bluuebunny/crossref_metadata_2025 huggingface dataset:
2437. First-line Fidaxomicin Use in High-risk Inpatients Reduces Recurrence Rates
Authors: Kohinke Rose , McDaniel Lauren , Perhac Angela , Everson Nathan
Published: October 2019

Background

Fidaxomicin is recommended by the 2018 Infectious Diseases Society of America (IDSA) guidelines as a first-line treatment in adult patients with uncomplicated Clostridioides difficile infection (CDI). Carilion Roanoke Memorial Hospital (CRMH) implemented a clinical decision order set directing providers to initiate fidaxomicin for CDI in patients at high risk of recurrence. The purpose of this study was to assess the impact of fidaxomicin on patient outcomes.

Methods

This quasi-experimental study included adults with a first episode or first recurrence of CDI before and after order set implementation. Patients receiving laxatives within 24 hours of testing and those with fulminant CDI were excluded. Pre-implementation was defined as May 2017 to November 2017 and post-implementation as May 2018 to November 2018. The primary endpoint was recurrence (diarrhea and a positive GDH with toxin or PCR within 30 days post-treatment). Secondary endpoints were clinical cure (resolution of symptoms within 2 days of completing therapy), global cure (cure with no recurrence at 3 months), mortality, and readmissions. Partial courses of fidaxomicin (i.e., patients discharged on another agent) were also evaluated.

Results

A total of 282 patients were included. In the pre-group, 59.1% received metronidazole, 39.6% oral vancomycin, and 1.3% fidaxomicin. In the post-group, fidaxomicin use increased to 52.3% and oral vancomycin was 44.5%. There was a significant improvement in recurrence (30.2% vs 17.1%, P = 0.019). Global cure and CDI upon readmission also improved in the post-group (Table 1). In patients receiving partial courses of fidaxomicin, recurrence (9.3% vs 25%, P = 0.19), global cure (86% vs 75%, P = 0.44), and infection on readmission (28.6% vs 37.5%, P = 0.67) were similar.

Conclusion

Fidaxomicin as a first-line agent in high-risk CDI patients decreased recurrence and increased global cure.

Disclosures

All authors: No reported disclosures.
2448. Clinical Presentation and Outcomes of Long-Term Care Residents with Coronavirus Respiratory Infection: A Retrospective Cohort Study
Authors: Williams Victoria R , Pajak Dariusz , Salt Natasha , Leis Jerome A
Published: October 2019

Background

Human coronaviruses (CoVs) are a major cause of respiratory infection and institutional outbreaks, yet the epidemiology and clinical outcomes of these viruses is poorly described among the elderly residing in long-term care facilities (LTCFs).

Methods

We performed a retrospective cohort study of LTCF residents with positive nasopharyngeal or mid-turbinate swabs for CoVs (OC43, 229E, NL63 and HKU1) between January 2013 and December 2018. Demographic and clinical data were obtained from resident charts including clinical presentation, treatment, outcome, and transmission to other residents. Variables were compared using univariate analysis.

Results

3268 residents met inclusion criteria (median age 93 years, 90% male) comprising 7.5% (246/3268) of all positive respiratory virus specimens detected during the study period. 97(39%) of cases were associated with a respiratory outbreak while 149(61%) were sporadic cases that did not result in transmission. OC43 (52%) was the most commonly identified CoV and was more commonly associated with outbreak cases (76% vs. 37%; P < 0.001). In total, 87% of all cases had two or more of runny nose/congestion, cough, sore throat/hoarse voice or fever. The most common symptoms among residents were cough (85%), runny nose/congestion (79%), and sore throat/hoarse voice (59%) and only 17% of residents had a measured temperature of ≥ 37.8C. Only 6% of residents received antibiotic treatment for suspected secondary bacterial pneumonia. The 30-day mortality rate was 3.7% with 67% of deaths attributable to the CoV infection. There was no statistically significant difference in symptoms, treatment or outcomes associated with outbreaks or seasonality.

Conclusion

CoVs make up an important proportion of respiratory viral infections among LTCF residents and may result in frequent outbreaks. Most residents remain afebrile and have self-limited illness while only a small minority develop secondary bacterial pneumonia and death. Given these findings the benefits of control measures should be weighed against the impact on resident quality of life.

Disclosures

All authors: No reported disclosures.
2460. Hospital-Wide Outbreak of Serratia marcescens of Unclear Source: When Extensive Infection Control Measures Are Needed
Authors: Tayyar Ralph , Weyhmuller Carol , Fasano Caitlin , Aridi Jad , Sherman Eileen , Ingerman Mark , Gilbert Brett
Published: October 2019

Background

Nosocomial outbreaks of Serratia marcescens have been widely reported and the source is identified in most cases. We report a Serratia marcescens outbreak in a community hospital with no obvious source.

Methods

An epidemiologic investigation was started after an outbreak was suspected. Clinical data were collected from charts of patients with positive culture for Serratia marcescens. Molecular relatedness of available isolates was determined by pulsed-field gel electrophoresis.

Results

Between December 2016 and August 2017, 13 non-pigmented Serratia marcescens isolates were identified from 11 patients. Bacteria were isolated from blood, abdominal and respiratory cultures. Susceptibility profiles showed variable resistance to ceftriaxone, ceftazidime, imipenem, tobramycin and aztreonam. Infection control measures: Isolates were identified from adult patients who underwent various cardiothoracic/vascular surgeries. Patients were traced back to a single floor of the new hospital building. To control this outbreak, the infection prevention team started with hand hygiene initiatives and observations, environmental sampling, and reviewing management of ventilator, dialysis equipment, and ECMO machines. Ice machine carbonless filters were installed, UV disinfection systems were used, and new TEE cleaning rooms were designated. In conjunction with recommendations of department of health, hospital was contracted with a water cleaning company; laminar flow aerators were installed, water sampling plan was implemented and ultimately the whole building’s water system was hyper-chlorinated.

Conclusion

While water contamination was the most likely source, a specific cause could not be identified. An important lesson learnt is the quick implementation of infection control measures after identifying infected patients is key in controlling an outbreak.

Disclosures

All authors: No reported disclosures.
2468. Is On-Demand Multilocus Sequence Typing of Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridioides difficile Hospital Isolates Useful for Infection Control Practice?
Authors: Holodniy Mark , Winters Mark , Aseo Rowena , Markman Laura , Chary Aarthi
Published: October 2019

Background

MRSA and C. diff are important causes of hospital-onset (HO) or healthcare-associated infections (HAI). Molecular sequencing of bacterial pathogens is often used retrospectively during outbreak investigations to determine phylogenetic linkage. We evaluated the utility of on-demand multilocus sequence typing (MLST) in characterizing hospital transmission events.

Methods

Using VA or NHSN criteria, inpatients with MRSA-HAI or HO-C. difficile infection (HO-CDI) were identified by infection preventionists (IPs) for MLST (by time and location) during active hospital surveillance starting October 2016 or September 2017 (for C. difficile and MRSA, respectively) through March 2019. Vitek 2 identified MRSA from blood or other sources, and stool samples positive for C. difficile by Cepheid Xpert® C. difficile or FilmArray® Gastrointestinal (GI) Panel were collected and C. diff isolated on CCFA plates. Sequence types (STs) were generated by Sanger sequencing and MLST using standard protocols (pubmlst.org). C. difficile genes included adk, atpA, dxr, glyA, recA, sodA, tpi. MRSA genes included arc, aro, glp, gmk, pta, tpi, yqil. Staphylococcal protein A gene (spa) type was determined by spa gene sequencing.

Results

MLST assay (C. diff 33, MRSA 26) intervals ranged from 1–4 weeks based on IP request. 109 C. diff isolates from 105 patients representing 44 STs (10 unique) were found. ST1 and ST2 (27, 20) were most common. 5 patients had 2–3 identical ST isolates over 21–180 days. Of 72 HO-CDI identified, 9 possible person-to-person transmissions events (33 cases) were ruled out; 3 events (9 cases) were ruled in; 14 events (21 cases) were not resolved due to missing samples or no growth. 100 MRSA isolates from 96 patients representing 26 STs (9 unique) were found. ST8/spa t008 (USA300) and ST5/spa t002 (USA100) (44, 29) were most common. 11 patients had 2–3 identical ST isolates over 2–367 days. Of 16 MRSA-HAI identified, 1 transmission event (4 cases) was ruled out, 1 event (2 cases) lacked one strain and was unresolvable.

Conclusion

Common MRSA and C. diff STs predominated among hospital isolates, yet significant heterogeneity was seen over a 2-year period and few true transmission events were documented. On-demand MLST-augmented IP surveillance was useful to rule-out hospital transmission.

Disclosures

All authors: No reported disclosures.
2472. Point Prevalence of Healthcare-Associated Infections and Antibiotic Use in a Tertiary Care Teaching Hospital in Nepal: A Cross-Sectional Study
Authors: Kumar. Shrestha Sailesh , Shrestha Swarup
Published: October 2019

Background

Healthcare-associated infections (HAIs) are a growing threat to patient safety, particularly in resource-limited settings. Information on the burden of HAIs will help in surveillance and prevention efforts. This study aims to estimate the prevalence of HAIs and antibiotics use in a tertiary care teaching hospital in Nepal.

Methods

We conducted a descriptive cross-sectional point prevalence survey in a 350 bedded acute care teaching hospital at Kathmandu, Nepal on April 2019 in a single day for every ward. We studied all the patients aged ≥ 18 years admitted for at least two calendar days on the day of the survey to collect data on patient characteristics, hospital stay, and invasive devices and antibiotics used. We evaluated for the three common HAIs – pneumonia, urinary tract infection and surgical site infection, active on the day of data collection using the clinical criteria by European Center for Disease Prevention and Control protocol version 5.3. We summarized continuous variables with median and interquartile range (IQR) and categorical variables with proportions. We reported the prevalence of HAIs as a proportion of the number of HAIs by the number of patients studied.

Results

Of 213 inpatients, 160 were eligible, 25 (15.6%) among them were from critical care units. The median age was 50 years (IQR 34–65). The median duration of hospital stay was 6 days (IQR 4–9). There were 18 HAIs for the prevalence of 11.25%. Urinary tract infection was the most common HAI (13 HAIs, 72.2% of all HAIs). We found invasive devices used in 42 patients (26.2%), the most common was urinary catheter (37 patients, 23.1%). The number of patients with any antibiotic used was 114 (71.25%) with 61 (38%) patients receiving two or more antibiotics. Third-generation Cephalosporins were the most common antibiotics (74, 64.9%) used. We found 91 (79.8%) patients being treated for community-acquired infections.

Conclusion

This study provides an estimate of the burden of HAIs in our center that is comparable to that of the reports from other resource-limited settings. However, we believe a higher burden will be revealed when we add microbiological criteria as well to diagnose HAIs. This highlights an urgent need for HAI surveillance system, infection prevention and control, and antibiotics stewardship programs in our center.

Disclosures

All authors: No reported disclosures.
2474. The 10 Years Scientific Contribution of the Cologne Cohort of Neutropenic Patients (CoCoNut) for Evaluating Treatment and Outcome of Healthcare-associated Infections
Authors: Jakob Carolin , Heimann Sebastian , Classen Annika , Gillis Meyke , Thelen Philipp , Holtick Udo , Scheid Christof , Cornely Oliver , Janne Vehreschild Jörg
Published: October 2019

Background

Healthcare-associated infections (HAIs) are a leading cause for morbidity and mortality in neutropenic patients.

Methods

The Cologne Cohort of Neutropenic Patients (CoCoNut) is an ongoing, prospective, longitudinal cohort, collecting inpatient data for analysis of epidemiology, risk factors, and outcome of neutropenic patients (at least one day of absolute neutrophil count < 500/µL) at risk for HAIs. The CoCoNut contains comprehensive data, i.e. patient characteristics, medication, chemotherapy, clinical data (e.g., diarrhea, body temperature), as well as laboratory, microbiological, virologic, and radiological results. The purpose of this cohort is to improve the knowledge on HAIs and management of anti-infective prophylaxis and therapy.

Results

To date, the CoCoNut includes 8,176 inpatient stays from 3,354 neutropenic patients treated at the hematology/oncology department of the University Hospital of Cologne between January 2009 and December 2018. Hodgkin and Non-Hodgkin lymphoma (32%), acute leukemia (28%), and chronic leukemia (10%) were the predominant underlying diseases; comprising 843/8,176 (10%) inpatient stays with allogenic stem cell transplantation. The overall number of neutropenic days and fever days (body temperature ≥ 38 °C) was 56,824 and 25,347, respectively. Blood stream infections (occurrence of fever and positive blood culture) occurred in 1,283/8,176 (16%) inpatient stays, and the overall mortality rate was 9% (n = 716/8,176). By now, 17 peer-reviewed articles analyzing epidemiology, treatment, and outcome of HAIs were published based on data from the CoCoNut.

Conclusion

Data extracted from the CoCoNut underlines the important role of evaluating innovative treatment strategies. Considering the remaining high infection rate for HAIs of neutropenic patients, the growing development of antimicrobial drug resistance, and the existing powerful methods for data processing (e.g., artificial intelligence), we will continue to utilizing and expanding the CoCoNut in the future.

Disclosures

All authors: No reported disclosures.
2475. Incidence of Multidrug-Resistant, Extensively Drug-Resistant and Pandrug-Resistant Gram-Negative Bacteria in Brazilian Intensive Care Units
Authors: Souza Gregory Lauar , Rocha Rhayssa Fernanda de Andrade , Silveira Andressa Do nascimento , Dias Duarte de Carvalho Handerson , Oliveira Cristóvão D M , Leite Edna M M , Silva Estevão Urbano , Giarola Lucca G , Couto Bráulio R G M , Starling Carlos E F
Published: October 2019

Background

The Centers for Disease Control and Prevention (CDC) proposed standard definitions for acquired resistance in bacterias. Resistant bacteria were categorized as multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR). This study describes the incidence of Gram-negative MDR, XDR and PDR in 12 private and adult intensive care units (ICU’s) from Belo Horizonte, Minas Gerais, the sixth most populated city in Brazil, with approximately 3 million inhabitants.

Methods

Data were collected between January/2013 to December/2017 from 12 ICU’s. The hospitals used prospective healthcare-associated infections (HAI) surveillance protocols, in accordance to the CDC. Antimicrobial resistance from six Gram-negatives, causing nosocomial infections, were evaluated: Acinetobacter sp., Klebsiella sp., Proteus sp., Enterobacter sp., Escherichia coli, and Pseudomonas sp.. We computed the three categories of drug-resistance (MDR+XDR+PDR) to define benchmarks for the resistance rate of each Gram-negative evaluated. Benchmarks were defined as the superior limits of 95% confidence interval for the resistance rate.

Results

After a 5 year surveillance, 6,242 HAI strains were tested: no pandrug-resistant bacteria (PDR) was found. Acinetobacter sp. was the most resistant Gram-negative: 206 strains from 1,858 were XDR (11%), and 1,638 were MDR (88%). Pseudomonas sp.: 41/1,159 = 3.53% XDR; 180/1,159 = 15.53% MDR. Klebsiella sp.: 2/1,566 = 0,1% XDR; 813/1,566 = 52% MDR. Proteus sp.: 0/507 = 0% XDR; 163/507 = 32% MDR. Enterobacter sp.: 0/471 = 0% XDR; 148/471 = 31% MDR. Escherichia coli: 0/681 = 0% XDR; 157/681 = 23% MDR. Benchmarks for the global resistance rate of each Gram-negative (MDR+XDR+PDR): Acinetobacter sp. = 92%; Klebsiella sp. = 62%; Proteus sp. = 40%; Enterobacter sp. = 48%; Escherichia coli = 33%; Pseudomonas sp. = 30%.

Conclusion

This study has calculated the incidence of Gram-negative MDR, XDR and PDR, and found a higher incidence of MDR Acinetobacter sp., with an 88% multiresistance rate. Henceforth, developing countries healthcare institutions must be aware of an increased risk of infection by Acinetobacter sp.. Benchmarks have been defined, and can be used as indicators for healthcare assessment.

Disclosures

All authors: No reported disclosures.
2476. External and Internal Validation of the Healthcare-associated Infection Data in the Korean National Healthcare-associated Infectious Surveillance System (KONIS)
Authors: Kwak Yee Gyung , Song Je Eun , Choi Young Hwa , Kim Sung Ran , Han Su Ha , Yoo So-Yeon , Yoo Hyeon Mi , Choi Ji-youn , Shin Myoung Jin , Choi Jun yong , Lee Sang-Oh , Kim Hong Bin , Lee Mi Suk , Kim Tae Hyong , Park Sun Hee , Choe Pyoeng Gyun , Kim Young Keun
Published: October 2019

Background

National surveillance data should be validated to identify data quality issues. This study tested the validity of healthcare-associated infection (HAI) data in the Korean National Healthcare-associated Infections Surveillance System (KONIS), intensive care unit (ICU) module.

Methods

The validation process consisted of external (EV) and internal (IV) validation phases. For the 10 hospitals that were selected based on the HAI rate, among the 193 participating hospitals between July 2016 and June 2017, both EV and IV were performed. For the EV, the validation team reviewed 295 medical records of 60 patients with reported HAIs, including 20 urinary tract infections (UTIs), 27 bloodstream infections (BSIs), and 13 cases of pneumonia (PNEU), and 235 patients with no reported HAI during 1-day visits conducted in November and December 2017. The reviewer’s diagnosis of HAI was regarded as the reference standard. IV was conducted by the staff of each hospital and evaluated whether UTI or BSI were present. Primary IV was performed for 279 patients who were subject to EV. Secondary IV was performed on 203 patients in another 11 selected participating hospitals that did not report HAIs to KONIS during the 1-year study period.

Results

In the EV, the diagnosis of UTI in the participating hospitals had a sensitivity of 72.0% and specificity of 99.3%. The sensitivity of BSI and PNEU was 63.2% and 70.6%, respectively, and specificity was 98.8% and 99.6%. The agreement (kappa) between the EV and primary IV was significant, with κ = 0.754 for UTI and κ = 0.674 for BSI. The results of the secondary IV showed that the hospitals that had no reports of HAI had few hospital beds and performed few blood or urine culture tests. In the secondary IV, eight UTIs and three BSIs were newly diagnosed in three hospitals, respectively. The reasons for not reporting the HAIs were presumed to be a lack of understanding of the surveillance standards and fear of the disadvantages of disclosing the HAI.

Conclusion

This study shows the need for ongoing validation and continuous training of surveillance personnel to maintain the accuracy of surveillance data. We also confirmed that IV can be used as an alternative monitoring method to examine validity and accuracy.

Disclosures

All authors: No reported disclosures.
2477. Antimicrobial Resistance patterns of Enterobacteriaceae and Pseudomonas aeruginosa from Colombian clinical isolates. 2017–2018
Authors: Rojas Monica Maria Rojas , López Catalina , Ruiz Jaime , Pavía Jacquleine , Oñate Jose , Hernández-Gómez Cristhian
Published: October 2019

Background

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide initiative to monitor in vitro susceptibility of clinical Gram-negative isolates to several antimicrobial agents. Surveillance initiatives are essential to provide real-world evidence to support local guidelines development. Colombia has participated since 2012 with isolates from complicated intrabdominal infections (cIAI), complicated urinary tract infections (cUTI) and respiratory tract infections (RTI). This study describes resistant patterns of Escherichia coli (Eco), Klebsiella pneumoniae (Kpn) and Pseudomonas aeruginosa (Pae) clinical isolates collected in Colombian hospitals in a 2 years period (2017–2018).

Methods

Isolates from patients with cIAI, cUTI and RTI were collected. Identification confirmation was done in central laboratory. Minimum inhibitory concentrations (MIC) were performed by broth microdilution and interpreted according to 2018 CLSI guidelines, same criteria for Extended-spectrum β-lactamase (ESBL) classification. The antimicrobial activity was evaluated for aztreonam (ATM), ceftolozane/tazobactam (C/T), ceftazidime (CAZ), colistin (COL), ertapenem (ETP), cefepime (FEP), imipenem (IMP), meropenem (MEM) and piperacillin–tazobactam (TZP).

Results

During 2017–2018, 1492 isolates were collected. The main organism was Eco (51%) followed by Kpn (29%) and Pae (20%). In vitro susceptibility activity is presented in Table 1. COL, C/T, ETP, MEM and IPM exhibited over 95% susceptibility in Eco. ESBL prevalence was 18% for Eco (53/314) and 22% for Kpn (36/165). COL and C/T were the most active agents against Pae isolates. For Kpn, MIC50/90 values were: MEM (0.12 / 8), C/T (0.5 / 8) and for TZP (8 / > 64), meanwhile for Pae were MEM (0.5 / 32), C/T (0.5 / 32) and for TZP (8 / > 64).

Conclusion

Continued antimicrobial resistance surveillance initiatives are critical to guide the empiric treatments decision in a multidrug resistance era. This study shows that Ceftolozane/Tazobactam, MEM and COL have the best susceptibility profile against Eco, Kpn and Pae of cIAI, cUTI and RTI cases in Colombia. The C/T susceptibility rates and low MIC distribution provide evidence to support its use as a non-carbapenem therapeutic alternative for Gram-negative infections.

Disclosures

All authors: No reported disclosures.
2481. Comparing inter-hospital patient movement patterns to better understand mechanisms for regional dissemination of carbapenem-resistant Enterobacteriaceae
Authors: Wolford Hannah , O’Hagan Justin , Paul Prabasaj , Reddy Sujan , Attell Brandon , Jernigan John A , Slayton Rachel
Published: October 2019

Background

Understanding inter-hospital movement of patients provides insight into regional transmission of multidrug-resistant organisms (MDROs) that can guide containment efforts. Movement of general patient populations are often used for this purpose, but movement of the specific patient population of MDRO carriers may be more useful. We sought to compare movement of CRE patients with that of other patient populations to explore whether CRE carriers move differently, and if so, to determine whether administrative data can be used to identify patient populations with transfer patterns that mimic CRE patients.

Methods

We used New York’s Statewide Planning and Research Cooperative System (SPARCS), to create a patient network of all acute care hospital encounters (“overall hospital population”) during 2013–2015. We identified the subset of CRE cases in the network by linking the SPARCS data to CRE cases reported to the National Healthcare Safety Network in 2014, matching on admission date, date of birth, gender, and facility. We described patient characteristics and movement patterns across 3 cohorts: (1) CRE cases, (2) overall hospital population, (3) CRE surrogate (patients clinically similar to CRE cases based on length of stay [LOS] ≥14 days and Clinical Classification Software [CCS] category of sepsis plus at least one of the following additional CCS categories: adult respiratory failure, acute renal failure, procedure complication or device complication). Correlations between cohorts were calculated using patient transfer matrices to determine similarities between the networks.

Results

The average LOS for CRE cases was 25× higher than the overall hospital population (31.4 vs. 1.3 days, Figure 1a), and CRE cases were more likely to die or be discharged to a skilled nursing facility (Figure 1b). CRE movement networks were only moderately correlated with the overall hospital population (R2 = 0.51); there was higher correlation between CRE case and CRE surrogate networks (R2 = 0.73).

Conclusion

CRE patients have different healthcare experiences in the hospital and between hospitals in New York compared with the overall hospital population. The CRE surrogate cohort transfer patterns were more similar, and could be used to understand CRE patient movement in the absence of CRE culture data.

Disclosures

All authors: No reported disclosures.
2486. Clinical Outcomes of Patients Treated with Dolutegravir Functional Monotherapy or Dolutegravir plus an Active Non-cytosine Nucleoside Analog: A Retrospective Observational Cohort Study of Treatment-Experienced Patients
Authors: Rolle Charlotte-Paige M , Bryant Beth , Tucker Colton J , Camila Castro Maria , Nguyen Vu , Hinestrosa Federico , DeJesus Edwin
Published: October 2019

Background

Dual dolutegravir (DTG)-containing regimens (DCRs) are currently approved for the treatment of antiretroviral (ARV) naïve and experienced patients with HIV-1 infection. DTG monotherapy has resulted in unacceptable rates of virologic failure and subsequent development of DTG resistance. Here, we evaluate the “real-world” efficacy and “barrier to resistance” of DCRs containing 0–1 active ARVs.

Methods

This is a retrospective observational study evaluating clinical outcomes of treatment-experienced patients on combination DCRs found to be on DTG functional monotherapy or DTG plus an active non-cytosine analog between 2013 and 2014. The primary endpoint was virologic suppression (HIV-1 RNA< 50 copies/mL) at week 48. Virologic failure (VF) was defined as confirmed HIV-1 RNA≥ 50 copies/mL 12 weeks after initiating DTG or any time after achieving HIV-1 RNA< 50 copies/mL. Adherence, adverse events (AEs) and laboratory parameters were analyzed throughout the study.

Results

Thirty-nine patients were included in the analysis, 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG plus a non-cytosine nucleoside analog. The median age (range) was 53 (40–74) years, median baseline CD4+ count (range) was 564 (92–1217) cells/mm3, 22 (56%) had baseline HIV-1 RNA< 50 copies/mL, and 24 (62%) had previously used INSTIs (Table 1). At Weeks 48 and 96, virologic suppression was observed in 78.3% and 86% of patients respectively (Figures 1 and 2). Among 7 VFs (2 on DTG functional monotherapy, 5 on DTG plus a non-cytosine nucleoside analog), there was no evidence of treatment-emergent resistance to DTG. There was a significant median increase in CD4+ count from baseline to Week 48 (+90 cells/mm3, 95% confidence interval: [14.18, 165.9]). No significant changes in lipid parameters were observed. Treatment-related AEs occurred in 17/39 (44%) patients (all Grade 1–2) and 1 patient discontinued DCR treatment due to rash.

Conclusion

In this “real-world” cohort of treatment-experienced patients, we observed that DTG functional monotherapy and DTG plus a non-cytosine nucleoside analog maintained long-term virologic control and was well tolerated. These data supports use of DTG as a partner for dual DCRs given its high efficacy in patients with underlying ARV resistance.

Disclosures

All authors: No reported disclosures.
2499. Perceptions of and Preferences for Oral or Long-Acting Injectable Antiretroviral Treatment Regimens in the United States and Canada
Authors: Garris Cindy , Heidenreich Sebastian , Arthurs Erin , Spinelli Frank , Cutts Katelyn , Lowman Erik , Rice Howard L , Lebouche Bertrand , Collacott Hannah , Nie Chua Gin , Gelhorn Heather
Published: October 2019

Background

Antiretroviral treatment (ART) for patients living with HIV (PLHIV) has improved greatly, however, challenges with daily oral dosing remain. New ART options with reduced dosing frequency and innovative delivery methods may help address these challenges. This study assesses patient and physician satisfaction with current treatments and preferences for switching to a monthly or every other month long-acting injectable (LAI) ART.

Methods

This is a cross-sectional online survey of PLHIV and physicians treating PLHIV in United States and Canada. A literature review, clinical expert input, and qualitative and quantitative pilots informed survey design. Eligible PLHIV were on ART for ≥ 6 months and virally suppressed (self-reported). Survey questions for patients evaluate satisfaction and adherence to current ART. Treatment preferences are assessed using a discrete choice experiment (DCE), where respondents choose between staying on current ART, switching to another oral ART or switching to a LAI ART. DCE treatment attributes include dosing frequency, side effects, forgivability, food/mealtime restrictions, and mode of administration. Pilot data for US patients is included here; the main survey will include approximately 550 patients and 450 physicians.

Results

Of 51 PLHIV completing the pilot survey, 80% were male, mean age was 54 years, and 63% were on ART for ≥10 years. Switching ART was common, with 55% reporting changing their ART ≥ 3 times. Just under half of patients (47%) were not totally satisfied with their current ART. Most common reasons for dissatisfaction included daily reminder of having HIV (31%) and having to take medicine every day (28%). Just over a quarter of patients (28%) reported forgetting to take their ART in the prior month. Across all DCE choices, patients preferred to remain on their current treatment 47% of the time, while 45% of the time patients preferred switching to the LAI, and for the remaining 8%, patients chose switching to another oral ART regimen.

Conclusion

Despite advances in ART, treatment challenges remain. Among the treatment-experienced PLHIV in this pilot survey, over half of their choices resulted in switching to an alternative regimen, and when opting to switch, most patients preferred the long-acting injectable treatment regimen.

Disclosures

All authors: No reported disclosures.
2500. Fostemsavir Drug–Drug Interaction Profile, an Attachment Inhibitor and Oral Prodrug of Temsavir, for Heavily Treatment Experienced HIV-1-Infected Patients
Authors: Moore Katy P , Mageau A Savannah , Magee Mindy , Gorycki Peter D , Ackerman Peter , Llamoso Cyril
Published: October 2019

Background

Fostemsavir (FTR) is a first-in-class attachment inhibitor being evaluated in heavily treatment-experienced (HTE) HIV-1-infected patients. Active temsavir (TMR) binds to viral envelope glycoprotein 120 and prevents viral attachment and entry into host CD4+ T cells. TMR is primarily metabolized by esterase-mediated hydrolysis with contributions from cytochrome P450 (CYP) 3A4. TMR does not inhibit/induce major CYP or uridine diphosphate glucuronosyltransferase (UGT) enzymes and is a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate. TMR and/or its metabolites inhibit BCRP and organic anion transporter protein 1B1/3 (OATP1B1/3). FTR DDI profile informs coadministration with antiretrovirals (ARV) and other therapeutic classes.

Methods

DDI data from 13 studies were compiled to inform the impact of 17 drugs or drug combinations on TMR and the impact of TMR on 15 drugs such as ARVs, rifamycins, opioid substitutes, statins, oral contraceptives (OC), and H2-antagonsits.

Results

FTR with CYP3A4, P-gp, and/or BCRP inhibitors increase TMR concentrations; but, do not pose clinical concern at therapeutic dose. TMR may be administered with weak/moderate inducers with or without coadministration of CYP3A4, P-gp, and/or BCRP inhibitors such as RTV or COBI. Coadministration with strong inducers is contraindicated. FTR may be coadministered with RBT with or without a PK enhancer. However, co-administration of FTR with RIF is contraindicated. FTR can be given with drugs that increase gastric pH; famotidine did not impact TMR PK. TMR may increase concentrations of drugs that are substrates of OATP1B1/3 and BCRP; therefore, most statins require dose reduction (e.g., rosuvastatin dose is limited to ≤10 mg QD). TMR increased EE exposure 40% with no impact on NE; therefore, FTR may be coadministered with OCs containing ≤30 µg EE. TMR had no clinically meaningful impact on TDF, DRV/RTV, ATV/RTV, ATV, RTV, ETR, MET, or BUP/norBUP PK (Table 1).

Conclusion

FTR can be coadministered with ARVs and most common treatments used to manage HIV co-infections or comorbidities without dose adjustment of either drug except for select HMG-CoA reductase inhibitors and EE-containing OCs. Strong CYP3A inducers are contraindicated.

Disclosures

All authors: No reported disclosures.
2504. Laboratory Evaluation of HIV-1 Viral Load Pooling with Marker-Assisted Deconvolution
Authors: Holland Sabina , DeLong Allison , Liu Tao , Makaretz Anna , Coetzer Mia , Ledingham Lauren , Xu Yizhen , Sam Soya , Sagoe Kwamena , Caliendo Angela , Daniels Michael , Hogan Joseph , Kantor Rami
Published: October 2019

Background

Cost still limits HIV-1 viral load (VL) routine monitoring in resource limited settings (RLS), preventing early detection of virologic failure (VF). Pooled VL testing reduces cost over individual testing (IND). We previously showed in simulation, that additional cost benefits over previously-used pooling deconvolution algorithms can be achieved by using low-cost, routinely-collected clinical markers to determine the order for VL testing in deconvolution (termed marker-assisted minipool plus algorithm; mMPA). This algorithm has not been assessed in-vitro.

Methods

150 samples from 99 Ghanaian adults with HIV on first-line therapy (VF 17%; CD4-VL correlation −0.35) were used to construct 30, 5-sample pools: n = 10 with 0, n = 5 with 1, and n = 15 with 2 individuals with VF. VL testing was with Abbott M2000. Accuracy, number of tests and rounds of testing to deconvolute pools were estimated using four strategies: (1) IND; (2) Minipooling (MP); (3) Minipooling with algorithm (MPA); and (4) mMPA.

Results

Compared with IND, MP and MPA, mMPA reduced total number of tests per pool needed to ascertain VF: MP average 4.3 (95% confidence interval (CI) 3.5–5.2, p> 0.05), MPA 3.0 (95% CI 2.4–3.5, P < 0.001), and mMPA 2.5 (CI 2.0–3.0, P < 0.001). Compared with MP and MPA, mMPA further reduced VL tests by 42% (1.9 tests/pool, CI 1.3–2.4, P < 0.001) and 17% (0.5, CI 0.2–0.8, p = 0.004); and required fewer testing rounds than MPA by 17% (P < 0.01), thus producing results quicker. IND and MP had 100% sensitivity and specificity. MPA and mMPA had similar sensitivity of 96.1% (MPA CI 90.7–100%; mMPA CI 88.0–100.0%) and specificity of 99.5% and 99.2% (98.5–100.0% for MPA and 97.5–100.0% for mMPA). Specifically, 3/150 samples were misclassified with MPA and mMPA: one suppression as VF, and two VF as suppressed.

Conclusion

Laboratory evaluation confirms that deconvolution using mMPA with CD4 or other routinely-collected clinical information as low-cost biomarkers reduces the number of VL assays required to identify VF in a setting with a low prevalence of VF. Implementation of pooled VL testing using mMPA for deconvolution may increase the availability of VL monitoring in RLS. Work is ongoing to reduce complexity and misclassification, required prior to widespread implementation.

Disclosures

All authors: No reported disclosures.
144. Organism Identification and Antibiotic Susceptibilities with Verigene Blood Culture Assay: a Retrospective Single-Center Study
Authors: Tchen Stephanie , Smoke Steven , DeVivo Maria
Published: October 2019

Background

The Verigene blood culture assay is a rapid molecular testing platform for positive blood cultures. Verigene detects a limited number of bacteria and a limited number of antibiotic resistance determinants. While certain Verigene results have clear implications for optimal antibiotic therapy prior to complete antibiotic susceptibility testing, others do not. The purpose of this study was to compare the results of the Verigene blood culture assay with standard organism identification and antibiotic susceptibility testing.

Methods

This was a retrospective cohort study conducted at a single academic medical center. The study period was 14 months from November 2017 to December 2018. All Verigene results from the study period were reviewed and compared with the results of standard organism identification and susceptibility testing. Organism identification and antibiotic susceptibility testing were performed by Vitek MS and Vitek 2. Duplicate results from the same patient were excluded. The primary outcome was the percentage of blood cultures correctly identified by Verigene. Secondary outcomes included the antibiotic susceptibility of organisms identified by Verigene in the presence and absence of resistance determinants and the identity and frequency of organisms not detected by Verigene.

Results

A total of 782 Verigene results were screened. After exclusions, 675 Verigene results including 737 organisms from 597 patients were included. Of 737 organisms, Verigene correctly identified 611 (82.9%), incorrectly identified 19 (2.6%) and was unable to identify 107 (14.5%) off-panel organisms. Tables 1 and 2 outline the antibiotic susceptibility of organisms by the presence or absence of resistance determinants in Gram-negative and Gram-positive bacteria, respectively. Table 3 describes the identities of the organisms not detected by Verigene, stratified by Gram stain result.

Conclusion

The Verigene blood culture assay demonstrated accuracy in identifying organisms and predicting antibiotic susceptibility. These results will help inform the prospective interpretation of Verigene results and subsequent antibiotic selection at the study institution.

Disclosures

All authors: No reported disclosures.
2518. Development And Characterization Of Human Microglial Models To Elucidate HIV Transmission Events And Pathogenesis
Authors: Rai Mohammad Ali , Hammonds Jason E , Spearman Paul , Spearman Paul
Published: October 2019

Background

HIV-associated neurocognitive disorders cause significant morbidity and mortality despite the advent of antiretroviral therapy. An understanding of fundamental mechanisms underlying HIV infection and transmission events in the central nervous system (CNS) is needed. Microglia are resident myeloid cells that are readily infected by HIV and may constitute a CNS reservoir. We evaluated and compared existing microglial cell lines and primary cell-derived microglia as potential model systems for studying HIV-microglia interactions.

Methods

We cultured two immortalized human microglial lines (HMC3, C20) and developed two primary microglial models: induced microglia (iMG) derived from primary human monocytes; and microglial-like cells (iMGL) differentiated from induced pluripotent stem cells (iPSCs). We compared these four microglial cell types to commercially available fetal microglia (PM) for a microglial comparator, and monocyte-derived macrophages as a non-microglial comparator cell. Each cell type was evaluated for the presence of typical myeloid and microglia-specific markers by flow cytometry and immunofluorescence microscopy. HIV infection was performed using macrophage-tropic HIV or VSV-G-pseudotyped HIV.

Results

After differentiation, the iMG and iMGL displayed characteristic microglial morphology: a spindle shape and a reduction in the central body, along with ramified cell processes. Flow cytometry revealed significant differences in surface markers among the cell types. iMG and iMGL displayed CD11b, CD45, CXCR4, CCR5 and lack of expression of CD4 and CX3CR1. In contrast, HMC3, C20, and PM were negative for CD11b, CD45, CX3CR1, CD4, CXCR4. Immunostaining showed that iMG and iMGL were positive for microglial markers TMEM119 and P2RY12. RNA Seq analysis is currently underway to determine gene expression differences between the microglial cell lines and our microglia models. In preliminary results, iMG and iMGL were both readily infected with HIV, and comparison with other lines is ongoing.

Conclusion

There is no standard model available for defining the molecular and cellular events involved in HIV infection of microglia. Significant differences in microgial markers and in HIV receptor and coreceptor levels were noted in this study. iMG and iMGL appear to be viable microglial models susceptible to HIV infection.

Disclosures

All authors: No reported disclosures.
2526. Side Effects of Antiretroviral Therapy in Children with HIV in a Referral Center in Mexico
Authors: Diaz Luis Xochihua , Ortega Javier Ordoñez , Lopez Karen Alejandra Linares , Garcia Itzel Villanueva , Gutierrez Jose Luis Copado
Published: October 2019

Background

Human Inmunodeficiency Virus infection (HIV) is still a challenge in many parts of the world, mainly in children. In Mexico the infection has been decreasing, however we still have cases, in 2018 we had 40 perinatal new cases reported. The antiretroviral therapy has shown to be effective to control the disease but it is not free of adverse effects, the children with vertical transmission are exposed to many years of the antiretroviral therapy.

Methods

Retrospective, observational descriptive study at Instituto Nacional de Pediatría during 2004–2019. We included every children under 18 years old who received treatment for HIV and had a complete medical record.

Results

We found 61 patients under 18 years that fulfill the data for the analysis. 37 (60%) were male, the mean age at diagnosis of HIV infection was 47 months, the antiretroviral therapy that received 57 patients (93.4%) of the study was zidovudine, lamivudine and lopinavir/ritonavir, only 4 received another therapy: 3 of them received abacavir, lamivudine, and lopinavir/ritonavir and the missing one received abacavir, lamivudine and raltegravir. 43% of the children of our study showed adverse effects after the antiretroviral therapy, the mean time of adverse effects presentation was 37 months after the beginning of the treatment. The most common effect was hypertriglyceridemia with 13 cases, in second place we found hypercholesterolemia in 7 cases, and both in 5 cases, other frequent effects were hepatotoxicity in 5 cases, diarrhea in 4 cases, anemia in 3 cases, vomit in 3 cases, abdominal pain and night terrors in 2 cases each one. It was necessary the change of the therapy because of adverse effects in 6 cases (9.8%).

Conclusion

Antiretroviral therapy is effective although it has many side effects. We observe that adverse effects are frequent, almost the half, in pediatric population, it depends on the antiretroviral selection, for children we had only a few options because of the little doses they need or the inability to swallow tablets. It′s important to monitor and control all the adverse effects because they increase morbidity and mortality, especially dyslipidemia, that has been associated with cardiovascular risk and it was the most common effect found in our study.

Disclosures

All authors: No reported disclosures.
2529. Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations with 24-Month Growth and Neurodevelopment
Authors: Moraka Natasha Onalenna , Moyo Sikhulile , Ibrahim Maryanne , Mayondi Gloria , Leidner Jean , Powis Kathleen , Cassidy Adam R , Kammerer Betsy , Smith Christiana , Weinberg Adriana , Musonda Rosemary , Shapiro Roger , Gaseitsiwe Simani , Lockman Shahin
Published: October 2019

Background

HIV-exposed but uninfected (HEU) children are at increased risk for poorer growth outcomes compared with HIV-unexposed/uninfected (HUU) children. Mechanisms underlying the poorer growth and delays in development of HEU children compared HUU children are not fully understood. We sought to define the relationship between child CMV status and HIV− exposure status and determine if a correlation existed between CMV status and growth (and neurodevelopmental) outcomes by 24 months of age in Botswana.

Methods

We used existing data and samples from the observational Botswana Tshipidi study, pregnant women living with HIV (WLHIV) and those without HIV, as well as their infants were enrolled and followed prospectively through 2 years postpartum. We tested 18-month child plasma samples from all available children for anti-HCMV IgG. We evaluated the association between positive (vs. negative) child CMV status at 18 months, and child growth, using the World Health Organization’s Growth Standard adjusted for age and sex and neurodevelopment at 24 months of age, using the Bayley Scales of Child Development (BSID) III.

Results

Of 317 children tested for CMV IgG at 18 months, 215 (67.8%) tested positive. Significantly higher proportions of HUU children had positive CMV serology (82.6%) compared with HEU children (47.4%, P < 0.01); 96.7% of HUU vs. 10.5% of HEU children breastfed. Child CMV infection was not associated with head circumference, weight-for-age, weight-for-height, nor height-for-age z-scores at 24 months. BSID III scores in receptive and expressive language, fine and gross motor, and cognitive domains at 24 months of age also did not differ by child CMV status.

Conclusion

We observed high rates of CMV seropositivity in 18-month-old children in Botswana with significantly higher CMV seropositivity among HUU children likely owing to breastfeeding. Positive CMV serostatus was not associated with child growth or neurodevelopmental outcomes at 24 months.

Disclosures

All authors: No reported disclosures.
2532. Identifying Educational Needs and Improving Provider Knowledge Regarding the Management of Febrile Neutropenia
Authors: Chang Amy , Deresinski Stan , Subramanian Aruna , Medeiros Bruno , PharmD Emily Mui, , Meng Lina , Liedtke Michaela , Holubar Marisa
Published: October 2019

Background

In a retrospective chart review of 211 first episodes of febrile neutropenia (FN) in in-patients with acute myelogenous leukemia evaluating rates of appropriate vs. inappropriate management, we identified frequent noncompliance with national guidelines for the management of FN. We utilized these data to develop an educational intervention targeting front-line providers.

Methods

Based on findings from our chart review, we developed and implemented an interactive, case-based didactic session for advanced practice providers (APPs) and medical students/residents rotating on hematology, targeting inappropriate antibiotic use. Pretest questions were embedded into the lecture, preceding content related to each learning objective. Lecture material included content from national guidelines, literature addressing misconceptions (e.g., vancomycin usage for persistent fever), and data from our institutional antibiogram (Figure 1). A post-test was given directly after the lecture to evaluate knowledge gained.

Results

Five inappropriate behaviors were identified (Figure 2): (1) changing empiric therapy despite clinical stability, (2) misunderstanding piperacillin/tazobactam’s spectrum of activity, (3) inappropriate initiation of antibiotics active against resistant Gram-positive organisms; (4) failure to de-escalate therapy at 72 hours and (5) failure to add Gram-positive coverage when using aztreonam. Lectures were provided to 13 APPs and 17 medical students/residents over 6 sessions. An improvement in knowledge was noted for most learning objectives except for the third, for which misconceptions remained, especially regarding need for vancomycin in the setting of mucositis (Figures 3 and 4). Higher baseline knowledge was noted for medical students/residents than APPs. 93% of learners rated the lecture very/extremely helpful. Learners recommended future content focus on antifungal therapy.

Conclusion

We utilized local practice data to develop educational content for front-line providers. We will convert this lecture into a video-format to be incorporated into hematology rotations to reinforce key concepts. A prospective cohort study to evaluate the impact on prescribing behavior is underway.

Disclosures

All authors: No reported disclosures.