bluuebunny/crossref_metadata_2025 huggingface dataset:
1178. A Multicenter Prospective Study of Clinical and Molecular Epidemiological Analysis of Carbapenem-Resistant Enterobacteriaceae (CRE) and Carbapenemase-Producing Enterobacteriaceae (CPE) in Japan
Authors: Hayakawa Kayoko , Kato Hideaki , Hase Ryota , Hasumi Jumpei , Nei Takahito , Nakano Ryuichi , Yano Hisakazu , Nagashima Maki , Ohmagari Norio
Published: November 2018

Background

Data of a multicenter study on CRE from Japan are limited. Comparative analyses of carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing CRE (NCP-CRE) have not yet been conducted.

Methods

Cases with CPE or CRE (defined as (1) meropenem [MPM] MIC, ≥2 mg/L or (2) imipenem [IPM] MIC, ≥2 mg/L and cefmetazole MIC, ≥64 mg/L [CLSI criteria]) were included from August 2016 to May 2017. PCR was used to detect carbapenemase.

Results

From five tertiary hospitals, 24 isolates (14 CPE and 10 NCP-CRE) were collected from 22 patients. Of the 10 NCP-CRE, seven were Enterobacter aerogenes and three were Enterobacter cloacae; of the 14 CPE, five were Klebsiella pneumoniae; 3, E. cloacae; 3, E. coli; 2, Citrobacter freundii; and 1, E. aerogenes. CPE were frequently isolated from the urine (5 [42%]) and sputum (3 [25%]) and NCP-CRE from sputum (4 [40%]), bile (3 [30%]), and urine (2 [20%]). Cases with CPE were older with more frequent use of urinary catheter and/or NG tube than NCP-CRE (table). The 30-day mortality or length of hospital stay (LOS) did not differ between the two groups. Majority (n = 12) of CPE were identified to carry blaIMP (MPM MIC, ≥2 mg/L), and two CPE were positive for blaOXA-181 and blaOXA-232 (MPM MIC, ≤1 mg/L). All NCP-CRE had IPM MIC of ≥2 mg/L; 7 (70%) had MPM of ≤1 mg/L. Resistance to amikacin (AMK) and levofloxacin (LFX) was noted in one and five CPE, respectively, whereas all NCP-CRE were sensitive, and nine blaIMP and 1 blaoxa-232 were transferable by conjugation.

Conclusion

CPE and NCP-CRE had different clinical characteristics. Non-β-lactam treatment options were more available for NCP-CRE than CPE. CPE and NCP-CRE might require different control strategies.

Disclosures

All authors: No reported disclosures.
1193. Comparison of the Clinical Outcomes of Patients With IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Sensitive Enterobacteriaceae in Japan
Authors: Saito Sho , Hayakawa Kayoko , Ishikane Masahiro , Tajima Taichi , Matsunaga Nobuaki , Ide Satoshi , Kinoshita Noriko , Kusama Yoshiki , Fujitomo Yumiko , Nakamoto Takato , Toda Yuta , Ohmagari Norio
Published: November 2018

Background

Carbapenem-resistant Enterobacteriaceae (CRE) infections are spreading worldwide and have become a global menace. Different types of carbapenemases contribute to carbapenem resistance. The outcome of patients with IMP-type carbapenemase-producing CRE (IMP-CRE) is not well known.

Methods

A matched case–control study from January 2012 to December 2016 was conducted at NCGM. All unique patients with IMP-CRE isolation were included and matched with carbapenem-sensitive Enterobacteriaceae (CSE) patients. Meropenem non-susceptible and/or ceftazidime-resistant Enterobacteriaceae, per CLSI criteria, were tested for metallo-β-lactamase production with further confirmation of blaIMP by PCR. Multivariate analyses were conducted for outcomes, adjusting for a propensity score predicting the likelihood of isolation of CRE vs. CSE. The balance of each group was determined by standardized biases <0.25 for variables on baseline characteristics.

Results

In total, 192 patients (96 CRE, 96 CSE) were included (132 Enterobacter sp., 60 Klebsiella pneumoniae). Isolations sites were sputum (n = 76 [39.6%]), urine (n = 62 [32.3%]), blood (n = 22 [11.3%]), and wound (n = 14 [7.2%]). The median age of the patients was 75 years [IQR: 66–84], and 109 (56.8%) were male. Thirty-one (32.3%) patients with CRE and 55 (57.3%) patients with CSE developed infections. The others were considered as colonization. qSOFA was positive (≥2) in seven patients with CRE infection and nine with CSE infection. In bivariate analysis, mortality and length of hospital stay (LOS) after CRE/CSE isolation were similar between the two groups, even after stratification by bacterial species and infection/colonization. After controlling for the propensity score (table), mortality and LOS remained similar between the two groups.

Conclusion

IMP-CRE might not contribute to the worsened clinical outcomes when compared with CSE. Further evaluations are needed for additional outcome parameters.

Disclosures

All authors: No reported disclosures.
1211. Increasing Incidence of Invasive Methicillin-Resistant and Methicillin-Sensitive S. aureus Infections Among Persons Who Inject Drugs, 2014–2017
Authors: Felsen Christina B , Gellert Anita , See Isaac , Dumyati Ghinwa
Published: November 2018

Background

In 2011, persons who inject drugs (PWID) were estimated to be 2.6% of the US population 13 years of age and older. Infectious endocarditis (IE) and hepatitis C infections among PWID are increasing. We describe trends in invasive Staphylococcus aureus (iSA) infections among PWID.

Methods

Population-based surveillance for invasive (from normally sterile site) methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) has been conducted in Monroe County, NY (2010 Census population: 744,344) as part of the CDC’s Emerging Infections Program since September 2014. Cases are county residents with an iSA infection; iSA incidence was calculated as cases/100,000 census population.

Results

During September 2014–August 2017, 1,460 iSA cases were identified; 150 (10%) in PWID. The incidence of PWID-associated iSA doubled among 18–49 year olds during years 1–3 (Table 1). The proportion of cases occurring in PWID increased among both MRSA (7% to 20%) and MSSA (6% to 11%). PWID were significantly younger (P < 0.0001) than noninjection drug users, and more often White (P = 0.003) and non-Hispanic (p = 0.004). Among PWID with iSA, 45% had IE. Almost all PWID with iSA used other illicit drugs (n = 112, 91% of 123 unique cases); 89% (110) were smokers, and 46% (56) had chronic liver disease. PWID with iSA had a longer mean length of stay (26 days [SD 22] vs. 21 [37], P = 0.01); PWID with MRSA were more likely to have septic shock (22% vs. 8%, P = 0.03) and pneumonia (9% vs. 1%, P = 0.04) when compared with PWID with MSSA. Among iSA, a history of recurrent skin abscess/boil (24% vs. 8%, P = 0.02) was more common in PWID with MRSA; fewer PWID with MRSA were obese (2% vs. 15%, p = 0.02).

Conclusion

The increasing incidence of invasive MRSA/MSSA among PWID, frequently accompanied by concurrent chronic liver disease, polysubstance use, and need for extended hospital stays, poses an increasing challenge to the public health and clinical communities. This highlights the critical need to prevent worsening of the epidemic of injection drug use and provide comprehensive treatment for individuals engaging in highest risk drug-related behaviors.

Disclosures

All authors: No reported disclosures.
1241. Surveillance for Viral Respiratory Infections in Pediatric Chronic Care Facilities
Authors: Prill Mila M , Kim Lindsay , Wilmont Sibyl , Whitaker Brett L , Lu Xiaoyan , Neu Natalie , Gerber Susan I , Garg Shikha , Stone Nimalie D , Larson Elaine , Saiman Lisa
Published: November 2018

Background

Residents of pediatric chronic care facilities (PCCFs) are vulnerable to acute respiratory infections (ARIs) due to their underlying medical conditions and infection control challenges in congregate living.

Methods

We conducted active, prospective surveillance for ARIs (defined as ≥2 new signs/symptoms of respiratory illness) among all residents in three PCCFs near New York City from December 7, 2016 to May 7, 2017. The parents/guardians of some residents also provided consent for research specimen collection at the start of the study. In that subset, nasopharyngeal swabs were obtained ≤4 days of ARI symptom onset and weekly for 4 weeks of follow-up to assess viral shedding. Influenza, respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (229E, NL63, OC43, HKU1), parainfluenzavirus (PIV 1–4), metapneumovirus (MPV), adenovirus (AdV), bocavirus (BoV), enterovirus, parechovirus, and M. pneumoniae were tested by the Fast Track Diagnostics Respiratory Pathogens 21 real-time RT-PCR panel.

Results

Subset with research specimen collection: Among 79 residents (aged 0–20 years, median = 8), 60 ARIs were reported in 37 (47%) residents. Swabs were obtained at illness onset for 53/60 ARI episodes; among these, there were 25 single-virus detections and five co-detections. An additional 33 single- and five co-detections occurred in 175 follow-up swabs (table). Molecular typing of 32 RV+ specimens identified 13 RV types.

All residents: During the 2016–2017 influenza season, 308/322 (96%) age-eligible residents received influenza vaccine and 168/364 (46%) received prophylactic antivirals for influenza exposures. Although influenza was not detected in research swabs, it was detected in 3/200 tests conducted for clinical purposes.

Conclusion

ARIs were common among residents of three PCCFs, and a variety of respiratory viruses were detected. The rarity of influenza may reflect strong infection control practices in these facilities, including vaccination and prophylactic use of antivirals.

Disclosures

All authors: No reported disclosures.
1246. Acinetobacter baumannii in the Post-Acute Care Setting: Prevalence and Resistance Rates in Patients, Health Care Personnel and the Environment
Authors: Cassone Marco , Zhu Ziwei , Gibson Kristen , Lansing Bonnie , Cao Jie , Mody Lona
Published: November 2018

Background

Acinetobacter baumannii is an important agent of healthcare-acquired infections, sporting high resistance to major antibiotics in acute care. Since A. baumannii is an opportunistic pathogen commonly found in the environment, we aimed to investigate: (1) its prevalence as colonizer on patients, environment, and healthcare personnel (HCP) in Nursing Facilities (NFs) with intermediate intensity of care but high antibiotic pressure and (2) whether resistance rates in colonizing strains vary between patient, environmental, and HCP isolates.

Methods

We analyzed A. baumannii patient and HCP colonization and environmental contamination in six NFs in Michigan. Samples were collected from HCPs hands, and from multiple patient body sites and high-touch surfaces at admission, 14 days, and monthly up to 6 months. Ciprofloxacin, imipenem, and ceftazidime resistance was tested according to CLSI guidelines.

Results

651 patients were screened (average follow-up time was 29 days). Patient colonization with A. baumannii was found in 59/1,620 (3.64%) of visits, and environmental contamination in 267/1,620 visits (16.48%) (P < 0.001). Interestingly, HCP showed at least as high or possibly higher colonization rates than patients (32/574) (5.25%) (P = 0.06). Resistance rates differed significantly between HCP, environmental, and patient isolates, ranging from 35 to 38% for patient isolates, 26 to 30% for environmental isolates, and only 8 to 17% for HCP isolates (table).

Conclusion

In our NFs, A. baumannii is more likely to be found on HCPs than on patients. However, HCP isolates have much lower resistance rates. Environmental contamination is alarmingly common, with worrisome resistance rates even in post-acute care settings.

Disclosures

All authors: No reported disclosures.
1256. New Acquisitions of ET-12 Burkholderia cenocepacia in Adults With Cystic Fibrosis: Role of Whole Genome Sequencing in Outbreak Investigation
Authors: Blanchard Ana C , Tadros Manal , Tang Lin , Muller Matthew , Spilker Theodore , Waters Valerie , Lipuma John , Tullis Elizabeth
Published: November 2018

Background

Transmission of Burkholderia cenocepacia ET-12 strain (ET-12Bc) can cause epidemics in the cystic fibrosis (CF) population. The Toronto Adult CF center currently follows 500 patients; 20% have infection with B. cepacia complex (BCC), including 48 patients infected with ET-12Bc. The center adheres to the 2013 infection prevention and control guidelines and patients are also segregated by clinics. Despite this, there have been 11 new acquisitions of ET-12Bc since 2008. The objective of this study was to describe the investigation of an ET-12Bc outbreak in CF patients, using whole-genome sequencing (WGS).

Methods

Investigations included multilocus sequence typing (MLST) and WGS of 34 isolates (11 new ET-12Bc acquisitions, 18 isolates of known ET-12Bc patients (including all patients with hospital admissions that overlapped with new acquisitions), four isolates from CF patients in the USA and the J2315 reference strain). Each of the seven MLST alleles from ET12Bc strain J2315 was downloaded from PubMLST and used to “Blast” each of the 16 WGS databases. WGS was done using 150 bp paired-end runs on an Illumina HiSeq4000. Single nucleotide polymorphisms (SNPs) between the newly sequenced strains and J2315 were profiled.

Results

Ten patients had a hospital admission within the 2 months preceding their first ET-12Bc positive sputum culture, except for one in whom ET-12Bc was detected 12 months following hospital admission. In all isolates, the seven alleles (atpD, gltB, gyrB, recA, lepA, phaC and trpB) matched 100% to sequence type 28 and clonal complex 31, and were identical to J2315. WGS SNP analysis confirmed that transmission occurred from known cases on the unit in 10/11 (90.9%) patients. To date, 8/11 patients with new acquisitions have died (median survival of 95 days).

Conclusion

Our investigations found epidemiological evidence suggestive of ET-12Bc transmission on the CF unit, which was confirmed by MLST and WGS SNP analysis. Compared with MLST, WGS SNP analysis had better discriminatory power and was well correlated with the identified epidemiological links between patients. Recognition of ET-12Bc transmission with associated high mortality rates has led to a change in our hospital policy. ET-12Bc positive patients will no longer be cared for on the same unit as ET-12Bc negative patients with CF.

Disclosures

All authors: No reported disclosures.
1290. A Model for “At-Distance” PrEP Navigation: Acceptability and Early Insights
Authors: Perlson Jacob , Kruger Blake , Padullaparti Sravanthi , Eccles Elizabeth , Lahey Tim
Published: November 2018

Background

HIV pre-exposure prophylaxis (PrEP) awareness and uptake among at-risk individuals remains suboptimal despite clear evidence of efficacy. Health navigators and peer educators have been employed to facilitate linkage and retention in many aspects of HIV prevention and care, including to improve PrEP utilization. Yet, the use of health navigators to improve PrEP utilization has not been well-explored in rural areas where unique challenges to HIV care have been well documented. Little is known, too, about how telemedicine may strengthen these efforts. We assessed acceptability and evaluated a health navigation program that primarily engages clients through at-distance technology-based methods.

Methods

To guide the design and implementation of a pilot PrEP tele-navigation program, we conducted a survey in at-risk clients contacted through social networks and at a state-funded STI clinic in New Hampshire. Approximately nine months after the launch of the navigation platform, we analyzed characteristics of client-navigator interactions. Feedback surveys were distributed to clients 3 months following engagement with the navigator.

Results

From July 2017 to April 2018, 139 individuals engaged the navigator program via email, text, chat, phone call, or in-person. Among the most common services provided were PrEP counseling (n = 63 or 45% of inquiries), referral to STI/HIV testing (22%), and risk reduction counseling (19%). Eight clients have been linked to PrEP care to-date. Qualitative analysis of client-navigator interactions revealed a variety of recurring barriers expressed by clients including concerns maintaining confidentiality with parents and partners, side effects of PrEP, and financial constraints. Clients provided suggestions for program improvement and indicated they felt engagement with the program increased knowledge of PrEP as well as linkage to testing and HIV prevention services.

Conclusion

Our pilot program highlighted the diverse obstacles to PrEP utilization in at-risk rural clients, and suggests at-distance PrEP navigation and telemedicine can support improved PrEP utilization in the rural United States. Such a navigator program should be equipped to engage clients along the PrEP care continuum.

Disclosures

All authors: No reported disclosures.
1300. Young Heterosexual Men in Rural South Africa Want Access to PrEP
Authors: Hannaford Alisse , Khoza Bulelani , Moll Anthony P , Shenoi Sheela V
Published: November 2018

Background

While many HIV prevention services in South Africa specifically support women and girls, substantial gaps exist in HIV prevention, testing and treatment services targeting men and boys. We aimed to characterize HIV prevention knowledge, sexual-risk behaviors and interest in HIV pre-exposure prophylaxis (PrEP) among young men in rural KwaZulu-Natal.

Methods

Men were identified at community settings such as taverns, fast-food restaurants, and local stores. Interviews were conducted confidentially and anonymously in Zulu, and were recorded, translated and transcribed. Transcripts were coded to identify themes.

Results

Thirty-one HIV negative men (median age 26, IQR 23–31) were interviewed, 52% with a history of STI and 77% unemployed. While most (61%) perceived themselves to be at risk for HIV, less than half had tested for HIV in the prior 3 months (36%), the majority reported inconsistent condom use (87%), and most reported partners outside their relationship (84%). While only a quarter had previously heard of PrEP, all were interested in initiating. Four participants felt PrEP should only be for men because polygamy is acceptable. While most men wanted their partners on PrEP (77%), they also felt that their female partners initiating PrEP would signify a lack of trust in the relationship, while paradoxically acknowledging that their own multiple sexual relationships put their partner at risk. Men expressed fear of destabilizing new relationships by asking about HIV status, and admitted being less likely to discuss HIV status and condoms during sexual encounters involving alcohol. Men felt that using PrEP might lead to decreased condom use and enable their female partners to be sexually active with other men. Men were concerned that if they initiated PrEP they would be mistaken as HIV positive.

Conclusion

Men in heterosexual relationships in rural South Africa acknowledge engaging in high HIV risk behaviors and feel that they should have access to PrEP. They report contradictory perspectives about their female partners accessing PrEP, and are concerned about PrEP increasing HIV risk behaviors, which needs further exploration. Heterosexual men in sub-Saharan Africa should be targeted for combination HIV prevention services, including PrEP.

Disclosures

S. V. Shenoi, Amgen Pharmaceuticals: Spouse does part-time contract work, Salary.
1301. Evaluation of the Rates of HIV Post-Exposure Prophylaxis Completion After the Implementation of an Automated Referral System in the Emergency Department
Authors: Schwarz Erika Reategui , Gysi Madeleine , Schubert Finn , Ita-Nagy Fanny
Published: November 2018

Background

A 28-day regimen of Post-Exposure Prophylaxis (PEP) administered within 72 hour significantly reduces HIV infection, for both occupational and nonoccupational exposures (NOE); however, adherence to PEP for NOE has been reported to have poor rates of completion.1 To optimize PEP referrals from our ED to our clinics, we implemented an automated referral system to maximize PEP completion and link patients to outpatient care and HIV pre-exposure prophylaxis (PrEP), if appropriate.

Methods

In our ED, PEP patients receive a starter kit from an automated medication dispensing system. Starting in March 2017, a daily automated report of patients who received a starter kit in the ED was generated and emailed to patient navigators who would contact patients and offer follow-up appointments. Our main objective was to describe the rate of outpatient follow-up of patients initiated on PEP for NOE from March 2017 to March 2018, as well as patient demographics and linkage to PrEP.

Results

Out of 128 patients seen in the ED for PEP, 30% (38) were for NOE. Of these, 68% were female, with a median age of 27 years old (range: 14–59). Nearly half had no insurance (45%). The majority (84%) reported sexual intercourse or sexual assault as the exposure. Most patients were contacted for follow-up (76%) and half (48%) had a follow-up appointment. Patients who presented to the ED >24 hours after exposure were less likely to complete a follow-up (35% vs. 75%, P = 0.035), as were uninsured patients (24% vs. 57%, P = 0.052). From 38 patients, 13 (34%) qualified for PrEP, eight (62%) followed as outpatients and one (8%) was started on PrEP.

Conclusion

The automated system ensured that half our PEP patients were seen by an outpatient provider, increasing their likelihood of finishing the 28 days of PEP. Patients presenting late to the ED and uninsured patients were less likely to follow-up. Further research is needed to identify interventions to improve follow-up. Finally, transition to PrEP was low and additional interventions should be explored to improve this process.

Reference

1. Kahn JO, Martin JN, Roland ME, et al. Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injection drug use exposure: the San Francisco PEP Study. J Infect Dis 183(5):707–714.

Disclosures

All authors: No reported disclosures.
1304. From Information Bolus to Continuous Infusion: Resident Knowledge and Satisfaction With an “Antibiotic of the Month” Educational Initiative at an Academic Children’s Hospital
Authors: Madigan Theresa , Radel Luke , Fatemi Yasaman , Rajapakse Nipunie
Published: November 2018

Background

Medical trainees play a critical role in the prescribing of antimicrobials. Prescriber education is one of the CDC core elements of antimicrobial stewardship programs. Optimal strategies for educating residents about antimicrobials have not been identified; however, the common practice of teaching all classes of available antibiotics over a short period of time (usually a single 1–2 hour lecture or “bolus”) is generally not well received and likely ineffective.

Methods

We developed a novel antibiotic of the month (AOTM) education program (“continuous infusion”) for pediatric residents. It included a monthly 10-minute presentation by an infectious diseases physician or fellow about a single commonly prescribed antibiotic, a handout summarizing important aspects of the antibiotic and a display posted in the resident workroom. An anonymous survey was sent to all pediatric residents before and 6 months after implementation of the AOTM program. The survey consisted of questions on demographics, satisfaction with the program, and antibiotic knowledge. Responses were tabulated and analyzed using Microsoft Excel. Responses were summarized and reported as a proportion of total responses.

Results

Both pre- and post-implementation surveys were completed by 21 pediatric residents (51% response rate). Prior to the AOTM program, 55% of respondents felt very or somewhat uncomfortable about their current level of knowledge about antimicrobials and antimicrobial prescribing. Six months after initiation of the program, 86% and 76% agreed or strongly agreed that their knowledge of antimicrobials and antimicrobial resistance, respectively, had improved. After introduction of the program, 81% felt more comfortable or much more comfortable with antimicrobial prescribing. Fifty-seven percent had referenced the handout at some point after the teaching session and 100% agreed that the program was worthwhile continuing in the next academic year.

Conclusion

A continuous infusion of antimicrobial education in the form of an AOTM education program was well received among pediatric residents and increased their knowledge and comfort level with antimicrobial prescribing. Further studies to measure knowledge retention with this strategy are required.

Disclosures

All authors: No reported disclosures.
1306. Antimicrobial Resistance Knowledge, Attitudes, and Perceptions Among Medical Students in Southern India
Authors: Menden Olivia , Prabhu Sumathi , Shetty Veena , Pandith Chaithra , Giri Shobha , Shetty Avinash
Published: November 2018

Background

Antimicrobial resistance (AMR) is a major public health problem in India. The World Health Organization recognizes that the education of medical students on antimicrobial stewardship plays a critical role in the efforts to combat AMR, but data related to knowledge, attitudes and practices (KAP) regarding AMR is limited in India.

Methods

This cross-sectional study was conducted in July-August 2017. Medical students at K.S. Hegde Medical Academy in Mangalore, India were surveyed with an anonymous questionnaire using a convenience sampling method involving second year, third year, fourth year, and intern students (n = 347). Data about demographics, sources of information, and antimicrobial training were collected. In addition, AMR knowledge and attitude scores were calculated. A Mann–Whitney U test was used to determine factors that were associated with significant differences in knowledge scores and attitude scores. The primary outcome measure of this study was to determine positive predictors of increased confidence in prescribing antimicrobials in the future using multivariate analysis.

Results

A total of 347 surveys were analyzed (response rate of 98.9%). The mean total knowledge score was 11.47 out to 31 with a standard deviation (SD) of 3.39, and the mean attitude score was 5.99 out of 16 (SD = 4.207). While 13.2% of students were “very familiar” or “familiar” with the term “Antimicrobial Stewardship,” and 88.2% of students said they would like more antimicrobial education in medical school. On multivariate analysis, female gender (OR 2.51, 95% CI (1.51, 4.18)), clinical vignette antimicrobial knowledge scores (OR 1.26, 95% CI (1.05, 1.51)), positive attitude scores (OR 0.94, 95% CI (0.88, 0.995)), awareness of Infection Control Policy (OR 1.87, 95% CI (1.09, 3.22)), and > 3 years of antimicrobial prescribing clinical training (OR 2.48, 95% CI (1.29, 4.75)) were predictors of confidence in antimicrobial prescribing.

Conclusion

This study identifies several possible interventions for improving confidence such as increased clinical knowledge through clinical experience, increased awareness of infection control policies and antimicrobial guidelines, and empowering students to be antimicrobial stewards to combat AMR.

Disclosures

All authors: No reported disclosures.
1310. Improving Infectious Disease Electronic Medical Records Documentation: A Quality Improvement Study in an Academic Teaching Hospital
Authors: Lakshmi Seetha , Asquith Johonna , Alrabaa Sally , Sampson Mindy , Kraitman Natan , Akoghlanian Garabet , Balakrishnan Maya , Casanas Beata
Published: November 2018

Background

Improving efficiency of documentation and sign outs during transitions of care were identified as areas of interest by the University of South Florida Infectious Disease (ID) Division. Our aim is by May 2018, we will achieve >50% improvement in our ID EMR note efficiency score for any adult patient at Tampa General Hospital. Note efficiency score involves listing all of the following key elements with 1 point awarded for each: active problem in the subjective section, updated hospital course under assessment, active problem prioritized first under assessment and non-relevant problems removed from assessment.

Methods

Institute of Healthcare Improvement’s model with Plan-Do-Study-Act (PDSA) cycles was used for project implementation from March 2018 to May 2018 (Figure 1). Cycle 1: Conducting a needs assessment survey and education. Cycle 2: Changing the existing template and implementing a new standardized template that includes the key elements, along with removal of auto populated non relevant information. Audits of notes with a 4-point system scoring was done. A pre and post implementation physician survey was conducted.

Results

ID fellow and faculty completed the baseline survey (N = 25). Less than half (46%) felt that they could interpret patient assessments with ease and even fewer respondents (36%) felt there was adequate weekend sign out. More than one-third (36%) reported writing majority of notes after 5 pm (Figure 1). Pilot project involved nine ID faculty and fellows. We had 95% compliance with use of the standardized EMR template. Notes were evaluated at baseline (n = 190), cycle 1 (n = 85), and cycle 2 (n = 56). An increase in average note efficiency score from baseline, cycle 1 and cycle 2 occurred as follows (Mean ± SD): 2.0 ± 0.84 vs. 2.8 ± 0.95 vs. 3.6 ± 0.5 (Figure 2). Compared with baseline, cycle 2 achieved 42% improvement in the ease of interpretation of patient assessments and 41% improvement in adequate sign out. No increase in note writing after 5pm (36% vs. 30% baseline and cycle 2, respectively) reported.

Conclusion

Targeted education and changing the EMR note template can achieve improved efficiency of ID note. These efforts to improve documentation enhance physician’s ease of interpretation of patient assessments and sign out during transition of care.

Disclosures

All authors: No reported disclosures.
1313. Does Time Fly When Having Fun? A Study Assessing the Relationship Between Estimated Time on Task and Enjoyment of Infectious Diseases Serious Games
Authors: Jeffres Meghan , Biehle Lauren R
Published: November 2018

Background

Mastering the fundamentals of infectious diseases (ID) requires students to memorize large volumes of material about pathogens, antibiotics, patients, and the interactions between the three. It is hypothesized that there is a positive relationship between time on task and engagement. The objective of this study was to explore the relationship between enjoyment of a serious game and the estimated time spent playing.

Methods

During a one-time session, students from two colleges of pharmacy engaged in three ID game-based active learning strategies each lasting a pre-specified time. These strategies included a card game about calculations (Fightin Figures, FF), a quiz game about antibiotic fundamentals (Rapid Rounds, RR), and a board game using NAPLEX practice examination questions (Pills and Placebos, PP). Students completed a survey for each game assessing enjoyment and estimated time spent playing each game.

Results

Eighty-four students participated. Demographics of the sample include female 53%, mean age 26.7 years, and mean GPA 3.6. Using a Likert scale from 1–10 (1 = not enjoyable, 10 = very enjoyable) student rated each game: FF 6.5 ± 2.2, RR 7.2 ± 2.3, PP 8.4 ± 1.8. The time estimation ratio, calculated by dividing the estimated time by the actual time for each game was 0.9 ± 0.5 for FF, 1.5 ± 0.6 for RR, and 1.0 ± 04 for PP. The percentage of students who underestimated time spent playing was 57% for FF, 8% for RR, and 41% for PP. There were no differences in time estimation ratio based on sex, age, or GPA.

Conclusion

Although a small study, there was no trend toward association of time underestimation and enjoyment of these teaching methods. Students enjoyed the board game PP the most yet the time estimation ratio was 1.0, indicating estimated and actual time on task were the same. Students enjoyed FF the least but this was the only game they underestimated time spent on task.

Disclosures

All authors: No reported disclosures.
1326. Inter-Professional Education and Training to Build Capacity Among Healthcare Workers in Singapore
Authors: Michaels Jessica , Olszyna Dariusz , Ng Frank , Lee Cheng Chuan , Archuleta Sophia
Published: November 2018

Background

People Living with HIV (PLHIV) in Singapore continue to face stigma and confidentiality concerns in their interactions with Healthcare Workers (HCWs). There is a recognized gap in HIV-related knowledge and lack of training opportunities for HCWs in Singapore, particularly amongst nonphysicians and other HCWs who do not regularly care for PLHIV. The HCW HIV Education Series was conceptualized to address these issues and to improve the HIV-related knowledge, attitudes and practices of HCWs in Singapore.

Methods

The HCW HIV Education Series is organized by an interprofessional organizing committee. The series is made up of four half day modules which are conducted quarterly. The modules are designed and implemented to cater to as many HCWs as possible. The modules function as a series but can also be run as standalone education sessions. The modules are: HIV Basics, Working with PLHIV, Basic HIV Clinical Care and Advanced HIV Clinical Care. In its pilot year (2016–2017), 334 HCWs, predominantly nurses, pharmacists, and social workers attended the series. The HCWs attended from diverse healthcare settings, including public and private hospitals, nursing homes, faith based and community organizations. Pre- and post-module evaluations were completed by participants.

Results

Only 5% of Module 1 attendees had previously received training in HIV. Across all four modules, there was a marked improvement in knowledge and confidence pre- and post-training. 95% of attendees across all modules felt that they had gained new skills that would add value to their work. While 97% of attendees of Module 1 planned to attend future modules, the attrition rate between modules was high.

Conclusion

The HCW HIV Education Series is highly evaluated and well attended. Efforts to maintain and strengthen attendance across all modules is needed, the delivery of the modules over a 2-day period may be an effective way to achieve this. Research into the experiences of PLHIV in healthcare facilities should also be considered.

Disclosures

All authors: No reported disclosures.
1354. Novel Formulation SUBA-Itraconazole in Fed and Fasted Healthy Volunteers: Expanding the Clinical Utility of the Established Mold Active Agent
Authors: Lindsay Julian , Mudge Stuart
Published: November 2018

Background

Itraconazole has been established as an effective mold active agent; however, wide interpatient variability in bioavailability and poor gastrointestinal tolerability have made using the agent challenging. A novel formulation, SUBA-Itraconazole (SUperBioAvailable) has been developed by Mayne Pharma to alleviate these negative properties.

Methods

An open-label, randomized, cross-over study of SUBA–Itraconazole capsules 65 mg (2 × 65 mg BID) in healthy adults under fasting and fed conditions was assessed for steady-state levels. Subjects (n = 20) were administered two capsules of SUBA–Itraconazole twice daily on Days 1–14 and once on the morning of Day 15, either on an empty stomach or with a meal. Safety was monitored by vital signs measurements, electrocardiogram measurements, clinical safety laboratory tests (liver and kidney function tests), and physical examination.

Results

Overall, SUBA–Itraconazole demonstrated similar concentrations at the end of the dosing interval (trough), with modestly lower total and peak exposure when administered under fed conditions compared with the fasted state (fed/fasted ratios of 78.09% for AUCtau [14,183.2 vs. 18,479.8] 73.05% for Cmax,ss [1,519.1 vs. 2,085.2] and 91.53% for Ctrough[1,071.5 vs. 1,218.5]); see Figures 1 and 2. The administration of SUBA–Itraconazole 65 mg capsules was well-tolerated by the healthy subjects participating in this study.

Conclusion

The results demonstrate a promising clinical utility for SUBA–Itraconazole in practice. Unlike the conventional capsule formulation which requires a high fat meal for absorption, or the oral solution formulation which requires a fasted administration, SUBA–Itraconazole reached a therapeutic steady state in both fasted and fed states. The similar trough level, however higher peak with fasted state, likely represents a more gradual absorption of drug in the fed state. The slightly higher bioavailability in a fasted state, without gastrointestinal intolerability, is particularly promising for the clinical use of SUBA–Itraconazole in patients unable to have a high fat content meal due to chemotherapy or post-surgery such as hematology patients and transplant recipients.

Disclosures

J. Lindsay, Mayne Pharma: Consultant, Consulting fee. S. Mudge, Mayne Pharma: Employee, Salary.
1361. Pharmacokinetics and Safety of Ridinilazole (RDZ), a Potential New Therapy for Clostridium difficile Infection (CDI): From Animal Models to Patients
Authors: Duperchy Esther , Chowdhury Sumita , Vickers Richard , Robinson Neil
Published: November 2018

Background

CDI is the leading cause of nosocomial diarrhea associated with 29,000 deaths p.a. in the United States. RDZ is a novel oral drug highly selective for C. difficile limiting collateral damage to the gut microbiota. Here we present a combined analysis of all pharmacokinetic (PK) and tolerability data obtained throughout the development of RDZ from animal models to Phase 2, including new human PK data.

Methods

RDZ levels were measured in plasma and in the GI tract of infected hamster after a single oral dose at 25 mg/kg. Quantitative whole-body autoradiography (QWBA) and excretion mass balance studies were performed in rats following a single 50 mg/kg oral dose of 14C RDZ. In GLP toxicology studies, RDZ was administered orally for 28 days to dogs and rats at 1,000 mg/kg/day. Toxicokinetic, clinical pathology, and histopathology analysis were performed. The Phase 1 study enrolled 56 healthy male subjects receiving single ascending doses from 2 to 2,000 mg, or, 200 or 500 mg BID for 10 days. The Phase 2 enrolled 100 patients assigned 1:1 to 10 days oral RDZ 200 mg BID or VAN 125 mg QID treatment. Both clinical trials quantified RDZ in plasma and feces, and assessed safety and tolerability.

Results

In all animal studies, plasma levels of RDZ were below or at the limit of quantification (LOQ, 1.0 ng/mL). In the GI tract of hamsters, RDZ levels were highest in the colon. QWBA and excretion studies showed RDZ accumulated in the cecum and colon, the site of infection; >99% of radioactivity was excreted in feces and no radioactivity was detected systemically. 28 days repeat dosing in dog and rat resulted in no observations from treatment, histopathology or in-life parameters. In Phase 1 and 2 studies, RDZ plasma levels were generally near or below the LOQ (0.1 ng/mL). Concomitant medications, CDI severity, and age had no impact on exposure. In Phase 1, AEs were mild with no dose-dependent relationship, occurring and at a similar incidence to placebo. No significant findings from clinical laboratory, ECGs or other assessment were observed. RDZ was well tolerated in Phase 2 with the incidence of AEs and SAEs similar in both RDZ and VAN groups.

Conclusion

In both clinical and nonclinical studies to date, RDZ has been well tolerated and associated with low systemic absorption. Further assessment of safety, tolerability, and PK in Phase 3 studies is warranted.

Disclosures

E. Duperchy, Summit Therapeutics: Employee, Salary. S. Chowdhury, Summit Therapeutics Inc.: Employee and Shareholder, Salary and Shareholder. R. Vickers, Summit Therapeutics: Employee, Salary and Stock options. N. Robinson, Summit Therapeutics: Consultant, Consulting fee.
1367. Clinical Cure in Secondary Efficacy Populations in Patients With Complicated Urinary Tract Infection Treated With ZTI-01 (Fosfomycin for Injection): Findings From the ZEUS Trial
Authors: Kaye Keith , Rice Louis B , Stus Viktor , Sagan Olexsiy , Fedosiuk Elena , Das Anita , Skarinksy David , Eckburg Paul B , Manvelian Kristina , Ellis-Grosse Evelyn J
Published: November 2018

Background

ZTI-01 (fosfomycin for injection) is an investigational epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has a broad spectrum of in vitro activity, including multidrug-resistant Gram-negative pathogens, and is being developed for the treatment of patients with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.

Methods

ZEUS was a multicenter, double-blind, Phase 2/3 trial in hospitalized adults with cUTI and AP to evaluate safety and efficacy. Randomized patients received 6 g ZTI-01 q8h or 4.5 g IV piperacillin/tazobactam (PIP-TAZ) q8h for 7 days; patients with baseline bacteremia could receive up to 14 days; study continued to late follow-up (LFU, 26 ± 2 days). Oral step-down therapy was prohibited. ZTI-01 met the primary endpoint of noninferiority to PIP-TAZ. Secondary objectives included comparing clinical cure rates (assessed by investigator) in the modified intent-to-treat (MITT), microbiologic MITT (m-MITT), clinical evaluable (CE), and microbiologic evaluable (ME) populations at test-of-cure (TOC, Day 19 ± 2 days).

Results

There were 464 patients randomized who received study drug. In all populations, clinical cure rates at TOC were high and similar between treatment groups (>90%) (table).

Conclusion

These results demonstrate consistent efficacy in multiple secondary efficacy populations for patients with cUTI and AP who were treated with either ZTI-01 or PIP-TAZ. If approved by FDA, ZTI-01 may provide a new IV option with a differentiated MOA for patients in the United States with serious Gram-negative infections.

95% confidence intervals (CIs, two-sided) were computed using a continuity-corrected Zstatistic.

Disclosures

K. Kaye, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. L. B. Rice, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. V. Stus, Zavante Therapeutics, Inc.: Investigator, Research support. O. Sagan, Zavante Therapeutics, Inc.: Investigator, Research support. E. Fedosiuk, Zavante Therapeutics, Inc.: Investigator, Research support. A. Das, Zavante Therapeutics, Inc.: Consultant, Consulting fee. D. Skarinksy, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. P. B. Eckburg, Zavante Therapeutics, Inc.: Consultant and Shareholder, Consulting fee. K. Manvelian, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. E. J. Ellis-Grosse, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary.
1382. Acute Kidney Injury with Piperacillin–tazobactam and Vancomycin in the Intensive Care Unit
Authors: Smith Tameka , Lewis James S , Forrest Graeme N
Published: November 2018

Background

Several recent retrospective studies have suggested that the combination of vancomycin (V) with piperacillin–tazobactam (PTZ) is associated with increased nephrotoxicity. We prospectively evaluated the outcomes of patients admitted to all of our medical and surgical intensive care units (ICU) with a normal baseline creatinine clearance (CrCl) that received vancomycin in combination with either cefepime (CEF) or PTZ to determine whether kidney injury occurs using RIFLE criteria.

Methods

ICU patients who received combinations of V with either PTZ or CEF were prospectively evaluated from June 1, 2017 to April 28, 2018 using Theradoc. V and PTZ dosing were standardized per ICU policy and monitored by clinical pharmacists. We included patients between ages 18 and 90, and receipt of >72 hours of combination antibiotic therapy. We excluded patients that were pregnant, had a hematologic malignancy, chronic kidney disease, or neuromuscular disease. Data collected included, CrCl, V troughs, dosage and length of all antibiotics used, ICU length of stay (LOS), and co-administered nephrotoxic medications (e.g., NSAIDs and IV contrast). The primary objective was to compare the incidence of AKI in these study groups, as defined by the RIFLE criteria.

Results

Of 233 patients evaluated, 58 (25%) met inclusion criteria, 45 received PTZ-V and 13 CEF-V. Only eight of 58 (14%) MRSA-positive culture.

We found no correlation with co-administered nephrotoxic agents, vancomycin troughs, or body weight and AKI.

Conclusion

Our prospective observational study data revealed significant AKI with PTZ-V compared with CEF-V but it did not impact patient long-term outcomes. Caution with PTZ-V may be required when used in ICU settings even in patients with normal baseline CrCl.

Disclosures

J. S. Lewis II, Merck: Consultant, Consulting fee.
1384. RSV Monoclonal Antibody (MK-1654) Phase 1 Pharmacokinetics (PK) in Healthy Adults and Population PK Modeling to Support Pediatric Development
Authors: Maas Brian , Aliprantis Antonios , Wolford Dennis , Fayad Ghassan , Vora Kalpit , Geng Dong , Ma Hua , Caro Luzelena
Published: November 2018

Background

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection and hospitalization in infants. MK-1654 is a monoclonal antibody (mAb) being developed to prevent RSV infection in infants and is undergoing evaluation in a Phase 1 study. Incorporation of YTE mutations extend its half-life to allow for dosing once every RSV season. Preliminary Phase 1 PK results and the development of a population PK model that characterizes adult PK to predict pediatric exposures are presented here.

Methods

In this double-blinded Phase 1 study, 152 healthy males and females of nonchildbearing potential aged 19–59 years were randomized in a 3:1 ratio to receive a single dose of MK-1654 or placebo as a bolus intramuscular injection (IM) or in an intravenous infusion (IV) over 2.5 hours. Dose levels included 100 mg IM, 300 mg IM, 300 mg IV, 1,000 mg IV and 3,000 mg IV. Serial serum samples were collected to measure MK-1654 PK via a validated LC/MS assay. A noncompartmental PK analysis was conducted using preliminary data from 60 subjects up to Day 150 (900 observations). A population PK model was developed to simultaneously characterize the IM and IV adult PK data and to predict pediatric PK through allometric scaling. Pediatric MK-1654 PK was predicted for several IM doses for a typical sized infant (35 weeks gestational age at birth; 4 months chronological age at dosing; 50th percentile weight).

Results

In adults, the median time to maximum concentration observed was ~6–10 days following IM injection. The apparent half-life of MK-1654 ranged from ~70–85 days after either IM or IV doses. The estimated IM bioavailability was ~71%. Cmax and AUC0-90 days increased dose proportionally following IV administration. MK-1654 adult PK was best characterized using a two-compartment model with first-order elimination. IM absorption was described using a first-order rate constant with lag time. Inter-individual variability was included for clearance (CL and Q), central volume (V2), and absorption rate (Ka). The pediatric model suggested apparent terminal half-life in a typical infant is shorter than adults, likely being driven by infant growth during treatment.

Conclusion

Predicted infant PK profiles support further development of MK-1654 in children.

Disclosures

B. Maas, Merck: Employee and Shareholder, Salary and stock options. A. Aliprantis, Merck: Employee and Shareholder, Salary and stock options. D. Wolford, Merck: Employee and Shareholder, Salary and stock options. G. Fayad, Merck: Employee and Shareholder, Salary and stock options. K. Vora, Merck: Employee, Salary. D. Geng, Merck: Employee and Shareholder, Salary and stock options. H. Ma, Merck: Employee and Shareholder, Salary and stock options. L. Caro, Merck: Employee and Shareholder, Salary and stock options.