bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV in Ecuador: A Current Perspective of the Epidemics from a Major HIV Care Center.
Authors: Cevallos Leonardo Cano , Cevallos Edison Cano , Vera Andrea Vélez , Suárez Nathalie , Delgado Maryuri , Ollague Xavier Delgado 
Published: October 2017

Abstract

Background
Human Immunodeficiency Virus (HIV) infection is estimated to affect 36.7 million people (persons living with HIV [PLWH]). In Latin America and Caribbean exist around 2 million of PLWH. Ecuador estimates are close to 35.000 PLWH with prevalence of 3 cases per 1000 population, being 31.4% woman. Since the first case of HIV reported in the country in 1983 the efforts have been made to improve prevention and treatment of the disease being epidemiology paramount in planning. Herein we present a current panorama of HIV in Ecuador from a major center serving approximately 2 million people in the coastal zone.

Methods
Patients with diagnosis of HIV/AIDS (ICD-10 B24) from January to December 2015 were included from a database comprising 346.386 visits to outpatient clinics. The variables we consider were demographics, newly vs. previously diagnosed, type of antiretroviral regimen, AIDS-defining conditions, CD4 count and viral load. The statistical analysis was made on Microsoft Excel.

Results
A total of 3776 HIV positive patients were found during the study period. Median age was 37 ± 15, 37 ± 15 for males and 38 ± 15 for females (P &gt; 0.05). Male to female ratio was 4.72:1. More than half patients (2588, 68.5%) were receiving antiretroviral therapy. The most common therapy used was tenofovir + emtricitabine + efavirenz, followed zidovudine + lamivudine + efavirenz for 472 (18.2%). Most patients (91.97%) with HIV infection were not in AIDS stage. Newly diagnosed HIV was seen in 824 patients (21.82%), of which 59 (7%) were on AIDS stage at time of diagnosis. There was only 45 cases in this group (5.46%) with CD4 &lt;200 cells/mm3 possibly suggesting rapid progression or advanced disease.

Conclusion
HIV infection is a public health concern in Ecuador affecting mostly young males. More than half patients are on antiretroviral therapy and most patients are not in AIDS stage. This study comprises a current view of the epidemiological situation of HIV/AIDS in the coast of Ecuador and allows for planning and further research.

Disclosures
All authors: No reported disclosures.
PrEP Uptake and Emergent HIV infections in Southern Arizona: Is There A Disconnect?
Authors: Georgescu Anca , Egurrola Cesar , Schaff Spencer , Fisher Julia , Smith Shannon , Florita Catalin , Guido Alyssa , Klotz Stephen 
Published: October 2017

Abstract

Background
Despite expansion of antiretroviral therapy in recent years and growing evidence for PrEP (pre exposure prophylaxis) efficacy, HIV incidence has continued to rise while PrEP uptake has remained low, particularly in populations at risk. Our goal is to compare these populations and further identify discrepancies in populations at risk in Southern Arizona.

Methods
We retroactively reviewed health records for patients evaluated at Banner University Medical Center Tucson outpatient clinics between January 2014 and September 2016, either with a new HIV diagnosis or prescribed tenofovir/emtricitabine for PrEP.

Results
We identified 147 patients with new HIV diagnoses and 65 patients evaluated for PrEp. 63% of the newly diagnosed HIV were of Hispanic, African American or American Indian descend (46%, 14% and 3% respectively) while the majority of PrEP patients were White (58%) with a statistically significant difference between the groups (P = 0.006). There was no significant difference between the age groups [28 (19%) of the HIV and 13 (20%) of the PrEP were 18–24] or gender (88% of people accessing HIV care were men, vs. 91% men seen for PrEP). Insurance information at the time of presentation was available for 145 HIV and 64 PrEP patients with statistically significant differences between the groups. 31(21%) newly diagnosed HIV had no insurance and 71 (49%) had a Medicaid plan while 45 (70%) of PrEP patients has a private insurance plan (P &lt; 0.001). None of the people accessing PrEP reported iv drug use as a risk factor compared with 16 (11%) of the newly diagnosed (P = 0.003). Retention in care at 3 months was similar (76% of HIV and 75% of PrEP). The predominant risk categories were MSM with multiple partners and/or condomless anal sex for both groups.

Conclusion
To our knowledge this is the first study evaluating HIV and PrEP health care disparities in a border region of the Southwestern US, which is home to a large Hispanic minority population. Our findings suggest that low income minority populations, such as Hispanic, African American and American Indian in this region continue to have a higher risk for HIV acquisition and highlights the ongoing need to expand research on how these populations perceive their risk for HIV and navigate complex systems, such as health insurance, when seeking clinical services for PreP.

Disclosures
All authors: No reported disclosures.
A Novel Vancomycin Standardized Calculations Method Achieved Therapeutic Trough Goals in Obese and Non-obese Patients in a Veterans Affairs Health Care System
Authors: Foral Pamela , Dalke Brian , Brondum Ashley , Hrdy Michaela , Horne John , Destache Christopher 
Published: October 2017

Abstract

Background
Pharmacokinetic dosing of vancomycin in obese patients has not been standardized. Limited literature is available on appropriate dosing of vancomycin in this increasing population. We evaluated the utilization and impact of a standardized calculation method (SCM) in obtaining therapeutic vancomycin levels.

Methods
A SCM, including the use of an adjusted body weight for dosing and volume of distribution in obese patients, was implemented at our institution April 2014. Retrospective medical records review of hospitalized patients with a vancomycin steady-state trough level pre- (February 2013 to March 2014) and post-implementation (June 2014 to July 2015) of the SCM. Patients with dialysis, paraplegia/quadriplegia, vancomycin level drawn &lt; 48 hours of admit, trough level drawn &gt; 2 hours prior to next dose, during or after vancomycin infusion were excluded. Appropriateness of vancomycin levels were evaluated between the pre- (PreG) and post-groups (PostG), as well as BMI classification. Nephrotoxicity was defined as a rise in serum creatinine &gt; 0.5 mg/dl or &gt; 50% from baseline during or up to 72 hours after stopping vancomycin therapy. Appropriate statistical tests were analyzed using SPSS-PC (ver. 24, Chicago, IL).

Results
There were no significant differences in the PreG (n = 97) and PostG (n = 97) for age, gender, length of vancomycin therapy, and non-obese and obese patients. In the PostG, significant improvement in the overall use of the SCM (P &lt; 0.001) was determined. Other significant (P &lt; 0.001) factors associated with vancomycin patient management in the PostG were found. There was an overall significant improvement in achieving a therapeutic trough goal of 10–20 (±1 mcg/ml) in BMI classes, predominantly in BMI Class 4 PreG 26% and PostG 74%, P &lt; 0.05. More patients in the PreG (11) had the first trough &gt;21 mcg/ml than the PostG, (4), P = 0.104. Patients who developed nephrotoxicity included PreG 15% and 0% PostG, P = 0.115.

Conclusion
SCM of vancomycin regimens resulted in a significant improvement in obtaining therapeutic trough levels overall, including the obese BMI class 4. Defined nephrotoxicity was absent in the PostG group.

Disclosures
All authors: No reported disclosures.
Spatio-temporal Activity of Human-Simulated Exposures of Meropenem (MEM) and Ceftolozane (TOL) on Pseudomonas aeruginosa Biofilms
Authors: Rajan Srijay , Verotta Davide , Sutherland Christina , Nicolau David P , Spormann Alfred , Yang Katherine 
Published: October 2017

Abstract

Background
TOL and MEM possess in vitro activity against P. Aeruginosa grown in planktonic culture. Less is known about the activity of TOL and MEM on antibiotic-tolerant biofilms, such as those residing in the lungs of cystic fibrosis (CF) patients. The objective of this study is to compare the spatial and temporal activity of TOL and MEM on early and mature P. Aeruginosa biofilms grown in flow-chambers.

Methods
PAO1 and a clinical strain (strA) isolated from a child with CF were used. Isolates were cultivated in flow-chambers for 24 or 72 hours. Early (24-hours) biofilms were treated with the simulated human concentrations of 1 dose of either 2 g of TOL or MEM. Peak concentrations were 150 mg/L and 107.53 mg/L for TOL and MEM. Mature (72-hours) biofilms were treated with 3 doses of MEM or TOL administered every 8 hours. Images were acquired during antibiotic treatment using confocal laser scanning microscopy. Images were processed with Imaris and analyzed using COMSTAT 2.0. Pharmacodynamic modeling was performed with NONMEM.

Results
PAO1 and strA were susceptible to TOL and MEM per CLSI guidelines. Kill rates for TOL and MEM are shown below. TOL displayed smaller killing rates compared with MEM for early biofilms; TOL and MEM showed similar activity against the mature clinical strain (strA). MEM and TOL were less effective against strA compared with PAO1.

Conclusion
TOL and MEM displayed similar spatial activity against P. Aeruginosa biofilms grown in flow-chambers. Temporal differences in kill rates and bacterial recovery between TOL and MEM may inform future dosing strategies for biofilm-associated infections such as CF.

Disclosures
D. Verotta, Merck: Grant Investigator, Grant recipient. D. P. Nicolau, Merck: Investigator and Speaker’s Bureau, Research support. K. Yang, Merck: Grant Investigator, Grant recipient.
Incidence of Nephrotoxicity Among Patients Initiated on Vancomycin and Β-lactam Combination Therapies
Authors: Shah Megha , Rajasimhan Suraj , Bias Tiffany 
Published: October 2017

Abstract

Background
Vancomycin and β-lactam combinations are used to provide empiric coverage in hospitalized patients. Recent literature has illustrated an increased incidence of nephrotoxicity with such combinations, predominantly with piperacillin-tazobactam and vancomycin. The objective of this study is to evaluate the incidence of nephrotoxicity among patients receiving vancomycin and piperacillin-tazobactam vs., cefepime, or aztreonam.

Methods
A retrospective, observational, cohort study was conducted at Hahnemann University Hospital in adult patients who received vancomycin plus piperacillin-tazobactam, cefepime, or aztreonam for at least 48 hours between June 2013 and August 2016. Patients were excluded if they had chronic kidney disease Stage III or higher or on continuous renal replacement therapy. The following data were collected: demographics, renal function, number of concomitant nephrotoxic agents, total duration of combination therapy, and vancomycin levels. The primary outcome was the incidence of nephrotoxicity according to the Risk Injury Failure End Stage Renal Disease (RIFLE) criteria. Secondary outcomes were the total length of hospital (LOS) and intensive care unit (ICU) LOS. Statistical analyses were conducted using the Analysis of Variance and the Chi-square test.

Results
A total of 757 charts were reviewed of which 203 were included in the analysis; 69 in the piperacillin-tazobactam arm, 74 in the cefepime arm, and 60 in the aztreonam arm. The incidence of nephrotoxicity as assessed by the RIFLE criteria was higher in the piperacillin-tazobactam arm (41%) compared with cefepime (15%) and aztreonam arms (17%); P = 0.052. Majority of patients with nephrotoxicity experienced injury according to the RIFLE criteria. No differences were found in the total LOS, ICU LOS, or duration of nephrotoxicity. Patients who experienced nephrotoxicity in the piperacillin-tazobactam arm occurred earlier upon antibiotic initiation at 48 hours compared with the other arms extending past 72 hours; P = 0.004.

Conclusion
There was a trend towards more patients experiencing nephrotoxicity in the piperacillin-tazobactam arm compared with the other groups. Clinicians should remain vigilant when utilizing combination therapy.

Disclosures
T. Bias, Merck: Grant Investigator, Research grant. The Medicines Company: Speaker’s Bureau, Speaker honorarium.
Creation and Validation of a Pediatric Vancomycin Nomogram for a Goal Trough of 10–15 mg/L at a Quaternary Care Children’s Hospital
Authors: Lee Philip , Frye Jessica , Chen Xing , Chang Susanna , Singh Birender , Soma Vijaya 
Published: October 2017

Abstract

Background
Recent data suggest a serum vancomycin (vanc) trough (VT) of 11mg/L correlates with an AUC/MIC24 &gt; 400 which has shown to be the optimal concentration to eradicate MRSA infection and improve mortality. There are currently limited published recommendations on how to achieve such a VT in children. This study validates a vancomycin nomogram used to achieve a VT of 10–15 mg/L in pediatric inpatients (pts) at a quaternary care children’s hospital.

Methods
This is an 18 month (mo) prospective analysis beginning in September 2015. Included pts were ≥2 mo of age and had ≥2 consecutive VT. Pts receiving renal replacement therapy or those with a serum creatinine (Scr) of ≥0.5 mg/dL from a prior admission or within 48 hours of vanc initiation were excluded. The starting dose (SD) of vanc was determined by age and creatinine clearance (CrCl) (Tables 1 and 2). CrCl was measured by Bedside Schwartz equation for patients ≤18 years old (yo) and Cockcroft-Gault equation for patients &gt;18 yo. The maximum CrCl was set to 120 ml/minute. Patients who were on vanc and experienced a Scr increase of ≥0.5 mg/dL were considered to have acute kidney injury (AKI). The study had a 6 mo evaluation period which led to a revised version (RVN) on March 2016. The primary endpoint (PE) was achievement of 10–15 mg/L by the Second VT for patients with the First trough outside of this range, using our RVN (Table 3).

Results
Overall, a total of 276 patients received vanc, 17 and 29 patients were dosed according to the initial and RVN, respectively. For young children (Table 1), the SD for patients with a CrCL ≥90 ml/minute was therapeutic, sub-, and supra-therapeutic in 43.75%, 47.5% and 8.75%, respectively. For older children (Table 2), the SD for patients with a CrCl ≥100 ml/minute was therapeutic, sub-, and supra-therapeutic in 41.1%, 35.7% and 23.2%, respectively. The initial VN was successful 12/17 (70.6%) in achieving the PE. Success in achieving the PE after the RVN was 26/29 (89.7%). In the RVN group, the most common initial troughs were 5–7 mg/L (33.3%), followed by &gt;18 mg/L (27.6%). The mean VT using the RVN was 13.7 mg/L. The overall AKI incidence throughout the study was 3.2% (9/276) and 0% using the RVN.

Conclusion
Our RVN led to a Second VT within a target range of 10–15 mg/L for 89.7% of patients, allowing for more accurate and safer use of vancomycin in our institution.

Disclosures
All authors: No reported disclosures.
Viral Infections of the Central Nervous System in Qatar: Epidemiology, Pathogenesis and Clinical Outcomes
Authors: Abid Fatma Ben , Abukhattab Mohammed , Salameh Obada , Gohar Ahmed , Al Masalmani Muna , Al-Khal Abdullatif , Butt Adeel 
Published: October 2017

Abstract

Background
Viral central nervous system (CNS) infections are common causes of morbidity and mortality globally. There are no existing data about viral CNS infections in Gulf Cooperation Council countries. We conducted this study to determine the etiology, clinical and epidimiological characteristics, and outcomes of viral central nerveous system infection in patients in Qatar.

Methods
We retrospectively evaluated all cerebrospinal fluid findings from January 2011–March 2015 at any of the 7 hospitals in the Hamad Medical Corporation. We included those with an abnormal CSF findings and excluded those with missing medical records, no clinical evidence of CNS infection and those with proven bacterial infection. Based on pre-defined clinical and CSF (lab, culture, PCR) criteria, patients were classified as having meningitis, meningoencephalitis, encephalitis or myelitis. We reviewed the laboratory results to determine the proportion of persons with confirmed viral etiology.

Results
Among 7690 patients with available CSF results, 550 cases met the case definition criteria for viral CNS infection (meningitis 75%; meningoencephalitis 16%; encephalitis 9%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16-60 years old. The most common presenting signs and symptoms are listed in the table. Persons of Southeast Asian origin accounted for 39.6% of all infections. A definitive virologic etiologic agent was found in 38%, with enterovirus being the most common (44.3%) followed by Epstein–Barr virus (31%) and varicella-zoster virus (12.4%). The clinical outcome was overall good, only 2 cases died and the rest were discharged to home. Among those with confirmed viral etiology, 83.8% received ceftriaxone (mean duration 7.3 ± 5.2 days), 38% received vancomycin (mean duration 2.7 ± 5.4 days) and 38% received at least one other antibiotic.

Conclusion
Viral etiology is common among those evaluated for CNS infection in Qatar, and is most commonly seen in Southeast Asian immigrants. Clinical outcomes are generally excellent in this group of patients. Antibiotics are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of CNS infections.

Disclosures
A. Butt, Merck: Investigator, Grant recipient
Implementation of In-house PCR Testing for Herpes Simplex Virus Encephalitis: Impact on Patient Acyclovir Exposure
Authors: Beaulieu Ronald , Veron Katie , Hamer Diana , O’Neal Catherine , O’neal Hollis 
Published: October 2017

Abstract

Background
HSV encephalitis is a life-threatening disease process that requires prompt treatment. Diagnosis is often dependent upon nucleic acid studies of CNS samples. We introduced the Film Array Meningitis/Encephalitis (ME) Panel, a qualitative multiplexed nucleic acid-based diagnostic test for a variety of CNS pathogens, including HSV, in June 2016. It replaced an equivalent reference laboratory nucleic acid amplification test. The intent was to provide a more timely result and decrease unnecessary drug exposure to the patient.

Methods
We conducted a retrospective chart review of adult patients (&gt;18 yo) admitted between June-September 2015 and June-September 2016 who underwent CSF testing for HSV and received empiric acyclovir. The aim was to determine whether the newly available test resulted in fewer doses of acyclovir in those who tested negative for a herpes virus as compared with those tested with the previously available assay. We excluded those found to be positive for HSV-1, HSV-2, or VZV in the CSF. We defined a dose as any administration of acyclovir or valacyclovir to the patient.

Results
Results of the diagnostic assay returned significantly faster after institution of the ME panel (4.9 days (118 hours) vs .09 days (2.25 hours)). Due to the non-normal distribution of acyclovir dosing, comparisons were made with the Wilcoxson Rank-sum. The institution of the ME panel for all CSF studies significantly impacted our use of acyclovir, as patients with negative tests for HSV PCR in the CSF received fewer doses of acyclovir after implementation of the ME panel (median (25th–75th percentiles) 6 (2–13.5) vs 3 (1–6), P = .018).

Conclusion
Implementation of a rapid diagnostic PCR based test for HSV 1 and HSV 2 in 2016 significantly reduced the number of empiric acyclovir doses administered during the summer of 2016 compared with the summer of 2015 in patients testing negative for the condition.

Disclosures
All authors: No reported disclosures.
Phase 1 Clinical Trial of a Replication-Defective Human Cytomegalovirus (CMV) Vaccine
Authors: Adler Stuart , Lewis Nicole , Conlon Anthony , Christiansen Mark , Al-Ibrahim Mohamed S , Rupp Richard , Fu Tong Ming , Bautista Oliver , Tang Huaping , Culp Timothy , Das Rituparna , Beck Karen , Tamms Gretchen , Musey Luwy 
Published: October 2017

Abstract

Background
Congenital CMV remains an unmet medical need worldwide. Naturally acquired CMV immunity in women prior to pregnancy has been shown effective in reducing maternal-fetal transmission. V160 is engineered as a replication-defective CMV, and its replication in culture is controlled by a synthetic chemical. V160 can’t replicate in humans but it maintains all virological properties for presentation of viral antigens, including gH/gL/pUL128-131 pentameric complex, important for potent neutralizing antibodies (NABs).

Methods
Approximately 190 CMV seronegative and seropositive adults at study entry received 3 doses of V160 or placebo administered via intramuscular (IM) or intradermal (ID) route on Day 1, Month 1, and Month 6. Four antigen levels (10, 30, 100, and 250 units per dose) formulated with or without aluminum phosphate adjuvant were evaluated. In each vaccination group, approximately 10 and 4 subjects received study vaccine and placebo, respectively. Injection site and systemic adverse events (AEs) were collected for 14 days after each vaccination. Serious AEs (SAEs) were assessed up to Month 18. Viral shedding (urine and saliva) were monitored up to Month 12. CMV-specific NABs and cell-mediated immune responses (CMI) were measured prior and 1 month after each vaccination, and at Months 12 and 18.

Results
During the study, no serious AEs were reported and only one CMV seropositive subject had non-vaccine type viral shedding. In both seronegative and seropositive cohorts, proportion of subjects who reported injection site AEs was higher in V160 recipients than placebo controls. Proportion of subjects who reported systemic AEs was comparable across V160 doses/formulations and placebo. In the CMV seronegative cohort, immune responses increased with incremental dosing. More importantly, recipients of V160 from several dose levels mounted NAB and CMI responses at 1 month post dose 3 (PD3) that were comparable to baseline levels measured in seropositive subjects.

Conclusion
V160 had acceptable safety profile across all dose levels and formulations studied; Vaccine was immunogenic and elicited NAB and CMI responses at 1 month PD3 that were comparable to natural CMV infection.

Disclosures
S. Adler, Merck: Investigator, Research grant. N. Lewis, Merck: Employee, Salary. A. Conlon, Merck: Employee, Salary. M. Christiansen, Merck: Investigator, Research grant. M. S. Al-Ibrahim, Merck: Investigator, Research grant R. Rupp, Merck: Investigator, Research grant. T. M. Fu, Merck: Employee, Salary. O. Bautista, Merck: Employee, Salary. H. Tang, Merck: Employee, Salary.T. Culp, Merck: Employee, Salary. R. Das, Merck: Employee, Salary. K. Beck, Merck: Employee, Salary. G. Tamms, Merck: Employee, Salary. L. Musey, Meck: Employee, Salary.