bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors Associated with Persistence of Zika Virus Nucleic Acid in Serum and Semen
Authors: Lozier Matthew , Rosenberg Eli , Doyle Katherine , Adams Laura , Klein Liore , Muñoz-Jordan Jorge , Alvarado Luisa I , Sharp Tyler , Paz-Bailey Gabriela 
Published: October 2017

Abstract

Background
Identifying factors associated with time-to-loss of Zika virus (ZIKV) RNA in serum and semen is important to inform diagnostic testing and prevention recommendations. CDC currently recommends RT-PCR testing of serum up to two weeks after symptom onset. We evaluated such associations among participants of the Zika virus Persistence (ZiPer) study in Puerto Rico.

Methods
Patients presenting for care with Zika-like illness and ZIKV RNA detected by RT-PCR in serum or urine (index cases) were offered study participation. Index cases’ household members were offered study participation, and those with detectable ZIKV RNA were eligible for the prospective cohort. Serum and semen were collected weekly for the first month, and biweekly thereafter for participants with detectable ZIKV RNA in any fluid and at 2, 4, and 6 months post-enrollment for all others. We used chi-squared and Fischer’s exact tests to assess if detecting ZIKV RNA in specific specimens at any point was associated with sex, age, Zika-like symptoms (rash, fever, arthralgia, or conjunctivitis), or pregnancy. We performed Weibull regression models to estimate time-to-loss of ZIKV RNA in days post symptom onset (DPO) and evaluated associations between covariates and duration of detection.

Results
Among 295 participants, 260 (88.1%) had ZIKV RNA detected in serum at any point. Participants aged ≥18 years (n = 244) had a significantly longer median time-to-loss of ZIKV RNA in serum than participants aged &lt; 18 years (n = 50) (13.1 vs. 7.8 DPO, respectively; P = 0.003) (Figure 1). Among women aged 18–39 years (n = 60), pregnant women (n = 9) had a significantly longer median time-to-loss of ZIKV RNA in serum than non-pregnant women (n = 51) (37.4 vs. 15.5 DPO, respectively; P = 0.0005) (Figure 2). The proportion of men who had detectable ZIKV RNA in semen at any point was significantly higher among men with conjunctivitis (47 of 82) than among men without conjunctivitis (3 of 14) (P = 0.01). No other associations were significant.

Conclusion
Time-to-loss of ZIKV RNA in serum was longer among adults than children, and conjunctivitis was associated with detecting ZIKV RNA in semen. This study provides evidence that time-to-loss of ZIKV RNA is longer among pregnant women than non-pregnant women. Findings may inform the recommended period to test pregnant women for ZIKV using RT-PCR.

Disclosures
All authors: No reported disclosures.
Cancer Mortality among Persons with Human Immunodeficiency Virus Infection in New York City, 2001–2015
Authors: Ramaswamy Chitra , Westheimer Emily , Braunstein Sarah 
Published: October 2017

Abstract

Background
With the prolonged life-span of persons with HIV (PWH) due to anti-retroviral therapy, their cancer burden has increased. Cancer continues to be a leading cause of death among PWH. Studying cancer mortality can inform and guide the development of cancer screening and prevention strategies for PWH.

Methods
We analyzed data for all persons &gt; = 13 years who were diagnosed with HIV from 2001 to 2015 and reported to the New York City (NYC) HIV surveillance registry (HSR). Using the HSR and the underlying cause of death obtained from the NYC vital statistics registry and the National Death Index, we examined age-specific and age-standardized mortality rates from cancer and compared time trends of deaths due to HIV-related8 cancer to deaths from non-HIV-related cancers.

Results
There were 34,190 deaths reported among 154,688 PWH of whom nearly half (n = 16,804; 49.1%) died due to HIV (excluding HIV-related cancers). Among all deaths, HIV was the leading cause, followed by cancer (both HIV and non-HIV-related) (n = 5,271; 15.4%) and cardiovascular disease (n = 3,724, 10.9%). The top three causes of non-HIV-related cancer deaths were lung cancer (n = 1,040; 19.7%), liver cancer (n = 552; 10.5%), and colorectal cancer (n = 315; 5.6%). Although the mortality rate among PWH decreased over time (24.4 to 13.9 per 1,000 person-years from 2001 to 2015), the proportion of deaths attributable to all cancers increased (10.6% in 2001 to 19.9% in 2015, p &lt; .0001). This increase was driven by non-HIV-related cancers (6.1% of all deaths in 2001 to 15.8% in 2015, p &lt; .0001). The mean age increased from 2001 to 2015 among the dead (46 to 56 years) and among the censored (35 to 49 years). After controlling for demographic factors, transmission risk, and last CD4 count, the hazard ratio for cancer deaths was higher among people who inject drugs (HR = 1.5; 95% CI = 1.4–1.7) and those with last CD4 count &lt; 200 (HR = 9.3; 95% CI = 8.3–10.5).

Conclusion
Although mortality rates are decreasing in PWH, deaths due to non-HIV-related cancers are increasing. The upward trend in the mean age suggests that aging may be contributing to this increase. Routine screening for liver and colon cancers along with smoking cessation may reduce lung, liver and colon cancer deaths.

Disclosures
All authors: No reported disclosures.
Real-Time PCR Targeting Mosaic penA XXXIV for Prediction of Extended-Spectrum Cephalosporins Susceptibility in Clinical Neisseria Gonorrheae Isolates
Authors: Hemarajata Peera , Wong Lisa , Soge Olusegun , Humphries Romney , Klausner Jeffrey 
Published: October 2017

Abstract

Background
Antimicrobial-resistant Neisseria gonorrheae (NG) is a global public health problem, resulting in limited empirical treatment options. Due to increasing minimum inhibitory concentrations (MICs) of ESCs against NG in the US, it is critical that susceptibility to ESCs be monitored. Since few laboratories routinely perform culture and susceptibility testing for NG, there is a need for a rapid test to predict susceptibility to ESCs. More than 98% of isolates with decreased susceptibility to cefixime (CFM) in the US carry mosaic penA XXXIV. In this study, we developed a multiplex real-time PCR for mosaic penA XXXIV and previously validated gyrA to predict ESCs MICs and ciprofloxacin (CIP) susceptibility.

Methods
150 NG isolates with known cefpodoxime (CPD), CFM, ceftriaxone (CRO) and CIP MICs were obtained from Neisseria Reference Laboratory at University of Washington and CDC Antimicrobial Resistance Bank. DNA extracted from culture was used in multiplex HybProbe real-time PCR on Lightcycler 480. gyrA was genotyped by melt curve and served as internal control, while presence of mosaic penA XXXIV was detected by selective amplification.

Results
All 32 (100%) CIP-susceptible and 118 (100%) CIP-resistant isolates, as determined by Clinical and Laboratory Standards Institute breakpoints, demonstrated wild-type and Ser91 mutant gyrA genotype, respectively. Melt curve genotyping demonstrated mosaic penA XXXIV melt patterns in 66/68 (97%) isolates with at least one ESC MIC above alert value set forth by the CDC (CPD and CFM MICs ≥0.25 µg/ml; CRO MIC ≥0.125), while all 82 (100%) isolates with ESC MICs under alert values did not amplify. The first of the 2 false-negative isolates had MICs above alert values for all ESCs tested and harbored IX mosaic type, while the second one had CRO MIC above alert value and harbored XII mosaic type. Both of these mosaic types did not share homology with mosaic penA XXXIV in the region targeted by the assay.

Conclusion
The mosaic penA XXXIV assay demonstrated 97% sensitivity and 100% specificity in predicting alert ESCs MIC values among clinical isolates tested, and was successfully multiplexed with gyrA assay. Clinical utility of this assay may be limited due to false negativity in isolates with non-XXXIV mosaic types, but it could serve as a useful surveillance tool for XXXIV mosaic.

Disclosure
R. Humphries, Roche: Consultant, Consulting fee
β-d-Glucan Testing Is Overused in Patients Without Solid Organ/Stem Cell Transplant or Hematologic Malignancies
Authors: Markou Theodore , Fabre Valeria , Mehta Seema , Shoham Shmuel , Cosgrove Sara E 
Published: October 2017

Abstract

Background
The β-d-glucan (BDG) assay aids in diagnosis of some invasive fungal infections (IFI) in at-risk patients. Due to an increase in the number of BDG tests ordered at Johns Hopkins Hospital in patients not at high risk for IFI, we evaluated the appropriateness of testing and conducted a survey to understand providers’ knowledge about the test.

Methods
From December 2015 to July 2016, we identified inpatients &gt;17 years with at least one BDG test. We did not evaluate patients with solid organ/stem cell transplant or hematologic malignancies as they generally have indications for BDG testing. Using a standard data collection form, one infectious disease (ID) physician reviewed all test for appropriateness; 20% of cases were reviewed by an additional ID physician. Students, housestaff and allied staff from departments of medicine and surgery were surveyed regarding their knowledge of BDG test characteristics including indications and causes of false-positive results.

Results
355 patients with at least one BDG were included. 33% (n = 116) had a risk factor for IFI (e.g., AIDS, immunosuppressing medication, malignancy, total parenteral nutrition, and prolonged ICU stay) although only 13% (n = 48) of these had proved or possible IFI. 49% (n = 173) had no indication for testing. Of these, 4% (n = 8) had inappropriate antifungals started based on BDG results. Being at an intensive care unit or having cirrhosis was associated with inappropriate BDG use (P = 0.03). Most of the 47 clinicians surveyed recognized the utility of BDG in the diagnosis of candidiasis (63%) and Aspergillosis (78%) but only 49% recognized its utility in diagnosis of Pneumocystis. Fifty-two percent identified its lack of utility for diagnosis of Cryptococcus infection but only 44% recognized lack of utility for diagnosing Zygomycetes. The majority of those surveyed were unable to identify causes of false-positive results of the assay.

Conclusion
In patients without solid organ/stem cell transplant or hematologic malignancies, clinicians ordered the BDG assay in the absence of clinical risk or evidence of IFI in almost 50% of patients. Survey results suggest an incomplete understanding of organisms associated with positive BDG tests. Clinicians must be educated about the correct patient population in which a new test should be used.

Disclosures
All authors: No reported disclosures.
Risk Factors Predicting Candida glabrata Bloodstream Infection
Authors: O’Halloran Jane , Kronen Ryan , Lin Charlotte , Hsueh Kevin , Powderly William , Spec Andrej 
Published: October 2017

Abstract

Background
Increased incidence of Candida glabrata (CG) infection is a growing concern in recent years due to the higher rates of fluconazole resistance associated with C. glabrata . This study aimed to create a risk predictive model for C. glabrata in patients with culture-positive candidemia.

Methods
Demographic data, risk factors, laboratory parameters, and outcomes were retrospectively collected on all cases of candidemia occurring at a large tertiary referral hospital between January 2002 and January 2015. Between-group differences were compared using 2 square tests. A risk predictive model was built using multivariate logistic regression.

Results
Of 1,913 subjects with candidemia, 398 (21%) had C. glabrata isolated. Those with C. glabrata were older (mean [SD] 61 [23] vs. 58 [23] years; P &lt; 0.001) and more often female (231 (58%) vs. 681 (45%); P &lt; 0.001). On univariate analysis, age (OR 1.01 [95% CI 1.01,1.02]), gender (0.6 [0.5, 0.7]), history of rectal cancer (2.00 [1.2, 3.5]), other GI malignancy (3.0 [1.5, 6.2]), breast cancer (1.8 [1.1, 3.0]), enteral and parenteral feeding (1.9 [1.2, 3.2]), bowel resection (3.0 [1.4, 6.2]), temperature (0.9 [0.8, 1.0], recent fluconazole use (2.0 [1.4, 2.9]), and The presence of urinary catheter (2.3 [1.4, 3.6]), central line (1.4 [1.1, 1.7) or ventilator (2.2 [1.3, 3.8]) were all associated with C. glabrata infection (P &lt; 0.05) and included in the multivariate modeling. Age, gender, history of rectal malignancy, other GI malignancies, use of enteral or parenteral feeding and recent fluconazole use remained significant (effect size 1.2 [95% CI 1.1, 1.3]; 1.8 [1.4, 2.3]; 2.0 [1.1, 3.6]; 3.0 [1.3, 6.9]; 1.9 [1.0, 3.3]; 2.0 [1.3, 3.0], respectively). The final model had a c-statistic of 0.66 [95% CI 0.63–0.69]). Ninety-day mortality in the C. glabrata group was not significantly different from the non-C. glabrata group (40% (158/398) vs. 42.5% (644/1515).

Conclusion
Underlying bowel pathology was more commonly associated with C. glabrata candidemia than with other candida species. Further exploration of the direct association between C. glabrata and GI malignancy and indirect effects of prior surgery or antifungal use on risk of C. glabrata candidemia are required. Interestingly, mortality did not differ between groups with glabrata and non-glabrata candida blood stream infections. This may reflect increasing empiric use of echinocandin therapy.

Disclosures
A. Spec, Astellas Pharma US, Inc.: Grant Investigator, Research grant
Real-World Experience of Voriconazole Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Single-Center Study
Authors: Chan Shuk-Ying , Neofytos Dionysios , Hughes Rachel M , Huang Yao-Ting , Perales Miguel-Angel , Papanicolaou Genovefa 
Published: October 2017

Abstract

Background
High rates of discontinuation of voriconazole (VCZ) antifungal prophylaxis (AFP) due to toxicities have been reported from single centers in allogeneic hematopoietic (allo-HCT) recipients. We sought to describe (i) adherence to AFP guidelines and (ii) reasons for premature VCZ discontinuation (D/C).

Methods
Retrospective review of 215 adult allo-HCT recipients from September 1, 2014–December 31, 2015 at our center. Per standards of care (SOC), patients received micafungin from Day 2 post-allo-HCT, then switched to VCZ by D7 unless contraindicated, and remained on AFP until cessation of immunosuppression or D100 for high-risk patients. AFP modification, D/C and treatment emergent adverse events (TEAE) regardless of causality were captured through D100. Standard definitions were used for invasive fungal infections (IFI).

Results
Of 215 patients, 42 had contraindications to VCZ at baseline. Of 173 patients included in the analysis, 65 (37.6%) received ex vivo T-cell depleted (TCD) peripheral blood (PB), 15% cord and 47.4% conventional PB or marrow allografts. All TCD recipients received myeloablative conditioning (MA) and all cord recipients received reduced intensity conditioning (RIC). For conventional transplant, 65.9 and 26.8% of the patients received RIC and MA, respectively. One hundred and sixty-eight (97%) patients had normal liver function tests (LFT) at VCZ initiation. One hundred and twenty-nine (74.6%) patients started VCZ by D7 and 95% started by D15. Median duration of VCZ AFP was 68D (IQR 22–91). Abnormal LFTs was the most frequently encountered TEAE (42/58, 72%), followed by neurologic/visual TEAE (11/58, 19%) leading to VCZ D/C. Median time to VCZ D/C due to neurologic/visual TEAE (4D, IQR 4–9) was significantly shorter than abnormal LFTs (25D, IQR 16–42) (P &lt; 0.05). Eight (5%) breakthrough proven/probable IFIs were observed by D180, without significant difference based on transplant types or AFP duration. Duration and reasons for VCZ D/C were shown in Table 1 by HCT type.

Conclusion
75% of the patients started VCZ per SOC and 95% by D15. Most TEAE leading to VCZ D/C were abnormal LFTs in all HCT types, and most commonly in cord HCT. 3) Neurologic/visual TEAE were similar across types. Rates of IFI were 3–4% in CONV and TCD and 12% in UCB.

Disclosures
Y. T. Huang, Merck & Co.: Grant Investigator, Research grant. M. A. Perales, Merck: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. Astella: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. G. Papanicolaou, Astellas Pharma: Consultant and Grant Investigator, Consulting fee, Research grant and Research support. Merck &Co: DSC member and Investigator, Consulting fee, Research grant and Research support
Invasive Mold Infections (IMI) among Liver Transplant Recipients (LTR): Is It Time to Reconsider the Risk Factors that Determine Antifungal Prophylaxis?
Authors: Neyra Karyna , Brizendine Kyle 
Published: October 2017

Abstract

Background
IMI have high mortality among LTR. Prevention is critical. Data supporting guideline-recommended three-tiered approach to antifungal prophylaxis based on risk for IMI are lacking.

Methods
Retrospective study of 534 adult LTR at the Cleveland Clinic (CCF) August 2010–December 2014. We analyzed the association between IMI and risk factors: retransplantation, hemodialysis, reoperation, and fulminant hepatic failure. Model of end-stage liver disease (MELD) was evaluated as novel risk factor. We compared the incidence of IMI among three subgroups: no antifungal prophylaxis, prophylaxis against yeast alone, and prophylaxis against yeast and mold.

Results
Mean age was 56 ± 11 years. 68% were male (n = 364). The most common underlying diseases were hepatitis C virus (32%), hepatocellular carcinoma (28%), alcoholic cirrhosis (19%), and nonalcoholic steatohepatitis (19%). The overall incidence of IMI was 0.9% (n = 5). The incidence of IMI among LTR with (n = 128) and without (n = 406) risk factors was 0.78 and 0.98%, respectively (see Figure). Table 1 details the risk factors and outcomes by subgroups. Only one patient with IMI had a risk factor for mold (reoperation). The other four had none. Incidence of IMI among LTR who did not receive antifungal prophylaxis was 1 and 0% in those who received yeast or mold prophylaxis. There was no association between MELD and IMI.

Conclusion
Risk factors and MELD did not predict IMI. Because risks are used to recommend mold-active prophylaxis, antifungal agent overuse may be a concern. Additional studies are needed to reconsider risk factors so that transplant providers may target antifungal agents appropriately, practice antifungal stewardship and improve outcomes.

Disclosures
All authors: No reported disclosures.
Antifungal Resistance Patterns in Molds Isolated from Wounds of Combat-Related Trauma Patients
Authors: Keaton Nicholas , Mende Katrin , Beckius Miriam , Farmer Aaron , Rizzo Julie , Ganesan Anuradha , Murray Clinton K , Tribble David R , Blyth Dana M 
Published: October 2017

Abstract

Background
An outbreak of trauma-related invasive fungal infections (IFI) occurred in US service members injured in Afghanistan. Empiric treatment included voriconazole (VORI) and amphotericin (AMB) and aggressive surgical debridement. Antifungal susceptibilities (AS) and relation to outcomes are yet to be described.

Methods
Between 2009 and 2013, military trauma patients with initial unique and serial (&gt;3 days after initial isolation) molds isolated from wounds and admitted to Brooke Army Medical Center as part of the Trauma Infectious Disease Outcomes Study were assessed. The AS to AMB, VORI, posaconazole (POSA), isavuconazole (ISA), itraconazole, and caspofungin were determined by broth microdilution with CLSI breakpoint interpretations for Aspergillus spp. and mucormycetes (MM).

Results
Included are 18 patients with 28 initial mold isolates with 72% of IFI diagnosed via histopathology. All patients were male with a median of eight operations. There was a median of 11 days post-injury to mold culture. Initial isolates were five Aspergillus spp., three MM, three Fusarium spp., and combinations of three Aspergillus and MM, two Aspergillus and Fusarium, one Aspergillus and Bipolaris, one MM and Fusarium. A. flavus (AFL) and A. fumigatus (AFU) were all susceptible to AMB and POSA and 25% of AFL were intermediate to VORI. Four A. terreus (AT) isolates had MICs to AMB of 0.25, 1, 2, and 4, and were susceptible to VORI. ISA MIC50 and 90 were one and two for Aspergillus spp. Fusarium spp. MICs were &gt;16 for VORI, POSA, and ISA, with AMB MIC50/90 of two and three. Among MM isolates, 86% were susceptible to AMB and 29% to POSA, and ISA MIC50 and MIC90 were 8 and &gt;16. Five patients had serial isolates. One with serial AFL and AFU received no antifungal therapy, one with AT was treated with VORI, AMB, and POSA, and one with AFL was treated with AMB with no new resistance. The patient with serial MM was treated with AMB and VORI and remained resistant to POSA, but susceptible to AMB. Serial A. elegans acquired new POSA and AMB resistance and ISA MIC increased from 4 to 16 after AMB and VORI exposure.

Conclusion
Antifungal exposure to AMB and VORI was not associated with new resistance within Aspergillus spp., but 50% of MM exposed to this combination developed POSA and AMB resistance. Despite resistance of Fusarium, it was not isolated on subsequent debridements.

Disclosures
All authors: No reported disclosures.
Do Liver Transplant Recipients Have a Higher Risk for Cryptococcosis Than Non-liver Transplant Recipients?
Authors: Sun Hsin-Yun , Cheng Aristine , Ho Cheng-Maw , Hu Rey-Heng , Chou Nai-Kuan , Wang Shoei-Shen , Chen Yee-Chun , Chang Shan-Chwen 
Published: October 2017

Abstract

Background
Patients with liver cirrhosis have an increased risk for cryptococcosis. However, it is unknown whether they remain at a higher risk for cryptococcosis after liver transplantation.

Methods
Patients undergoing solid organ transplantation at a tertiary hospital in Taiwan were included for analysis. Cryptococcosis was defined based on criteria proposed by the European Organization for Research and Treatment in Cancer and the Mycoses Study Group. Only Nystatin oral suspension but no systemic anti-fungal agents was prescribed routinely post-transplant.

Results
From 2001 to 2016, in total, 1576 patients underwent solid organ transplantation, including 756 kidney, 411 liver, 336 heart, 61 lung, and 12 multi-organ transplantation. Cryptococcosis developed in 20 patients (1.3%), including cryptococcemia in 9, pulmonary/urine in 6, meningitis in 3, and surgical site infection in 2. Its incidence was 3.2% (13/411) in liver, 1.5% (5/336) in heart, and 0.3% (2/756) in kidney transplant recipients. Compared with 1165 non-liver transplant recipients, 441 liver transplant recipients had a significant higher incidence of cryptococcosis (3.1% vs. 0.6%, P &lt; 0.01) and developed the disease with a shorter median duration after transplantation (75 vs. 213 days). Cryptococcosis with very-early onset (&lt;30 days after transplantation) developed in 38.5% (5/13) of liver transplant recipients with cryptococcosis, but only 14.3% (1/7) in non-liver transplant recipients. Six patients (30%) died after a median follow-up duration of 399 days, and only two deaths were related to cryptococcosis.

Conclusion
Our findings showed that liver transplant recipients still had a higher risk for cryptococcosis, and the disease developed earlier after transplantation than non-liver transplant recipients.

Disclosures
All authors: No reported disclosures.