bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 < 0.01) and developed the disease with a shorter median duration after transplantation (75 vs. 213 days). Cryptococcosis with very-early onset (<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.
The Spectrum of Pediatric Osteoarticular Infections: A Comparative Study
Authors: Alhinai Zaid , Elahi Morvarid , Foo Bill , Lee Brian , Chapin Kimberle C , Dennehy Penelope H , Koster Michael , Sanchez Pablo J , Michelow Ian C
Published: October 2017

Background

There is a paucity of data relating to pediatric subacute or chronic hematogenous osteomyelitis (SCHO), non-hematogenous osteoarticular infections (NHO), and osteoarticular hardware infections (HI). A comparative analysis of the entire spectrum of pediatric osteoarticular infections was conducted to identify distinguishing clinical features and biological markers.

Methods

Using ICD9/10 code searches, we identified pediatric patients ≤18 years of age at Hasbro Children’s Hospital (2006–2016) and Nationwide Children’s Hospital (2015–2016) with osteoarticular infections. Cases of Lyme arthritis or ENT-related infections were excluded. Eligibility criteria were confirmed by reviewing medical records and clinical and laboratory data were collected systematically.

Results

428 children met inclusion criteria: 211 (49%) had acute hematogenous osteomyelitis (AHO), 61 (14%) suppurative arthritis (SA), 42 (10%) SCHO, 60 (14%) NHO, and 54 (13%) HI. The age distribution differed significantly across the five infection types: AHO (median, 9.2 years), SA (5.0), SCHO (10.2), NHO (11.5), and HI (14.5); P < 0.001. Median initial CRP values were significantly higher (P < 0.001) in AHO (65 mg/dl) and SA (44) compared with SCHO (15), NHO (15) and HI (24). An ESR >19 mm/hours at presentation was more sensitive than a CRP >8.0 mg/dl in identifying SCHO (80% vs. 64%; P = 0.035). Bacteremia occurred more frequently in AHO (42%) and SA (25%) compared with SCHO (7%), NHOI (5%) and OHI (4%); P < 0.001. Patients with HI had significantly more complications as reflected by more ICU admissions (33% vs. ≤3% for other groups), and longer antibiotic treatment durations (median, 65 vs. ≤37 days for other groups); P < 0.001 for each comparison. S. aureus was the most common organism isolated for all infections, but the proportion of other Gram- and Gram-negative pathogens was significantly higher in SCHO, NHO, and HI compared with AHO and SA (P < 0.001). The ratio of MSSA to MRSA among isolates was 3:1, and did not differ significantly across the infection types.

Conclusion

SCHO, NHO, and HI commonly present with minimal evidence of inflammation, and differ in the spectrum of causative pathogens compared with AHO and SA. Further studies are required to optimize the diagnosis and management of non-acute, non-hematogenous osteoarticular infections.

Disclosures

All authors: No reported disclosures.
Septic Arthritis due to Oral Streptococcal Species Following Intra-articular Injection: A Case Series and Retrospective Chart Review
Authors: Cain Stacy , Sifri Costi D , Lewis Jessica
Published: October 2017

Background

Oral streptococcal species are a rare cause of septic arthritis. We hypothesized that one possible source of infection is oral bacteria from the mouth of a practitioner performing joint injection without a mask. While the use of a face mask is standard practice during lumbar puncture and other spinal procedures due to the risk of iatrogenic meningitis, mask usage during joint injection is not a standard recommendation.

Methods

The clinical microbiology laboratory database was reviewed to identify joint fluid cultures positive for oral streptococcal bacteria between January 2007 and December 2015. The corresponding patient charts were reviewed for evidence of joint injection within 90 days prior to the positive culture.

Results

We identified 18 cases of septic arthritis due to oral streptococcal species. Of those joint injection was performed prior to the development of acute septic arthritis in four (22%) cases. The implicated pathogen was Streptococcus mitis/oralis in two cases, Streptococcus sanguinis in one case, and Abiotrophia defectiva in one case. All four cases occurred in males over the age of 60 and affected native joints. Three of four patients had underlying osteoarthritis, and three of four had a history of diabetes. The patients all presented with acute worsening of joint pain and swelling 2–5 days after undergoing joint injection. Three cases followed corticosteroid injection and 1 followed an MRI arthrogram. All four patients underwent at least one surgical procedure (two required repeat irrigation and debridement) to treat the infection and received at least 4 weeks of antibiotic therapy.

Conclusion

Oral streptococcal species should be considered in the differential of causative species of septic arthritis in patients presenting with worsening pain after a joint injection. The use of a face mask during joint injection should be explored as a simple and inexpensive precaution to prevent this rare but serious complication.

Disclosures

All authors: No reported disclosures.
Clinical Experience with Tigecycline in the Treatment of Prosthetic Joint Infections
Authors: Lastinger Allison , Dietz Matthew , Guilfoose John , Sarwari Arif R
Published: October 2017

Background

As the population in the United States ages, the number of people who will require a joint arthroplasty is expected to rise dramatically. The most serious complication of this surgery is prosthetic joint infection (PJI) which can lead to long-term morbidity and even mortality. Biofilms play a major role in these infections, and studies have suggested that tigecycline may work better than other antimicrobials in the setting of biofilms. In this study, we examined our institution’s experience with using tigecycline to treat PJI.

Methods

This was a retrospective review of all adult patients with PJI treated at West Virginia University from January 2008 to March 2016 who received tigecycline for 50% or greater of the treatment course. Demographic data, rationale for tigecycline use, type of surgery, microbiologic data, outcome and complications were assessed. Failure was defined as need to return to the operating room for an infectious complication or persistent drainage from the joint.

Results

In total, 34 patients met inclusion criteria. The median age was 65 years, and 62% of the patients were female. The most common reason for tigecycline use was empiric therapy, but other reasons included antimicrobial allergies and resistant organisms. The antimicrobial was used as frontline therapy in 29 cases (85%), and the mean duration of tigecycline therapy was 38 days. The most common organisms isolated were methicillin resistant Staphylococcus aureus (n = 7), coagulase negative Staphylococci (n = 5), and Enterococcus species (n = 4), but 12 cases (35%) were culture negative. Treatment success was documented for 21 cases (62%); though, there was limited follow-up (2 months or less) in four of the successful cases. Nausea and vomiting was the most common adverse event, occurring in three patients.

Conclusion

Tigecycline is a glycylcycline approved for use in a variety of infections including intra-abdominal and skin soft-tissue infections, but little is known about its use in the treatment of PJI. We found that tigecycline is well tolerated even when given for 6 weeks duration. Twenty-one of the 34 patients (62%) met our definition of successful treatment outcome with tigecycline. More studies are needed to assess tigecycline’s use in the treatment of PJI.

Disclosures

All authors: No reported disclosures.
Factors Associated with Not Using a Condom at Last Sex Among Sexually Active US Navy and Marine Corps Personnel Across a Shipboard Deployment
Authors: Harbertson Judith , De Vera Kimberly , Scott Paul , Shaffer Richard , Michael Nelson , Hale Braden
Published: October 2017

Background

Condom use is highly effective in preventing sexually transmitted infections (STIs); however, data on this are limited among US military personnel who may be at a higher risk for STI acquisition across a deployment cycle. This study examined factors associated with no condom use at last sex at three time points, pre- (T1), during (T2), and post-deployment (T3), across a US military shipboard deployment cycle.

Methods

Data were collected among active duty US Navy and Marine Corps personnel assigned to 11 deploying ships using an anonymous, voluntary, self-completed survey, including demographics, condom use at last sex, sexual risk behavior, STI diagnosis, alcohol misuse (Alcohol Use Disorders Identification Test–Consumption), and drug use with sex. Descriptive and generalized regression model analyses were conducted to determine the effects of main exposures after adjusting for demographic characteristics, with statistical significance defined as P < 0.05. When longitudinal data were included, generalized estimating equations were used. Models included their interaction with time.

Results

Among participants, n = 1,900 (T1), n = 549 (T2), and n = 1,168 (T3) reported age and sex, were sexually active, and included in the analysis. The proportion of individuals who used a condom at last sex was significantly higher during T2 (53%, P < 0.0001) than T1 (27%) and T3 (28%), with an STI prevalence of 1% (T1), 7% (T2), and 2% (T3). In adjusted models, participants not using a condom at last sex were significantly more likely to report an STI diagnosis (OR 2.26, 95% CI 1.19–4.28), screen positive for hazardous alcohol use (OR 1.44, 95% CI 1.21–1.71), and use drugs to enhance sex (OR 1.37, 95% CI 1.06–1.77), but less likely to engage in transactional sex (OR 0.69, 95% CI 0.50–0.94). Associations between condom use and main exposures did not differ significantly by time point.

Conclusion

Although condom use was significantly higher during T2, STI prevalence remained high, which suggests those who do not use a condom during deployment are at a higher risk for STI acquisition than pre- or post-deployment. These data may inform interventions targeting high STI acquisition risk individuals and time periods to increase condom use.

Disclosures

All authors: No reported disclosures.
Reducing Dissemination of Viruses from Computer Touchscreens through Patient Hand Hygiene and an Automated Ultraviolet-C Touchscreen Disinfection Device
Authors: Alhmidi Heba , Cadnum Jennifer , Piedrahita Christina , John Amrita , Donskey Curtis
Published: October 2017

Background

Computer touchscreens in patient waiting areas are a potential source for spread of viral and bacterial pathogens in healthcare facilities. Patient hand hygiene is recommended to prevent acquisition of pathogens on hands.

Methods

We tested the efficacy of patient hand hygiene alone or in combination with a novel automated ultraviolet-C (UV-C) touchscreen disinfection device for reduction in dissemination of the nonpathogenic non-enveloped virus bacteriophage MS2 from contaminated touchscreens. Subjects randomized to control, alcohol hand sanitizer (10 or 30 second application), UV-C (30-second cycle), or alcohol hand sanitizer plus UV-C contacted 4 sites routinely used during operation of the touchscreen and then fingerpads were cultured. The log plaque-forming units (PFU) recovered were compared for each group. Patients were observed to determine the frequency of hand hygiene after use of a touchscreen in a waiting area.

Results

As shown in the figure, the mean log10PFU of bacteriophage MS2 recovered from fingerpads was significantly reduced by each of the interventions (P < 0.001). However, only the combination of hand hygiene and UV-C was effective in completely preventing virus transfer. Of 20 patients observed in a waiting area, 0 (0%) used hand sanitizer that was available adjacent to the touchscreen.

Conclusion

Our results suggest that use of alcohol hand sanitizer alone or in combination with an automated UV-C touchscreen disinfection device could reduce transmission of viruses from contaminated touchscreens. There is a need for education of patients on the importance of hand hygiene after contact with touchscreens.

Disclosures

All authors: No reported disclosures.
An Appeal to Incorporate Hand Hygiene Education into Standard Elementary School Curriculum
Authors: Watson Jasmine , Owens Alexandria , Imrit-Thomas Kavita , Malone Miranda , Tobias Andy , Goudar Lakshmi
Published: October 2017

Background

The Center for Disease Control and Prevention reports that 160 million school days are lost each year due to infectious illnesses. Hand hygiene is one of the most effective ways to prevent illness that can lead to absenteeism among school-aged children, yet few schools have a formal education program as a preventative strategy.

Methods

A Pilot Hand Hygiene experiment was initiated for 90 second grade students at a Virginia Beach Public School. The experiment was designed to bring awareness and to satisfy a scientific module requirement. Students cultured their hands on general purpose agar plates with the assistance of physicians and a microbiologist. The proper hand washing technique was demonstrated. Students were equally divided into two groups: hand washing group and sanitizer group. They were instructed to re-culture hands after intervention. Students observed cultures for five days and documented results.

Results

Overall, student observation of decreased microbial growth was an average of 91% (Figure 1). Education improved compliance, which resulted in a favorable behavioral change on average of 89% (Figure 2). There was a 71% decrease in incidence of illness-related absences 30 days after the hand hygiene intervention (Figure 3). In three out of five classes, hand sanitizer was more effective when compared with hand washing. In addition, a random sample of cultures were incubated in a microbiology lab to identify the common microbes among the second-grade elementary school population. It revealed both resident and transient flora. Post-intervention, there was a rise in coagulase-negative Staphylococci resident flora. This indicated a successful decrease in transient flora, which is most likely to cause illness.

Conclusion

Hand Hygiene education is remarkably beneficial, especially in children who are at greater risk of illness. It is clearly effective in decreasing infectious disease risk, while teaching a life-long skill. For the impact as a preventative strategy to be felt, its implementation into elementary school curriculum is warranted.

Disclosures

All authors: No reported disclosures.
Bivalent Norovirus VLP Vaccine Candidate in Older Adults: Impact of MPL and a Second Dose in a Randomized, Controlled, Double-Blind Clinical Trial
Authors: Sherwood Jim , Cramer Jakob , Cam Nancy Bouveret Le , Lin Stella , Baehner Frank , Mendelman Paul , Borkowski Astrid
Published: October 2017

Background

Acute norovirus (NoV) gastroenteritis may cause significant morbidity in healthy adults and can prove fatal in older subjects. We investigated the safety and immunogenicity in older adults of one or two doses of an intramuscular bivalent virus-like particle (VLP) vaccine candidate (genotypes GI.1 and multivalent consensus GII.4c) formulated with alum and with and without MPL (3-O-deacyl-4′-monophosphoryl lipid A) adjuvant.

Methods

In a phase II, double-blind, controlled trial, 294 healthy adults  ≥ 60 years of age randomized to 4 equal groups received one or two immunizations 28 days apart. One dose groups received placebo (saline) on Day 1. Vaccine formulations contained 500μg Al(OH)3adjuvant with 15μg GI.1 and 50μg GII.4c VLP antigens, with or without 15μg MPL adjuvant. A fifth group of 26 healthy 18–49 year-olds received one dose of MPL-free vaccine. Humoral immunity was assessed as ELISA pan-Ig and histo-blood group antigen blocking (HBGA) antibody titers at Days 1, 8, 29 and 57. Cell-mediated immunity (CMI) and avidity indices (AI) were also measured. Safety was assessed as solicited local and systemic adverse events (AE) for 7 days, and unsolicited AEs until Day 28 after each vaccination.

Results

Marked increases in pan-Ig and HBGA to both genotypes occurred by Day 8 after first vaccination. Geometric mean titers were similar in magnitude in all groups and persisted at similar levels through Day 56. No increases were observed with a second vaccine dose on Day 29 or with the formulations containing MPL. Responses were similar in magnitude when assessed by age groups (60–74, 75–84 and ≥ 85 years of age) and when compared with those to a single vaccine dose in 18–49 year-olds. No clinically relevant differences in CMI responses or changes in antibody avidity were observed between formulations. Both formulations were generally well tolerated, the most frequent reaction being mild pain at the injection site. No vaccine-related SAEs were reported.

Conclusion

Older adults aged over 60 years displayed immune responses to NoV VLP vaccines that were similar to those in younger adults with no apparent signs of immunosenescence. These data support the further development of the MPL-free vaccine candidate in older adults.

Disclosures

J. Sherwood, Takeda Pharmaceuticals International AG: Employee, Salary; J. Cramer, Takeda Pharmaceuticals International AG: Employee, Salary; N. Bouveret Le Cam, Takeda Vaccines Inc.: Employee, Salary; S. Lin, Takeda Vaccines Inc.: Employee, Salary; F. Baehner, Takeda Pharmaceuticals International AG: Employee, Salary; P. Mendelman, Takeda Vaccines Inc.: Employee, Salary; A. Borkowski, Takeda Pharmaceuticals International AG: Employee, Salary
HIV Risk Assessment using Longitudinal Electronic Health Records
Authors: Feller Daniel , Zucker Jason , Yin Michael , Gordon Peter , Elhadad Noemie
Published: October 2017

Background

Universal HIV screening programs are costly, labor-intensive, and in practice unable to identify all individuals at risk of HIV infection. Automated risk assessment methods that leverage longitudinal electronic health records (EHRs) could catalyze targeted screening programs in Emergency Departments and across public health jurisdictions. While information on social and behavioral determinants of health are typically collected in unstructured fields, previous analyses have only considered structured EHR data. We sought to characterize whether clinical notes can improve predictive models of HIV diagnosis.

Methods

181 individuals who received care at an academic medical center in New York City prior to a confirmatory HIV diagnosis were included in the study cohort. 543 HIV- controls with similar utilization patterns were selected using propensity score matching. Demographics, laboratory tests, and diagnosis codes were extracted from longitudinal records. Clinical notes were preprocessed using both topic modeling and an n-grams approach. We fit 3 predictive models using Random Forests including a baseline model which included only structured EHR data, the baseline model plus topic modeling, and baseline model plus clinical keywords.

Results

Predictive models demonstrated a range of performance with F-measures of 0.59 for the baseline model, 0.63 for the baseline plus topic modeling and 0.74 for the baseline plus clinical keyword model. The baseline plus topic model displayed low precision but high recall while the baseline plus clinical keyword model displayed high precision but low recall. Clinical keywords including ‘msm’, ‘unprotected’, ‘hiv’, and ‘methamphetamine’ were indicative of elevated risk.

Conclusion

Clinical notes improved the performance of predictive models for automated HIV risk assessment. Future studies should explore novel techniques for extracting social and behavioral determinants from unstructured text in longitudinal EHRs.

Disclosures

All authors: No reported disclosures.
Assessment of personal experiences navigating medical systems and society for patients of a midwestern Ryan White funded HIV Clinic
Authors: Cruz Chancelor , Melendez Elsa Vazquez , Farrell John
Published: October 2017

Background

In the early years of the HIV/AIDS crisis, the debilitating consequences of HIV/AIDS stigma and discrimination became known as part of “the 3rd phase of the epidemic.” Many of these consequences still impact HIV/AIDS care today. In the state of Illinois, the HIV prevalence in Chicago and its collar counties does supersede the prevalence of HIV elsewhere in the state of Illinois, and past HIV research has utilized mostly urban MSM populations. Unfortunately, although HIV is not an exclusively urban disease, little is known about HIV stigma in smaller communities and lower prevalence contexts.

Methods

Participants were recruited from our local HIV clinic in a county population of 184,000 people. The clinic serves the HIV/AIDS population of Peoria proper as well as the 14 surrounding, more rural counties. Twenty participants were invited for a 1 hour recorded interview speaking of their experiences with HIV stigma. Using a qualitative approach in grounded theory, two researchers independently coded the transcripts and then came to a consensus. Core themes were then summarized.

Results

Sources of stigma included the general community in central Illinois, other outpatient medical clinics, medical testing facilities such as ancillary laboratories, and the LGBT community. Major sources of support included family and loved ones, the HIV medical clinic, and the HIV patient community. Many patients reported HIV education to be assuring, and though facing many social obstacles, ultimately feeling strengthened by adversity. In order to address HIV stigma in the community patients suggested greater networking among HIV infected patients and increased education for the general public.

Conclusion

HIV stigma is still a distressing social force to HIV infected patients in the heart of Illinois. Though medical management of HIV has advanced significantly in recent years, the stigma that accompanies a diagnosis of HIV infection remains to be effectively addressed in a comprehensive and conscientious manner. Our study points to the need for tailored interventions in outpatient medical settings, as well as throughout the general community in central Illinois.

Disclosures

All authors: No reported disclosures.
Clinical Outcomes Following the Use of Archived HIV-1 DNA Sequencing to Guide Antiretroviral Therapy Regimen Adjustment and Simplification
Authors: Ellis Kristen , Nawas George , Chan Connie , York Lawrence , Mar Alexander , Zangeneh Tirdad
Published: October 2017

Background

While favorable new antiretroviral therapy (ART) options are available for HIV disease, the Department of Health and Human Services guidelines recommend against switching suppressive regimens unless there is evidence that the new regimen will be fully active. A new assay analyzes archived HIV pro-viral DNA and can detect resistance mutations when HIV RNA is below the limit of detection, when standard genotyping (GT) is not possible. Small studies have correlated archived DNA GT to historical plasma RNA GT, but there is minimal available data on treatment outcomes when using this assay to determine antiretroviral therapy switch strategies. We evaluated clinical outcomes following ART adjustment based upon results of archived DNA GT testing.

Methods

A retrospective review of electronic medical records was performed at our medical center from October 2014 to October 2016. Inclusion criteria included age ≥ 18 years, archived DNA GT result available, ART changed after archived GT result, and follow up HIV RNA available after ART switch. Data was collected prior to and after ART switching. McNemar’s test was used for categorical variables and paired t-test for continuous variables.

Results

A total of 38 patients were included. Most patients were male (89%), Caucasian (66%), had a history of AIDS diagnosis (45%), had HIV for >10 years (74%), and had baseline ART resistance (24% resistant to 1 class, 37% resistant to ≥ 2 classes). Median baseline CD4 was 532 cells/mm3. At baseline, 31 (82%) patients had HIV RNA < 50 copies/mL. Compared with baseline, 35 (92%) patients were undetectable at furthest follow up (P = 0.22). Median time to furthest follow up was 146.5 days (range 12–485). Overall, 36 (95%) patients had at least one undetectable HIV RNA after switching. None of the patients with an initial undetectable HIV RNA became detectable after switching ART. Average number of pills per day and administrations per day decreased from 3.84 to 1.97 (P < 0.001) and 1.47 to 1.05 (P < 0.001) respectively. The number of patients on protease inhibitors (PIs) decreased from 66% to 21% (P < 0.001).

Conclusion

The use of archived DNA GT to guide ART adjustment may result in maintained viral suppression while allowing for regimens with optimized long-term safety and decreased pill burden.

Disclosures

All authors: No reported disclosures.
The Safety of Substitution of Antiretroviral Regimen in Non-Clinical Trial Settings in Asian Countries
Authors: Jung In Young , Boettiger David , Wong Wingwai , Lee Man Po , Kiertiburanakul Sasisopin , Chaiwarith Romanee , Avihingsanon Anchalee , Tanuma Junko , Kumarasamy N , Kamarulzaman Adeeba , Zhang Fujie , Kantipong Pacharee , Ng Oon Tek , Sim Benedict Lh , Law Matthew , Ross Jeremy , Choi Jun Yong
Published: October 2017

Background

Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the safety of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries.

Methods

HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD) were included in this analysis if they started combination antiretroviral therapy (cART) after 2002, were being treated at a center that documented a median rate of viral load (VL) monitoring ≥ 1 tests/patient/year, and experienced a minor or major treatment substitution while on virally suppressive cART (VL < 200 copies/mL). Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. Virologic failure was defined as having had two viral load measurements > 400 copies/mL. The patterns of substitutions and rate of virologic failure after substitutions were analyzed.

Results

Of 3,994 adults who started ART after 2002, 3,119 (78.1%) had at least one period of virological suppression. Among these, 1,170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of virological failure were 1.48/100person years (95% CI 1.14–1.91) in the minor substitution group and 2.85/100person years (95% CI 1.88–4.33) in the major substitution group, and 2.53/100person years (95% CI 2.20–2.92) among patients that did not undergo a treatment substitution.

Conclusion

The rate of virological failure was relatively low in both major and minor substitution groups, showing that regimen substitution is generally safe in non-clinical trial settings in Asian countries.

Disclosures

All authors: No reported disclosures.
Gender Differences in Virologic Response after Antiretroviral Therapy in Treatment-naïve HIV-infected Individuals: Results from the 550 Clinic HIV Cohort Study.
Authors: Vega Andrea Reyes , Loban Alejandra , Srinivasan Kavitha , Furmanek Stephen , English Connor , Bishop Mary , Spencer Cathy , Truelove Daniel , Ramirez Julio , Raghuram Anupama , Peyrani Paula
Published: October 2017

Background

Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals.

Methods

This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value <0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis.

Results

A total of 70 women and 90 men were included in the study. Median age was 41 years (19) for women and 34 years (19) for men (P < 0.001). Virologic suppression was documented in 76% of women and 64% of men (p 0.166). Immune recovery was documented in 60% of women and 68% of men (p 0.323). Multivariate analysis of virologic success is shown in Figure 1 and immunologic recovery is shown in Figure 2.

Conclusion

In our study, gender was not found to be associated with differences in response to ART. As expected, drug abuse continues to be an independent variable associated with lack of virologic suppression. If one of the goals of treatment is to achieve a rapid immunologic response, our study may indicate that regimens containing protease inhibitors should be the ones selected.

Disclosures

All authors: No reported disclosures.
Vancomycin Prescribing Habits – Are We Still Afraid of Mississippi Mud?
Authors: Bulik Catharine C , Bader Justin C , Bhavnani Sujata M , Rubino Christopher M , Sweeney Kim L , Ambrose Paul G , Owens Robert C
Published: October 2017

Background

Debates over the safety and efficacy of vancomycin have plagued clinical practice for more than half a century. A recent paradigm shift has occurred as the science of PK-PD has encouraged the use of optimized regimens which achieve targeted exposures. However, change is slow and we suspect prescribing habits may not be in line with this consensus approach. Herein, using data from electronic decision support software (EDSS), we describe clinicians’ vancomycin prescribing habits.

Methods

Data obtained over a 20-month period from an EDSS included: 1) clinician demographics; 2) patient demographics; 3) clinician-selected antimicrobials; and 4) EDSS suggested PK-PD optimized antimicrobial regimens. A vancomycin regimen was considered to be PK-PD optimized if the EDSS provided percent probability of PK-PD target attainment (PTA) was ≥90%.

Results

Data for 87 clinicians and 104 vancomycin-treated cases were available. Of all clinicians, 62% were clinical pharmacists, 38% were physicians, with close to half of being ID specialists. Of all the clinicians, 55% had ≥10 years of clinical experience. Of the 104 cases, the median (min, max) patient age, weight and creatinine clearance were 43.5 (23, >90) years, 81.6 (47.6, 170.6) kg, and 100.2 (7.3, 188.1) mL/min/1.73 m2, respectively. For 61.5% of selected vancomycin regimens, PTA were ≥90%. The distribution of PTA for the remaining 38.5% of cases is shown in Figure 1. Among these 38.5%, an alternative optimized regimen was presented 97.5% of the time. Further evaluation of clinician demographics among cases with a PK-PD optimized regimen demonstrated that 61% had ≥ 10 years clinical experience while only 44% of those who did not chose a PK-PD-optimized regimen had the same experience. While the majority of clinicians in both the optimized and non-optimized groups were clinical pharmacists, ID physicians represented 55% of all physicians who chose a non-optimized vancomycin regimen.

Conclusion

Data obtained from an EDSS demonstrated that clinicians who chose a non-optimized vancomycin regimen had less experience than those who chose an optimized regimen. Data suggest that education for optimizing vancomycin dosing using PK-PD is needed as part of antimicrobial stewardship training initiatives.

Disclosures

S. M. Bhavnani, ICPD Technologies: Shareholder, stock options. C. M. Rubino, ICPD Technologies: Shareholder, stock options. P. G. Ambrose, ICPD Technologies: Shareholder, stock options.
Vancomycin (VAN) administered as continuous infusion (CIV) vs. intermittent infusion (IIV) in children with Methicillin-Resistant Staphylococcus aureus (MRSA) infections
Authors: Dakhlallah Abe , Adler-Shohet Felice C , Arrieta Antonio , Tran M Tuan
Published: October 2017

Background

Guidelines for treatment of MRSA infections recommend VAN trough (TR) of 15–20 mg/L to achieve a 24-hour ratio of area-under-the-curve (AUC24) over minimum inhibitory concentration (MIC) ≥ 400, the primary pharmacodynamic (PD) parameter that predicts VAN efficacy. However, achieving this target TR in children is difficult in clinical settings and may not be necessary to achieve AUC24/MIC ≥ 400. Additionally, higher doses and TR >15 mg/L have been associated with increased risk for VAN nephrotoxicity. The use of CIV may lead to lower VAN exposure and subsequent toxicity while achieving the desired AUC24/MIC ratio. To our knowledge there are no reports exploring differences in VAN exposure, AUC24/MIC ratio and toxicity between CIV and IIV VAN in children.

Methods

We conducted a retrospective, cohort study between January 1, 2011–December 30, 2016. Children ages 3 months–18 years with an MRSA infection were included. Only the highest VAN level and total daily dose (TDD) within the first 72 hours of treatment were included for analysis. Patients with CrCl < 30 mL/minute/1.73m2 were excluded. Primary outcome was differences in TDD, AUC24 and AUC24/MIC. Secondary outcomes evaluated adverse events.

Results

Twenty-two patients were evaluated, 11 received IIV and 11 received CIV VAN. Median age, weight, gender, baseline serum creatinine, VAN clearance and volume of distribution were similar in both groups. Fewer patients in the IIV group received concomitant nephrotoxic drugs compared with CIV group (5/11 (45%) vs.. 10/11 (91%), P = 0.03). Patients in the IIV group received more VAN (median 85 mg/kg/day vs. 67 mg/kg/day, P = 0.08) and had higher AUC24 (723 mg*hours/L, (IQR 669–752) vs. 572 mg*hours/L, (IQR 459–633), P = 0.02) compared with CIV. Patients in IIV group had lower median TR (16 mg/L vs. 25 mg/L) that required longer time to attain (50.9 hours, (IQR 42–70) vs. 21.5 hours (IQR 17–34), P = 0.04) than serum levels in CIV. Both groups had a median VAN MIC 1 mg/L with a trend towards higher AUC24/MIC observed in IIV group (752 vs. 621, P = 0.07). More patients in IIV group experienced VAN-related adverse events (renal toxicity, infusion reactions, phlebitis) compared with CIV (7/11 (64%) vs. 1/11 (9%), P = 0.01).

Conclusion

In pediatric patients, CIV VAN achieved the recommended PD target in shorter time, and with fewer adverse events compared with IIV.

Disclosures

All authors: No reported disclosures.
Plasma Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Subjects with Cystic Fibrosis
Authors: Larson Kajal , Bradley John S , Arrieta Antonio , Yang Shan , Yu Brian , Johnson Matthew G , Rizk Matthew , Rhee Elizabeth
Published: October 2017

Background

Ceftolozane/tazobactam (TOL/TAZ), a novel anti-pseudomonal cephalosporin/β-lactamase inhibitor combination, is approved for the treatment of complicated intra-abdominal infections (cIAI) and urinary tract infections (cUTI) in adults. TOL/TAZ has potent activity against Gram-negative pathogens associated with pulmonary infections in cystic fibrosis (CF). Limited data exists on the pharmacokinetics (PK) of TOL/TAZ in the CF population. The aim of this analysis is to evaluate plasma PK parameters in CF and non-CF pediatric subjects to assess whether CF alters the PK of TOL/TAZ.

Methods

Nine subjects with CF were enrolled in the 2 to <18 y old cohort of an ongoing Phase 1 PK study of a single dose of intravenous TOL/TAZ in pediatric subjects with suspected or proven Gram-negative infection (NCT02266706). Population PK models for TOL and TAZ were developed using PK data from 12 adult studies and preliminary PK data from pediatric subjects. An exploratory analysis comparing model-derived plasma TOL and TAZ PK parameters between CF (N = 9) and non-CF (N = 9) pediatric subjects was conducted.

Results

Mean (range) age and weight of the 9 CF subjects were 11.4 y (5.5–17.5 y) and 37.4 kg (17.4–60 kg), respectively. For TOL, the mean (SD) systemic clearance (CL) normalized by weight was 0.16 (0.03) and 0.15 (0.03) L/hours/kg in CF and non-CF subjects, respectively, suggesting no difference in CL; similar observations were made for volume of the central compartment normalized by weight. All subjects achieved the plasma PK/pharmacodynamic (PD) target of %fT>MIC of at least 30% for an MIC of 4 µg/mL.

Differences in weight-normalized CL were more pronounced for TAZ in CF and non-CF subjects (mean [SD]: 0.73 [0.25], 0.42 [0.13] L/hours/kg, respectively). However, the half-life was similar in CF and non-CF subjects (mean [SD]: 0.99 [0.15] hours, 1.08 [0.15] hours, respectively), suggesting that differences are unlikely to be clinically meaningful. At the recommended dose being advanced into Phase 2, subjects are projected to achieve the TAZ plasma PK/PD target of %fT>threshold concentration (Ct) of >20% for a Ct of 1 µg/mL.

Conclusion

Preliminary exploratory analysis of TOL/TAZ PK in a small group of pediatric patients supports evaluation of the same TOL/TAZ dose in children with and without CF in future clinical studies.

Disclosures

K. Larson, Merck: Employee, Salary. S. Yang, Merck: Employee, Salary.; B. Yu, Merck: Employee, Salary. M. G. Johnson, Merck: Employee, Salary. M. Rizk, Merck: Employee, Salary. E. Rhee, Merck: Employee, Salary.
Epidemiology, Outcomes and Prognosis of Central Nervous System Infections in Singapore. Preliminary results from The Singapore Neurologic Infections Programme (SNIP)
Authors: Chan Fu Zi Yvonne , Wijaya Limin , Tan Kevin , Chan Monica , Soon Derek , Ooi Say-Tat , Shafi Humaira , Ei Mon Soe , Ooi Eng Eong , Low Jenny
Published: October 2017

Background

Central Nervous System (CNS) infections frequently result in devastating consequences although the aetiology is seldom definitively identified. To address this knowledge gap, we conducted a prospective study to describe the epidemiology of CNS infections in Singapore.

Methods

Patient enrollment was conducted in 5 adult tertiary hospitals in Singapore, between August 2013 and December 2016. Patients aged ≥16 years who met the inclusion criteria were enrolled. Demographic data, neuroimaging, neurophysiology and biochemical results were collected. Cases were classified as “Confirmed” or “Probable” depending on whether the aetiological agent was detected by either culture or molecular methods in the CSF. The modified Rankin Scale (mRS) was recorded at enrollment, 2 weeks and 6 months, with scores of 0–2 classified as good and 3–6 as poor outcome.

Results

A total of 2061 patients were screened, of whom 199 met the inclusion criteria.

A total of 106 (53.2%), 65 (32.7%) and 28 (14%) cases of meningitis, meningoencephalitis and encephalitis were diagnosed, respectively. An aetiologic agent was identified in 119 (60%) of cases. Mycobacterium tuberculosis (MTb) was the most common cause of meningitis and meningoencephalitis with 23 (13.5%) cases. Herpes simplex virus was the most common aetiology for encephalitis with 3 (10.7%) cases. Immune-mediated aetiologies accounted for 8 (4%) of the total cases. Fatal outcomes were observed in 7 (3.5%) patients.

The absence of focal weakness (aOR 0.024 95% CI 0.001–0.535 P = 0.018) and absence of altered mental status (aOR 0.03; 95% CI 0.002–0.43; P = 0.009) at admission predicted good outcomes at 6 months. Vomiting was associated with poor prognosis (aOR 17.91; 95% CI 1.12–286.04; P = 0.041).

Conclusion

It is surprising that MTb was the most common aetiologic agent although none were fatal. Our study identified aetiologic diagnoses, clinical and biochemical results that correlated with outcome of CNS infections although it also underscores the need for better diagnostic tools for aetiologic confirmation.

Disclosures

All authors: No reported disclosures.
Infectious Causes and Infectious Mimics of Acute Encephalitis: a Prospective Study from Thailand
Authors: Skulsujirapa Benjawan , Wacharapluesadee Supaporn , Petcharat Sininat , Hemachudha Thiravat , Wasontiwong Abhinbhen Saraya , Putcharoen Opass
Published: October 2017

Background

Previous reports of infectious encephalitis in Thailand showed viruses as major pathogens similar to worldwide data. Major viruses in studies varied among Japanese encephalitis, Enteroviruses and Herpesviruses. Infectious etiologies vary by regions, seasons and preventive strategies done. Dynamic change of pathogen is believed to occur continually. Local data in each region is important to develop an algorithm of investigations for the cost-effectiveness.

Methods

This is a prospective study of patients with encephalitis between January 2014 to March 2017 at a tertiary hospital in Bangkok. Microbiological and serological studies were done according to an algorithm based on initial cerebrospinal fluid analysis. Initial tests were for bacteria, fungus, mycobacterium and commonly prevalent viruses. Further tests for infectious etiology were done by stepwise approach if initial tests yielded negative.

Results

Fifty-two patients were enrolled. Twenty-seven (51.9%) patients had no etiology identified. Three patients (5.8%) had bacterial etiology, 10 (19.2%) had viral etiology, and 12 (23%) had immune-mediated encephalitis. Among viral etiologies, VZV was identified in 4 cases, HSV in 3 cases, CMV in 2 cases and measles in 1 case. Baseline characteristic of HIV infection or skin rash was associated with viral infection (p 0.031, p 0.006). Patients with VZV encephalitis might not have active skin lesion. The presence of prodrome, duration of prodrome, neurological onset to peak and physical examination of focal neurodeficit, meningeal irritation signs, and reflex were similar across all etiologies. White blood cell [mean 7.0 (range 0–30) cells/µL] and protein [mean 32.5 (range 11–70.4) mg/dL] from the cerebrospinal fluid of noninfectious etiologies tended to be lower than the levels of infectious causes (p 0.009, p 0.020). All patients survived at 7 days after admission.

Conclusion

A quarter of patients presenting with acute encephalitis in this study had autoimmune and paraneoplastic encephalitis. Infections caused by herpesviruses was the most prevalent viral etiology. Autoimmune and paraneoplastic encephalitis should be kept in the differential diagnosis in patients with acute encephalitis.

Disclosures

S. Wacharapluesadee, USAID: Investigator, Research grant. O. Putcharoen, USAID: Grant Investigator, Research grant.
Development of a Novel Anthrax Vaccine Comprising LF-PA Chimera
Authors: Aggarwal Somya , Somani Vikas , Bhatnagar Rakesh
Published: October 2017

Background

Bacillus anthracis (BA), the etiological agent of anthrax, secretes protective antigen (PA), lethal factor (LF), and edema factor (EF) as major virulence factors. Among them, PA based vaccines are most indispensable for providing immunity against BA, but the low shelf life limits its reliability. Previous studies revealed that PA domain IV includes B-cell epitopes designated as ID I, ID II, and ID III; among them, ID II and ID III have been found to possess more toxin neutralization activity and produce high antibody titre. Moreover, N-terminal region of both LF and EF carries binding site of PA which are homologous to each other. Here, in this study we have developed and evaluate the vaccine efficacy of chimeric vaccine containing ID II-ID III region of PA and N-terminal region of LF and EF (ID-LFn).

Materials and Methods

ID-LFn was generated by overlapping PCR followed by cloning in pET28a. The recombinant protein was then expressed and purified by Ni-NTA chromatography. Reactivity of ID-LFn with anti-PA/LF/EF antibodies was checked by ELISA. Stability was assessed using Circular Dichroism Spectroscopy. The vaccine potential of ID-LFn was evaluated by toxin neutralization assay, lymphocyte proliferation assay, and cytokine analysis. The protection efficacy was analyzed by challenge studies in mice.

Results

ID-LFn was found to be significantly stable as compared with protective antigen. Anti-ID-LFn antibodies recognized PA, LF as well as EF. Though, the total antibody titre, toxin neutralization activity was found to be less than PA but surprisingly, the protection efficacy of ID-LFn was found similar as PA.

Conclusion

The ID-LFn vaccine might be second next generation vaccine showing equal protection but higher shelf life as PA with the capability of neutralizing PA, LF as well as EF at the same time. Thus, it may prove an efficient and reliable treatment strategy against anthrax.

Disclosures

All authors: No reported disclosures.