bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct and Indirect Impact of 13-valent Pneumococcal Conjugate Vaccine (PCV13) on Invasive Pneumococcal Disease (IPD) Among Children and Adults in the U.S.
Authors: Pilishvili Tamara , Gierke Ryan , Farley Monica , Schaffner William , Thomas Ann , Reingold Arthur , Harrison Lee , Lynfield Ruth , Zansky Shelley M , Petit Susan , Miller Lisa , Baumbach Joan , Beall Bernard , Whitney Cynthia 
Published: October 2017

Abstract

Background
In February 2010, PCV13 was introduced for routine use among children aged &lt; 5 years. In June 2012, PCV13 was recommended for use in series with 23-valent polysaccharide vaccine (PPSV23) for adults ≥19 years with select medical conditions, and in August 2014, for all adults ≥65 years. We evaluated the direct and indirect effects of PCV13 6 years post-introduction on invasive pneumococcal disease (IPD).

Methods
IPD cases (isolation of pneumococcus from sterile sites) were identified among residents of Active Bacterial Core surveillance (ABCs) sites during July 2007–June 2016. Isolates were serotyped by Quellung, PCR, or whole genome sequencing and classified as PCV13 or non-vaccine type (NVT). Incidence changes were estimated as percent changes (one minus rate ratio) and 95% confidence intervals (95% CI) between pre-PCV13 (2007–2009) and two post-PCV13 periods (July 2014–June 2015 and July 2015–June 2016).

Results
ABCs identified 31,190 IPD cases between 2007 and 2015, with 2,750 cases among children &lt;5 years and 10,930 among those ≥65 years. During the two post-PCV13 periods, overall IPD rates were 33%-62% lower relative to 2007–2009 among all age groups, including &lt;5 years and ≥65 years (Figure). Significant reductions in PCV13-type IPD incidence were observed for all age groups during both post-PCV13 periods, with incidence 84% (q95% CI 78, 88%) and 68% (95% CI 63, 73%) lower in 2015–2016 among children &lt; 5 years and adults ≥65 years, respectively. PCV13-type IPD reductions were driven by serotypes 19A and 7F. IPD due to non-vaccine types also declined significantly among children &lt; 5 years (−27%, 95% CI –42, –9%) and adults ≥65 years (-24%, 95% CI –34, –14%). PCV13-type IPD incidence did not differ significantly between the two post-PCV13 periods.

Conclusion
IPD incidence declined among children and adults in the U.S. following PCV13 introduction among children. The lack of difference in PCV13 rates between 2014–2015 and 2015–2016 suggests no measurable early impact of PCV13 introduction among adults ≥65 years. To date, we found no evidence of significant replacement disease with non-PCV13 types. Further work is needed to explain reductions in non-vaccine type disease observed in the post-PCV13 era.

Disclosures
W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee; L. Harrison, GSK: Scientific Advisor, Consulting fee
Risk Predictive Model for 90-Day Mortality in Candida Bloodstream Infections
Authors: Lin Charlotte , Kronen Alyssa , Hsueh Kevin , Powderly William , Spec Andrej 
Published: October 2017

Abstract

Background
Candida bloodstream infections (CBSI) continue to be associated with high mortality, despite changes in antifungal treatment and diagnostics.

Methods
All patients age 18 or greater with a first episode of CBSI by blood culture from 1/2002 to 1/2015, admitted to Barnes-Jewish Hospital, a tertiary referral hospital in St. Louis, MO, were included. We collected data on demographics, comorbidities, laboratory values, vital signs, indwelling devices, and medical treatments of interest from the electronic medical record. We analyzed the potential predictor variables using univariate logistic regression. Variables associated with mortality were considered for model inclusion. The final model was built using multivariable binary logistic regression. A predictive equation was created, and a receiver–operator curve (ROC) was calculated to determine the appropriate cut-off points and c-statistic.

Results
Of the 1873 episodes of CBSI identified, 789 (42%) resulted in death in 90 days. The variables included in this model were age (40–49: OR 0.463, 95% CI 0.291–0.736; 50–69: 0.542, 0.342–0.860; ≥70: 0.560, 0.400–0.785); history of CAD (1.616, 1.171–2.230), chronic liver disease (2.247, 1.327–3.806); maximum heart rate (1.496, 1.126–1.989) and temperature (0.537, 0.408–0.708); AST (1.817, 1.343–2.459) and platelet count (1.563, 1.178–2.073); the presence of ventilator (1.847, 1.321–2.582), urinary catheter (1.365, 1.008–1.847), two or more central lines (1.658, 1.020–2.694); removal of lines after positive culture (0.259, 0.181–0.370); ophthalmology consult during admission (0.441, 0.329–0.592); thoracentesis/chest tube (3.827, 1.550–9.448); diagnosis of secondary malignancy (2.131, 1.488–3.053); whether antimetabolites (2.119, 1.353–3.318), dapsone (4.507, 1.450–14.012), linezolid (1.605, 1.059–2.435), quinolones (1.384, 0.998–1.920) were ordered 90 days before positive culture. An ROC curve was calculated with an internal c-statistic of 0.806.

Conclusion
We created a risk predictive model for 90-day mortality in patients with CBSI, with 81% probability of predicting mortality. This model can lead to development of point-of-care applications to aid decision-making regarding escalation/de-escalation of care.

Disclosures
W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant Gilead: Scientific Advisor, Consulting fee Astellas: Grant Investigator, Research grant A. Spec, Astellas: Grant Investigator, Grant recipient
Coccidioidomycosis After Solid Organ Transplantation: A Population-Based Study
Authors: George Ige , Santos Carlos 
Published: October 2017

Abstract

Background
Coccidioidomycosis is an invasive fungal infection in solid organ transplantation (SOT) recipients with an incidence of 1.4–6.9% in endemic regions. There are no population-level data describing the incidence and outcomes of coccidioidomycosis in SOT recipients.

Methods
We assembled a large cohort of adult SOT recipients using ICD-9-CM billing data from the California State Inpatient Databases from 2004 to 2011. Demographics, comorbidities, coccidioidomycosis coded during hospitalization and inpatient death were identified. We used Cox proportional hazard multivariate analyses to identify risk factors for coccidioidomycosis and death.

Results
20,602 SOT recipients were identified during the study period (median follow-up time = 1507 days). Eighty-seven patients (0.42%) with coccidioidomycosis were identified of whom 17 (20%) were coded with progressive/disseminated disease. Median time to diagnosis was 164 days (IQR 16–844) from transplantation. Fifty-one of 87 (58%) of these infections were diagnosed within the first year posttransplant and 29/87 (33.3%) were identified within the first month. Twenty-one of 87 (24%) of patients with coccidioidomycosis died compared with 1928/18587 (9.4%) of patients without coccidioidomycosis (P &lt; 0.001). Coccidioidomycosis was independently associated with death (HR, 3.1; 95% CI, 2.0–4.4), after adjusting for age, type of transplantation, transplant failure/rejection, and other comorbidities (Table) (Figure).

Conclusion
Coccidioidomycosis resulting in hospitalization is rare in an endemic region in the current era of screening and prophylactic antifungal therapy. Preventing infection in solid organ transplant recipients is imperative because overall mortality remains high.

Disclosures
All authors: No reported disclosures.
Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis
Authors: Myint Thein , Bloch Karen , Raymond-Guillen Luke , Wheat L Joseph 
Published: October 2017

Abstract

Background
Central nervous system (CNS) histoplasmosis is a life-threatening condition, and represents a diagnostic and therapeutic challenge. Although CSF (1,3)-β-d-glucan (CSF BDG) is available as a biologic marker for diagnosis of fungal meningitis, there are limited data on its use for diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection using the Fungitell assay in patients with CNS histoplasmosis and controls.

Methods
Patients were classified as cases if there was CNS inflammation (CSF WBC ≥ 5 mm3/ml) plus laboratory confirmation of H. capsulatumin CNS samples or from extra-CNS sites with no alternative etiology for CSF pleocytosis. Controls were patients with histoplasmosis but no evidence of CNS involvement, an alternative diagnosis, or other fungal meningitis.

Results
In total, 47 cases and 153 controls were evaluated (Table 1). Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. CSF BDG was positive in 25 (53.2%) cases using a level of ≥80 pg/ml, the median CSF BDG level was 140.5 pg/ml (range from &lt;31 to 500 pg/ml). The detection of CSF BDG level ≥80 pg/ml was not associated with positive CSF Histoplasma antigen (P = 0.28) or positive CSF Histoplasma culture (P = 0.56). The sensitivity for detection of CSF BDG was 53.2% and the specificity was 87.3%, compared with 78.7% &#x2028;(P = 0.009) and 96.4% (P = 0.003), respectively, for detection of antigen. CSF BDG was positive in 20 of 153 (13.1%) patients in the control group. Seven of 11 (63.6%) other CNS fungal meningitis cases (five Cryptococcus, two Aspergillus, two Blastomyces, one Candida, and one suspected fungal meningitis) had CSF BDG ≥80 pg/ml.

Conclusion
A positive CSF BDG supports the diagnosis of fungal meningitis but cannot distinguish among the different etiologies. The sensitivity and specificity of detection of CSF BDG was lower than that of antigen detection.

Disclosures
L. J. Wheat, MiraVista: President and owner, equity and Salary
Natural History of Non-CNS Disseminated Coccidioidomycosis
Authors: Bays Derek , Thompson George R , Reef Susan , Snyder Linda , Huppert Milton , Salkin David , Galgiani John 
Published: October 2017

Abstract

Background
The number of patients with coccidioidomycosis continues to increase yearly. Patients with CNS disease require lifelong antifungal therapy due to the high morbidity and mortality of this disease. However, the morbidity and mortality in non-CNS disseminated disease has not been well characterized.

Methods
We conducted a retrospective study of 373 VA-armed forces coccidioidomycosis patients diagnosed between 1955 and 1958 and followed to 1966. Groups were identified as non-disseminated disease, non-CNS disseminated disease with and without multisite dissemination, and disseminated disease to the CNS with and without multisite dissemination. Clinical variables including demographic information, duration and severity of symptoms, coccidioidal serologies, type of infection and complications, time to disseminated disease, and mortality were abstracted from patient charts.

Results
Mortality attributed to coccidioidomycosis in the non-disseminated group was 0.3% (1/297) compared with the non-CNS disseminated group of 8.5% (4/47, median survival 12 months, range 12–24 months, P = 0.0002). Mortality in the CNS disseminated group was 86% (19/22, median survival of 12 months, range 12–156 months, P &lt; 0.0001 compared with non-CNS disseminated). The single site non-CNS disseminated group had a mortality of 4.1% (1/24, survival of 12months) compared with the multiple site non-CNS disseminated group of 13% (3/23, median survival of 18 months, range of 12–24 months, P = 0.57).

Conclusion
This retrospective cohort study demonstrates significant mortality differences between different forms of disseminated coccidioidomycosis. CNS dissemination exhibited the highest mortality rate; however, non-CNS dissemination also exhibited an unacceptably high mortality rate. There was no significant difference in mortality between single site non-CNS disseminated disease and multiple site non-CNS disseminated disease.

Disclosures
All authors: No reported disclosures.
Invasive Mold Infections (IMIs) of the Central Nervous System (CNS) in Patients with Hematologic Cancer (HC) (2000–2016): Uncommon but Deadly
Authors: Economides Minas Platon , Ballester Leomar , Kumar VInc.e , Jiang Ying , Tarrand Jeffrey J , Prieto Victor , Torres Harrys , Kontoyiannis Dimitrios P 
Published: October 2017

Abstract

Background
There is paucity of data regarding IMIs of the CNS in patients with HC or stem cell transplantation (SCT).

Methods
Review of the records of patients with HC and/or SCT recipients who were diagnosed with CNS IMIs at MD Anderson Cancer Center (1/1/2000–5/31/2016). IMIs were classified as proven or probable (EORTC/MSG criteria). We excluded patients with mixed CNS infections. Risk factors for survival at day 42 post diagnosis (dx) were assessed. A multivariate logistic regression analysis was performed to identify independent predictors of mortality.

Results
We identified 40 patients (16 proven; 40%). Most patients were white (29; 73%) and male (33; 83%). Median age was 58 years. The most common HC was acute leukemia (23; 58%). Seventeen patients (43%) were SCT recipients; 13 (76%) had GVHD. Most patients had active HC and neutropenia at dx (38; 95% and 21; 53%, respectively). Twenty-seven patients (68%) were in the ICU at dx. Aspergillus sp. (13; 33%) and Mucorales (8; 20%) accounted for &gt;50% of cases. CNS IMIs were deemed to be secondary to direct extension or hematogenous spread in 9 (23%) and 31 (77%) patients, respectively. In the latter group, 28/31 (90%) had fungal pneumonia. Of the 27 and 9 patients who had Aspergillus galactomannan antigen tested from serum and CSF, respectively, 18 had positivity in serum (66%) and 3 in CSF (33%). Most patients (30; 75%) had exposure to mold-active agents within 30d of dx. Most patients (34; 85%) received lipid AMB and were treated with combination therapy (33; 83%). Most CNS lesions presented as ring-enhancing abscesses radiographically (26; 65%). Absence of giant cells and granulomas in the pathologic examination of the brain lesions were associated with increased 42 days mortality (0% vs. 70%, P = 0.01 and 0% vs. 60% in those who survived, P = 0.03, respectively). In multivariate analysis, co-infection at the time of dx was associated with increased mortality (OR: 16.5, 95% CI: 1.4–198.3, P = 0.03) while steroid tapering was associated with decreased mortality (OR: 0.06, 95% CI: 0.01–0.53, P = 0.01). There was a trend towards protective role of surgical drainage (ORn = 0.18, 95% CI = 0.03–1.14, P = 0.07).

Conclusion
CNS IMIs occur in ill patients with active HC who are often pre-exposed to antifungals. Immune response in pathology, steroid tapering and possibly surgical drainage are associated with improved outcome.

Disclosures
D. P. Kontoyiannis, Pfizer: Research Contractor, Research support and Speaker honorarium. Astellas: Research Contractor, Research support and Speaker honorarium. Merck: Honorarium, Speaker honorarium. Cidara: Honorarium, Speaker honorarium. Amplyx: Honorarium, Speaker honorarium. F2G: Honorarium, Speaker honorarium
Comparing Diagnostic-Driven Approaches to Empiric Therapy in the Treatment of Invasive Aspergillosis in Patients with Hematologic Malignancy
Authors: Dib Rita Wilson , Chaftari Anne-Marie , Ghaly Fady , Jiang Ying , Hachem Ray Y , Raad Issam 
Published: October 2017

Abstract

Background
Early antifungal therapy of invasive aspergillosis (IA) has been shown to be associated with improved outcome. Given the difficulty to establish the diagnosis of IA based on conventional methods, early initiation of empiric antifungal therapy has been used in patients with clinically suspected IA. Diagnostic-driven approach (DDA) relies on using novel diagnostic methods (e.g., early galactomannan testing). In this current study, we compared the outcomes of hematological malignancy (HM) patients with IA who were treated with Voriconazole using the DDA (DDA-Vori) vs. empiric therapy with a non-Voriconazole containing regimen (EMP-non-Vori) or empiric therapy with Voriconazole (EMP-Vori).

Methods
We retrospectively reviewed the medical records of 604 HM patients with documented, proven or probable IA (according to EORTC/MSG criteria) diagnosed between July, 1993 and February, 2016 at our center. We included 346 patients with underlying host factors, a suggestive CT findings of IA, and positive biopsy, fungal culture or galactomannan indicative of IA, and who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all causing mortality and IA attributable mortality.

Results
The patients’ median age was 54 years and 59% were males. By multivariate analysis, factors that were predictive of a favorable response included: localized/sinus IA vs. disseminated/pulmonary IA (P &lt; 0.0001), not receiving WBC transfusion (P &lt; 0.01), and DDA-VORI vs. EMP-non-Vori (P &lt; 0.0001). On the other hand, predictors of mortality within 6 weeks of initiation of IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (P &lt; 0.01), not having stem-cell transplant within 1 year prior of IA (P = 0.01) and EMP-non-Vori vs. DDA-Vori (P &lt; 0.001).

Conclusion
DDA-Vori is associated with a better outcome (response and survival) when compared with EMP-non-Vori and equivalent outcome to EMP-Vori. The superior to equivalent outcome associated with the DDA approach could also reduce unnecessary costs and adverse events associated with widespread use of empiric therapy.

Disclosures
I. Raad, Merck: Grant Investigator, Research grant. Allergan: Grant Investigator, Research grant. Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Raad is a s and Shareholder, Licensing agreement or royalty
In Vitro Interactions of Echinocandins with Triazoles Against Multidrug-Resistant Candida auris
Authors: Badalii Hamid 
Published: October 2017

Abstract

Background
Blood stream infections due to Candida auris are related to a high mortality rate and treatment failure attributed to resistance to fluconazole, voriconazole, amphotericin B, and caspofungin. Thus, the precise identification of agents and in vitro antifungal susceptibility testing is highly recommended. Novel therapeutic strategies, such as combination therapy, are essential for increasing the efficacy and reducing the toxicity of antifungal agents. Therefore, we investigated the in vitro combination of micafungin plus voriconazole against multidrug-resistant C. auris isolated from cases of candidemia.

Methods
The in vitro interactions between echinocandins and azoles were determined against ten multidrug-resistant Candida auris strains by using a microdilution checkerboard technique.

Results
Results revealed that MICs range for voriconazole and micafungin were 0.5–8 and 0.25–8 mg/l, respectively. The checkerboard analysis revealed that the combination of micafungin with voriconazole exhibited synergistic activity against all 10 multidrug-resistant C. auris isolates (FICI range: 0.15–0.5). Overall, no antagonistic effects were observed in this experiments.

Conclusion
In vitro studies have previously suggested that among azoles isavuconazole and posaconazole are more active drugs against C. auris. In addition, the majority of isolates reported are resistant to fluconazole. Remarkably, unsuccessful treatment of C. auris infections with fluconazole, voriconazole, amphotericin B, caspofungin, and anidulafungin has been already on record. Here in we demonstrates that interaction between micafungin with voriconazole exhibited synergistic activity against multidrug-resistant C. auris isolates. It seems that lower concentrations of drugs cause fewer side-effects and improve the treatment outcomes. However, in vivo studies with suitable animal models of C. auris infection is highly recommended.

Disclosures
All authors: No reported disclosures.
Clinical Outcomes of the Oral Suspension vs Delayed-Release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections
Authors: Tallman Gregory B , Furuno Jon P , Noble Brie N , Bubalo Joseph S , Forrest Graeme N , Lewis James S , Bienvenida Ana F , Holmes Courtney A , Weber Bo R , McGregor Jessina C 
Published: October 2017

Abstract

Background
Posaconazole is effective prophylaxis for invasive fungal infections (IFIs). We compared incidence of breakthrough IFI (bIFI) and early posaconazole discontinuation between patients receiving delayed-release tablet and oral suspension formulations.

Methods
This was a retrospective cohort study of patients receiving posaconazole at Oregon Health & Science University Hospital between 1/1/2010 and 6/30/2016. Oral suspension was the preferred formulation until 2/2014; afterwards the tablet was preferred. We included all courses of primary prophylaxis for each patient during the study period. Data were extracted from an electronic health record repository and via chart review. Three independent reviewers identified bIFI using European Organization for Research and Treatment of Cancer criteria. We assessed rationale for early discontinuation of posaconazole for patients that were still indicated for antifungal prophylaxis based on National Comprehensive Cancer Network (NCCN) criteria.

Results
547 patients received 859 courses of posaconazole (53% oral suspension and 48% tablet). Prophylaxis was indicated according to NCCN criteria in 91% of courses. The primary indications for prophylaxis were acute myelogenous leukemia (68%), graft-vs-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indication between patients receiving the different formulations. The overall incidence rate of bIFI was 4.15/10,000 posaconazole-days (16 total bIFI events). Incidence of bIFI was not significantly different between patients receiving the different formulations (P = 0.92). Posaconazole was discontinued early in 147 (17%) courses; frequency of discontinuation was not significantly different between the tablet (20%) and oral suspension (15%) formulations (P = 0.10). The primary reasons for early discontinuation were elevated liver function tests or QT prolongation (25%), inability to take an oral formulation (17%), and drug cost (17%).

Conclusion
Among patients receiving posaconazole prophylaxis, incidence of bIFI was low and not significantly different between those receiving the tablet vs oral suspension formulations.

Disclosures
J. P. Furuno, Merck & Co.: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium. J. S. Lewis II, Merck & Co.: Consultant, Consulting fee. J. C. McGregor, Merck & Co.: Grant Investigator, Research grant