bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Risk of Invasive Meningococcal Disease Associated with Primary and Secondary Immunodeficiency
Authors: Lundbo Lene Fogt , Harboe Zitta Barrella , Smith-Hansen Lars , Benfield Thomas 
Published: October 2017

Abstract

Background
Risk of invasive meningococcal disease (IMD) is increased for persistent complement deficiency and HIV infection. However, risk associated with other primary and secondary immunodeficiency is unknown.

Methods
Nationwide case–control study of adults aged &gt;18 years. Cases and matched controls were identified by registry linkage. Primary and secondary immunodeficiencies diagnosed prior to IMD were based on International Classification of Disease (ICD), eight or tenth revision. Odds ratios (OR) with 95% confidence intervals (CI) were estimated by conditional logistic regression after adjustment for sex, age, and the year of IMD.

Results
We identified 2,179 IMD cases (46% male) with a median age of 44 years (interquartile range: 24–63 years). Increased risk of IMD was associated with HIV infection (OR 10.03 [95% confidence interval (CI), 2.91–34.66]), splenectomy/splenic resection (OR 6.88 [95% CI, 3.9–14.82]), solid organ transplantation (SOT) (OR 20.00 [95% CI, 5.00–79.96]), hemolytic anemia (OR 7.78 [95% CI, 2.90–20.90]), antibody deficiency (OR 6.67 [1.11–39.90]) and autoimmune diseases (OR 1.80 [95% CI, 1.44–2.14]). Primary immunodeficiency overall was not associated with an increased risk (OR 1.43 (95% CI, 0.61–3.36)).

Conclusion
This large study of Danish adults with IMD over four decades showed an increased risk of IMD associated with HIV infection, SOT, asplenia, hemolytic anemia, antibody deficiency, and autoimmune disease ranging from 2- to a 20-fold increased risk. Vaccination may be warranted in these populations.

Disclosures
Z. Barrella Harboe, Pfizer: independent physician, Travel grants.
Use of Adjunctive Steroids and Incidence of Delayed Cerebral Venous Thrombosis in Adults with Bacterial Meningitis
Authors: Gallegos Cinthia , Salazar Lucrecia , Tobolowsky Farrell , Nigo Masayuki , Hasbun Rodrigo 
Published: October 2017

Abstract

Background
Bacterial meningitis is associated with significant morbidity and mortality. Adjunctive steroids decrease mortality in adults with meningitis due to Streptococcus pneumoniaebut its use has been recently linked to the development of delayed cerebral thrombosis (DCT). The purpose of our study was to determine the utilization of adjunctive steroids and its incidence.

Methods
A retrospective multicenter study involving 10 Houston area hospitals from 2008 to 2016. Data was gathered from 120 adults with culture proven community-acquired bacterial meningitis. An adverse clinical outcome was defined as a Glasgow outcome score of 1–4.

Results
There was a total of 120 patients enrolled; of which, 55% were male. Adjunctive intravenous steroids were administered in 82 (68%) patients with bacterial meningitis. The steroid median duration was 3.8 days. The average age of patients was 55.3 years (range 20–92). There was no difference in Charlson comorbidity score, immunosuppression, presence of sinusitis or otitis, fever, meningeal signs or symptoms, abnormal neurological findings, Gram stain or severity of illness, based on Aronin score (P &gt; 0.05), between patients who received steroids and those that did not. Older patients, age &gt;65, were less likely to receive adjunctive steroids (P = 0.028). The most common organism isolated was Streptococcus pneumoniae, which occurred in 46 (38%) patients. An adverse clinical outcome was seen in 46 (38%) patients with no difference between groups (P = 0.819). Delayed cerebral thrombosis was seen in a total of 9 (7.5%) patients with bacterial meningitis. Of these, 1 patient (2.6%) did not receive steroids and the remaining 8 (10.9%) patients received steroids (P = 0.158). Five cases of meningitis that were complicated by DCT were caused by Streptococcus pneumoniae, 1 by Listeria monocytogenes, and 2 with Staphylococcus aureus.

Conclusion
Adjunctive steroids are being used in the majority of adults with bacterial meningitis but it is possibly associated with DCT, a devastating complication

Disclosures
All authors: No reported disclosures.
A Single-center, Quasi-experimental Study to Evaluate the Impact of a Multiplex Polymerase Chain Reaction System Combined with Antimicrobial Stewardship Intervention on Time to Targeted Therapy in Patients with Suspected Central Nervous System Infection
Authors: Powell Kelsey , Revolinski Sara , Gibble Allison , Daniels Anne , Wainaina J Njeri , Huang Angela 
Published: October 2017

Abstract

Background
Empiric treatment for central nervous system (CNS) infections consists of coverage with multiple antimicrobial agents that may be continued until a pathogen can be identified. Identification may take significant time to result, leading to extended durations of multiple antimicrobial agents, delays in targeted therapy and subsequent adverse effects, such as nephrotoxicity and Clostridium difficile infection. A multiplex polymerase chain reaction (PCR) system that can identify 14 pathogens responsible for community-acquired CNS infections in 1 hour was recently FDA-approved for cerebrospinal fluid (CSF) analysis. The objective of this study was to determine the effect of this PCR paired with antimicrobial stewardship (AMS) team intervention on the time to targeted therapy.

Methods
During the intervention (Int) phase (January 25, 2017–April 30, 2017), all PCR results were called to the AMS team, who reviewed clinical data and provided antimicrobial recommendations per pre-determined protocol. Recommendations consisted of de-escalation or addition of therapy. The pre-intervention (PI) group consisted of patients with CSF culture obtained between January 25, 20116 and April 30, 2016.

Results
A total of 138 patients were evaluated; 46 in the Int group and 92 in the PI. Of the 46 patients in the Int group, 25 had a negative PCR result and were never initiated on antimicrobials. One patient required antimicrobial escalation. Twenty patients were started on empiric therapy and were candidates for de-escalation. In the PI group, there were no patients with CSF cultures that required therapy escalation, while 33 patients were initiated on empiric antimicrobials. Results from the subgroup of patients in whom empiric therapy was started as shown in Table 1.

Conclusion
Implementation of a multiplex PCR with AMS intervention resulted in decreased time to targeted therapy.
This project was funded through a competitive stewardship grant provided by Merck & Co.

Disclosures
S. Revolinski, Merck: Grant Investigator, Research grant; J. N. Wainaina, Merck: Grant Investigator, Research grant; A. Huang, Merck: Grant Investigator, Research grant
Strongyloides stercoralis Infection Incidence, Risk Factors and Outcomes Among Solid Organ Transplant Candidates and Recipients; a Florida Center Experience
Authors: Castro Robert , Aslam Sadaf , Albers Christopher , Gutierrez Louise , Gonzalez Marijesmar , Alrabaa Sally 
Published: October 2017

Abstract

Background
Most infections of Strongyloides stercoralis are asymptomatic but can be fulminant in the immunosuppressed. Fatal infections in transplant patients have been reported in United States but incidence estimates are lacking. Our protocol for Strongyloides until 2009 screened immigrants and those with travel history to endemic areas. In 2010, we began universal screening of SOT candidates due to a case of disseminated Strongyloidiasis in an unscreened lung transplant recipient with unknown risk factors. We calculated the incidence of Strongyloides stercoralis in our SOT candidates and associated risk factors, treatment, and outcomes since protocol change.

Methods
A retrospective review was performed of patients who underwent transplant evaluation from January 2014 to July 2016. Patients positive for Strongyloides stercoralis were reviewed for age, sex, ethnicity, place of birth, travel history, occupation, eosinophilia, treatment, and outcome. We report descriptive statistics.

Results
Of a total of 2,351 SOT patients, 116 tested positive (heart 33, lung 24, kidney 26, liver 31, pancreas 2) with an incidence of 4.9%. A total of 113 charts were available for review. The characteristics of the patients are summarized in Table 1. Fifty patients had traditional risk factors (44%) and 63 lacked them (56%). Eosinophilia was present in 15% of cases. Of those transplanted, 87% received prophylaxis and none developed active Strongyloidiasis.

Conclusion
Our results show that S. stercoralis infection has a relatively high incidence in SOT patients and universal screening identified a substantial number that otherwise would go undetected, placing the transplant patient at risk of a fatal, yet preventable complication.

Disclosures
All authors: No reported disclosures.
Outcomes of Kidney Transplantation with a CMV Matching Allocation Schema
Authors: Strasfeld Lynne , Basuli Debargha , Norman Douglas , Langewisch Eric , Olyaei Ali , Lockridge Joseph 
Published: October 2017

Abstract

Background
Cytomegalovirus (CMV) infection continues to be a major cause of morbidity in kidney transplant recipients. The CMV donor-positive (D+)/recipient-negative (R−) serostatus pairing poses highest risk for CMV disease.

Methods
In September 2012, we adopted a CMV matching allocation policy at the centers served by our organ procurement organization, the Pacific Northwest Transplant Bank. CMV serostatus was used as a criterion in determining deceased donor kidney allocation, whereby R− kidney transplant recipients were preferentially paired with a D− organ, and R+ recipients with an R+ organ. We performed a retrospective analysis of CMV-related outcomes for 400 consecutive kidney recipients, 196 prior to (January 1, 2010– August 31, 2012) and 204 following (September 1, 2012–December 3, 2014) implementation of the CMV matching allocation schema at our center. We also looked at waitlist time for patients transplanted during the same period.

Results
The percentage of D+/R− transplants performed decreased from 17.3% to 2.5% (P &lt; 0.001) after implementation of the CMV matching allocation strategy (Figure 1). CMV viremia decreased from 13.3% to 5.9% (P = 0.0118), and CMV syndrome or disease decreased from 9.2% to 2.9% (P = 0.00859) (Table 1). The percentage of patients treated for CMV infection overall decreased from 10.7% to 5.4% (P = 0.0498). Median days on the waitlist prior to transplantation increased from 793 (PRE) to 944 (POST) due to growing wait list size, but neither R− nor R+ patients appeared to be disadvantaged: wait times increased from 808.5 to 958 for the R− subset and from 777.5 to 933 for the R+ subset (Figure 2).

Conclusion
CMV disease occurred infrequently in our cohort, in the context of 6 months of valganciclovir prophylaxis post-transplant and post-prophylaxis pre-emptive monitoring strategy for our D+/R− recipients. Following implementation of an allocation schema that took CMV serostatus into account, the rate of CMV infection and antiviral treatment decreased significantly.

Disclosures
L. Strasfeld, Merck: Independent Contractor, Salary
Collaborative Use Repurposing Engine (CURE): FDA-NCATS/NIH Effort to Capture the Global Clinical Experience of Drug Repurposing to Facilitate Development of New Treatments for Neglected and Emerging Infectious Diseases
Authors: Stone Heather , Sacks Leonard , Tiernan Rosemary , Duggal Mili , Sheils Timothy , Southall Noel 
Published: October 2017

Abstract

Background
Repurposing approved products has proven a critical strategy to serve unmet medical needs. Historically, 40% of drugs approved for treatment of tropical diseases were repurposed, including albendazole for echinococcosis and neurocysticercosis, and azithromycin for trachoma. Advantages of repurposing include that approved drugs are well characterized, do not require expensive development programs needed for new drugs, and are frequently active against multiple diseases. Owing to the limited number of drugs approved to treat neglected tropical diseases (NTDs) and emerging or drug-resistant infections, healthcare practitioners use existing drugs in novel ways to treat patients with these conditions. This clinical experience, regardless of whether the outcomes are positive or negative, often is not reported or shared, and the knowledge is therefore lost.

Methods
FDA and NCATS/NIH have built a pilot program called Collaborative Use Repurposing Engine (CURE) to capture and centralize the global experience of new uses of approved medical products to treat emerging threats, NTDs, and multidrug-resistant organisms. CURE includes a website (https://cure.ncats.io/) and a mobile app (download “PROJECT CURE” at Google Play Store). CURE provides a simple case report form for health care providers to report their experiences, and a collection of cases that have already been reported (including successful and unsuccessful treatments) which they can browse. Healthcare providers who register can also participate in a Treatment Discussion Forum, allowing for engagement with fellow clinicians. CURE could be a global network connecting major treatment centers, academics, private practitioners, government facilities, and other clinicians serving as a means of rapid communication of treatment outcomes between providers treating patients with these conditions.

Results
See attached screen shots.

Conclusion
Although this evidence may be insufficient to establish the safety or effectiveness of a new use for an existing product, this clinical experience may provide signals and generate hypotheses for future clinical study. It may allow for rapid identification of promising treatment approaches in urgent situations such as during outbreaks of emerging infectious threats.

Disclosures
All authors: No reported disclosures.
Evolution of Antibiotic Tolerance During Oxacillin, Daptomycin and Dalbavancin Therapy Results in Breakthrough Staphylococcus aureus Bacteremias
Authors: Berti Andrew , Schroeder Jeremy , Rottier Aaron , McCrone Sue , Wang Jade , Rose Warren 
Published: October 2017

Abstract

Background
Clinicians can employ suppressive antimicrobial therapy in patients with persistent or relapsing bacteremia. However, bacteria with favorable susceptibility profiles may exhibit antimicrobial tolerance wherein bacteria cannot proliferate yet can survive in high concentrations of antibiotics. The antimicrobial tolerance phenotype can thwart efforts to prevent bacteremia recurrence with prolonged exposure to antimicrobials and may contribute to breakthrough bacteremias while the patient is receiving active therapy. Here we present a patient case consisting of multiple episodes of breakthrough Staphylococcus aureus bacteremia over several years in the setting of appropriately dosed antimicrobial suppressive therapy and describe organism mutations that developed during therapy.

Methods
Six clinical bloodstream isolates were recovered from the patient during distinct episodes of MSSA bacteremia over a 5-year period. The identified source for each bacteremia was a central line infection (CLABSI). Isolates recovered were susceptible to the individual therapies received, which included oxacillin, daptomycin, and dalbavancin. Bacterial whole genome sequence data were collected using Illumina technology.

Results
The first two isolates (USA600) and the last four isolates (USA800) represent distinct populations and suggest that a distinct MSSA strain displaced the previous population between bacteremia episodes 2 and 3. Of note, all of these strains were able to survive and establish breakthrough bacteremias despite favorable susceptibility profiles to the agents used as suppressive therapy. Although the MICs remain low and in the susceptible range to oxacillin, daptomycin, and dalbavancin, these isolates progressively developed significant antimicrobial tolerance phenotypes, which coincided with mutations in walK (yycG), htrA2, ftsW, ebh and iarS that may be advantageous to survival under antibiotic pressure.

Conclusion
These genetic, phenotypic and patient case data identify important changes that can occur in bacterial populations over time that are distinct from antibiotic susceptibility. These findings point to factors that may result in breakthrough bacteremia, limiting the clinical utility of antimicrobial suppressive therapy.

Disclosures
W. Rose, Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Merck: Grant Investigator, Research grant; The Medicines Company: Speaker’s Bureau, Speaker honorarium; Visante, Inc: Consultant, Consulting fee.
Carbapenem-resistant Enterobacteriaceae (CRE) or Delayed Appropriate Therapy (DAT)—Does One Affect Outcomes More Than the Other Among Patients With Serious Infections Due to Enterobacteriaceae?
Authors: Lodise Thomas , Berger Ariel , Altincatal Arman , Wang Rosa , Bhagnani Tarun , Gillard Patrick , Bonine Nicole G 
Published: October 2017

Abstract

Background
While CRE and DAT are both associated with worse outcomes, their relative impact to the clinical and economic burden among patients with infections due to Enterobacteriaceae is not well understood. This study assessed the independent and combined effect of these two items on selected outcomes among patients with these infections.

Methods
Hospitalized adults between July 2011 and September 2014 were identified from Premier Hospital Database. Patients were diagnosed with complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, and had a positive culture for Enterobacteriaceae from a site consistent with infection type (date of culture draw was index date). Patients were required to receive antibiotics on this date or ≤2 days after. Delayed therapy was defined as no receipt of an antibiotic with microbiologic activity during this period. CRE was defined as resistant to ≥1 carbapenems. Inverse probability weighting and multivariate regression analyses were used to estimate the associations between CRE status, DAT and outcomes. Logistic models were used for composite mortality (in-hospital death or discharge to hospice), in-hospital mortality, and discharge to home (reference group was timely therapy plus non-CRE); generalized linear models, for post-index duration of antibiotic therapy, hospital length of stay (LOS), and costs.

Results
A total of 50,069 patients were included in the analyses; 514 had CRE and 16,414 received DAT. A gradient effect was observed across strata as the burden of serious infections was least among the reference group, and greatest among patients with CRE infection who received DAT (Figure). For example, as compared with the reference group, the risk of composite mortality increased nearly fourfold in patients with CRE infection who received DAT; total in-hospital costs more than doubled.

Conclusion
DAT has a stronger association than CRE on outcomes, and their effects are synergistic. Given these findings, better methods of early pathogen identification (especially organisms such as CRE) should reduce time to appropriate therapy, thereby improving outcomes in this patient population.

Disclosures
T. Lodise, Allergan plc: Consultant, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; A. Berger, Allergan plc: Consultant, Consulting fee; A. Altincatal, Evidera: Consultant, Salary; R. Wang, Evidera: Employee, Salary; T. Bhagnani, Allergan plc: Consultant, Consulting fee; P. Gillard, Allergan plc: Employee, Salary; N. G. Bonine, Allergan plc: Employee, Salary
HIV Transmission Rates and Factors Associated with Recent HIV Infection: Results from the Ndhiwa HIV Impact Assessment, South Nyanza, Kenya, 2012
Authors: Agyemang Elfriede , Zeh Clement , Mukui Irene , Maman David , Kim Andrea 
Published: October 2017

Abstract

Background
Identifying populations with high HIV transmission rates is important for prevention and treatment strategies. Persons with recently acquired HIV infection are drivers of HIV transmission due to high levels of HIV viral load (VL). We assessed annual HIV transmission rates and factors associated with recent infection to inform targeted interventions in a hyperendemic region in Kenya.

Methods
The Ndhiwa HIV impact assessment was a population-based survey among persons aged 15–59 years living in South Nyanza, Kenya in 2012. Respondents were tested for HIV using rapid tests per national guidelines and provided blood for centralized testing. Specimens from HIV+ persons were tested for VL and recent infection. Recent infection was defined as normalized optical density value &lt;1.5 on the Limiting Antigen Enzyme Immunoassay, VL &gt;1,000 copies/mL, and no report of HIV treatment. The annual HIV transmission rate per 100 persons living with HIV (PLHIV) was calculated as HIV incidence divided by HIV prevalence, multiplied by 100. Annualized HIV incidence was estimated, assuming a mean duration of recent infection of 141 days (confidence interval [CI] 123–160). Multivariate analysis identified independent factors associated with recent infection. Estimates were adjusted for survey design.

Results
Of 6,076 persons tested, 1,457 were HIV+, and 28 were recently infected. HIV incidence and prevalence were 1.7% (CI 1.5–2.0) and 24.1% (CI 22.6–25.5), respectively. Per 100 PLHIV, the annual HIV transmission rate was 7.0 and varied by sex (4.6 male vs. 8.3 female), age (5.2 aged 30+ vs. 10.4 aged &lt;30), and residence (1.4 Kobama vs. 12.0 Riana vs. 12.1 Pala divisions). After controlling for age, sex, and residence, recently infected persons were significantly more likely to reside in Pala division (AOR 8.3, CI 1.1–62.9) than HIV-uninfected persons.

Conclusion
Approximately 7 in 100 PLHIV transmitted to HIV-uninfected persons in South Nyanza in 2012, similar to national rates observed in the 2012 Kenya AIDS Indicator Survey. HIV transmission rates were higher in females than males, younger than older, and Riana and Pala than other divisions. Residence in Pala was a risk factor for recent infection. These findings could guide prioritization of interventions to interrupt HIV transmission in this hyperendemic setting.

Disclosures
All authors: No reported disclosures.