bluuebunny/crossref_metadata_2025 huggingface dataset:
1289. Knowledge, Attitudes and Barriers of Pre-exposure Prophylaxis for HIV Infection Among Resident Physicians in Rural, Eastern North Carolina
Authors: Morrison Arianne , Dortche Ciarra , Fadul Nada
Published: November 2018

Background

North Carolina bears a high burden of HIV and was ranked number 8 for the number of new infections in 2015. In 2014, the Centers for Disease Control and Prevention (CDC) published updated practice guidelines recommending the use of pre-exposure prophylaxis (PrEP) with daily oral dosing of tenofovir/emtricitabine to help prevent HIV infection in high-risk individuals. However, the use of PrEP in the primary care setting remains low and 1 in three primary care physicians is not aware of PrEP. The objective of our study was to evaluate PrEP knowledge among primary care resident physicians.

Methods

149 resident physicians were surveyed at East Carolina University from the following specialties; Internal Medicine, Medicine-Pediatrics, Obstetrics Gynecology and Family Medicine. We collected participants’ age, biological sex, current residency program, and current year within the residency program.

Results

Sixty out 149 residents completed the online survey. 20% of residents had never heard of PrEP. 17% of residents did not feel comfortable discussing sexual preferences with their patients. 15% of residents thought prescribing would increase risky sexual behaviors and 12% would not prescribe PrEP to patients with multiple sexual partners. Only 3% of residents identified potential side effects of PrEP (e.g., an increase in creatinine levels or decrease in mineral bone density) as a reason to not prescribe PrEP. One resident had ever prescribed PrEP. 83% of residents wanted more information on PrEP and 95% of residents would be willing to prescribe PrEP if educational workshops were offered.

Conclusion

PrEP is an underutilized tool among resident physicians in Eastern, NC. We identified lack of knowledge of PrEP and concern for increased risky sexual behaviors as barriers to prescribing. Resident physicians require more education on PrEP in order to prescribe it to their patients.

Disclosures

All authors: No reported disclosures.
1296. Potential use of Sexually Transmitted Infection (STI) Testing for Expanding HIV Pre-Exposure Prophylaxis (PrEP) at an Urban Hospital Center
Authors: Pitts Robert , Holzman Robert , Greene Richard , Lam Emily , Carmody Ellie , Braithwaite Scott
Published: November 2018

Background

Despite the high efficacy of PrEP, it continues to be underutilized. We examined the extent to which patients with a documented positive test for STIs were provided PrEP at an urban municipal medical center.

Methods

We reviewed data of all patients seen between January 1, 2014 and July 30, 2017 who were > 18 years old and had an initial HIV negative test and ≥1 positive test for Chlamydia, Gonorrhea, or Syphilis. We examined PrEP prescription data by gender, race/ethnicity, and clinic location. Differences between groups were compared using Chi-squared analysis and logistic regression.

Results

Of 1,142 initially HIV− patients who were identified as having a positive STI result, 52% were female, 89% either Black or Hispanic, with a median age of 40 years (quartiles 30, 47). 58% had Medicare/Medicaid and 34% were self-pay or uninsured (Table 1). Only 25 (2.1%) of 1,142 patients who had ≥1 STI test positive were prescribed PrEP. No women received PrEP. Whites (aOR: 21.7 [95% CI:4.4, 107, P < 0.001] and Hispanics (aOR:6.64 [95% CI:1.35, 32.8, P = 0.02] were both more likely to receive PrEP than Blacks, after adjusting for age, sex, marital status, and insurance. All PrEP prescriptions originated from the Medicine, Emergency, or HIV specialty clinics although most STI testing was obtained in Emergency and Obstetrical/Gynecological clinics (Table 2).

Conclusion

There were significant missed opportunities for HIV prevention among patients with STIs within the medical center, particularly among Hispanic and Black patients. Enrichment programs to educate providers and increase PrEP prescriptions may have a major impact on expanding HIV prevention, especially for women.

Disclosures

All authors: No reported disclosures.
1297. Characteristics for PrEP Uptake, Retention, and Discontinuation: Data From the ANCHOR Study
Authors: Mathur Poonam , Kattakuzhy Sarah , Nussdorf Laura , Hill Kristi , Silk Rachel , Gross Chloe , Akoth Elizabeth , Sidique Nadeera , Chaudhury Chloe , Sternberg David , Masur Henry , Kottilil Shyam , Rosenthal Elana
Published: November 2018

Background

People who inject drugs (PWID) have an increased risk for HIV, and HCV infection may foreshadow HIV acquisition in current epidemics. Studies of PWID have demonstrated a desire to obtain HCV treatment; however, use of pre-exposure prophylaxis (PrEP) in this population has not been well studied.

Methods

The ANCHOR study is an ongoing single-center study evaluating treatment of HCV in PWID. Enrolled patients have chronic HCV, opioid use disorder, and inject opioids. Patients are treated with sofosbuvir/velpatasvir and offered PrEP. Patients complete baseline community health worker (CHW)-administered surveys, physician assessment of PrEP eligibility, and are offered PrEP uptake.

Results

Of 89 enrolled patients, 49 (55%) met CDC criteria for PrEP, and 21 (24%) patients started PrEP. Reasons for not starting PrEP are in Figure 1. Though most patients are black (n = 82, 92.1%) and heterosexual (n = 81, 91%), these patients were less likely to start PrEP (P = 0.0068 and P = 0.0283, respectively). Baseline interest in starting PrEP was correlated with uptake (P = 0.0023), however, self-identifying as high-risk for HIV acquisition or meeting CDC criteria for PrEP were not. Though more patients endorsed sharing of injection equipment to a CHW than a physician (17% vs. 7%), endorsement to a physician rather than CHW was associated with starting PrEP (P = 0.0307). To date, 13 (62%) patients discontinued PrEP, 7 (54%) due to side effects.

Conclusion

Preliminary results of the ANCHOR study support that engagement in HCV care provides an opportunity for PWID to participate in PrEP intake; however, we found relatively low uptake in these patients, despite over half meeting CDC criteria. Our findings highlight the importance of counseling by physicians for initiation of PrEP, and suggest that improved communication between CHW and physician regarding risk behaviors could improve uptake. These data also reinforce that patients must be counseled and managed for side effects in order to retain them in care. Given the increasing opioid epidemic in the United States, more consideration needs to be given regarding how to incorporate PrEP into care, and how to effectively target and improve interest in PrEP for high-risk populations with poor uptake, including minorities and PWID.

Disclosures

C. Gross, Merck, Pfizer, Johnson and Johnson: Shareholder, stock. E. Rosenthal, Gilead Sciences, Merck: Grant Investigator, Grant recipient.
1305. Application of Standard Antibiotic Use Criteria to Evaluate Inpatient Antibiotic Use
Authors: Campion Maureen , Dionne Emily , Radigan Elizabeth , Scully Gail , Zoubi Moamen Al , Zivna Iva , Theodoropoulos Nicole
Published: November 2018

Background

It is estimated that 30–50% of antimicrobial agents prescribed inpatient are not optimal. Historically, antimicrobial evaluation has been based primarily upon expert opinion of ID trained individuals. Spivak and colleagues proposed standard terminology and definitions to assess antimicrobial prescribing practices. At UMass Memorial Medical Center we utilized Spivak’s criteria to measure antimicrobial use within point prevalence studies (PPS) and assessed the ability of Spivak’s criteria to provide consistent results between different evaluators.

Methods

A PPS was conducted in September 2017 (SEPT) by infectious disease (ID) attendings and ID trained pharmacists. A follow-up PPS was completed in November 2017 (NOV) by a pharmacy practice resident (PGY-1) and first year ID fellow. Patients were included if they were prescribed antibiotics at the time of review, greater than 18 years of age, and admitted to an inpatient unit. Patients only receiving antiretroviral therapy or antifungal prophylaxis were excluded from the study. Antibiotics, indications, days of therapy, and appropriateness or reason for inappropriateness, as defined by Spivak’s criteria, were collected.

Results

Four hundred five patients in SEPT and 475 patients in NOV were reviewed. Baseline characteristics between SEPT and NOV, including sex, age, average length of hospital stay (LOS) at time of review were similar between groups, (SEPT vs. NOV: male sex: 53.2% vs. 51.1%; age: 60.4 vs. 61.7; LOS:8.55 vs. 8.36 days). Number of antibiotics per patient was different between PPS (SEPT 1.69 vs. NOV 1.28). For non-intensive care unit (ICU) patients, 64.9% of use was considered appropriate in SEPT vs. 69.3% in NOV. The top reasons for inappropriate use in non-ICU patients in both PPS were no indication and excess length of therapy. Within the ICU, 89.4% of use was considered appropriate in SEPT, with 75% of use considered appropriate in NOV. The top reason for inappropriate use in ICU patients in both PPS was overly broad therapy.

Conclusion

Application of standard antibiotic evaluation criteria can assist healthcare professionals with different levels of ID training to assess antibiotic use in non-ICU patients. Further evaluation should be considered for critically ill patients.

Disclosures

All authors: No reported disclosures.
1314. From Book to Bedside: Theoretical and Applied Knowledge on the Topic of Healthcare-Associated Infections in Second-Year Nursing Students from a Croatian University
Authors: Mestrovic Tomislav , Kozina Goran , Neuberg Marijana , Ribic Rosana
Published: November 2018

Background

Adequate training of health workers is pivotal in the prevention of healthcare-associated infections (HAI). Our aim was to assess the theoretical and applied knowledge about the risk factors and effective measures of HAI prevention (most notably the use of standard precautions and hand hygiene practices) in second year undergraduate university nursing students that have already completed obligatory courses in microbiology, infectious diseases and epidemiology.

Methods

This study included a whole generation of second year undergraduate nursing students, comprised of 161 female and 25 male participants (186 in total), from a public university in Croatia (University Centre Varaždin, University North). They were given an anonymous questionnaire (developed on the model used by Tavolacci et al. in 2008) covering three domains: General Knowledge of HAI, Standard Precautions (SP) and Hand Hygiene (HH). The acceptable score overall (max. 30) and for each area (max. 10) was arbitrarily set at ≥ 20 and ≥ 7, respectively (in accordance with prior research).

Results

The age range of surveyed students was 19–37 (mean: 21.97, median: 21, mod: 20). An accurate definition of nosocomial infections was provided by 98.92% students (with 60.75% of them defining it as the infection occurring 48 hours after hospital admission). The overall score was 21.5, which indicates sufficient level of applied knowledge of healthcare-associated infections. Very high level of knowledge was observed for the SP area (total score of 9.5); however, the level of knowledge in HAI and HH domains was inadequate (5.9 and 6.1, respectively). There was no statistically significant difference in the overall or specific scores between male and female students (P > 0.05). Formal teaching during the curriculum was students’ primary source of information (60.22%), followed by practical learning in the ward during work (23.65%), formal teaching in the ward (9.68%) and self-learning (6.45%).

Conclusion

Periodical checking of nursing students’ knowledge on HAI and corresponding curriculum modifications in obligatory courses tackling this topic are advised in order to fill the knowledge gaps, improve training, reduce infection rates and increase compliance with prevention measures.

Disclosures

All authors: No reported disclosures.
1320. Continuing Education Improves HIV Screening and Use of PrEP in High-Risk Patients
Authors: Robinson Katie , Dietze Derek , Esgro Robert , Elion Richard
Published: November 2018

Background

Since approval in 2012, the uptake of PrEP in high-risk patients remains low, especially among primary care providers (PCPs) who lack knowledge and confidence regarding its use. Continuing education (CE) has been extensively used to address such knowledge and practice gaps, yet little evidence exists supporting the impact of these initiatives on direct patient care and cost.

Methods

Vindico Medical Education partnered with Improve CME to assess the impact of seven CE programs targeted to PCPs from 2015 to 2017 regarding the use of PrEP in high-risk patients. An outcomes analysis model was used and designed to estimate (1) patients newly identified as HIV+ or HIV−, (2) patients newly on PrEP or HIV treatment, and (3) associated costs of care due to the CE.

Results

Prescribing providers (n = 4,550) who each see an average of 16.8 patients at high-risk for HIV infection per month, participated. Prior to learning only 44% of participants reported that they frequently offer HIV testing to high-risk patients; and only 13% frequently use PrEP clinical guidelines. Six-month post-education, however, 83% and 68% of providers reported using HIV testing and PrEP guidelines, respectively. We then used evidence-based parameters to project the number of high-risk patients who, based on our pool of patients directly impacted by the education, would be willing to accept an HIV test, those who would be HIV+ vs. HIV−, and those who would be willing to accept and adhere to either HIV treatment or PrEP. The model estimated that over the course of 1 year, 135,941 high-risk patients would be newly offered an HIV test. Of those accepting the test (n = 54,376), 163 would be newly identified as HIV+. Of the 54,213 newly identified as HIV−, at least 3,914 would be placed on PrEP. Using accepted values for direct cost of care, this translates to $1.26 million per year for patients newly treated for HIV and $92.4 million per year for those patients newly on PrEP.

Conclusion

Targeted CE to PCPs increased screening rates for HIV infection in high-risk patients, increased awareness and use of PrEP, and linked patients with appropriate care. These findings validate the need for ongoing CE programs to address persisting unmet needs and show that modeling can be used to estimate patient outcomes from CE programs.

Disclosures

R. Elion, gilead: Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. ViiV: Consultant, Consulting fee.
1322. Impact of Hospital Medicine on Trends in Infectious Diseases and Other Subspecialty Fellowship Applications
Authors: Santhosh Lekshmi , Babik Jennifer
Published: November 2018

Background

Over the last decade, the rapid growth of hospital medicine has raised concerns that fewer graduating internal medicine (IM) residents might be pursuing fellowship,1 including in ID.2 We analyzed national trends in applications to subspecialty fellowships over the last 10 years to examine the potential impact of hospital medicine on resident career choice.

Methods

We examined 2009–2018 data from the National Resident Matching Program Specialties Matching Service3 for applicants to eight IM subspecialties. The number of third year residents (R3s) was obtained from the American Board of Internal Medicine Resident Workforce Data.4

Results

The number of matched applicants increased significantly over the last 10 years from 2,889 to 3,640 (P < 0.0001) and was highly correlated with the increase in number of R3s (r2 = 0.93, P < 0.001). All subspecialties saw a significant increase in matched applicants over time except ID and nephrology, which both saw initial decreases that reversed after converting to an “all-in” match. In 2018, ID had its highest number of matched applicants in the last 10 years.

Conclusion

Despite concerns that the growth in hospital medicine would lead to fewer IM residents pursuing subspecialty fellowship, the number of matched applicants to subspecialty fellowships has actually increased over the last 10 years, and has kept pace with the growth in R3s over this time. Initial decreases in the number of matched applicants in ID have now reversed after conversion to the “all-in” match, and the next few years will be critical to determine whether this trend continues.

References

1. Santhosh L, Babik J, Looney MR, Hollander H. Whither the pulmonary ward attending? Preserving subspecialty exposure in United States IM residency training. Ann Am Thorac Soc. 2017;14(4):565–568.

2. Bonura EM, Armstrong WS. Increasing subspecialization in the field of infectious diseases: Evaluating challenges and strategies to move forward. J Infect Dis 2017;216(Suppl 5):S594–S599.

3. National Resident Matching Program. Results and Data: Specialties Matching Service 2009–2018 Appointment Years. National Resident Matching Program, Washington, DC. 2009–2018.

4. American Board of Internal Medicine. Resident and Fellow Workforce Data, 2018.

Disclosures

All authors: No reported disclosures.
1323. Implementation and Effectiveness of the Asia Pacific HIV Practice Course: Building Capacity of Healthcare Workers in the Region
Authors: Michaels Jessica , Olszyna Dariusz , Banerjee Sumita , McGill Scott , Lin Jing Yi , Law Hwa Lin , Yong Joy , Wong Nicole , Lee Cheng Chuan , Archuleta Sophia
Published: November 2018

Background

Building the capacity of healthcare workers (HCW) can positively influence service quality and patient care. Given the limited HIV training opportunities in the Asia Pacific Region, the Asia Pacific HIV Practice Course (APHPC) aims to improve knowledge and skills and encourage patient-centered practice.

Methods

The APHPC is organized by an interprofessional organizing committee. The course was developed based on a needs assessment of HCWs in the region and is run over 4 days. Using didactic and interactive learning approaches, the course covers psychosocial, biomedical and service delivery topics. One hundred HCWs, predominantly nurses, social workers/counselors and, pharmacists have attended the course over 2 years (2016 and 2017). Participants have attended from Singapore, Sri Lanka, Indonesia, Malaysia, Philippines, Bangladesh, Papua New Guinea, Myanmar, and Vietnam. Pre- and post-course evaluations were completed, as well as daily session evaluations and a 3-month post-course evaluation. Participants rated their confidence from 1 to 5 (not confident–very confident). A paired-samples t-test was conducted to compare mean (M) confidence levels pre- and post-course in the various topics covered.

Results

There was significant improvement in mean confidence scores pre-course (M = 3.40, SD 0.27) and post-course (M = 4.09, SD = 0.13); t(11)= 13.1958, P < 0.0001. This was seen across all topics (figure) with the most marked improvement found in models of care and barriers to care, topics that are not routinely or explicitly covered in the same detail or frequency as HIV basics, testing, treatment and prevention. In the 3-month post-course survey, participants shared the changes they have made to their local practice since attending the APHPC. Changes include, additional staff training, revisions to counseling models and services and the implementation of monitoring and evaluation structures.

Conclusion

The APHPC has proven to be an impactful and highly evaluated course. To ensure the course continues to influence and improve practice, the content of the course can be expanded to cover nonstandard topics, and further interactive learning experiences can be incorporated.

Disclosures

All authors: No reported disclosures.
1324. Development of HIV-ASSIST, an Online, Educational, Clinical Decision Support Tool to Guide Patient-Centered ARV Regimen Selection
Authors: Maddali Manoj , Li Jonathan , Shah Maunank
Published: November 2018

Background

Multiple antiretroviral (ARV) regimens are effective at achieving HIV viral suppression but differ in pill burden, resistance profile, side effects, and impact on comorbidities. Current guidelines advocate for an individualized, patient-centric approach to ARV regimen selection, including simplification of ARV regimens in patients with stable viral suppression. Synthesizing these modifying factors is necessary for effective care but is a complex and time-consuming process for infectious disease and primary care practitioners.

Methods

We sought to develop an online, interactive tool for ARV decision support that incorporates patient, viral, and therapeutic factors to provide evidence-based recommendations for individualized ARV regimen selection. We additionally incorporated educational materials within the tool to enhance provider learning while simultaneously improving real-time clinical care. Our goal is to optimize ARV regimen selection to provide personalized HIV care that improves patient outcomes, minimizes adverse effects, and enriches clinician knowledge of antiretrovirals.

Results

We developed HIV-ASSIST (https://www.hivassist.com) as a freely available, online resource to support clinicians caring for HIV patients. Our tool utilizes decision-analysis principles based on current guidelines, scientific literature, and expert opinions to deliver tailored recommendations on ARV regimen selection specific to each patient encounter. Decision algorithms were optimized in an iterative fashion using feedback on complex case scenarios from regional HIV experts. HIV-ASSIST evaluates and “ranks” all possible multi-drug ARV regimens across a variety of domains, including common laboratory markers (viral load, genotype, etc.) and patient-specific characteristics (medical comorbidities and drug interactions, treatment history, adherence, etc.). Through a user-friendly interface, clinicians are shown the impact of these modifying factors on ARV regimens and dosing, along with supporting clinical trial evidence.

Conclusion

HIV-ASSIST is a patient-centric tool to improve patient outcomes through real-time ARV decision support and enhance knowledge of evidence-based HIV care guidelines.

Disclosures

All authors: No reported disclosures.
1332. West Coast Transplant ID Conferences, A Model for Building Community in ID Disciplines?
Authors: Allyn Paul , Schaenman Joanna , Schwartz Brian , Vijayan Tara
Published: November 2018

Background

Transplant infectious diseases (TID) is a young and rapidly changing field. Providers need to make patient care decisions with limited clinical data. Challenges faced by TID providers may be different than others in their local ID community. We describe a model where TID faculty from six major transplant centers on the West Coast held periodic web-based conferences to discuss challenging cases and controversial topics in TID.

Methods

In 2011, faculty from six major transplant centers in the states of Washington, Oregon, and California began participating in web-based conferences. To assess impact, we distributed a 30-item survey generated in Qualtrics via email in Spring 2018. Participants were invited if they had ever attended one of the conferences. The survey collected quantitative and qualitative data on how the conferences changed clinical practice and helped build community. Data on conference topics was also collected.

Results

West Coast Transplant ID Conferences were held 12 times between 2011 and 2018 with TID topics covered including management of RSV, antifungal prophylaxis, CMV, and LTBI among others. Sixteen participants responded to the survey representing all six institutions. eight (50%) of respondents spent at least half of their time in the practice of TID. Six (37%) of respondents worked for <5 years and five (31%) reported working more than 10 years in TID. 56% of participants attended ≥4 conferences in the last 3 years. 93% of participants included trainees on the conference call. All respondents agreed or strongly agreed that the topics covered were relevant to their practice. 87.5% felt that the calls generate consensus about difficult or controversial topics. 62.5% reported that they had changed their practice because of the conferences. Only 1 respondent reported that they collaborated on research because of the conference. 100% agreed or strongly agreed that the conferences built a sense of community within TID.

Conclusion

Given improvements in web-based technologies, a community of practice can be easily created despite geographic distance allowing for TID providers to discuss relevant topics that impact practice and enhance sense of community. This model could be reproduced in other areas of infectious diseases.

Disclosures

All authors: No reported disclosures.
1363. Sulopenem Activity Against Enterobacteriaceae Isolates From Patients With Urinary Tract Infection or Intra-Abdominal Infection
Authors: Puttagunta Sailaja , Aronin Steven , Huband Michael , Flamm Robert K , Dunne Michael
Published: November 2018

Background

Sulopenem is a thiopenem antibacterial with oral and parenteral formulations being developed for the treatment of urinary tract infection (UTI) or complicated intra-abdominal infection (cIAI). The activity of sulopenem aligns with the most urgent drug-resistant antimicrobial threats defined by the Centers for Disease Control (CDC), including ESBL-producing strains of Escherichia coli and Klebsiella species. We evaluated the in vitro antibacterial activity of sulopenem against clinical Enterobacteriaceae isolates from patients in North America with UTI or cIAI collected during 2016–2017.

Methods

Sulopenem and other antimicrobial agents were tested for in vitro activity against 1,008 recent (2016–2017) consecutive Enterobacteriaceae isolates collected through the SENTRY Antimicrobial Surveillance Program from patients in North America with UTI (906 isolates) or cIAI (102 isolates). Reference broth microdilution susceptibility testing was conducted using frozen-form panels produced by JMI Laboratories according to CLSI (M07, 2018) guidelines using cation-adjusted Mueller–Hinton broth. Quality control (QC) and interpretation of results were performed in accordance with CLSI M100 (2018) guidelines.

Results

Table 1. Activity of sulopenem and comparator antimicrobial agents against 1,008 Enterobacteriaceae North American isolates

The sulopenem MIC50/90 values for Enterobacteriaceae were 0.03/0.25 µg/mL. For Escherichia coli, Klebsiella species and Proteus mirabilis, the MIC50/90 results were 0.03/0.03 µg/mL, 0.03/0.06 µg/mL, and 0.12/0.25 µg/mL, respectively.

Conclusion

Sulopenem demonstrated potent in vitro activity against organisms commonly implicated in UTI and cIAI. These data support the further clinical development of sulopenem for Gram-negative infections.

Disclosures

S. Puttagunta, Iterum Therapeutics: Employee and Shareholder, Salary. S. Aronin, Iterum Therapeutics: Employee and Shareholder, Salary. M. Huband, JMI Labs: Research Contractor, Grant recipient. R. K. Flamm, Allergan: Research Contractor, Research support. M. Dunne, Iterum Therapeutics: Employee and Shareholder, Salary.
1373. Activity of Ceftriaxone–Sulbactam–EDTA Against Multi-Drug-resistant A. baumannii, P. aeruginosa and Enterobacteriaceae Isolates (WHO Critical Priority Pathogens) Collected from Various Hospitals in India
Authors: Girotra Ruchi , Pyasi Anurag , Chaudhary Manu , Patil N S , Mir Mohd Amin , Chaudhary Saransh , Mandale Pankaj ,   Other Investigators
Published: November 2018

Background

Ceftriaxone–Sulbactam–EDTA (CSE) is the first cephalosporin–β-lactamase inhibitor combination with an antibiotic resistance breaker–disodium edetate, recently evaluated in a Phase 3 clinical trial for treatment of adults with complicated urinary tract infections (NCT03477422). The addition of Sulbactam and EDTA expands the spectrum of activity of Ceftriaxone to include extended-spectrum-β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing bacteria. This study evaluated the in vitro activity of CSE against 3,150 isolates (716 (22.73%) E. coli; 435 (13.81%) K. pneumoniae; 1,075 (34.13%) A. baumannii; 924 (29.33%) P. aeruginosa) collected from 22 hospitals in India during 2013–2016.

Methods

A total of 3,150 nonduplicate Gram-negative clinical isolates were collected, and susceptibility testing was conducted using reference broth microdilution method for CSE and comparators. CLSI defined phenotypic methods were used for ESBL and MBL detection, and thereafter, all isolates were further characterized genotypically using single PCRs and a panel of primers for detection of most β-lactamase enzymes, including blaTEM, blaSHV, blaCTX-M, blaAmpC, blaOXA, blaKPC, blaVIM, blaNDM, and blaIMP.

Results

Of the 3,150 isolates, 2,717 (86.25%) were β-lactamase producers, of which, 851 (31.32%) tested positive for ESBL, 1,591 (58.56%) tested positive for MBL, while 275 (10.12%) tested positive for both ESBL and MBL production during phenotypic evaluation. Once the genotype data were available, isolates were re-characterized as per the functional classification of β-lactamases into four distinct categories, including ESBL, AmpC, Carbapenemase and MBL. An astonishing 1,866 (59.23%) isolates harbored at least one MBL gene, of which, the prevalence was the highest in A. baumannii (78.6%), followed by K. pneumoniae (63%), P. aeruginosa (46.6%) and E. coli (44.1%). A summary of the results of susceptibility testing is shown in Figures 1, 2, and 3.

Conclusion

CSE showed a high overall susceptibility in ESBL- and MBL-producing bacteria and could provide a useful alternative to carbapenems and colistin in clinical settings.

Disclosures

R. Girotra, Venus Medicine Research Centre: Employee, Salary. A. Pyasi, Venus Medicine Research Centre: Employee, Salary. M. Chaudhary, Venus Medicine Research Centre: Board Member and Shareholder, Salary. M. A. Mir, Venus Medicine Research Centre: Employee, Salary. S. Chaudhary, Venus Medicine Research Centre: Employee and Shareholder, Salary. P. Mandale, Venus Medicine Research Centre: Employee, Salary.
1376. Antifungal Activity of Cerium Nitrate Against Fungal Isolates Associated with Combat-Related Injuries Including Burns
Authors: Pomerantz Heather , Beckius Miriam , Blyth Dana , Akers Kevin S , Tribble David R , Mende Katrin
Published: November 2018

Background

Fungal infections are a critical cause of morbidity and mortality in burn patients. In addition to debridement and systemic antifungal therapy, various topical adjuncts have been used, and topical burn care is a key component of infection prevention and treatment. Cerium nitrate (CN) has been used in combination with silver sulfadiazine (SS) in burn care. Previous studies showed that CN had bacteriostatic activity, and suggested anti-biofilm activity against Candida biofilms. In this study, we evaluated the in vitro activity of CN against fungal isolates associated with combat-related injuries.

Methods

The efficacy of CN was evaluated against 14 mold (three Aspergillus spp., two Fusarium spp., five different mucormycetes, two Bipolaris spp., one Alternaria spp., one Exophiala spp.) and 21 Candida spp. isolates collected as part of the Trauma Infectious Disease Outcomes Study. Fungicidal activity of various concentrations of CN (2.2%, 1%, 0.5% and 0.2%) was determined using an established time-kill assay. Standard conidia/cell suspensions were prepared according to Clinical and Laboratory Standards Institute guidelines and then exposed to the CN solutions for 24 hours. At different times (0, 5, 15, 30 minutes, 1, 1.5, 3, 6, 12, and 24 hours) aliquots were plated and incubated at 35ºC. Colony forming unit (CFU) counts were determined after 24 hours incubation or after an appropriate time for slow growing molds.

Results

All mold isolates had persistent growth at 24 hours with most having no significant change in colony counts over the 24-hour period. The only exception was Mucor circinelloides, which appeared to have a time-dependent reduction in CFUs at 24 hours for all CN concentrations. Exophiala did not grow as well in CN solutions compared with the control (mean 65 vs. 28.2 CFUs with a difference of mean 37.4 CFUs, P = 0.0001), but this was not time or concentration dependent. All yeast species showed a time-dependent killing after 6–12 hours.

Conclusion

CN demonstrated time-dependent killing of the yeasts. However, very little activity was observed against the tested molds. Since CN is often used in combination with SS there might be a synergistic effect against molds. Further research will evaluate higher concentrations of CN and its toxicity for cells and tissue.

Disclosures

All authors: No reported disclosures.
1378. Evaluation of the In vitro Activity of Meropenem-Vaborbactam Against Carbapenem-Resistant Enterobacteriaceae, Including Isolates Resistant to Ceftazidime–Avibactam
Authors: Wilson William R , Kline Ellen , Jones Chelsea , Morder Kristin , Clancy Cornelius J , Nguyen M Hong , Shields Ryan K
Published: November 2018

Background

Meropenem-vaborbactam (M-V) is a novel antibiotic for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections. Our objective was to determine the in vitro activity of meropenem-vaborbactam against genetically-diverse CRE isolates, including those that have developed resistance to Ceftazidime–Avibactam (C-A).

Methods

Minimum inhibitory concentrations (MICs) were determined for meropenem (MER), M-V, and C-A by reference broth microdilution (BMD) methods in triplicate. Vaborbactam and avibactam were tested at fixed concentrations of 8 and 4 µg/mL, respectively. Quality control strains were used and within expected ranges. Polymerase chain reaction (PCR) with DNA sequencing was used to detect resistance determinants, including Klebsiella pneumoniae carbapenemase (KPC) subtypes and porin mutations.

Results

A total of 117 CRE isolates were tested, including K. pneumoniae (Kp; n = 83), E. cloacae (n = 17), E. coli (n = 10), and E. aerogenes (n = 7). Seventy-nine percent harbored blaKPC. KPC subtypes included KPC-2 (n = 32), KPC-3 (n = 41), KPC-3 variants (n = 16), and KPC [not typed] (n = 4, all E. coli). Among 74 K. pneumoniae, 95% had a premature stop codon in ompk35 and ompK36 genotypes included wild type (n = 48), IS5 insertion (n = 13), 135–136 DG duplication (n = 9), and other mutations (n = 4). The median (range) MICs for MER, C-A, and M-V were 8 (0.06 to ≥128), 1 (0.25 to ≥512), and 0.03 (0.015––16), respectively. Corresponding rates of susceptibility were 23, 84, and 98%, respectively. Fifty-three percent and 95% of C-A-resistant isolates were susceptible to MER and M-V, respectively. Among Kp, C-A MICs did not vary by KPC subtype or porin genotype. On the other hand, median M-V MICs were higher among KPC-2 than KPC-3 Kp (0.12 vs. 0.03; P = 0.002), and among Kp with ompK36 porin mutations compared with wild type (0.25 vs. 0.03; P < 0.001). Among Kp with KPC-3 variants (n = 16), the median M-V MIC was 0.03 (0.015––2); 100% were M-V susceptible. Median M-V MICs did not vary by CRE species. Only two isolates were M-V resistant, both were E. cloacae that did not harbor blaKPC.

Conclusion

M-V demonstrates high rates of in vitro susceptibility against diverse CRE isolates, including those that are resistant to C-A. As this agent is introduced into the clinic, it will be important to identify K. pneumoniae isolates harboring KPC-2 with ompK36 porin mutations that demonstrate higher MICs.

Disclosures

M. H. Nguyen, Merck: Grant Investigator, Research grant. Astellas: Grant Investigator, Research grant.
1386. Efficacy of Repeat Dosing of Oral Fosfomycin in a Dynamic Bladder Infection In Vitro Model
Authors: Abbott Iain , Wijma Rixt , Broos Nick , Peleg Anton , Mouton Johan
Published: November 2018

Background

Oral fosfomycin is indicated for uncomplicated urinary tract infections with activity against MDR-uropathogens. Despite off-label use of giving three doses every 2–3 days, limited supporting data are available. We performed pharmacodynamic profiling using a dynamic bladder infection in vitro model to assess adequacy of repeat doses of fosfomycin.

Methods

A bladder infection in vitro model simulating urinary fosfomycin concentrations after 3 g (equiv.) oral doses was used with Mueller–Hinton broth (MHB) with 25 mg/L glucose-6-phosphate. Fosfomycin exposures were validated by LC–MS/MS measurements. Pharmacodynamic response of 16 clinical Enterobacteriaceae isolates were examined (eight E. coli, four E. cloacae, four K. pneumoniae; agar dilution MIC 0.25–64 mg/L) following three doses of fosfomycin given every 72, 48 or 24 hours, compared with single dose therapy. Pathogen kill and resistance was assessed by quantitative cultures on drug-free and fosfomycin-containing Mueller–Hinton agar (MHA +64 mg/L, +512 mg/L).

Results

Fosfomycin exposure following single and multiple doses were accurately reproduced (mean deviation from target 5.0 ± 3.4%, max 11.8%) with minimal variability (mean relative SD 2.7 ± 1.7%, max 8.8%). Fosfomycin high-level heteroresistance was detected prior to drug exposure in 8/16 isolates (proportion 0.00002–0.001% of total population). All isolates with high-level heteroresistance regrew following single dose fosfomycin. Following three doses given every 72 hours, one additional K. pneumoniae isolate was killed. All other isolates regrew with amplification of HLR subpopulation (median proportion: 71.4%, IQR 57.5–100%). Despite dosing 48 and 24 hourly, the same isolates regrew, although HLR subpopulation amplification was reduced (48 hours dosing: 32.0%, IQR 0.005–83.3%; 24 hours dosing: 0.3%, IQR 0.0004–81.3%).

Conclusion

Dynamic in vitro modeling of multiple doses of oral fosfomycin fails to additionally suppress regrowth in the majority of isolates compared with single dose therapy. Baseline high-level heteroresistance is an important predictor for regrowth. These results suggest that giving multiple doses of fosfomycin is not necessarily better than standard single dose therapy. Earlier timing of repeat doses may help suppress the emergence of resistance.

Disclosures

All authors: No reported disclosures.
1389. Pharmacokinetic/Pharmacodynamic (PK/PD) Evaluation of a Novel Aminomethylcycline Antibiotic, KBP-7072, in the Neutropenic Murine Pneumonia Model Against S. aureus (SA) and S. pneumoniae (SPN)
Authors: Lepak Alexander J , Zhao Miao , Liu Qingmei , Wang Ping , Wang Yanli , Bader Justin C , Ambrose Paul G , Andes David R
Published: November 2018

Background

KBP-7072 is a novel aminomethylcycline antibiotic with broad-spectrum activity that includes organisms with drug-resistance to β-lactams and tetracyclines. We examined the PK/PD relationship between KBP-7072 drug exposures and treatment effect using a neutropenic murine pneumonia model against a diverse group of SA and SPN.

Methods

Five SAs (three MRSAs) and six SPNs (three PCNs NS, two TetR) strains were used. MICs were determined by CLSI Methods. Plasma and ELF PK was determined after SC dosing (range 1–256 mg/kg). Lung burden was assessed by CFU counts at the beginning and end of therapy (24 hours). Infected mice were treated with KBP-7072 by SC route: SA dose range 0.25–64 mg/kg/6 hours, SPN dose range 0.06–16 mg/kg/6 hours. The Emax Hill equation was used to model the dose–response data to the PK/PD index AUC/MIC. The magnitude of the PK/PD index (plasma free and ELF total concentrations) associated with net stasis, 1- and 2-log kill were determined in the pneumonia model for all strains.

Results

SA MICs were 0.25 mg/L for all isolates and SPN MICs were 0.008–0.016 mg/L. Plasma PK of KBP-7072 included: Cmax 0.12–25.2 mg/L, AUC0-∞ 1.1–234 mg hour/L, T1/2 3.2–4.6 h. ELF PK by urea correction methods included: Cmax 0.06–13.3 mg/L, AUC0-∞ 0.4–95 mg hour/L, T1/2 3.1–4 hours. ELF penetration based on free plasma drug concentrations (77.5% bound) ranged from 82 to 238%. AUC was linear over the dose range (R2 = 0.99). Potent dose-dependent cidal activity (3–5 log kill) was observed against all strains. AUC/MIC was a robust predictor of efficacy (SA R2 = 0.89, SPN R2 0.80). Median static, 1- and 2-log kill AUC/MIC values are shown in the table.

Conclusion

KBP-7072 demonstrated potent in vivo efficacy against SA and SPN, including strains with elevated minocycline MIC and β-lactam resistance, in the neutropenic murine pneumonia model. A 3–5 log kill was observed and AUC/MIC was strongly associated with efficacy. The AUC/MIC target for net stasis was comparable between SA and SPN at a plasma fAUC/MIC target of ~1 and ELF AUC/MIC target ~2. Cidal targets were similarly very low. All targets were numerically lower than comparative tetracyclines. These results should prove useful for clinical dosing regimen optimization.

Disclosures

A. J. Lepak, KBP Biosciences: Research Contractor, Research support. Q. Liu, KBP Biosciences: Employee, Salary. P. Wang, KBP Biosciences: Employee, Salary. Y. Wang, KBP Biosciences: Employee, Salary. J. C. Bader, KBP Biosciences: Research Contractor, Research support. P. G. Ambrose, KBP Biosciences: Research Contractor, Research support. D. R. Andes, KBP Biosciences: Research Contractor, Research support.
1391. Vancomycin Area Under the Curve (AUC) to Predict Nephrotoxicity: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Aljefri Doaa , Avedissian Sean , Rhodes Nathaniel J , Postelnick Michael , Scheetz Marc H
Published: November 2018

Background

Recent studies have proposed monitoring vancomycin area under the curve (AUC) as a more precise method of attaining goal exposures compared with trough monitoring. Different dosing methods and different exposure-toxicity thresholds have been proposed. Therefore, we aimed to analyze the relationship between vancomycin AUC and nephrotoxicity reported across recent studies.

Methods

A systematic review of Pubmed, Medline, Scopus and compiled references was conducted. We included randomized, cohorts and case–control studies that reported vancomycin AUCs and risk of nephrotoxicity from (January 1, 1990 to January 31, 2018). The primary outcome was nephrotoxicity, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on two or more consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Subset analyses were conducted when possible on the impact of AUC0-24 hours and AUC24-48 hoursr exposures and AUC vs. trough guided dosing on the outcome of nephrotoxicity. AUC nephrotoxicity thresholds ranged between 550 and 700 mg hour/L. We grouped values according to lower (i.e., <650) or higher average AUC, with a threshold value of ≥650 mg hour/L defining higher AUC based on a recent prospective trial.

Results

We identified eight eligible observational studies with a total of 2,491 patients. Of those, five studies reported AUC0-24 associated with nephrotoxicity, two studies reported AUC24-48, and two studies reported nephrotoxicity associated with AUC vs. trough-guided dosing. No RCTs were identified. Lower AUC0-24 values were associated with significantly reduced risk of nephrotoxicity (OR 0.36, 95% CI 0.23–0.56). In a sub-analysis of two studies, AUC24-48<650 mg hour/L was associated with significantly lower risk of nephrotoxicity (OR 0.45, 95% CI 0.27–0.75). Nephrotoxicity associated with AUC-guided dosing was significantly lower than trough-guided dosing (OR 0.68, 95% CI 0.46–0.99).

Conclusion

This meta-analysis suggests that AUC0-24 lower than 650 mg hour/L may result in a decreased risk of nephrotoxicity. AUC-guided vancomycin dosing may result in less vancomycin-associated nephrotoxicity. Additional investigations into the benefit of AUC-guided dosing are warranted.

Disclosures

All authors: No reported disclosures.
1396. Predictions of Isavuconazonium Sulfate Dosage in Patients Aged 6 Months: <18 Years by Physiologically Based Pharmacokinetic Modeling
Authors: Desai Amit , Kovanda Laura , Lademacher Christopher , Hope William , Neely Michael , Bonate Peter , Edginton Andrea
Published: November 2018

Background

Best practice to establish dosage regimens for “first-in-pediatric” clinical trials requires knowledge of efficacious and safe exposures in adults.

Methods

Pediatric equivalent doses were predicted for patients aged 6 months and <18 years using physiologically based pharmacokinetic (PBPK) modeling, and compared with predictions by allometric scaling. All simulations were completed using PK-Sim®, which implements a whole-body PBPK model with 15 organs and appropriate maturation of anatomical and physiological parameters for children. The adult PBPK model was built using knowledge of drug physico-chemistry and clearance partitioning (CYP3A4, CYP3A5, glomerular filtration). PK data following IV (40, 80, 160 mg 60-minute infusion) and oral (100, 200, 400 mg capsule) doses in adults were used for initial model development. This model was validated by matching observed adult concentrations after multiple oral 200 mg doses. From this adult model, a virtual pediatric population (n = 4,600) from 6 months to <18 years was created. Simulations with the pediatric model assessed optimal doses of isavuconazonium sulfate based on age and weight to achieve at least a median steady-state daily area under the curve (AUCss) of 100 mg hour/L, and the majority below 230 mg hour/L. These targets were derived from efficacy and safety data in clinical trials with adults.

Results

As shown in the figure, an isavuconazonium sulfate dose of 10 mg/kg is expected to result in AUCss within the target range for the majority of patients >1 year old, in agreement with that predicted by allometry for patients aged 2–17 years. For patients aged 6 months to 1 year, a dose of 6 mg/kg predicts comparable exposures.

Conclusion

A proposed isavuconazonium sulfate dose of 10 mg/kg administered every 8 hours for the first 2 days and once daily thereafter is predicted to result in safe and efficacious steady state exposures in patients aged 1–17 years, similar to predictions from allometric scaling for patients aged 2–17 years. For subjects aged 6 months to 1 year, a dose of 6 mg/kg is predicted to achieve similar exposures. These doses should be tested in clinical trials to confirm.

Disclosures

A. Desai, Astellas Pharma, Inc.: Employee, Salary. L. Kovanda, Astellas Pharma, Inc.: Employee, Salary. C. Lademacher, Astellas Pharma, Inc.: Employee, Salary. W. Hope, F2G: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Astellas: Grant Investigator and Investigator, Grant recipient and Research grant. Pfizer: Grant Investigator, Research support. Gilead: Consultant and Scientific Advisor, Consulting fee. P. Bonate, Astellas Pharma, Inc.: Employee, Salary. A. Edginton, Astellas Pharma Global Development, Inc.: Independent Contractor, Consulting fee.