bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of New HIV Infections among Adults ≥45 Years—New York City, North Carolina, San Francisco, 2011–2013
Authors: Evans Mary , Patala Anne , Campbell Ellsworth , Westheimer Emily , Gay Cynthia L , Cohen Stephanie E , Switzer William M , Peters Philip J 
Published: October 2017

Abstract

Background
While HIV prevention activities are often focused on younger people, older people can also be at risk for HIV infection. We aimed to characterize HIV transmission in older adults.

Methods
The STOP study was a multi-site prospective study of persons with acute HIV infection (AHI) from 2011 to 2013. Older adults were defined as ≥45 years and younger persons were 13–44 years. AHI was defined by a negative rapid test but a reactive antigen/antibody or HIV RNA test. We performed bivariate analysis using Pearson’s chi-square and odds ratios to examine associations between older age and transmission characteristics. Among persons with HIV-1 polymerase (pol) sequences, transmission linkages were inferred when the genetic distance between sequences was &lt;1.5% and did not indicate directionality of transmission.

Results
Among 86,836 participants (median age, 29 years; 75.0% male; 51.8% MSM), HIV infection was diagnosed in 176 (1.46%) of 12,036 older adults compared with 1,150 (1.53%) of 74,800 younger people (P = 0.56). Among HIV-infected persons, AHI was diagnosed in similar proportions of older and younger people (13.1% vs. 12.6%; P = 0.86). Among HIV-infected persons who participated in partner notification (n = 1,326), older adults were less likely to report meeting a sex partner online (11.3% vs. 26.9%; OR 0.52, 95% CI = 0.35–0.78) and were less likely to name ≥2 sex partners (31.5% vs. 46.8%; OR = 0.28, 95% CI = 0.15–0.53) compared with younger people. Among HIV-infected persons with HIV-1 pol sequences (n = 537), similar proportions of older and younger people had viruses that genetically linked with another study participant (15.9% vs. 23.5%; OR 0.62, 95% CI 0.31–1.22) (Figure).

Conclusion
In this study, older adults had a similar frequency of newly diagnosed HIV infection, acute infection, and genetic linkage compared with younger people, suggesting that increased HIV prevention efforts may be needed in this population.

Disclosures
All authors: No reported disclosures.
Impact of Procalcitonin Guidance on the Management of Adults Hospitalized with Pneumonia
Authors: Walsh Thomas , DiSilvio Briana , Hammer Crystal , Beg Moeezullah , Vishwanathan Swati , Speredelozzi Daniel , Moffa Matthew , Hu Kurt , Abdulmassih Rasha , Makadia Jina , Sandhu Rikinder , Naddour Mouhib , Chan-Tompkins Noreen , Trienski Tamara , Watson Courtney , Bremmer Derek 
Published: October 2017

Abstract

Background
Community-acquired pneumonia and healthcare-associated pneumonia are often treated with prolonged antibiotic therapy. Procalcitonin (PCT) has effectively and safely reduced antibiotic use for pneumonia in controlled studies. However, limited data exist regarding PCT guidance in real-world settings for management of pneumonia.

Methods
A retrospective, preintervention/postintervention quality improvement study was conducted to compare management for patients admitted with pneumonia before and after implementation of PCT guidance at two teaching hospitals in Pittsburgh, Pennsylvania. The preintervention period was March 1, 2014 through October 31, 2014, and the post-intervention period was March, 1 2015 through October 31, 2015.

Results
A total of 152 and 232 patients were included in the preintervention and postintervention cohorts, respectively. When compared with the preintervention group, the mean duration of therapy decreased (9.9 vs. 6.1 days; P &lt; 0.001). More patients received an appropriate duration of 7 days or less (26.9% vs. 66.4%; P &lt; 0.001). Additionally, mean hospital length of stay decreased in the postintervention group (4.9 vs. 3.5 days; P = 0.006). Pneumonia-related 30-day readmission rates (7.2% vs. 4.3%; P = 0.99) were unaffected. In the postintervention group, patients with PCT levels &lt; 0.25 µg/l received shorter mean duration of therapy compared with patients with levels &gt;0.25 µg/l (8.0 vs. 4.6 days; P &lt; 0.001) as well as reduced hospital length of stay (3.9 vs. 3.2 days; P = 0.02).

Conclusion
In this real-world practice study, PCT guidance led to shorter durations of total antibiotic therapy and abridged inpatient length of stay without affecting hospital re-admissions.

Disclosures
All authors: No reported disclosures.
Antibiotic Consumption and Antibiotic Resistance Across Organisms, Drugs, and Consumer Groups
Authors: Olesen Scott , Barnett Michael , MacFadden Derek , Lipsitch Marc , Grad Yonatan H 
Published: October 2017

Abstract

Background
Antibiotic consumption is considered a major driver of antibiotic resistance, but it remains unclear whether the consumption–resistance relationship is apparent for many organisms and drugs, and whether aggregate consumption is the best predictor of resistance.

Methods
We conducted a landscape assessment of the consumption-resistance relationship by comparing a 20% sample of Medicare Part D outpatient antibiotic pharmacy claims with a nationwide survey of hospital antibiotic susceptibility reports. Antibiotic consumption was summarized in individual states and hospital-referral regions (HRRs) using traditional, aggregate consumption or by metrics that account for the concentration of consumption in a few individuals (Gini coefficient). The consumption–resistance relationships for 17 organism–drug combinations were simultaneously evaluated (Spearman’s rho; linear models predicting resistance from aggregate consumption and Gini coefficient) and corrected for multiple-hypothesis testing (Benjamini–Hochberg).

Results
We identified a significant correlation between aggregate consumption of an antibiotic and an organism’s reported resistance to that antibiotic in only a few cases: quinolones and E. coli (Spearman’s rho = 0.65, adjusted P &lt; 10−4) and E. cloacae (rho = 0.50, adjusted P = 0.006). In other cases, notably E. coli with trimethoprim–sulfamethoxazole, the distribution of antibiotic consumption among consumers has a marginal relationship with antibiotic resistance (−1.0 p.p. resistance per p.p. Gini coefficient of consumption among consumers, unadjusted P &lt; 0.001).

Conclusion
There is a clear correlation between aggregate consumption of an antibiotic and resistance of an organism to that antibiotic in only a few cases, suggesting that antibiotic steward efforts might maximize their effectiveness by focusing on particular organisms, drugs, and consumer groups rather than overall, aggregate consumption.

Disclosures
All authors: No reported disclosures.
Incidence of UL97 Resistance Mutations in Infants with Congenital Cytomegalovirus Disease Receiving 6 Months of Oral Valganciclovir Therapy
Authors: James Scott H , Conner Ra’Shun L , Kimberlin David W , Whitley Richard , Prichard Mark N 
Published: October 2017

Abstract

Background
A recently completed Phase 3 randomized, controlled, double-blind, multicenter study of infants with symptomatic congenital cytomegalovirus (CMV) disease receiving 6 months of oral valganciclovir (VGCV) therapy represents the largest such population in which to evaluate treatment-emergent antiviral resistance. The most common mechanism of CMV antiviral resistance occurs through mutations in the CMV UL97 gene that confer resistance to ganciclovir (GCV). Genotypic resistance analyses were performed on infants receiving 6 months of VGCV to assess the incidence of antiviral resistance due to UL97 sequence variants.

Methods
Resistance analyses were performed by conventional DNA sequencing of the UL97 gene at multiple time points. Following CMV DNA extraction from frozen whole blood specimens, the UL97 gene was amplified with a double nested polymerase chain reaction method and sequenced to identify polymorphisms and mutations that might confer GCV resistance.

Results
Forty-six infants with symptomatic CMV disease who received a 6-month course of VGCV underwent resistance analysis to identify UL97 sequence variants. In addition to a range of natural polymorphisms known to have no effect on antiviral susceptibility, 2 subjects developed UL97 mutations known to confer resistance to GCV (A594V and G598S detected in one subject; E596G detected in another), yielding an incidence of 4%. Each of these resistance mutations occurred in specimens collected after at least 4 months of antiviral therapy. As evaluated in the original Phase 3 trial, neither of these infants showed an improvement in hearing outcome.

Conclusion
The development of treatment-emergent UL97 resistance mutations was determined in a controlled study population of infants with congenital CMV disease receiving 6 months of VGCV. This targeted resistance analysis demonstrated an incidence approaching the total incidence of antiviral resistance for CMV disease in some immunocompromised populations, such as solid-organ transplant recipients. Further studies within this study population are warranted to elucidate the risk of emerging antiviral resistance and to assess clinical impact as well as the potential need for combination antiviral therapy.

Disclosures
All authors: No reported disclosures.
Induced Hypothermia in Patients with Septic Shock and Ventilator-demanding Respiratory Failure
Authors: Itenov Theis Skovsgaard , Johansen Maria Egede , Bestle Morten , Thormar Katrin , Hein Lars , Gyldensted Louise , Lindhardt Anne , Christensen Henrik , Damby Stine Estrup , Pedersen Henrik Planck , Harmon Matthew , Soni Uday Kant , Perez-Protto Silvia , Wesche Nikolaj , Berthelsen Rasmus Ehrenfried , Skram Ulrik , Petersen Asger , Mohr Thomas , Waldau Tina , Poulsen Lone Museus , Strange Ditte , Christensen Ole , Juffermans Nicole P , Sessler Daniel , Tønnesen Else , Kristensen Dennis , Cozzi-Lepri Alessandro , Lundgren Jens , Jensen Jens Ulrik Stæhr 
Published: October 2017

Abstract

Background
Animal models of serious infection suggest that 24 hours of induced hypothermia improves circulatory and respiratory characteristics and enhances survival, but whether therapeutic mild hypothermia in such conditions is of clinical benefit remains unknown. We, therefore, tested whether reducing core temperature to 32–34oC in critically ill patients with septic shock and ventilator-demanding respiratory failure improves survival and reduces organ dysfunction.

Methods
In this multi-national trial, patients with septic shock were enrolled within 6 hours of onset of septic shock and ventilator-demanding respiratory failure and randomized 1:1, stratified by site (target sample = 560), to routine thermal management or 24 hours of induced hypothermia (target 32–34°C) followed by 48 hours of normothermia. Other aspects of care were per routine in each participating center. The primary endpoint was 30-day all-cause mortality.

Results
At the third ordinary interim analysis, after recruitment of 432 participants, the Data and Safety Monitoring Board recommended the trial be terminated for futility; the conditional power for rejection of the null hypothesis in favor of efficacy was null. In the induced hypothermia group, target temperature was reached within median 3.2 hours [IQR: 2.2, 4.8], and maintained for 24 hours [IQR: 24, 24] (Figure 1). There was no evidence for a difference in 30-day mortality risk in patients randomized to hypothermia (96/217) vs. routine thermal management (77/215): relative risk 1.24 [95% CI: 0.98, 1.56] (Figure 2). At the end of the temperature intervention (72 hours), more patients assigned to hypothermia were in continued shock (vasoactive medication 71% vs. 58%; P = 0.01), and fewer cooled patients had inflammatory control (32% vs. 47% had CRP decline of &gt;30%, P = 0.005). More harm from cooling was seen in patients entering the trial with normal renal function and with normal platelet count (P for interaction &lt; 0.05).

Conclusion
Among patients with septic shock and ventilator-demanding respiratory failure, induced hypothermia did not improve survival, but adversely affected the duration of shock, and inflammatory control. Induced hypothermia should not routinely be used in patients with septic shock.

Disclosures
All authors: No reported disclosures.
Prevalence and Acquisition of MRSA During Incarceration at a Large Inner-city Jail
Authors: Popovich Kyle J , Zawitz Chad , Aroutcheva Alla , Payne Darjai , Schoeny Michael , Richardson Emma , Hayden Mary K , Hota Bala , Weinstein Robert A 
Published: October 2017

Abstract

Background
USA300 MRSA is endemic in certain communities, with congregate settings such as urban jails potentially facilitating spread. The extent of MRSA transmission in jail is unclear, a controversy that impacts prevention strategies. We determined the prevalence of MRSA colonization at jail entrance and defined the acquisition rate during incarceration.

Methods
Men incarcerated at the Cook County Jail, one of the largest US single-site jails, were enrolled within 72 hours of intake. Surveillance cultures (nares, throat, groin) were collected to determine prevalence of MRSA colonization. A survey was administered to identify predictors of colonization. Detainees still in jail at Day30 had cultures repeated to determine MRSA acquisition rate. Univariate and multivariate analysis was performed to identify predictors of MRSA colonization.

Results
A total o 402 men (447 unique incarcerations) have so far been enrolled (77% AA, 11% Hispanic) with 92% previously in jail (20% in past 6 months). The prevalence of MRSA colonization at intake was 18.6% (83/447), with 39% of those colonized solely in the throat or groin. At 30 days: 10% (9/92) of initially negative men acquired MRSA; 14 admission positives remained colonized while 11 lost colonization. On univariate (Table), predictors of MRSA colonization at entrance to the jail were: methamphetamine use (METH), unstable housing, current skin infection, and care at an outpatient Clinic A that emphasizes comprehensive care to the LGBTQ community. In this cohort, METH use was associated with reporting being a man who has sex with men vs. not (35% vs. 9%, P &lt; 0.001) and was common among men with care at Clinic A (18% vs. 3%, P &lt; 0.001). On multivariate with adjustment for race/ethnicity and HIV status, current skin infection and care at clinic A were associated with MRSA. Preliminarily, sharing personal items was associated with MRSA acquisition at Day30 (OR = 5.6, 95% CI,1.3, 23.3, P = 0.02).

Conclusion
We found that a relatively high proportion of individuals enter the jail colonized with MRSA and the jail may amplify rates. Entrance colonization risk factors point to possible community reservoirs. Enrollment is ongoing but results suggest an intervention in jail could impact MRSA rates in the jail and in the surrounding community.

Disclosures
M. K. Hayden, Sage, Inc: Sage is contributing product to healthcare facilities participating in a regional collaborative on which I am a co-investigator. Neither I nor my hospital receive product., Sage is contributing product to healthcare facilities participating in a regional collaborative on which I am a co-investigator. Neither I nor my hospital receive product.; Clorox, Inc.: I have received funding from Clorox for an investigator-initiated clinical trial., Research support; CDC: Grant Investigator, Research grant
Strain-level Determination of the Contribution of Gut Microbiota to the Development of Bacteremia in Patients Undergoing Stem Cell Transplantation
Authors: Andermann Tessa , Tamburini Fiona B , Tkachenko Ekaterina , Senchyna Fiona , Banaei Niaz , Bhatt Ami 
Published: October 2017

Abstract

Background
Infection is a major preventable cause of transplant-related morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HCT). Bacteremia is the most common infectious complication in HCT, often occurring during periods of mucositis when the risk for microbial translocation from the intestine is increased. Prior research in HCT patients using 16S rRNA sequencing demonstrated that gut microbiota dominance by either Enterococcus spp. or Proteobacteria was associated with the development of bacteremia with Enterococcus spp. and Gram-negative organisms, respectively. No studies to date, however, have compared bacteremia isolates and gut microbiota samples at a strain-specific level using next-generation shotgun metagenomic sequencing (NGS).

Methods
In order to assess the degree of genetic similarity between bacteremia isolates and the gut microbiota, we identified patients who had undergone HCT at Stanford and developed a bacteremia between October 2015 and September 2016 for whom we had both saved blood culture isolates and stool samples within 30 days preceding bacteremia. We identified 15 patients from whom we had 17 bacteremia isolates, and performed NGS (Illumina HiSeq 4000) on stool and isolate DNA. We generated draft assemblies of isolate genomes using the SPAdes assembler, and aligned stool metagenomic reads to the draft isolate genomes using Bowtie2, filtering reads for perfect end-to-end alignment.

Results
Enteric gram-negative bacteremia isolates were identical to those in the gut microbiota, as has been demonstrated in prior studies using older strain-typing Methods. Surprisingly, we also identified gram-positive organisms that were identical in both the blood and stool prior to bacteremia, which challenges existing dogma regarding sources of gram-positive bacteremia-causing organisms.

Conclusion
Using a highly sensitive and accurate NGS-based strain typing method, we provide evidence of translocation of organisms from the gut microbiota and subsequent bacteremia. The gut was confirmed as a source for both classic enteric gram-negative and classically non-enteric Gram-positive bacteremia in HCT patients. These findings may have implications for the origins of bacteremia in HCT patients previously classified as CLABSIs.

Disclosures
A. Bhatt, Janssen Human Microbiome Institute / Johnson and Johnson: Consultant, Consulting fee
The Gut Microbiota of Healthy Infants in the Community is a Reservoir for ESBL and Carbapenemase Producing Bacteria.
Authors: Saleem Ali , Allana Ahreen , Hale Lauren , Qureshi Shahida M , Hotwani Aneeta , Rahman Najeeb , Khan Asia , Seed Patrick , Arshad Mehreen 
Published: October 2017

Abstract

Background
The recent rapid rise of Extended-spectrum Β Lactamase producing Gram-negative bacteria (ESBL-GNB) has seriously threatened the treatment of common infectious diseases. Neonates have an immature immune system and a delay in appropriate treatment due to ESBL-GNB sepsis can be fatal. This problem of delayed therapy is magnified in the developing world where 99% of the deaths from community acquired neonatal sepsis occur. Additionally ESBL E. coli such as the strain ST131 are known to be persistent gut and vaginal colonizers. In animal models, these strains out-compete colonization with drug-sensitive, commensal E. coli. Gut colonization with ESBL-GNB in infants may therefore have a profound impact on their microbiome and increase their risk of sepsis. Pakistan is a lower middle income country with high antibiotic use per capita and a sharp increase in ESBL-GNB infections. Recent data show that &gt;50% of E. coli isolates from reproductive-aged women of Pakistan are resistant to more than one class of antibiotics. We aimed to determine the rates of gut colonization with ESBL-GNB among healthy infants in a community setting.

Methods
Stool samples were collected from 100 healthy infants living in a Pakistani suburban community between the ages of 5 and 7 months. Samples were plated on MacConkey agar to select for Gram-negative bacteria. Isolates were screened for resistance against several antimicrobial classes. Molecular testing of the stool samples was done using primers targeting conserved regions of ESBL and carbapenemase genes.

Results
Forty-eight percent of the infants were positive for ESBL producing Gram-negative bacteria, the majority of which were E. coli, and 7.5% were positive for carbapenemase producers, all of which belonged to Klebsiella spp. Molecular testing showed that 85% of the infant stools were positive for TEM β-lactamase gene, 68% for the CTX-M β-lactamase gene and 33% for the KPC carbapenemase gene.

Conclusion
The widespread colonization of infants in a developing country with ESBL-GNB is highly concerning. Further, our studies have revealed that the resistome of otherwise healthy infants may be a major reservoir of antibiotic genes in the community. Gut microbiome analysis of the potential impact of colonization with antibiotic-resistant bacteria is on-going.

Disclosures
All authors: No reported disclosures.
The Effect of National Healthcare Safety Network (NHSN) Rebaselining on Community Hospital SIRs
Authors: Hostler Christopher , Moehring Rebekah W , Baker Arthur W , Smith Becky , Adcock Linda , Wood Brittain , Cook Evelyn , Crane Linda , Cromer Andrea , Lockamy Kathy , Louis Susan , Padgette Polly , Woods Christopher W , Sexton Daniel , Anderson Deverick , Lewis Sarah S 
Published: October 2017

Abstract

Background
The NHSN recently updated risk adjustment models and “rebaselined” Standardized Infection Ratios (SIRs) for healthcare-associated infections. The CDC expected that hospital SIRs would generally increase. However, the impact of rebaselining on individual hospitals’ SIRs was unknown. Accordingly, we assessed the impact of rebaselining on SIRs in a network of community hospitals.

Methods
We analyzed 2016 SIR data for CAUTI, MRSA LabID events, CDI LabID events, colon SSIs (COLO), and abdominal hysterectomy SSIs (HYST) from 38 hospitals in the Duke Infection Control Outreach Network (DICON). SIRs calculated using the old and new baselines were compared. Wilcoxon signed rank test was performed to determine whether hospitals’ SIRs changed significantly following rebaselining. Hospitals were ranked by SIR for each metric, and change in rank following rebaselining was determined. Meaningful change in rank was defined as increase or decrease by ≥4 places (greater than a decile). Hospitals that did not have an SIR calculated for a given metric were excluded from that metric’s analysis.

Results
Median hospital SIRs for CAUTI and CDI increased significantly after rebaselining (0.587 vs 0.307, P &lt; 0.001; and 0.825 vs 0.783, p = 0.04, respectively). Median MRSA SIRs increased (0.903 vs 0.797, P = 0.5), and COLO and HYST SIRs decreased (0.457 vs 0.586, P = 0.1; and 0 vs 0.489, P = 0.4); however, these changes were not statistically significant (Figure 1). For all metrics, a minority of hospitals had meaningful change in SIR rank following rebaselining (Figure 2).

Conclusion
SIRs increased following rebaselining for CAUTI and CDI but did not change significantly for MRSA, COLO, or HYST. The majority of hospitals’ SIR rank did not change meaningfully following rebaselining.

Disclosures
D. Sexton, Centers for Disease Control and Prevention: Grant Investigator, Grant recipient; Centers for Disease Control and Prevention Foundation: Grant Investigator, Grant recipient; UpToDate: Collaborator, Royalty Recipient