = 0.034). There was no difference in median Charlson Comorbidity Score (2, IQR 0–4). The most common sources of infection among those switched to PO agents were urinary (50, 44.2%) and intra-abdominal (25, 22.1%). The majority of patients were placed on a PO agent with high bioavailability (61, 54%), which included levofloxacin and moxifloxacin. There was a slightly higher proportion of use of high (vs. low) bioavailable antibiotics in patients with ID consult compared with those without (59% vs. 41%, P = 0.053). PO antibiotics were more frequently prescribed for patients discharged home (78, 69%) compared with patients discharged to Rehab/Short-term facility (28, 24.8%). Thirty-day hospital readmission was more common among the patients treated with PO antibiotics (18.6 vs. 8.1%, P = 0.006); however, ID-related readmission was rare (0.9% vs. 1%, P = 0.91).

Conclusion

Urinary and intra-abdominal sources and home discharge were common among those with PO antibiotic use. ID-related outcomes were similar among those treated with IV vs. PO agents. More research is necessary to determine optimal time to PO antibiotic switch.

Disclosures

K. Claeys, Nabriva: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. E. Heil, ALK-Abelló: Grant Investigator, Research grant.
1057. Treatment Efficacy of Ceftriaxone vs. Cefazolin for Methicillin-Susceptible Staphylococcus aureus Infections
Authors: Bhavan Kavita , Ganguly Anisha , King Helen , Schmalstieg Aurelia , Mang Norman , Collins Ryan
Published: November 2018

Background

Methicillin-susceptible Staphylococcus aureus (MSSA) infections are traditionally treated with intravenous (IV) nafcillin, oxacillin, or cefazolin, all antibiotics that require multiple doses per day. Despite theoretical limitations of using ceftriaxone in MSSA infections, some clinical studies suggest noninferiority of ceftriaxone compared with standard of care. At Parkland Memorial Hospital, many patients diagnosed with MSSA infections receive self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT). Daily-dosed ceftriaxone is often used for convenience and feasibility of medication adherence.

Methods

We conducted a retrospective cohort study among S-OPAT patients receiving cefazolin and ceftriaxone for treatment of MSSA infections. We compared infection type and planned duration of therapy as baseline differences between the treatment cohorts. Our clinical outcomes of interest were 30-day readmission rates and treatment failure as defined by repeat positive blood culture within 6 months.

Results

We identified 184 patients treated with cefazolin and 74 patients treated with ceftriaxone. Characteristics of treatment plan are shown in Table 1. There were no statistically significant differences in infection type or mean duration of therapy between the two treatment cohorts. Outcomes are shown in Table 2. There were no statistically significant differences in readmission rates and rate of treatment failure.

Conclusion

Our retrospective review suggests patients treated with ceftriaxone for MSSA bacteremia had similar clinical outcomes as those treated with cefazolin. While this study is limited in its retrospective nature, the findings suggest that ceftriaxone may be a safe and more convenient antibiotic option in certain MSSA infections.

Disclosures

All authors: No reported disclosures.
1070. Epidemiological and Clinical Features of Panton–Valenton Leukocidin-Positive Staphylococcus aureus Bacteremia: A Case–Control Study
Authors: Kausar Humera , Smith Stephen , Qu Ming Da , Lazar Peter G , Kroll-Desrosiers Aimee , Barton Bruce , Ward Doyle V , Ellison III Richard T
Published: November 2018

Background

The presence of the binary Panton-Valentine Leukocidin (PVL) toxin in Staphylococcus aureus has been associated with both severe pneumonia and skin and soft-tissue infections. However, there is only limited data on how this virulence factor impacts S. aureus bacteremia and whether it might affect the clinical course or complications of bacteremic infections.

Methods

Between September 2016 and March 2018, a convenience sample of S. aureus isolates from clinical cultures obtained in inpatient units and the Emergency Departments of UMass Memorial Medical Center underwent comprehensive genomic sequencing. Four hundred sixty-nine (29%) of 1,681 S. aureus sequenced isolates were identified as containing the LukF and LukSPV genes that encode for PVL. Case patients with one or more positive blood cultures for LukF/LukSPV + strains were randomly matched with control patients having positive blood cultures for LukF/LukSPV− strains for a retrospective chart review.

Results

The 55 case and 56 control patients were comparable in age and gender; case patients were more likely to have a history of injection drug use, while controls more likely to undergo hemodialysis or have had indwelling IV catheters. Case patients more commonly had chest pain and more prolonged fever; but had the same incidence of sepsis and septic shock. Isolates from 42 (76%) of case patients were methicillin resistant as compared with 16 (29%) from control patients. Elevations in serum creatinine and alkaline phosphatase were more common in control patients. Case patients had a higher incidence of pneumonia, with no differences seen in the incidence of endocarditis, osteomyelitis, or septic arthritis. The percentage of patients who were clinically cured or expired were comparable.

Conclusion

These results are consistent with prior observations associating the PVL toxin with community-acquired MRSA strains as well as severe staphylococcal pneumonia. However, it does not appear to otherwise influence the natural history of bacteremic S. aureus disease other than in prolonging the duration of fever.

Disclosures

All authors: No reported disclosures.
1084. Nocardia Cyriacigeorgica Endocarditis
Authors: Bhayani Nikhil , Priest Jaclyn
Published: November 2018

Background

Nocardia are beaded, branching Gram-positive rods that are partially acid fast and usually slow growing. Nocardia cyriacigeorgica was first described in 2001, and antimicrobial susceptibility patterns correspond with type VI Nocardia asteroides complex. Nocardia species are not a commonly associated with endocarditis, less than 20 cases to date have been documented. However, when Nocardia endocarditis is identified, the mortality rate is reported to be as high as 41% making antibiotic selection vital in the inpatient and outpatient

Methods

A 62-year-old male with a past medical history significant for severe chronic obstructive pulmonary disease (COPD), atrial fibrillation, atrial tachyarrhythmia, and congestive heart failure (CHF) presented to the emergency department (ED) with shortness of breath for 1 week. The patient was initiated on IV diltiazem, meropenem, and eventually required intubation. On hospital day, two blood cultures grew Gram-positive rods, which were eventually identified as aerobic Actinomycete. Culture was sent out for DNA sequencing and N. cyriacigeorgica was identified. Transthoracic echocardiogram showed possible mitral vegetation.

Results

Antimicrobial therapy was initially de-escalated from meropenem to ampicillin, but had to be escalated to ceftriaxone once N. cyriacigeorgica was identified by DNA sequencing. The organism was reported to be susceptible to amikacin, ceftriaxone, linezolid, tobramycin, and trimethoprim/sulfamethoxazole. The patient received 1 week of ceftriaxone therapy inpatient, and was discharged on an additional 3 weeks of ceftriaxone and 6 months of minocycline suppressive therapy.

Two months later the patient was re-admitted for N. cyriacigeorgica bacteremia and a pulmonary embolism. During his hospital stay, the patient had a STEMI, but due to multiple comorbidities did not undergo cardiac catheterization. The family elected to withdrawal care, and the patient expired.

Conclusion

N. cyriacigeorgica is more commonly identified in brain abscesses or skin infections, in the setting of immunosuppression. We report here on an unusual case of N. cyriacigeorgica endocarditis in a patient with COPD. Other than COPD the patient had no known risk factors for N. cyriacigeorgica, including chronic steroid use.

Disclosures

All authors: No reported disclosures.
1101. Comparison of Clinical Characteristics and Demographics of GII.4 vs. Other GII Noroviruses Associated With Sporadic Acute Gastroenteritis in Children in Nashville, TN, 2012–2015
Authors: Batarseh Einas , Hamdan Lubna , Piya Bhinnata , Stewart Laura , Chappell James D , Dunn John , Payne Daniel C , Wikswo Mary E , Vinjé Jan , Hall Aron J , Halasa Natasha
Published: November 2018

Background

Norovirus is a leading cause of acute gastroenteritis (AGE) in all age groups. Although at least 28 different genotypes infecting humans have been reported, most outbreaks over the last 15 years have been caused by genogroup II (GII) viruses, of which GII.4 viruses have caused more than 50%. Since clinical differences between different genotypes are poorly understood, we sought to compare clinical characteristics in children infected with GII.4 and non-GII.4 viruses.

Methods

Children between 15 days and 17 years who presented with AGE defined as diarrhea (≥3 loose stools in a 24 hour period) or vomiting (≥1 episodes in a 24 hour period) within 10 days duration were recruited in outpatient, emergency, and inpatient settings in Nashville, TN, during 2012–2015. Stool specimens were tested by RT-qPCR for GI and GII norovirus. Norovirus-positive specimens were genotyped by sequencing of a partial region of the capsid gene. In this study, we excluded children infected with GI, mixed GI/GII and non-typeable GII viruses.

Results

Of 3,705 AGE subjects enrolled, 2,892 (78%) specimens were collected, 637 (22%) tested norovirus-positive (567 [89%] GII, 62 [10%] GI, and 8 [1%] mixed GI/GII). Of the 567 GII viruses, 461 (81%) were able to be genotyped and of those 238/461 (51.6%) were typed as GII.4 and 223/461 (48.3%) were typed as other GII genotypes (non-GII.4, primarily GII.3 [65/ 461, 14.1%], GII.6 [48/461, 10.4%] and GII.7 [36/461, 7.8%]). Over three AGE seasons, GII.4 represented 64/117 (54%), 79/178 (44%), and 71/166 (57%), of the GII infections, respectively. Compared with non-GII.4 subjects, GII.4 subjects were more likely to be younger (15.5 vs. 21.3 months, P < 0.01), and less likely to attend daycare (23% vs. 39%, P < 0.01). GII.4 subjects also were more likely to present with diarrhea (75% vs. 57%, P < 0.01) and had higher median modified Vesikari score (7 vs. 6, P < 0.01).

Conclusion

Children infected with GII.4 viruses were younger, less likely to attend child care, more likely to present with diarrhea, and had a more severe illness compared with those with non-GII.4 infections. These data provide important information on the genotype distribution of norovirus in children with AGE in Tennessee and highlight GII.4 as the most prevalent strain.

Disclosures

N. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.
1124. Effects of Co-infection on the Severity, Response to Treatment and Duration of Hospital Stay in Patients with Clostridium difficile Infection
Authors: Shafiq Muhammad , Alturkmani Hani , Zafar Yousaf , Mittal Vishal , Lodhi Hafsa , Brewer Joseph
Published: November 2018

Background

According to the multicenter evaluation of the FilmArray® multiplex gastrointestinal (GI) panel for etiologic diagnosis of infectious gastroenteritis, the GI panel detected at least one potential pathogen in 53.5% of the stool specimens that were collected. Out of the positive samples, 31.5% tested positive for more than one potential pathogen. The samples that were co-infected showed that Clostridium difficile infection (CDI) was present in 53.4% of them. This lead to the idea of our project to determine whether the presence of another GI infection affects CDI outcomes in terms of severity, treatment escalation, duration of hospital stay and recurrence.

Methods

Inclusion criteria: 18-year-old and above patients. Exclusion criteria are GI panel performed on outpatient basis, presence of any co-founder that had independent effect on the outcomes such as end-stage renal disease, cirrhosis, presence of non-GI infection (pneumonia, urinary tract infection, osteomyelitis etc.), and recurrent CDI.

Out of the 2,576 GI panels performed from January 1, 2015 until December 31, 2016; only 235 patients were selected for retrospective chart review based on the above criteria. Out of 235 patients, 38 patients had co-infection (CDI + another GI infection = Group A) and reminder had only CDI (Group B). Chi-square test, Fisher’s exact test (for severity, treatment escalation and recurrence) and Independent T-test (for duration of hospital stay) were used to compare Group A with Group B. Alpha criterion was 0.05.

Results

The P-values for each outcome are given below: (a) 0.16 for severity according to definition of American College of Gastroenterology. (b) 0.77 for severity according to definition of Infectious Disease Society of America. (c) 0.23 for treatment escalation. (d) 0.41 for duration of hospital stay. (e) 0.49 for CDI recurrence.

Conclusion

All the resulted P-values are greater than 0.05. These results are suggestive of the fact that presence of another GI infection does not affect the outcomes for CDI in terms of severity, treatment escalation, duration of hospital stay, and recurrence. As there were only 38 patients in co-infection group, it limits the ability to determine the effect of individual infectious agent on the outcomes of CDI.

Disclosures

All authors: No reported disclosures.
1133. Epidemiology of Invasive Fungal Infections in Lung Transplant Recipients: Harnessing Data Mining Tools to Build a Comprehensive Database
Authors: Yek Christina , Xie Donglu , Barros Nicolas , Liu Terrence , Wallace Ashley , Adams-Huet Beverley , Haley Robert W , Hoz Ricardo La
Published: November 2018

Background

Despite advances in diagnostic and therapeutic tools, mortality of invasive fungal disease (IFD) in lung transplant (LT) recipients remains high. This study aimed to describe the epidemiology of IFD in LT recipients at a large academic center.

Methods

This retrospective single-center cohort study included all first-time LT recipients transplanted between 2010 and 2016 at the University of Texas Southwestern Medical Center in Dallas, TX. Data mining tools were used to extract data from the electronic health record and merge it with information from the Scientific Registry of Transplant Recipients and the Social Security Death Index (Figure 1). Medical records of subjects with positive fungal serologies, cultures or histopathology were manually reviewed and presence of IFD adjudicated using standardized definitions. Multivariable analysis was conducted using Cox proportional hazard models, with input variables treated as time dependent covariates where applicable, to identify risk factors for IFD and 1-year mortality.

Results

Of 393 LT recipients that met inclusion criteria, 68 (17%) developed a proven or probable IFD with median time to onset of 110 days (IQR 46–213) (Figure 2). The most common pathogens were: Aspergillus sp. (41%), and Candida sp. (34%). The most common sites of IFD were: lower respiratory tract (38%), tracheobronchial (25%), pleural/pericardial (15%), and bloodstream (7%). In multivariable analysis, incidence of IFD was associated with male gender (P = 0.02; HR=2.05, 95% CI 1.14–3.68), and prior CMV disease (P = 0.003; HR=4.16, 95% CI 1.65–10.50) (Figure 3). The 12-week mortality after the first episode of IFD was 3%; IFD was not associated with 1-year mortality (P = 0.51, HR = 1.27, 95% CI 0.63–2.53).

Conclusion

IFD is a frequent complication after LT. Efforts to identify risk factors may help guide the development of targeted interventions to reduce the burden of IFD in this vulnerable population.

Disclosures

All authors: No reported disclosures.
1142. Use of DNA Markers to Assess the Potential for Pathogen Transmission from Physicians’ White Coats
Authors: Van Aartsen Daniel , Thakur Manish , Dousa Khalid M , Kanwar Anubhav , Cadnum Jennifer , Wong Yilen Karen Ng , Mana Thriveen , John Amrita , Alhmidi Heba , Donskey Curtis J
Published: November 2018

Background

Physicians’ white coats are often contaminated, but seldom cleaned. A “bare below the elbows” dress code policy has been advocated as a strategy to reduce the risk for transmission of healthcare-associated pathogens by white coats. However, transfer of contamination by clothing has not been demonstrated in clinical settings and it is not known if long sleeves are the major source of transfer.

Methods

We observed physicians during routine patient encounters and characterized the frequency of direct and indirect contact between white coats and the patient or environmental surfaces. To assess transfer from white coats in clinical settings, we applied one cauliflower mosaic virus DNA marker to the sleeve cuffs and another to the coat pockets of physicians prior to routine patient encounters. Polymerase chain reaction was used to determine whether DNA markers from the clothing sites were transferred to patients or environmental surfaces.

Results

Ninety percent of observed patient encounters included one or more direct or indirect contacts between a physician’s white coat and a patient or the environment. Direct contact occurred on average 1.7 times per encounter and indirect contact (i.e., physicians’ hands contacting the coat prior to touching the patient or environment) occurred on average 2.3 times per encounter. The figure shows the frequency and distribution of sites of direct and indirect contact with white coats. Of 11 patient encounters with DNA-contaminated white coats, five (45%) resulted in transfer of one or both DNA markers; there were three transfers from sleeve cuffs and three from coat pockets.

Conclusion

Contaminated white coats may be an under-appreciated source for transmission of healthcare-associated pathogens. Our results provide support for the bare below the elbows policy, but also highlight the potential for indirect transfer of pathogens from other sites on white coats.

Disclosures

All authors: No reported disclosures.