bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Musculoskeletal Infection Society (MSIS) Diagnostic Criteria as Predictors of Treatment Success in Hip Arthroplasty Infections Treated with Two-Stage Exchange
Authors: Henry Michael , Russell Celeste , Nocon Allina , Westrich Geoffrey , Miller Andy
Published: October 2017

Background

Prosthetic joint infection (PJI) is a grave complication of total hip arthroplasty (THA). Predicting outcome is difficult. Musculoskeletal Infection Society (MSIS) criteria are sensitive and specific for the diagnosis of PJI. In prior work, we systematically studied the value of each MSIS criterion as a prognostic marker among a large cohort of patients with infected hip and knee arthroplasty treated with debridement, antibiotics, and implant retention (DAIR) at our specialized orthopedic hospital. We found that sinus tract drainage and culture positivity predicted explantation within 2 years of DAIR; the minor MSIS criteria were not predictive. Here, we sought to evaluate the utility of MSIS criteria in predicting outcomes of infected THR PJI treated with two-stage exchange arthroplasty. We sought to evaluate whether MSIS criteria can predict outcome of infected THR PJI treated with two-stage exchange arthroplasty.

Methods

A retrospective cohort of PJI from 2007 to 2014 treated with two-stage exchange was identified via an administrative database. Two-year implant retention was the primary outcome. Collected data included demographics and comorbidities, duration of symptoms, implant age, and pathogen. Continuous variables were assessed using the Mann–Whitney U-tests and categorical variables using the χ 2 test and Fisher’s exact test when appropriate.

Results

One hundred and thirty patients who underwent two-stage exchange for THA PJI meeting MSIS criteria were identified. Ninety percent remained infection free after 2 years of observation. Neither of the major criteria [the presence of sinus drainage[(P = 0.5416), and >1 positive culture (P = 0.1052)], nor any of the minor criteria, reached statistically significant association with treatment outcome.

Conclusion

Individual MSIS diagnostic criteria, which do have prognostic utility in hip and knee PJI treated with DAIR, may not be powerful predictors of outcome of hip PJI after two-stage exchange, likely in part because of the high success rate of this procedure.

Disclosures

All authors: No reported disclosures.
Assessment of a Modified Antibiotic Prophylaxis Open Fracture Protocol
Authors: Hill Brandon , Sanasi-Bhola Kamla , Okoye Stella , Madera Margaret , Ferren Janie , Justo Julie Ann , Bookstaver P Brandon
Published: October 2017

Background

National guidelines support antibiotic prophylaxis for open fracture with cefazolin +/− aminoglycoside based on fracture grade and contamination. The purpose of this study was to assess a modified adult antibiotic prophylaxis open fracture protocol (AOFP) which recommended weight-based cefazolin for low-grade fractures or ciprofloxacin plus vancomycin for high-grade fractures.

Methods

Adult patients with open fractures admitted to Palmetto Health Richland between January 2012 and December 2016 were screened for study inclusion. Exclusion criteria were receipt of antibiotics for reasons other than open fracture, death prior to wound closure, and local admission time >48 hours after time of injury. Compliance to all elements of AOFP was assessed. Clinical endpoints including open fracture infection rates, epidemiology, and drug-related adverse events were compared between pre-implementation (January 2012 – December 2012) and post-implementation period (November 2015 – December 2016). χ 2 and t-tests as appropriate were used to compare outcomes between groups.

Results

Following exclusions 189 patients were included in the analysis (90 pre- vs. 99 post-AOFP, respectively). Post-AOFP, a 17% (16/93) adherence rate to all AOFP elements was found. Appropriate agents were selected in 82.8% (77/93). The most common reasons for non-adherence were incorrect dosing and prolonged antibiotic duration. Fracture site infection rates were 23.3% (21/90) and 7.1% (7/99) in pre- and post-AOFP groups, respectively (P = 0.001). Infections primary caused by Gram-negative pathogens in pre-AOFP and Gram-negative organisms comprised 62 and 40% of open fracture site infections in pre- and post-AOFP groups, respectively. Incidence of acute kidney injury, Clostridium difficile-associated diarrhea, and other antibiotic-associated AEs were rare and comparable between groups. Change in median days to infection (55.6 days vs. 56.55 days, P = 0.71) and median duration of antibiotics in hours (48.0 vs. 54.7, P = 0.59) was not significantly different post implementation.

Conclusion

Local adherence to all elements of the modified AOFP was low, yet the appropriate agent(s) was used in majority of cases. The modified AOFP was associated with a numerical decrease in infection rates post-open fracture and comparable AEs.

Disclosures

P. B. Bookstaver, Rock Pointe: Content Developer, Consulting fee
Clinical Features and Treatment Outcomes of Bone-Joint Infection Between Bacteria and Mycobacterium Tuberculosis
Authors: Chumsaengsri Chumsaeng , Salee Parichat , Louthrenoo Worawit
Published: October 2017

Background

Bone-joint infection is an emergency condition that requires immediate management. Delayed in treatment or improper management can lead to a significant morbidity and mortality.

Methods

The medical records of patients with bone-joint infection seen at Maharaj Nakorn Chiang Mai Hospital between 1 November 2010 and 30 September 2015 were reviewed. The diagnosis of bone-joint infection was confirmed by pathogen identification or pathohistological report. Only those with adequate clinical features and treatment outcomes were included for analysis.

Results

Of 125 bone-joint infected patients seen during the study period, 92 patients were caused by bacterial infection and 33 from tuberculous infection. Their mean ± standard deviation age was 55.3 ± 17.7 years, and had total disease duration of 7.1 ± 8.2 months. Sixty-four percent were men. Of 33 TB cases, 24 (72.7%) had spinal involvement. Among 92 cases with bacterial infection, 52 (56.5%) had non-spinal joint involvement, and 38 (41.3%) had non-spinal bone involvement. Regarding clinical features, TB cases had mean duration of symptom of 5.3 ± 6.1 months. Multivariate logistic regression analyses showed that neurological manifestations (adjusted OR = 314.1, 95% CI 14.4–6831, P < 0.001), pulmonary symptoms (AOR = 222.1, 95% CI 3.0–16,560, P = 0.014), symptom duration over 1 month (AOR = 67.4, 95% CI 4.2–1070, P = 0.003), afebrile illness (AOR = 24.1, 95%CI 1.2–493.7, P = 0.039), ESR <70 mm/hour (AOR = 4.7, 95% CI 1.1–19.9, P = 0.039), and CRP <30 mg/l (AOR = 7.0, 95% CI 1.6–31.2, P = 0.010) were risk factor of TB bone-joint infection. There were 120 (96.0%) patients with clinical improvement, and five (4.0%) died patients. There were no significant differences among the clinical improvement, recurrent infection, and mortality between the two groups.

Conclusion

Distinguish of bone-joint infection between bacteria and mycobacterium tuberculosis is difficult. However, patients with TB bone-joint infections significantly had more symptom duration over 1 month, the presence of paraplegia, the presence of pulmonary symptoms, and the presence of afebrile illness than those with bacterial infection. There were no significant differences among treatment outcomes and mortality between the two groups.

Disclosures

All authors: No reported disclosures.
Optimizing Envitonmental Hygiene to Successfully Decrease Clostridiun Difficile Transmission
Authors: Carling Philip , Scott Mary
Published: October 2017

Background

In light of the challenges involved in reducing healthcare onset colstridium Difficile infection (HO-CDI), we implemented a multifaceted hospital wide intervention program to optimize environmental hygiene in our 197 bed regional referral hospital.

Methods

Following an 18 month period during which HO-CDI rates were monitored, we simultaneously replaced routine quartinary ammodium cleaning of patient rooms with an environmentally non-damaging sporicidal peroxyacetic acid/hydrogen peroxide disinfectant, implemented an educational program for environmental services staff which included ongoing objective monitoring of the thoroughness of disinfection cleaning (TDC). We also evaluated cleaned environmental surface bioburden elimination. terminal room cleaning efficiency and HO-CDI rates.

Results

During the 33 month intervention period, TDC rapidly improved from 81% to 92% and remained greater than 88% during the remainder of the study (P = . 01)(Figure 1.) Bioburden elimination of cleaned surfaces improved from 24% to 84% (P = .03) with sporacide use. Efficiency of terminal room cleaning improved by 33% (36minutes to 27 minutes)(P = .02). HO-CDI rates fell significantly during the intervention period from an average of 8.9 to 3.2 /10,000 patient-days (P =.0001, 95% CI 3.48 to 7.81)(Figure 2.) as did months without documented CDI cases (P .02). No changes in potential confounders including antibiotic use patterns, intensive care unit days, prevalence density of CDI at the time of admission, hand hygiene compliance rates, isolation practices and over all patient-days were identified.

Conclusion

In the context of a single site, quasi-experimental study design, this 44 month study documented a significant impact (P = .0001) of an objectively monitored hospital-wide sporicidal disinfection cleaning program on endemic HO-CDI. The program was also associated with significantly improved efficiency of cleaning and post cleaning bioburden elimination of cleaned patient zone surfaces. Assuming a continued incidence of HO-CDI without intervention, the program resulted in an average non-reimbursed cost savings of approximately $ 10,000./month during the intervention period.

Disclosures

P. Carling, Ecolab: Consultant, Royalty; M. Scott, Ecolab, Inc.: Research Contractor, Research support
Sustained Improvement in Hand Hygiene Compliance Using a Decentralized, Technology-Based Approach
Authors: Landon Emily , Pacholek Gretchen , Runjo Demetria , Garcia-Houchins Sylvia , Ridgway Jessica P , Weber Stephen G , Chu Vera , Marrs Rachel , Bartlett Allison H
Published: October 2017

Background

We aimed to use weekly PI calls in conjunction with 24/7 hand hygiene monitoring technology (HHMT) to engage front-line Intensive Care Unit (ICUs) clinicians in improving Hand Hygiene (HH) compliance

Methods

HHMT is used to monitor aggregate, unit-based HH compliance in real time and displayed on monitors at the nursing stations at our academic medical center. After installation and validation were completed, unit-based teams of nursing and physician leadership joined weekly 15-minute HH PI calls to discuss their previous week’s compliance rate, next steps in their own PI plan, and share successes and failures. Calls were suspended for 6 months and restarted in early 2017.

Results

Graph representation of weekly HH compliance rates for the ICUs are shown in figure 1. Units AandB underwent physical moves during the break, Unit C had no change, and Unit D moved and consolidated with other ICUs constituting a major change in personnel and patient population. Each ICU participated in 84 calls and recorded approx. 50,000–100,000 HH opportunities during each month resulting in over 8 million opportunities for HH compliance recorded during the call-in periods. Unit A had an average compliance of 39% for the first 4 weeks of calls and 64% during the same 4 week period one year later (P < 0.0001). After 6 months without the calls, HH compliance was 48% (P < 0.0001 compared with baseline compliance) and unit A implemented 20 separate PI interventions over the course of the calls. Compliance was also significantly improved (P < 0.0001 for all comparison to baseline) for units B, C, and D (Unit B: 42% baseline, 71% at 1 year, 67% after the break, 23 interventions; Unit C: 54% baseline, 58% at 1 year, 59% after the break, 19 interventions; Unit D: 41% at baseline, 56% after 1 year, 49% after the break, 19 interventions). Attendance was >90% for nursing leadership and <25% for physician leadership.

Conclusion

Weekly 15-minute calls were successful in engaging local nursing leadership to undertake performance improvement interventions and significantly improved HH compliance that was sustained over 18 months of calls and did not drop back to baseline even after a 6 month break.

Disclosures

E. Landon, GOJO: Speaker, travel expenses for speaking;   J. P. Ridgway, Gilead FOCUS: Grant Investigator, Grant recipient; A. H. Bartlett, CVS Caremark: Consultant, Consulting fee
The Use of Instructional Technology to Increase Independent Patient Hand Hygiene Practice of Hospitalized Adults in an Acute Care Setting
Authors: Knighton Shanina
Published: October 2017

Background

Despite recognition that hospitalized patients carry pathogens on their hands and demonstrate poor hand hygiene practice, little attention has been given to interventions that increase hand hygiene practices. Studies that have attempted to improve patient hand hygiene practice lack sustainability due to dependability on healthcare staff, and no prior studies have tested ways to improve independent patient hand hygiene practice. One such approach is using a patient-centered multi-modal educational intervention and electronic voice-recorded reminder cue to promote self- management of hand hygiene.

Methods

This comparative effectiveness study tested two educationally-based approaches to improve patient hand hygiene in older adults hospitalized for 4 days for elective lower extremity orthopedic or podiatry surgery at a veterans’ hospital. Group 1 (n = 41) received an educational video, an educational handout and a voice-recorded electronic audio reminder (EAR) an active cue, which verbally reminded the participant to clean their hands 3 times a day (7am, 12 pm, 5pm). Group 2 (n = 34) received the educational video and handout without the EAR. There were no significant differences between the two randomly assigned groups in terms of age, ethnicity and sex.

Results

Figure 1 shows the daily difference in product consumption Day 0 to Day 3. The average product consumption of ABHR (alcohol-based hand rub) in Group 1 (EAR) was 29.97 grams (SD 17.13). Group 2 (No EAR) averaged 10.88 grams (9.27) (P < 0.0001). Comparing post-operative day (POD) 0 to POD 3, and controlling for covariates (Disability of Arm, Shoulder, and Hand [QuickDASH], Hand Grip Strength, Surgical Pain, MRSA in Nares, and Education), multivariate analyses indicated that the electronic audio reminder was a significant predictor (β=.468) of ABHR consumption, R2 = .39, R2adj. = .34, F (6, 68) = 7.265, P < .001.

Conclusion

This study demonstrated that a short educational intervention that included a video, a handout, and a verbal audio reminder has the potential to increase patient-centered infection prevention in the acute care settings without increasing the workload of healthcare workers. Findings can be used for future infection prevention studies in institutionalized patients to improve self-managed care.

Disclosures

All authors: No reported disclosures.
Effectiveness of Live Zoster Vaccine in Preventing Herpes Zoster Ophthalmicus (HZO)
Authors: Aukes Laurie , Bartlett Joan , Fireman Bruce , Hansen John , Lewis Edwin , Earley Elizabeth , Marks Morgan , Saddier Patricia , Klein Nicola P
Published: October 2017

Background

Herpes zoster ophthalmicus (HZO), caused by reactivation of varicella-zoster virus in or around the eye, can be severe and often results in care-seeking that may be less discretionary than for uncomplicated herpes zoster (HZ). We compared the vaccine effectiveness (VE) of live zoster vaccine against HZO with the VE against HZ overall.

Methods

Kaiser Permanente Northern California (KPNC) members enter the ongoing cohort study when age-eligible for zoster vaccine starting in 2007. Incident HZ was defined as a new diagnosis of HZ with an antiviral prescription or a positive varicella viral test. Among those, an HZO case was defined as having an HZO diagnosis during an ophthalmology visit within 30 days of the initial HZ diagnosis. VE by age at vaccination and time since vaccination was estimated using Cox regression adjusted for age, race, sex and time-varying measures of healthcare use, comorbidities and immunocompromise status. Average VE over the first 5 years following vaccination was calculated as a weighted average of annual VE estimates.

Results

During 2007–2014, ~1.3 million individuals ≥50 years of age entered the study population and 29% were vaccinated. Among 48,889 incident HZ cases, 2,858 (6%) had HZO, 87% of whom were unvaccinated. For all ages combined, VE against HZO was 72% (95% CI, 64%-79%) in year 1, similar to 68% (95% CI, 65%-70%) against HZ. VE fell in years 2, 3, 4, and 5 to 47%, 45%, 42% and 27% for HZO and to 47%, 39%, 41% and 37% for HZ. For age groups 60 – 69 and 70 – 79, where we have the most data, initial VE and waning were similar for HZO and HZ. Numbers of HZO cases for 50–59 year olds were too small to evaluate at this time. Average VE against HZO over the first 5 years following vaccination was 52% (95% CI, 42%–60%) for ages 60–69, 51% (95% CI, 39%–61%) for ages 70-79, and 39% (95% CI, 14%-57%) for ages 80+; similarly, 5-year average VE against HZ was 49%, 46%, and 44% for these 3 age groups.

Conclusion

VE against HZO was similar to VE against HZ regardless of age at vaccination or time since vaccination. Effectiveness of live zoster vaccine in preventing HZO was highest in year one with subsequent waning.

Disclosures

E. Earley, Merck & Co.: Research Contractor, Salary; M. Marks, Merck and Co. Inc.: Employee, Restricted Stock and Salary; P. Saddier, Merck & Co., Inc.: Employee, Salary; N. P. Klein, GSK: Investigator, Grant recipient; sanofi pasteur: Investigator, Grant recipient; Merck & Co.: Investigator, Grant recipient; MedImmune: Investigator, Grant recipient; Protein Science: Investigator, Grant recipient Pfizer: Investigator, Grant recipient
How Acceptable Is A Wireless Pill Bottle That Monitors and Texts In Response To Missed Doses: Focus Groups With Young African American MSM Living With HIV
Authors: Dworkin Mark , Panchal Palak , Jimenez Antonio , Garofalo Robert , Haberer Jessica E , Wiebel Wayne
Published: October 2017

Background

African American MSM (AAMSM) living with HIV are less likely to have viral suppression than other racial groups. Wisepill, a wireless pill bottle, transmits a cellular signal to a server when opened and is designed to measure antiretroviral therapy (ART) adherence. The objective of this study was to explore the acceptability of a proposed intervention in these young AAMSM using the Wisepill device opening data to trigger a real-time text alert that ART may not have been taken during a planned time to either the user, a trusted social contact, or a healthcare worker, depending on the duration of consecutively missed doses (1 dose, 3 doses, 7 doses, respectively).

Methods

From December 2016 – May 2017, AAMSM living with HIV age 18–34 years (N = 25) participated in a study that included five focus groups (n = 23) and one on one interviews (n = 2). We performed theory-based discussion grounded in the Technology Acceptance Model. Specifically, we explored usefulness, convenience, concerns, and intention to use.

Results

Fifty-two percent missed at least one dose in the 4 days prior to the focus group meeting. Almost all participants (94%) favored the idea of a wireless pill bottle monitor and linked text message notification that ART may have been missed. The device was considered convenient for use at home or in a backpack, but too large for a pocket. Stigma and privacy were common concerns. For example, participants did not want to carry the device with them if the pills would “sound like a walking pharmacy” and did not want a text message that said, “You missed your HIV meds.” They preferred text message notifications that ranged from emoji icons to cryptic short texts and wanted to receive an email as a backup plan. Most believed that the device appearance would not gain unwanted attention. Thirty percent of the participants identified a partner as a social contact to whom the 3-day missed dose reminders would be sent whereas others designated their mother, aunt, brother, friend, pastor, and case-manager.

Conclusion

An adherence intervention using a wireless pill bottle monitoring device linked to text notifications was acceptable to most of the young AAMSM in this study. Acceptability may be enhanced by personalization of the responsive text messages and a backup email option.

Disclosures

J. E. Haberer, Merck: Consultant, Consulting fee; Natera: Shareholder, Stock ownership
Late Presentation among Patients Diagnosed with HIV in an Inpatient Setting
Authors: Leonard Michael , Figueroa-Sierra Marielys , Kindlick Dianne
Published: October 2017

Background

Despite improved morbidity and mortality with the advent of highly active antiretroviral therapy (HAART), late presentation, CD4< 200 and/or an opportunistic infection or malignancy, remains a major public health concern. Although mortality causes are more diverse in the HAART era, HIV associated deaths continue to be a result of late presentation.

Methods

Carolinas HealthCare System (CHS) is a nonprofit, vertically integrated healthcare system with approximately 12 million patient encounters per year. We identified new HIV positive patients from an institutional database within our multi-hospital healthcare system and retrospectively extracted clinical patient data. Patients with HIV, admitted to one of our eight acute care facilities were identified (n = 1,632) from medical records, of these, 93 were diagnosed during admission.

Results

We identified all newly diagnosed with HIV in the inpatient setting between July 2014 and March 2017 (n = 93). 70% of the newly diagnosed were male, 67% identified as Non-Hispanic black and had a median age of 42 years. The median CD4 count was 156 and 76% presented with a CD4<200. Only 50% of patients were insured prior to hospitalization. Although not statistically significant in this study, we noted that those who were insured prior to hospital discharge were more likely to follow-up and have continuity of care compared with the uninsured. 42% were prescribed HAART prior to discharge. Opportunistic infections or AIDS defining malignancies were present in 38%. An OI was present in 29% with PCP being the most common and an AIDs defining malignancy was present in 9% with NHL being the most common diagnosis.. Inpatient mortality was 10% in newly diagnosed HIV patients and of those the median CD4 was 45. All of those died of AIDS-related complications.

Conclusion

Patients in our study period presented too late in their illness with >75% presenting with a CD4<200. Our findings are limited by our small sample size and further prospective studies are needed to better identify effective strategies to prevent late diagnosis of HIV.

Disclosures

All authors: No reported disclosures.
Reviewing Clinical Outcomes of Patients with the E157Q Mutation in Detroit
Authors: Pavkovich David , Richmond Deborah , Veltman Jennifer
Published: October 2017

Background

Integrase Strand Transfer Inhibitor (INSTIs) transmitted resistance has remained uncommon, estimated at 0.04%, with E157Q being the mutation most commonly identified. E157Q is thought to cause low-level resistance to raltegravir and elvitegravir but has also been the only mutation implicated in a recent case of dolutegravir treatment failure. INSTI resistance testing is not currently recommended and little data is available on clinical outcomes on INSTI therapy in the presence of E157Q, therefore we reviewed all the patients in an urban clinic in Detroit with E157Q seen on genotype to determine its clinical impact.

Methods

We reviewed the records of all Wayne State University Adult HIV clinic attendees in Detroit, Michigan who had an INSTI genotype performed between February 2014 and February 2016 to identify those with an E157Q mutation. We reviewed demographics, HIV risk factors, treatment and clinical outcomes.

Results

292 patients had INSTI resistance testing during our study period. 24 patients (8.2%) had an E157Q mutation. These patients had a median age of 27.5 years. They were predominately male (87.5%), black (87.5%), and MSM (70.8%). Four patients had an additional mutation (N155H, T97S, L74V, and V151I). Eleven patients were treatment-naïve, consistent with transmitted E157Q drug resistance. One treatment-naïve patient had both the E157Q mutation and the T97S mutations. Of the 24 patients with E157Q, 15 were placed on an INSTI-based regimen and 6 (40%) achieved viral suppression at 12 months. 7 patients were lost to follow up at and 2 had stopped treatment at 12 months. Amongst patients adherent to INSTI based ART, there were no cases of treatment failure.

Conclusion

While our sample size was relatively small, our data suggests that E157Q is not an infrequent mutation and patients with E157Q who were started on INSTI based regimens and were adherent achieved viral suppression. This is reassuring for rapid ART start at time of HIV diagnosis with INSTI based ART without genotype data. Loss to follow up and poor adherence were seen frequently, limiting our ability to determine clinical outcomes on ART. In short, patients with E157Q mutation have good clinical outcomes on INSTI based ART.

Disclosures

All authors: No reported disclosures.
Pharmacokinetics of Temsavir, the Active Moiety of the Prodrug Fostemsavir, in Subjects with Hepatic Impairment
Authors: Sevinsky Heather , Magee Mindy , Ackerman Peter , Adamczyk Robert , Karkas Jennifer , Lubin Susan , Ravindran Palanikumar , Llamoso Cyril , Eley Timothy , Moore Katy
Published: October 2017

Background

Fostemsavir (FTR) is a prodrug of temsavir (TMR), a first-in-class attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into host CD4+ T cells. TMR is primarily metabolized via hydrolytic and oxidative pathways; impaired hepatic function may alter TMR pharmacokinetics (PK).

Methods

AI438053 (NCT02467335) was an open-label, nonrandomized study in healthy subjects (HS) and subjects with hepatic impairment (HI), defined by Child-Pugh (CP) score: mild (CPA), moderate (CPB), or severe (CPC). HS were matched for age, body weight, and sex. Subjects received a single oral dose of FTR 600 mg fasted and serial PK samples for TMR were collected up to 96 hours post-dose. Unbound TMR at 1 and 3 hours post-dose was determined. Total and unbound PK parameters were derived by noncompartmental methods. Geometric mean ratios (GMR) and 90% confidence intervals (CI) for HI vs.. HS were derived using linear mixed-effects models. Subjects were monitored for adverse events (AEs).

Results

18 subjects with HI (N = 6/CP group) and 12 HS received FTR and completed the study. Total and unbound TMR exposures increased with increasing HI severity (see Table). Total and unbound TMR CLT/F decreased with increasing HI severity. Mean % protein binding of TMR was 81.0% in HS and 79.9%, 81.9%, and 76.5% in CPA, CPB, and CPC HI, respectively, and was independent of TMR concentration. There were no deaths, serious AEs, or discontinuations during the treatment period.

Conclusion

TMR exposures increase with increasing severity of HI. The increase in TMR exposures in patients with mild or moderate HI is not expected to alter the safety profile of FTR. The risk/benefit of higher TMR exposures in severe HI is under evaluation.

Disclosures

H. Sevinsky, ViiV Healthcare: Employee, Salary; M. Magee, GlaxoSmithKline: Employee and Shareholder, Salary; P. Ackerman, ViiV Healthcare/GSK: Employee and Shareholder, Salary and Stock; R. Adamczyk, Bristol-Myers Squibb: Employee, Salary; J. Karkas, Bristol Myers Squibb: Employee and Shareholder, Salary; S. Lubin, Bristol-Myers Squibb: Employee, Salary; P. Ravindran, Bristol-Myers Squibb: Employee, Salary; C. Llamoso, ViiV Healthcare: Employee, Salary; T. Eley, Bristol-Myers Squibb: Former Employee during study conduct, Salary; K. Moore, ViiV Healthcare: Employee, Salary
Avoiding Inpatient Delays in Antiretroviral Therapy via Low Cost Formulary Management
Authors: Sundquist Hannah , Kassamali Zahra
Published: October 2017

Background

Of 8 formulary HIV medications at our institution, 3 are no longer first line treatments. Agents unavailable on formulary are administered from a patient’s own supply. We examined the impact of availability of antiretroviral therapy (ART) on time to appropriate therapy among HIV positive inpatients.

Methods

Adult inpatients who received ART from 11/2015 – 10/2016 were included in this single-center review. Data were evaluated by encounter; individuals with multiple admissions were counted per admit. Descriptive statistics were used to evaluate the time from admission to ART order and administration. We noted discrepancies between ordered and home ART regimen, and any administration of partial therapy. Patients not taking ART prior to admission or without documentation of a home ART regimen were excluded from the outcomes analysis. A cost analysis was conducted to describe the financial impact of any recommended formulary changes.

Results

36 patients with 55 inpatient encounters were evaluated; 46 (84%) had a documented home ART regimen. Mean age was 47.8 years, 67% were male, 36% met criteria for AIDS by CD4 cell count. Creatinine clearance was < 60 ml/minute in 33% of subjects, 25% were admitted for an infectious issue. Median length of stay was 5 days. Half (49%) were taking nucleoside reverse transcriptase inhibitors, 22% integrase inhibitors, 19% protease inhibitors, 3% non-nucleoside reverse transcriptase inhibitors. In the 7 encounters (15%) with all ART on formulary, 100% received their full ART regimens as inpatients vs. 69% of those with partial or no ART on formulary. Median time to therapy doubled in patients who had partial or no home ART on formulary: 25 hours (median of 1 missed dose) vs.. 12 hours (median of 0 missed doses). Anticipated annual cost of formulary revisions, including addition of 4 agents, was $6016.37.

Conclusion

Having a complete ART regimen on formulary substantially increased likelihood of complete ART administration without delay. Adding an NRTI alternative to tenofovir was needed due to high rates of renal dysfunction; adding agents with higher barriers to resistance, dolutegravir and darunavir, were important as genotypes and viral loads are not always known at admit. Expanding the ART formulary provides a significant improvement in quality of care at a reasonable cost.

Disclosures

All authors: No reported disclosures.
Knowledge, Attitude and Practice of Pre-exposure prophylaxis (PrEP) against HIV infection of medical providers at an academic center
Authors: Maude Rapeephan , Volpe Gretchen , Stone David
Published: October 2017

Background

Pre-exposure prophylaxis (PrEP) against HIV infection is available for people at risk of acquiring HIV infection and who are not positive for HIV infection. It is proven to be effective at preventing HIV infection in many studies in various populations. However, due to lack of knowledge or due to attitudes towards PrEP, this mode of prevention may be underutilized by people at risk and their providers. Our aim is to assess the baseline knowledge of, attitudes towards and practice of medical providers at Tufts Medical Center.

Methods

survey of 80 medical providers at Tufts Medical Center with a short questionnaire.

Results

The median age of the participants were 31 years old (IQR 28–34.5, range 22–71). 38.75% were male. Ethnicity were White (60%), Asian (20%), and others (20%). Fifty-five percent were Doctor of Medicine or Doctor of Osteopathic (MD/DO), 20% Physician assistant (PA), 8.75% Registered nurse (RN) and 7.5% were medical students. Other groups included Nurse practicioner (NP), medical assistant, research coordinator and PA student.

Knowledge. Approximately two-third (67.5%) of study participants heard of PREP. In MD/DO group, 81.81% (36/44) heard about PREp. 46.26% responded correctly that PREP should be given daily. 68.75% answered correctly that Tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC; Truvada) is the standard regimen.

Attitude. 31.81% of the MD/DO group were not comfortable prescribing PREP. Top three barriers perceived for prescribing PREP were “Not enough knowledge” 72.5%; “Lack of experience” 56.25% and “Not covered by insurance” 17.5%.

Practice. Of 61 participants who are eligible to prescribe medications (MD/DO, PA, NP), 15.27% prescribed PREP prior to the survey. Over 75% would refer patients to infectious diseases or other providers to prescribe PREP.

Conclusion

There are some knowledge and practice gap of PREP. Most are not comfortable prescribing PREP thus will refer patients to infectious diseases. It is essential to promote knowledge and attitude about PREP in medical providers who have an important role in advising at-risk patients about PrEP which will lead to a better practice.

Disclosures

All authors: No reported disclosures.
Predictors of First-Year Medication Adherence in a National Cohort of Veterans Initiating Pre-Exposure Prophylaxis (PrEP) to Prevent HIV Infection
Authors: Ohl Michael , Richardson Kelly , Beck Brice , Alexander Bruce , Van Epps Puja , Maier Marissa , Lund Brian , Vaughan-Sarrazin Mary
Published: October 2017

Background

Current guidelines for HIV Pre-Exposure Prophylaxis (PrEP) recommend daily use of tenofovir disoproxil fumarate / emtricitabine (TDF/FTC). Little is known about levels and predictors of long-term PrEP medication adherence in routine clinical settings.

Methods

We used a previously-validated algorithm and national Veterans Health Administration (VHA) administrative data to identify a cohort of Veterans initiating PrEP during 2012–2015 (i.e., TDF/FTC use, no other antiretroviral use, and no diagnosis codes for HIV, hepatitis B, or needle-stick injury). We used pharmacy refill data to calculate the proportion of days covered (PDC) by TDF/FTC in the 365 days after initiation, and multivariable logistic regression to identify patient characteristics associated with high adherence (i.e., PDC > 0.80).

Results

Most (96%) of the 706 Veterans initiating PrEP were men, reflecting the overall demographics of patients in VHA. The median age was 38. Reported race in administrative data was 141 (20.0%) black, 485 (68.7%) white, 42 (5.9%) other, and 38 (5.4%) missing. Only 30 PrEP users (4.2%) lived in rural areas. Co-existing diagnoses included substance use disorder in 264 (37.4%), hypertension in 250 (35.4%), and diabetes in 95 (13.5%). The median PDC for TDF/FTC in the first year was 0.78 (IQR 0.41–0.96), and a minority (N = 120, 17%) had only a single TDF/FTC fill. Predictors of high adherence were older age (OR 1.88, 95% CI 1.20–2.84 for age 50–64 compared with age < 35); white compared with black race (OR 1.96, 1.30–2.94), Male sex (OR 4.17, 1.67–12.50), absence of a substance use diagnosis (OR 1.47, 1.05–2.04), and presence of diabetes (OR 1.66, 1.02–2.75).

Conclusion

Adherence to TDF/FTC in the first year of PrEP was overall high. Racial, gender, and substance-use-related differences in PrEP adherence mirrored those previously described for PrEP uptake. Interventions to promote equitable PrEP uptake should include strategies to support adherence.

Disclosures

All authors: No reported disclosures.
Perceptions of HIV Pre-exposure prophylaxis (PrEP) among young pregnant women from KwaZulu-Natal, South Africa
Authors: Guillamet Laia Jimena Vazquez , Moll Anthony P , Kacin Alexa , Madi Jabulile , Ndlovu Ntombi , Shenoi Sheela
Published: October 2017

Background

Pre-exposure prophylaxis (PrEP) is effective for HIV prevention with good adherence. In high HIV prevalence settings, young women ages 18–24 are at high risk of HIV acquisition, particularly during pregnancy and the postpartum period, and would potentially benefit from PrEP. More information is needed to achieve successful implementation of PrEP in this population.

Methods

The study was performed in Tugela Ferry, one of the poorest subdistricts of South Africa. From June-August 2016,the study team interviewed 187 HIV negative pregnant women ages 18–24 anonymously at health care facilities. Interviews collected data on demographics, HIV and PrEP knowledge, HIV risk and readiness for oral PrEP.

Results

Among 187 pregnant women, the mean age was 20.3 years (SD1.97), 179 (95.7%) were unemployed, 93 (49.7%) completed secondary school, and 137 (73.3%) reported one partner in the last month. None reported having ever being paid for sex. While 185 (98%) knew that HIV can be transmitted through sex, only 117 (62.5%) knew that a woman can transmit HIV to her child, and only 95 (51%) knew that HIV can be transmitted through breastmilk. Sixty-eight (36.4%) women believed that a sexual partner had been sexually active with another person in the last month, though 182 (97.3%) had difficulty negotiating condom use with their partner, and only 7 (3.7%) women reported consistent use of condoms. The vast majority (97%) would start PrEP if a doctor recommended it though 100 (53.5%) were concerned about being mistaken for HIV positive.

Conclusion

Pregnant young women in rural South Africa are at risk for HIV acquisition and are interested in PrEP. Knowledge of risks of HIV lags, particularly with regard to mother to child transmission. Young pregnant women are not able to negotiate consistent condom use and need a HIV prevention tool that is within their control. Stigma may be a barrier to effective PrEP use among these women. Further research is needed to guide potential PrEP implementation in pregnant women.

Disclosures

All authors: No reported disclosures.
Microbiology and Clinical Characteristics of Industrial Oil Burns
Authors: Kelly Devin , Rizzo Julie , Yun Heather , Blyth Dana
Published: October 2017

Background

Injured oil workers are exposed to a broad microbiome in hydraulic fracturing fluids (HFF) and oil wells at the time of injury. This includes Pseudomonas, Stenotrophomonas, Acinetobacter, and rare human pathogens which may be harder to culture. This study evaluates oil-related burn (ORB) microbiology.

Methods

Patients admitted to the USAISR burn center enrolled in the Epidemiology of Workplace Burns and Injuries in Texas registry from April 2011 to November 2016 were included as cases and controls. Patients hospitalized ≤2 days were excluded. ORB was defined as exposure to HFF (FORB), or non-HFF (NFORB). Controls were patients admitted with industrial burns (non-ORB). Patient demographics and clinical cultures (days 1–15) were obtained through the registry and electronic medical record.

Results

149 industrial burns were included, of which 35 (23%) were ORB and 114 (77%) were non-ORB. Of the ORB, 11 (31%) were FORB and 24 (69%) were NFORB. ORB had a median age, TBSA, and Baux score of 31, 25, and 58 compared with non-ORB with 36, 4, and 44, respectively (P < 0.01). Twenty-five patients had positive cultures: 12 (48%) non-ORB and 13 (52%) ORB. Sixty Isolates identified from the ORB population included Flavobacterium, Pseudomonas, and Serratia. FORB accounted for three (25%) of the culture positive ORB. S. marcescens was isolated in 1 FORB (33%) compared with 0 NFORB and non-ORB (P < 0.05). Otherwise, there was no statistical difference in isolates. Median time to first positive culture differed among non-ORB (4 days), FORB (13 days), and NFORB (3.5 days, P = 0.03). Forty-six (31%) patients had cultures obtained during admission: three (7%) FORB, 12 (26%) NFORB, and 31 (67%) non-ORB. Of cultured patients, ORB had a median TBSA and Baux score of 44 and 90 compared with non-ORB with 11 and 47, respectively (P < 0.01). Comparing all cultured patients, ORB had more positive, negative, and total cultures compared with non-ORB with 2 vs. 0, 7 vs. 3, and 10 vs. 3, respectively (P < 0.01).

Conclusion

Within this cohort, ORB was associated with more severe injuries compared with non-ORB. They had more positive, negative, and total cultures, and recovery of S. marcescens was associated with FORB. Larger studies with non-culture based technology could help further define the microbiology of this uniquely exposed population.

Disclosures

All authors: No reported disclosures.
Pharmacokinetics of Tedizolid in Adults with Cystic Fibrosis
Authors: Wang Joshua , Park Jenny , Jayne Jordanna , Bensman Timothy , D’Argenio David , Fukushima Lynn , Rao Adupa , Beringer Paul
Published: October 2017

Background

The presence of MRSA in the airways of patients with CF is associated with more rapid lung function decline and a higher mortality. Tedizolid (TDZ) is an oxazolidinone antibiotic with potent activity against MRSA; however, the pharmacokinetics (PK) in CF have not been described. The purpose of this study was to determine the PK of IV/PO tedizolid in plasma in patients being treated for acute pulmonary exacerbations.

Methods

We conducted a prospective, multiple dose, randomized, crossover study. TDZ phosphate was administered as 200 mg IV over 1h or PO once daily x 3 under fed conditions, with a 2-day washout, followed by crossover. Laboratory studies were performed throughout the study as routine clinical care. Blood samples were obtained prior to the Third dose of IV and PO and at 8 additional timepoints over 48 hours. TDZ concentrations in plasma were determined by LC-MS/MS. The maximum concentration (Cmax) and time to maximum (Tmax) were obtained from the measured data. Area-under-the concentration curve (AUC24) was determined using the linear trapezoidal rule. Compartmental PK was performed using ADAPT 5 software. Data are described by mean ± SD.

Results

The patients (4M, 2F) had a mean age of 27 years (22–32), BMI 22.0 ± 4.2 kg/m2, and predicted creatinine clearance of 128 ± 44 mL/minute. There was one report of diarrhea and hoarseness of voice that was unlikely related to the study drug. There were no clinically relevant laboratory changes. The Cmax, Tmax, and AUC24 following IV and PO administration were 2.87 ± 0.64 mg/L / 2.26 ± 0.70 mg/L, 1.32 ± 0.49 hours /2.06 ± 1.29 hours, and 27.1 ± 4.74 mg/L x hours / 25.8 ± 6.03 mg/L x hours respectively. The PK parameters for TDZ were described by a 1-compartment model: Elimination rate constant (Kel) = 0.088 ± 0.014 hour-1, Volume of distribution (V) = 96.4 ± 27.4 L, absorption rate constant (Ka) = 0.869 ± 0.978 hours−1, and bioavailability (F) = 1.00 ± 0.101.

Conclusion

The oral bioavailability of TDZ in patients with CF is complete and the pharmacokinetics are similar to that reported for healthy volunteers indicating no dose adjustments are needed in future studies evaluating the efficacy and safety in patients with CF.

Disclosures

All authors: No reported disclosures.
Therapeutic Drug Monitoring (TDM) of Suspension (SUS), Extended-Release (ER), and Intravenous (IV) Posaconazole (POS) at a Large Transplant Center
Authors: Haidar Ghady , Shields Ryan K , Clancy Cornelius J , Nguyen Minh-Hong
Published: October 2017

Background

Data on ER and IV POS among organ transplant recipients (OTRs) are limited, and the role of TDM is unclear.

Methods

Retrospective study of patients (pt) receiving any formulation of POS who had serum troughs checked. Therapeutic was defined as 3 1 mcg/mL.

Results

We analyzed 88 pt and 340 levels (SUS: 88, ER: 197, IV: 55). Eighty-five pt were OTRs (97%), 73 were lung transplant recipients (LT) (83%), 17 had cystic fibrosis (CF) (19%). POS was used for treatment (70%) (probable aspergillosis (38%), possible aspergillosis (10%), mucormycosis (16%), other mycoses (6%)), prophylaxis (19%), and pre-emptive therapy (14%). POS was given for intolerance of or contraindication to other azoles (47%), salvage therapy (10%), resistance (19%), and failure to achieve therapeutic levels with other azoles (6%). Serum concentration/dose ratios were lower with SUS vs. ER/IV (P < 0.0001) but were similar in ER/IV groups (P = 0.51) (Figure). There was no difference in serum levels between pt receiving ER vs. IV POS at 300 mg once daily (median 1.2 vs. 1.3 mcg/mL, therapeutic 70% vs. 73%, P = 0.57 and >0.99, respectively). 3 pt had levels £ 0.2 mcg/mL on 300 mg ER: 2 had CF and had undergone LT (0.2 and 0 mcg/mL) and 1 had short-gut syndrome (0.1 mcg/mL). Sixty-six percent and 67 % of pt receiving ER or IV POS (300 mg once daily) achieved initial therapeutic levels, respectively; of these, 87% and 83% had median therapeutic follow-up levels, respectively. Serial levels were available for 7 pt whose dose was increased from 300 to 400 mg ER once daily for subtherapeutic levels. 4/7 pt achieved therapeutic levels on 400 vs. 0/7 on 300 mg ER once daily (P = 0.069). Metoclopramide use and CF were associated with subtherapeutic vs. therapeutic levels (25% vs. 4% and 37% vs. 13%, respectively, P = < 0.05). When pt with CF were excluded, neither age nor body mass index were associated with POS levels. CF pt had lower levels than non-CF pt on a dose of 300 mg ER once daily (median 0.8 vs. 1.3 mcg/mL, P = 0.018).

Conclusion

Therapeutic levels are more reliably achieved with ER & IV POS compared with SUS POS. Serial TDM is unnecessary for most, but is recommended for pt with CF or those on metoclopramide. Dose increases may effectively increase levels. Novel dosing strategies are needed for CF.

Disclosures

R. K. Shields, Astellas: Received research funding, Research support. Merck: Received research funding, Research support. C. J. Clancy, Merck: Received research funding, Research support. Astellas: Received research funding, Research support. Cidara: Received research funding, Research support. Astellas: Scientific Advisor, Advisory board. Merck: Scientific Advisor, Advisory board. Cidara: Scientific Advisor, Advisory board. Medicines Company: Scientific Advisor, Advisory board.