bluuebunny/crossref_metadata_2025 huggingface dataset:
1771. Gut Resistome Changes in Response to Prophylactic Antibiotic Administration During Chemotherapy in Children With Acute Lymphoblastic Leukemia
Authors: Margolis Ellie , Hakim Hana , Yao Jiangwei , Rosch Jason , Tang Li , Sun Yilun , Dallas Ronald , Wolf Joshua
Published: November 2018

Background

Antibiotic resistance harbored in gut microbiome contributes to the emergence of multi–drug-resistant organisms (MDRO). Pediatric leukemia patients typically receive extensive antibiotics and are at higher risk for infection due to MDRO.

Methods

A prospective cohort of children (n = 242) with acute lymphoblastic leukemia self-collected stool samples at diagnosis and after induction chemothearpy. A third of patients (n = 69) underwent protocol-driven antibiotic prophylaxis: Levofloxacin (LV) given once neutropenia develops. With neutropenic fever patients on prophylaxis stopped LV and all patients received cefepime. Using metagenomic sequencing, we identified bacterial community composition and after alignment to the Comprehensive Antibiotic Resistance Database were able to determine the presence of bacterial resistance genes in 168 stool samples from 49 patients.

Results

Expected changes in the community composition were discovered with LV prophylaxis, including the loss of many Enterobacteriaceae and Enterococcaceae species, offset by increases in Bacteroides species. Unexpectedly, LV prophylaxis reduced the acquisition of VanA cluster of vancomycin resistance genes and did not increase acquisition of β-lactamase or fluoroquinolone (FQ) resistance gene families.

Conclusion

LV prophylaxis during leukemia treatment imparts predictable changes in gut bacterial communities but counter intuitively decreases antibiotic resistance in the gut microbiome reservoir. The reduction in VanA cluster of genes is likely due to depletion of Enterococcaceae species via direct killing or loss of synergistic partners. The lack of increase in target (FQ) or off-target resistance suggests that prophylaxis altered community selective pressures or prophylaxis drug concentrations were sufficient to limit the outgrowth of resistant mutants.

Disclosures

J. Wolf, Karius Inc.: Investigator, Research support.
1775. Microbiome-Based Classifiers Accurately Differentiate Infectious Diarrhea From Functional Gastrointestinal Disorders and Provide Population-Scale Confidence Measures of Fecal Microbiota Restoration in Recurrent C. DifficileInfection
Authors: Wu Qinglong , Ross Cana , Jones Courtney , Blount Ken , Savidge Tor
Published: November 2018

Background

Fecal microbiota therapy is being actively pursued as treatment for recurrent C. difficile infection (rCDI), as well as for other GI disease indications associated with dysbiosis, for example, irritable bowel syndrome (IBS). RBX2660 is a microbiota-based drug designed to restore a healthier microbiome and has demonstrated clinical efficacy for preventing rCDI. Despite this and other treatment successes, our understanding of functional microbiota reconstitution at the population scale is still evolving, as is the ability to distinguish IBS from CDI recurrence. Herein we describe development of a Random Forest classifier for CDI diagnosis, and we evaluate microbiome restoration in participants of the Phase 2 trial of RBX2660.

Methods

Fecal 16S rDNA sequences from 2,129 subjects enrolled in diverse multi-center cohorts were analyzed (1,235 adults and 447 children with CDI, AAD, IBS, or controls). Technical variations due to different DNA extraction, primer region coverage, and sequencing platforms were addressed using closed-reference OTU picking with UCLUST. The RDP classifier and SILVA database assigned taxonomy for each OTU sequence. Stratified random sampling with 50 repeated tests of microbiota training sets was performed for supervised learning. Microbiota signatures of patients in the RBX2660 PUNCH CD2 trial were then assessed using classifiers built to predict CDI treatment outcomes and IBS misdiagnosis.

Results

Random Forest built the best classifiers accurately predicting 97.7% of CDI cases, and confidently distinguished CDI from IBS patients based on their microbiome signatures (figure). RBX2660 treatment significantly restored microbiota community composition in rCDI cases compared with placebo controls.

Conclusion

Random Forest classifiers built on a population-scale study of microbiota composition in patients with GI disease provide a highly accurate predictor of CDI cases versus potential IBS misdiagnosis in adults and children. RBX2660 significantly reduced disease classification scores in rCDI patients with a healthy-like microbiota reconstitution markedly accelerating after 30 days of treatment.

This study was funded by 1UO1 AI24290-01 and Rebiotix, Inc.

Disclosures

C. Jones, Rebiotix, Inc.: Employee, Salary. K. Blount, Rebiotix, Inc.: Employee, Salary. T. Savidge, Rebiotix: Grant Investigator, Research grant.
2553. Individual Patient-Level Data Meta-Analysis of Live Attenuated and Inactivated Influenza Vaccine Effectiveness Among US Children, 2013–2014 Through 2015–2016
Authors: Chung Jessie , Flannery Brendan , Begue Rodolfo , Caspard Herve , Demarcus Laurie , Fowlkes Ashley , Kersellius Geeta , Steffens Andrea , Fry Alicia M
Published: November 2018

Background

Quadrivalent live attenuated influenza vaccine (LAIV4) was not recommended for use in the United States for the 2016–2017 and 2017–2018 influenza seasons based on US observational studies of vaccine effectiveness (VE) from 2013–2014 to 2015–2016. We pooled individual patient data on children aged 2–17 years enrolled in 5 US studies during these 3 influenza seasons to further investigate VE by vaccine type.

Methods

Analyses included 17,173 children enrolled in the US Department of Defense Global Laboratory-based Influenza Surveillance Program, US Influenza Vaccine Effectiveness Network, Influenza Incidence Surveillance Project, Influenza Clinical Investigation for Children, and a Louisiana State University study. Participants’ specimens were tested for influenza by reverse transcription-polymerase chain reaction (RT-PCR), culture, or a combination of rapid antigen testing and RT-PCR. VE was calculated by comparing odds of vaccination with either inactivated influenza vaccine (IIV) or LAIV4 among influenza-positive cases to test-negative controls and calculated as 100 × (1 − odds ratio) in logistic regression models with age, calendar time, influenza season, and study site (random effect). Patients were stratified by prior season vaccination status in a subanalysis.

Results

Overall, 38% of patients (N = 6,558) were vaccinated in the current season, of whom 30% (N = 1,979) received LAIV4. Pooled VE of IIV against any influenza virus was 51% (95% CI: 47, 54) versus 26% (95% CI: 15, 36) for LAIV4. Point estimates for pooled VE against any influenza by age group ranged from 45% to 58% for IIV and 19% to 34% for LAIV4 during the 3 seasons (Figures 1 and 2). Pooled VE against influenza A(H1N1)pdm09 was 67% (95% CI: 62, 72) for IIV versus 20% (95% CI: −6, 39) for LAIV4. Pooled VE against influenza A(H3N2) was 29% (95% CI: 14, 42) for IIV versus 7% (95% CI: −11, 23) for LAIV4, and VE against influenza B was 52% (95% CI: 42, 60) for IIV and 66% (95% CI: 47, 77) for LAIV4. VE against influenza A(H1N1)pdm09 was lower for LAIV4 versus IIV across all strata of prior season vaccination (Figure 3).

Conclusion

Consistent with individual studies, our pooled analyses found that LAIV4 effectiveness was reduced for all age groups against influenza A(H1N1)pdm09 compared with IIV. This result did not vary based on prior vaccination status.

Disclosures

H. Caspard, AstraZeneca: Employee, Salary.
2555. Predicting Risk of Breakthrough Invasive Pneumococcal Disease in Children After 13-Valent Pneumococcal Conjugate Vaccination
Authors: Yildirim Melike , Pelton Stephen I , Keskinocak Pinar , Yildirim Inci
Published: November 2018

Background

Thirteen-valent-pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the childhood immunization schedule in Massachusetts beginning in April 2010. We evaluated the predictors of vaccine-type (VT) invasive pneumococcal infection (IPD) occurrence despite vaccination.

Methods

Cases of IPD in children <18 years of age were detected through an enhanced surveillance system in MA since 2001. All cases and Streptococcus pneumoniae (SP) isolates are submitted to Department of Public Health (MDPH) and parents/physicians are interviewed for confirmation of demographic and clinical data. All available isolates are serotyped by Quellung reaction. Children who received any dose of PCV7 were excluded from this study. We used 4-layer, feed-forward, neural network with backpropagation learning algorithm, random forest algorithm with 150 classification trees, and extreme gradient boosting (XGBoost) algorithm based on boosted trees with over than 200 iterations to make prediction about risk of nonvaccine serotype (NVST) causing IPD.

Results

Overall, 144 IPD cases have been identified between April 1, 2010, and March 31, 2017, and 27 (19%) were VT IPD. Compared with children with complete PCV13 vaccination, IPD among those with incomplete immunization was more likely to be due to VT (9%, 95% CI 4–18% vs. 19%, 95% CI 10–31%, respectively). Despite complete immunization, 80 of 144 (55.6%) of all IPD in >60 months was breakthrough IPD (Figure 1). Among children with ≥1 comorbid condition and incomplete PCV13, 4 of 18 (22%) IPD were due to VT. Children with incomplete vaccination and pneumonia were most likely (11/17, 65%) to have VT; however, bacteremia without focus cases with incomplete vaccination were most likely (44/45, 3%) to have NVST (Figure 2). Our algorithm performs with 85% accuracy and 92% precision scores.

Conclusion

IPD due to VT after PCV13 vaccination mostly occurs in older children with incomplete PCV13 immunization, among those with underlying comorbidity, and among those who present with pneumococcal pneumonia. Evaluating the immune response following PCV13 vaccination in children with comorbidity could increase our understanding of breakthrough pneumococcal infections despite vaccination with PCV13.

Disclosures

All authors: No reported disclosures.
2558. Predicting β-Lactam Resistance Using Whole Genome Sequencing (WGS) in Klebsiella pneumoniae: The Challenge of β-Lactam Inhibitors
Authors: Hujer Andrea , Long Wesley , Olsen Randall , Kreiswirth Barry N , Evans Scott R , Musser James , Bonomo Robert
Published: November 2018

Background

Antimicrobial susceptibility testing (AST) is the major driver in designing effective therapy. As multiple resistance determinants can demonstrate the same phenotype (e.g., inhibitor resistant [IR], extended spectrum [ES], and carbapenem hydrolyzing [CH] β-lactamases), critical information provided from AST for therapy, stewardship, and infection control is currently lacking. WGS provides more comprehensive genetic data, explaining phenotype, and provides insight into clonality. Efforts are in development that apply novel statistical methods (e.g., PRIMERS I-IV) and machine learning (Sci Reports, 2108, 8, 421) to interpret results accurately and anticipate AST. Using a collection of clinical strains that spanned a 3.5-year period, we tested how well the detection of problematic IR, ES, and CH bla resistance genes predicted phenotype.

Methods

Fourty-one isolates were chosen for AST from a collection of 1,777 WGS K. pneumoniae. Isolates chosen possessed the following β-lactamases: (9 isolates) NDM; (3) NDM and OXA-48; (5) KPC-8 or KPC-14; (24) with a very complex β-lactamase background (all possessed an inhibitor resistant TEM (IRT), SHV ESBL, +/− CTX-M, and/or +/− KPC). AST was performed using CLSI methods for piperacillin/tazobactam (PIP/TAZO), ceftazidime (CAZ), aztreonam (ATM), ceftazidime/avibactam (CAZ/AVI), CAZ/AVI/ATM, and ceftolozane/tazobactam (TOL/TAZO) by disk diffusion assay.

Results

Presented below.

Conclusion

In all cases, blaNDM-1 and blaNDM-1/OXA-48 containing isolates were resistant to CAZ/AVI; the addition of ATM fully restored susceptibility to CAZ/AVI. Surprisingly, clinical K. pneumoniae isolates bearing KPC-8 (V240G) and KPC-14 did not test fully resistant to CAZ/AVI, suggesting a more complex mechanism than the D179Y variant of KPC-3. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. Interestingly, TOL/TAZO maintained efficacy in these same complex backgrounds in the absence of NDM, KPC, and SHV-12. As previously shown in PRIMERS I-II, PIP/TAZO resistance was not observed in the majority of isolates as was predicted by the genotype. WGS in K. pneumoniae to predict AST results and potentially guide clinical decisions is improved for novel combinations like CAZ/AVI.

Disclosures

All authors: No reported disclosures.
2561. Using Whole Genome Sequencing to Assess the Emergence of Antibiotic Resistance During Treatment of Enterococcus faecium and Enterococcus faecalis Bacteremia at Mount Sinai Hospital
Authors: Chacko Kieran , Beckford Colleen , Molina Carlotta Calvi , Van Bakel Harm
Published: November 2018

Background

Multidrug-resistant Enterococci are a major cause of nosocomial infections, yet our understanding of how resistance emerges during antibiotic treatment remains incomplete. We performed whole- and complete-genome sequencing of all paired isolates from 11 Enterococcus faecium and 10 Enterococcus faecalis cases that acquired resistance during hospitalization at Mount Sinai Hospital. Comparative and phylogenetic genomic analyses identified novel mechanisms of resistance and heteroresistance.

Methods

2.5 years of electronic health records were analyzed to identify cases of bacteremia that acquired resistance to at least 1 of the 8 antibiotics. Core genome phylogenetic analyses of paired susceptible and resistant isolates was performed to confirm persistent single clone infections. Long read sequencing data, with Illumina error correction, were used to assemble and align complete genomes. Population analysis profile (PAP) assays were performed to assess the prevalence of heteroresistance.

Results

Among the 102 persistent enterococcal bacteremia cases, 57 isolates from 21 cases (20.6%) cases experienced a gain in resistance. Phylogenetic analyses confirmed that 80% of cases had single clone blood infections, with maximum of 138 days separating paired isolates. Known genetic determinants were responsible for emerging linezolid (LIN), vancomycin (VAN), and gentamicin synergy resistance in almost all cases. In 2 instances, emerging daptomycin (DAP) resistance was not accounted for by known resistance determinants. Notably, PAP assays revealed that LIN-, VAN-, and DAP-resistant subclones were present in only a subset of bacteria in clinical isolates. Longitudinal pairwise analyses of complete genomes revealed novel candidate SNPs for DAP resistance, both located in genes involving cell wall metabolism and maintenance, as well as multiplasmid recombination events that led to VAN heteroresistance.

Conclusion

Our study demonstrates the high prevalence of emerging antibiotic resistance during treatment. We find previously unreported single and structural genomic events that contribute rapid adaptation to antibiotic treatment.

Disclosures

All authors: No reported disclosures.
2570. HCV Screening Practices Among Adolescents and Young Adults in a National Sample of Federally Qualified Health Centers in the United States
Authors: Epstein Rachel L , Wang Jianing , Mayer Kenneth , Puro Jon , Horsburgh C Robert , Linas Benjamin P , Assoumou Sabrina A
Published: November 2018

Background

The opioid crisis has been associated with an increase in hepatitis C virus (HCV) infections among 15–30 year olds. Federally Qualified Health Centers (FQHCs) provide comprehensive healthcare to diverse and underserved communities. However, little is known about HCV screening practices among adolescents and young adults seen at FQHCs across the United States.

Objective. To characterize the continuum of HCV testing and care among adolescents and emerging adults in a large national sample of US FQHCs.

Methods

We used the OCHIN electronic medical record to create a retrospective cohort of 13 to 21 year olds who had a least 1 outpatient visit at any of 98 participating US FQHCs across 19 states from 2012 to 2017. Primary outcome was HCV testing during this timeframe. We also identified predictors of HCV screening using multivariable logistic regression adjusting for age, sex, race/ethnicity, and substance use.

Results

Among 269,287 youth who met inclusion criteria, 54.7% were female, 37.6% White, 33.5% Hispanic, 17.6% Black, and 11.3% other. Mean [SD] age at first HCV screening was 18.5 [2.2] years. Over the study period, 2.5% (6849/269,287) were tested for HCV and 153 (2.2%) had reactive HCV testing. Of those, 117 (76.5%) had confirmatory RNA testing and 65 (55.6%) had detectable RNA. Thirty-five percent (325/933) with ICD-9 codes for opioid-use disorder (OUD) and 8.9% (2080/23,345) with any ICD-9 code for drug use were tested for HCV. Only 10.6% (728/6,849) of individuals tested for HCV had also been tested for human immunodeficiency virus (HIV). Older age (19–21 vs. 13–15 years old at study end, aOR 5.64, 95% CI 5.13–6.19), Black race (aOR 1.88, 95% CI 1.76–2.00), and ICD-9 codes for substance-use disorder, in particular amphetamine (aOR 5.82, 5.10–6.64), opioids (aOR 3.50, 2.92–4.19), cocaine (aOR 2.90, 2.43–3.47), or cannabis (aOR 2.46, 2.31–2.62) were independently associated with HCV testing in multivariable analysis.

Conclusion

During the current opioid crisis, only a third of adolescents/young adults diagnosed with OUD in a large national sample of FQHCs were tested for HCV. In addition, only 10% of those tested for HCV were also screened for HIV. Initiatives are needed to increase HCV and HIV screening among at-risk youth at FQHCs.

Disclosures

All authors: No reported disclosures.
1169. Surveillance of Antibiotic-Resistant Bacteria Reported Among Healthcare-Associated Infections, California, 2011–2017
Authors: Rizzo Kyle , Horwich-Scholefield Sam , Epson Erin
Published: November 2018

Background

Antibiotic-resistant healthcare-associated infections (HAI) threaten patient safety and public health. HAI reported by California hospitals to the National Healthcare Safety Network include pathogen and antibiotic susceptibility information. We analyzed HAI data to measure regional changes in antibiotic resistance (AR) over time among select bacteria.

Methods

We analyzed central line-associated bloodstream infection (CLABSI) data using log binomial regression models to estimate annual change in the proportion of pathogens resistant to carbapenems, extended-spectrum cephalosporins, methicillin/oxacillin, and multidrug (MDR) combinations for the reporting years 2011–2017. We aggregated HAI CLABSI, catheter-associated urinary tract infection (CAUTI), and surgical site infection (SSI) data in 2-year increments (i.e., 2014–2015, 2016–2017) to assess changes in percent resistance by county when data for 30 or more pathogens were available.

Results

Among CLABSI reported from 2011 to 2017, there were no significant changes in the proportion of carbapenem-resistant Enterobacteriaceae (CRE) (Figure 1; risk ratio [RR]: 0.97, 95% CI: 0.92, 1.03; P = 0.32), methicillin/oxacillin-resistant S. aureus (MRSA) isolates (RR: 0.98, 95% CI: 0.96, 1.00; P = 0.06) or Pseudomonas aeruginosa with an MDR phenotype (RR: 1.02, 95% CI: 0.95, 1.10; P = 0.54). The proportion of E. coli with MDR and extended-spectrum β-lactamase (ESBL) phenotypes increased by 7% (RR: 1.07, 95% CI: 1.02, 1.12; P < 0.01) and 4% (RR: 1.04, 95% CI: 1.01, 1.08; P = 0.02) per year, respectively. Percentages of AR among aggregated CAUTI, CLABSI and SSI pathogens varied by county and time period (Figures 2 and 3).

Conclusion

Increases in antibiotic resistant phenotypes among E. coli, and unchanged prevalence of MDR Pseudomonas aeruginosa, CRE, and MRSA among reported HAI underscore the need for continued infection prevention and antibiotic stewardship efforts in California. Local public health departments can use these analyses to target coordinated AR prevention initiatives with healthcare facilities in their regions.

Disclosures

All authors: No reported disclosures.
1172. Travel-Associated Multidrug-Resistant Organism Acquisition and Risk Factors Among US Military Personnel
Authors: Buchek Gregory , Mende Katrin , Telu Kalyani , Kaiser Susan J , Tribble David R , Fraser Jamie , Mitra Indrani , Lalani Tahaniyat , Yun Heather
Published: November 2018

Background

International travel is a risk factor for incident colonization with extended spectrum β-lactamase (ESBL)-producing organisms. These and other multidrug-resistant (MDR) bacteria are major pathogens in combat casualties. We evaluated risk factors for colonization with MDR bacteria in US military personnel traveling internationally for official duty.

Methods

TravMil is a prospective observational study enrolling subjects presenting to military travel clinics. We analyzed surveys, antimicrobial use data, and pre- and post-travel self-collected perirectal swabs in military travelers to regions outside the continental United States, Canada, Western or Northern Europe, or New Zealand presenting to one clinic from December 2015 to December 2017. Gram-negative isolates recovered from swabs underwent real-time identification and susceptibility testing (BD Phoenix). Characteristics of trip and traveler were analyzed to determine risk factors for MDR organism colonization.

Results

One hundred ten trips were planned by 99 travelers (74% male, median age 38 years [IQR 31, 47.25]); 72 trips were completed by 64 travelers. Median trip duration was 21 days (IQR 12.75, 79.5). Of those with trips completed, 17% traveled to Mexico/Caribbean/Central America, 15% to Asia, 57% to Africa, and 10% to South America; 56% stayed in hotels and 50% in dormitories/barracks. Travelers used doxycycline (15%) for malaria prophylaxis, 11% took an antibiotic for travelers’ diarrhea (TD) treatment (fluoroquinolone 7%, azithromycin 4%). Incident MDR organism colonization occurred in eight travelers (incidence density 3.5/1,000 travel days; cumulative incidence 11% of trips [95% CI: 4%–19%]), all ESBL-producing E. coli. A higher incidence of ESBL-producing E. coli acquisition was associated with travel to Asia (36% vs. 7%, P = 0.02) but not with travel to other regions, TD, or use of antimicrobials. No relationship was seen between fluoroquinolone or doxycycline exposure and resistance to those antimicrobials.

Conclusion

Consistent with other studies of US military personnel travelers, incident colonization with MDR organisms following official travel occurs at a lower rate in this population compared with civilian travelers, with no identified modifiable risk factors. The highest incidence of ESBL acquisition was observed during travel to Asia.

Disclosures

All authors: No reported disclosures.
1176. Risk Factors for ESBL Enterobacteriaceae Colonization Identified by Universal Admission Screening in a London Teaching Hospital
Authors: Batra Rahul , Otter Jonathan , Natale Alex , Tosas Olga , Dyakova Eleonora , Edgeworth Jonathan
Published: November 2018

Background

Individual risk factors such as antibiotic use and foreign travel are typically associated with ESBL-producing Enterobacteriaceae (ESBL-E) carriage. Few studies have evaluated variations in community demographics or social and material deprivation as risk factors for ESBL-E carriage.

Methods

All admissions to a London hospital group were screened for ESBL-E carriage from rectal swabs for four months in 2015. Patients completed a risk factor questionnaire, and those with a residential postcode in the catchment area were linked to a database containing community-based risk factor data. Risk factors for ESBL-E carriage were determined by binary logistic regression. Isolates that were ESBL-E phenotypically were confirmed by microarray (CT103XL Check-MDR, CheckPoint). The Check-MDR array simlutaneously detects common ESBL and carbapenemase genes, including plasmid-mediated AmpC. Genotypic ESBL-E were split into three groups: CTX-M-15 (Group 1), CTX-M-9 (Group 2), and other (Group 3) for further analysis.

Results

Three hundred sixty (9.0%) of 4,006 patients carried ESBL-E; of which, 1,633 had a residential postcode within the catchment area. In multivariable analysis, risk factors for phenotypic ESBL-E carriage included travel to Asia (OR 5.0, CI 2.5–10.0) or Africa (OR 2.9, CI 1.2–7.0) in the past 12 months, and two or more courses of antibiotics in the past 6 months (OR 2.2, CI 1.5–3.4). Residence in an area with a high proportion of Arab residents and residence in an area with a low proportion of houses with two or more bedrooms were associated with ESBL-E carriage in univariable but not multivariable analysis. Risk factors for the three genotypic ESBL groups were broadly similar to the analysis of phenotypic ESBL carriage, although the number of days traveling abroad in the past 12 months was more associated with Group 1 (CTX-M-15) and Group 3 (other), and older age was associated with Group 3 (other) ESBLs.

Conclusion

We linked individual risk factor information with community-based risk factor information, concluding that individual risk factors (including antibiotic use and overseas travel) were more important than community-based risk factors for predicting colonization with ESBL-E at the time of hospital admission. This information is useful when identifying risk groups for targeted screening.

Disclosures

All authors: No reported disclosures.
1179. Incidence of Bacteremia and Bacteriuria With Antibiotic-Resistant Enterobacteriaceae After Transrectal Ultrasound-Guided Biopsy of the Prostate (TRUSBP)
Authors: Saade Elie , Dousa Khalid M , Wilson Brigid , Perez Federico , Donskey Curtis J
Published: November 2018

Background

Infection with Escherichia coli after TRUSBP is common, but other Enterobacteriaceae also occur. In the absence of microbiological data, prophylaxis with co-trimoxazole (TMP-SMX) or fluoroquinolones (FQ) is usually prescribed. We estimated the incidence of bacteremia and bacteriuria after TRUSBP with distinct species of Enterobacteriaceae and their rate of resistance to common antibiotics.

Methods

Using Veterans Healthcare Administration (VHA) databases, we identified patients undergoing TRUSBP between January 1, 2013 and December 31, 2017. We determined the incidence of Enterobacteriaceae isolated from urine and blood cultures obtained within 30 days of TRUSBP. Using microbiology data from VHA, we determined rates of resistance to TMP-SMX, FQ (ciprofloxacin as marker), ESC (ceftriaxone as marker), and carbapenems (Carb) (ertapenem as marker).

Results

Overall, 377 (0.3%) and 1,739 (1.4%) of 126,761 TRUSBPs were complicated by bacteremia or bacteriuria with Enterobacteriaceae, respectively. E. coli was predominant (91% of blood and 81% in urine). Rates of FQ resistance were low in Klebsiellaand Enterobacter but exceeded 60% in E. coli. In general, TMP-SMX resistance exceeded 30%. Of note, 16.6% of blood and 11% of urine Enterobacteriacaea were resistant to ESC, while Carb-resistance was rare.

Conclusion

FQ and ESC-resistant Enterobacteriaceae are prevalent in bacteremia and bacteriuria after TRUSBP. Antibiotics used for prophylaxis and empirical treatment are likely to be ineffective. The prevention and management of TRUSBP-related infections should include microbiology-guided approaches.

Disclosures

All authors: No reported disclosures.
1181. Use of the Combination Antibiogram in the Era of MDR Gram-Negative Pathogens
Authors: Klinker Kenneth , Cherabuddi Kartikeya , Redell Mark , Balogh Matthew , Massey Jill , Dudley Michael
Published: November 2018

Background

Combinations of two or more antimicrobial agents are frequently used in empiric therapy regimens to ensure at least one agent demonstrates activity against suspected pathogens. A combination antibiogram can assess the increase in empiric coverage of a particular combination vs. either of the agents alone (i.e., percent gain). These data could assist in developing empiric regimens that may be particularly useful in settings with problematic multidrug-resistant Gram-negative pathogens.

Methods

An Excel-based model to construct combination antibiograms was developed to assist clinicians in evaluating institutional susceptibility data. The University of Florida Health Shands Hospital microbiology laboratory supplied susceptibility data for ceftriaxone (CFX), cefepime (CEF), ciprofloxacin (CIP), and amikacin (AMI) to assess % gain achieved with combinations for E. coli all blood isolates (n = 206) and blood isolates with an ESBL phenotype (n = 35). The same laboratory provided susceptibility data for CEF, piperacillin–tazobactam (PTZ), AMI and CIP for P. aeruginosa (all, n = 250; carbapenem-resistant (CARB-R), n = 30).

Results

Percent gains achieved by adding AMI or CIP to CFX and CEF to capture at least one agent exhibiting in vitro susceptibility against all blood E. coli were calculated: CFX-AMI, 16%; CFTX-CIP, 3%; CEF-AMI, 10%; CEF-CIP, 1%. The percentage gain specific to E. coli blood isolates with an ESBL phenotype ranged from 9% to 86%. The combination with the greatest percent loss against blood E. coli isolates, comparing all blood isolates to those with an ESBL phenotype, was CFX-CIP (∆-66%). Percentage gain achieved against all isolates of Pa by adding AMI or CIP to PTZ and CEF were CEF-AMI, 8%; CEF-CIP, 5%; PTZ-AMI, 15%; PTZ-CIP, 9%; percent gain of the same combinations against P. aeruginosa CARB-R isolates were 23%, 10%, 47%, and 30%, respectively. Adding AMI to either β-lactam: PTZ % S increased from 47% to 77% (+CIP) and to 94% (+AMI); CEF % S increased from 60% S to 70% (+CIP) and to 83% (+AMI).

Conclusion

Combination antibiogram models can assist clinicians in identifying regimens which may provide improved targeting of MDR phenotypes through calculation of percent gain.

Disclosures

K. Klinker, Melinta Therapeutics: Consultant, Speaker honorarium. Nabriva Therapeutics: Scientific Advisor, Consulting fee. M. Redell, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. M. Balogh, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. J. Massey, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. M. Dudley, The Medicines Company: Employee, Salary.
1182. Risk Factors for the Acquisition of IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan: A Matched Case–control Study
Authors: Saito Sho , Hayakawa Kayoko , Ishikane Masahiro , Tajima Taichi , Matsunaga Nobuaki , Ide Satoshi , Kinoshita Noriko , Kusama Yoshiki , Fujitomo Yumiko , Nakamoto Takato , Toda Yuta , Ohmagari Norio
Published: November 2018

Background

The majority of CRE in Japan are IMP-type carbapenemase-producing CRE (IMP-CRE). However, research on risk factors for the acquisition of IMP-CRE has been limited, and questions exist regarding whether IMP-CRE have risk factors similar to other types of CRE such as KPC.

Methods

We conducted a matched case–control study involving patients from whom IMP-CRE had been isolated. The controls were selected among patients with carbapenem susceptible Enterobacteriaceae (CSE). Non-meropenem-susceptible per CLSI criteria and/or ceftazidime-resistant Enterobacteriaceae were screened, and metallo-β-lactamase–positive isolates were examined for blaIMP by PCR (January 2012 to December 2016).

Results

Ninety-six patients with CRE were matched with 96 patients with CSE. They comprised Enterobacter sp. (n = 132 [CRE: 66, CSE: 66], 68.8%) and Klebsiella pneumoniae (n = 60 [CRE:30, CSE:30], 31.2%), and bacteria were most commonly isolated from sputum (n = 76 [39.6%]), followed by urine (n = 62 [32.3%]). Background factors such as age (median = 75 [IQR: 66–84]), sex (male = 56.8%), and the Charlson comorbidity index (median = 2 [IQR: 1–3.8]) were similar between CRE and CSE. In multivariate analysis, independent risk factors were identified: history of gastrointestinal (GI) endoscopy or surgery, history of ICU stay, and a previous exposure within 1 month to penicillins with β-lactamase inhibitors, cephalosporines, or carbapabnems.

Conclusion

Histories of GI endoscopy and ICU stay as well as broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Infection control measures combined with enhanced antimicrobial stewardship are key to preventing the spread of IMP-CRE.

Disclosures

All authors: No reported disclosures.
1183. Epidemological, Clinical, and Microbiological Characteristics of Carbapenemase-Producing Entereobacteriaceae Bloodstream Infection in Republic of Korea
Authors: Park Jung Wan , Park Se Yoon , Lee Hyungmin , Kim Tae Hyong , Lee Eun Jung , Lee Eunyoung
Published: November 2018

Background

Carbapenemase producing Enterobacteriaceae (CPE) is major pathogens in nosocomial infections, and disease burden due to CPE is also on the rise globally. Nevertheless, only few studies have been conducted regarding CPE infection and its epidemiological factors in the Republic of Korea (ROK). In this paper, we analyzed clinical, microbiological, and epidemiological characteristics of CPE bloodstream infection (BSI) in ROK.

Methods

We designed retrospective cohort study by analyzing reports of epidemiological conducted by Epidemic Investigation Officers in KCDC from January 2015 to December 2016. CPE-infected cases were collected through the nationwide surveillance system. Numbers of sentinel surveillance hospitals included in the system were 100 hospitals in year 2015, and 115 hospitals in 2016. We selected cases with confirmed CPE BSI by Korea National Institute of Health that detected gene types of carbapenemase.

Results

Total of 131 CPE BSI were identified during the study period. Prevalence of CPE BSI among total CPE isolates was 7%. Nationwide, Klebsiella pneumoniae accounts for 69% of CPE BSI and 66% produced K. pneumoniae carbapenemase (KPC). The antibiotics susceptibility examination results showed that CPE prevalent in ROK had susceptibility to Amkacin, Tigecycline, or Gentamicin (76%, 41%, and 39%, respectively). Colistin sensitivity test was performed on only 29 patients, and 1 of those patients showed colistin resistance. 85% (111/131) of cases were classified to hospital acquired infections. Prevalence of CPE BSI among CPE isolates was 7% (131/2020). Most common BSI sources were lung (29%), primary (16%), and biliary tract (15%). Thirty-day mortality rate due to CPE BSI was 47.3%. A multivariable analysis showed that use of adequate antibiotics for CPE (p = 0.01) and APACHE II score (P < 0.001) at the time of CPE detection in the blood stream were significantly associated with decreased 30-day mortality.

Conclusion

CPE bacteremic episodes were already prevalent in the Republic of Korea. Moreover, most of CPE BSI originated from hospital acquired infection, pointing out the need for improvement of hospital infection control strategies. The use of adequate antibiotics therapies upon recognition of CPE infection could decrease mortality due to CPE blood stream infections.

Disclosures

All authors: No reported disclosures.
1187. Retrospective and Prospective Analysis of Acinetobacter Modern-Day Clinical Isolates in a Large Mid-West Hospital System
Authors: Calix Juan , Burnham Carey-Ann D , Feldman Mario
Published: November 2018

Background

The epidemiology of contemporary Acinetobacter calcoaceticus-baumannii complex (AcbC) strains in the United States is understudied. In addition to increasing multidrug resistance, there is concern that the rates of AcbC infections acquired outside of hospitals and the anatomic distribution of these infections may differ from what is previously reported. Furthermore, the epidemiology of non-AcbC clinical isolates is poorly characterized.

Methods

We retrospectively identified all cases associated with Acinetobacter clinical isolates in the Barnes-Jewish/Children’s Hospital system (St. Louis, MO) from 2007 to 2017. First isolates were classified as AcbC or non-AcbC. Tissue of origin, hospital-day of isolation, and antibiotic resistance profiles were determined. Results were compared with an ongoing prospective analysis of Acinetobacter isolates in the same system, started in July 2017.

Results

We identified 2,959 and 1,243 cases associated with AcbC and non-AcbC isolates, respectively. In both groups, isolates were most commonly obtained from respiratory (34% and 30% of total isolates) and connective tissue (34% and 27% of total isolates) sites. Urinary tract specimens were more likely to occur among AcbC isolates compared with non-AcBC isolates (664/2,959 [22%] vs. 147/1,243 [12%], P < 0.001). The percentage of isolates obtained prior to hospital-day-2 are 62% and 78% for AcbC and non-AcbC isolates, respectively. AcbC isolates were markedly more resistant to all classes of antibiotics. Analysis of 77 AcbC and 58 non-AcbC prospectively collected isolates revealed similar clinical findings.

Conclusion

Our study confirms the protean nature of Acinetobacter clinical isolates, and begins to describe relevant differences between AcbC and non-AcbC strains. These distinctions support the practice of identifying clinical isolates using AcbC and non-AcbC labels. Ongoing studies will further describe the patient characteristics and clinical outcomes associated with Acinetobacter disease in our system.

Disclosures

All authors: No reported disclosures.
1190. Reduction of Carbapenem-Resistant Enterobacteria (CRE) Infections and Total Polymyxin B Use Due to a Comprehensive Infection Control Strategy in Colombia
Authors: Velez Juan Diego , Rosso Fernando , Mora Barbara Lucia , Cedano Jorge , Orrego Marly , Beltran Ivan Andres , Echeverry Jhon Jairo
Published: November 2018

Background

Colombia is an endemic country for CRE infections, with an increased rate of hospital-acquired infection due to this microorganism. Therefore, we have a high empirical use of carbapenem, colistin, and polymyxin B in nosocomial suspected septic patients. Infection control strategies could reduce CRE infection rates and lower antibiotic consumption.

Methods

Since 2014, a Comprehensive Infection control strategy was implemented in our hospital. This strategy included: (1) Hospital daily CHX bathing (4% soap or 2% pads) was applied to all patients in our institution (intensive care units and medical/surgical wards). Additionally, recommendations for patient care were provided to patients and family. (2) Active surveillance of perirectal CRE screening was implemented toward high suspected patients. (3) Isolation of all CRE colonized or-infected patient, and gloves use, and alcohol for hand sanitation was reinforced. To evaluate the effectiveness of this strategy, annually nosocomial infection rates due to CRE were compared. Defined daily dose (DDD) of polymyxin B use was obtained annually.

Results

After introducing this protocol, we found a progressive decrease in CRE bacteremia from 2.24 infections per 10,000 patients-day in 2014, to 1, 26 during 2015, 0.92 in 2016 and 0.78 infections per 10,000 patients day during 2017. This was also correlated to a decrease in the use of polymyxin in the adult population, DDD drop from 2.36 to 1.06.

Conclusion

Universal hospital daily CHX bathing, CRE screening, and Isolation as a comprehensive strategy was effective decreasing CRE nosocomial infections and polymyxin use.

Disclosures

All authors: No reported disclosures.
1195. Where You Live Matters: United States Region as a Significant Predictor of Mortality for ESBL Infection Based on a Descriptive Study Using NIS Database
Authors: George Elizabeth , Aurit Sarah , Destache Christopher , Vivekanandan Renuga
Published: November 2018

Background

Extended-spectrum β-lactamase (ESBL) enzymes are produced by multidrug-resistant (MDR) pathogens and confer resistance to β-lactam antibiotics. Infections due to MDR organisms, particularly those ESBL producing pathogens, are of major concern worldwide and are associated with prolonged hospital stay and increased case-fatality rate. Carbapenems are the treatment of choice for severe infections however overuse of this class of antibiotics is leading Carbapenemase-producing pathogens. Variations have been observed in the prevalence of ESBL strains from different US regions; however, it is unclear whether morbidity and mortality follow a similar pattern. This study was conducted to explore the incidence of ESBL infections in the inpatient setting and factors that affect morbidity/mortality.

Methods

The National Inpatient Sample (NIS) was used to identify all hospitalizations during 2002 to 2014; all primary and secondary diagnoses were searched to identify-resistant infection that utilized the ICD-9 code “V091.” All hospitalizations were stratified based on the indication of resistant infection, and comparisons were made with the chi-square test and linear regression for categorical and continuous variables, respectively. A multivariable binary logistic regression model was used to examine survival for those with ESBL infection. All analyses were conducted with SAS version 9.4; P < 0.005 was considered significant.

Results

The analysis identified 320,888,511 hospitalizations with 17,732 identified with ESBL infection. Significant differences for those with and without an ESBL infection were found based on the US region with the pertinent results as follows; Northeast: 19.95% vs. 23.30%, Midwest: 14.71% vs. 16.81%, South: 25.14% vs. 40.53%, and West: 40.20% vs. 19.35%; P < 0.001. Results indicated the US region as a significant predictor of mortality for those with ESBL infection. Regions identified in Figure 1.

Conclusion

Notable findings from this study include a statistically significant variation in mortality risk between US regions. Comparatively lower risk of mortality as related to ESBL infection was noted in the Midwest region when compared with the West region. A greater understanding of the regional epidemiology of β-lactamases is needed to clarify why this disparity exists.

Figure 1

Disclosures

All authors: No reported disclosures.
1197. Microbiological Surveillance of Duodenoscopes Before and After High-Level Disinfection Following Endoscopic Retrograde Cholangiopancreatography (ERCP)
Authors: Lopansri Bert K , Fernley Tasha , Coombs Jana , Gazdik Michaela A , Smit Lori , Dascomb Kristin K , Burke John
Published: November 2018

Background

Transmission of antibiotic-resistant bacteria during endoscopic retrograde cholangiopancreatography (ERCP) has been linked to the complex design of the duodenoscope (scope) elevator channel and cantilever. We implemented a scope culturing program to monitor the efficacy of disinfection and to identify frequency of pre-disinfection exposure to antibiotic-resistant bacteria.

Methods

Facilities performing ERCPs within the Intermountain Healthcare system voluntarily submit scope cultures to the Infectious Diseases Epidemiology Laboratory. Cultures are collected at designated intervals based on procedure volumes at each site. Samples are submitted by endoscopy techs trained to collect flush and swab samples of the distal end of the scope using a previously described method before (PRE) and after (POST) high-level disinfection. Selective media is used to screen for Gram-negative bacilli-resistant to third-generation cephalosporins (ESBL) and vancomycin-resistant Enterococcus (VRE).

Results

Between March 7, 2016 and April 18, 2018, 1,255 scope samples from 10 facilities were cultured (533 PRE samples and 722 POST samples). 483 (90.6%) PRE samples were positive, with 75 (15.5%) screening positive for an antibiotic-resistant organism (60 ESBL and 15 VRE). 19 (2.6%) POST samples were positive, with 4 (21.1%) screening positive for ESBL. One of the four ESBL positive POST samples had a corresponding PRE sample for comparison; E. coli and Klebsiella variicola were isolated in both indicating residual contamination. Two of the ESBL-positive POST cultures did not have corresponding PRE samples and one had a PRE culture negative for ESBL. No POST samples contained VRE. Endoscopy personnel were contacted for each positive POST culture and endoscopy reprocessing practices were reviewed. Additionally, scopes were quarantined, reprocessed and re-cultured. Scopes were returned to use once POST cultures were negative.

Conclusion

Contamination of scopes with antibiotic-resistant bacteria during ERCP is common. High-level disinfection is effective at reducing bacterial burden but is imperfect. Routine surveillance for post-reprocessing bacterial colonization has been helpful to minimize patient exposure and to maintain focus on the importance of reprocessing.

Disclosures

All authors: No reported disclosures.
1198. Clinical Characteristics and Outcomes of Klebsiella pneumoniae Infections in Service Members Who Sustained Trauma in Iraq and Afghanistan
Authors: Kiley John , Mende Katrin , Kaiser Susan J , Carson Leigh , Lu Dan Z , Whitman Timothy J , Petfield Joseph L , Tribble David R , Blyth Dana M
Published: November 2018

Background

Klebsiella pneumoniae infections present a challenge to the clinician due to increasing resistance. K. pneumoniae was the third most common species of multidrug-resistant (MDR) Gram-negative organism in trauma patients sustaining injuries in Iraq and Afghanistan from 2009 to 2014. This study aims to elucidate the epidemiology of these infections by characterizing clinical aspects, risk for MDR infections, and outcomes.

Methods

All initial and serial (≥7 days from prior isolate) infecting K. pneumoniae isolates were collected from the Trauma Infectious Disease Outcomes Study (TIDOS) (6/09-12/14). Antimicrobial susceptibilities were determined using the BD Phoenix Automated Microbiology System and CLSI criteria. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of an ESBL or KPC.

Results

Of 588 K. pneumoniae isolates in the TIDOS registry, 141 infecting isolates (98 initial) from 51 patients met inclusion criteria. Initial isolates were respiratory (31%), wound (25%), blood (20%), urine (10%), intra-abdominal (8%) and other (6%). All patients were male with a median age of 23 years (IQR 21–28). The majority of patients (82%) suffered blast injuries; of which, 88% were from improvised explosive devices. Patients had a median injury severity score (ISS) of 38 (IQR 30–45) and time from injury to first infecting K. pneumoniae isolate was 15 days (IQR 8–31). The median hospital stay was 49 days (IQR 28–70) and four patients died. All patients had received antibiotics prior to diagnosis. Twenty-three (46%) patients had initial isolates classified as MDR. There was no difference in age, ISS, or time from injury to first isolation among those who did and did not have initial MDR isolates. Sixteen patients had 64 serial isolates, of which 24 were wound, 20 respiratory, 14 blood and six urine. Three of these 16 patients died compared with 1 of 35 patients without serial isolates.

Conclusion

K. pneumoniae infections are common among combat casualties. Patients with K. pneumoniae infections were severely injured and almost half of initial infecting isolates were MDR, complicating treatment.

Disclosures

All authors: No reported disclosures.