bluuebunny/crossref_metadata_2025_split huggingface dataset:
464. Fecal Staphylococcus aureus in the Neonatal Intensive Care Unit
Authors: Carl Mike , Milburn Olivia , Uible Emma , Haslam David 
Published: October 2019

Abstract

Background
Staphylococcus aureus colonization in infants in the neonatal intensive care unit (NICU) often leads to repeated infections and severe disease. Methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) infections are major causes of NICU outbreaks. Current national practice in NICUs utilizes nare swab surveillance for S. aureus. We hypothesize that infants colonized in the stool with S. aureus may go unrecognized particularly when nare swab negative, allowing for a transmission reservoir. While it is unclear why some S. aureus nare carriers are also stool colonized, isolates tend to have clonality. A true prevalence of S. aureus fecal carriage is not well understood and variable.

Methods
Available stool samples were prospectively collected from 42 of 55 infants admitted in a level IV NICU on a single day, per Cincinnati Children’s institutional review board approval. Nare swab results were obtained from electronic medical records. DNA was isolated from stool and shotgun metagenomic sequencing was performed via Hiseq Illuminex 2500. The presence of S. aureus and MRSA were defined as having >100 sequencing reads and a mecA DNA read fraction ratio >40 per stool sample, respectively.

Results
Of the 42 stool samples sequenced, 33 were S. aureus (15 MSSA, 18 MRSA) positive. All infants with nare positive MSSA (n = 9) were colonized in the stool with a 93% and 100% sensitivity and specificity, respectively. While infants with nare positive MRSA (n = 10) were stool colonized with 100% and 83% sensitivity and specificity, respectively. Three nare positive infants with MRSA had S.a. in the stool but lacked the presence of mecA. When comparing clinical nare swabs to stool metagenomic surveillance, sensitivities were 60% for MSSA and 56% for MRSA.

Conclusion
Infant colonization of S. aureus in the NICU remains a major problem despite current national surveillance and isolation practices. We found that nare swab surveillance for S. aureus in infants significantly underestimated colonization rates when compared with shotgun metagenomics of stool. These results suggest that nare swabs alone may not have adequate sensitivity and the implementation of stool surveillance should be considered to augment current practices. Future study is necessary to understand how the S. aureus stool reservoir contributes to transmission

Disclosures
All authors: No reported disclosures.
470. Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in Patients with Significant Drug Abuse: Outcomes from Global Phase 3 Studies of Delafloxacin (DLX)
Authors: Overcash J Scott , O’Riordan William , Quintas Megan , Lawrence Laura , Tseng Carol , Cammarata Sue 
Published: October 2019

Abstract

Background
Delafloxacin (DLX), an IV/oral anionic fluoroquinolone antibiotic, is approved for the treatment of ABSSSI including those due to MRSA and Gram-negative pathogens including P. aeruginosa. Two global phase 3 ABSSSI trials included patients with substance abuse including IV drugs.

Methods
Two multicenter, double-blind, double-dummy trials of adults with ABSSSI randomized patients 1:1 to receive either DLX monotherapy or vancomycin 15 mg/kg + aztreonam (VANAZ) for 5–14 days. Study 302 used DLX 300 mg BID IV only; study 303 used DLX 300 mg BID IV for 3 days with a mandatory blinded switch to DLX 450 mg oral BID. Key endpoints were Objective Response at 48–72 hours with ≥20% reduction in lesion size, and Investigator assessment of outcome at Follow-up (FU, Day 14), both in the Intent To Treat population.

Results
In the 2 studies, 620 patients with substance abuse, excluding alcoholism, including heroin, cocaine and methamphetamine abuse, were randomized in the United States. 71% were male with mean age 44 years. Average erythema area at baseline was ~230 cm2. 16% percent had cellulitis, 30% abscesses, and 53% wound. S. aureus (SA) was the most frequent pathogen. DLX was non-inferior to VANAZ for the Objective Response: 85.9% DLX vs. 84.4% VANAZ [∆2.6 (95% CI −2.9, 8.1)] as well as the assessment of outcome at FU: 82.0% DLX vs. 79.3% VANAZ [∆3.2 95% (CI −3, 9.4)]. Micro success in evaluable patients with SA was seen in 99.1% DLX vs. 100% VANAZ as well as 98.2% DLX vs. 100% VANAZ in patients with MRSA. The overall % of patients with at least one adverse event (AE) was comparable for DLX (49.0%) compared with VANAZ (56.1%). The most frequent treatment-related AEs were gastrointestinal in nature, including nausea seen in 9.7% DLX and 5.8% VANAZ patients, primarily mild to moderate in severity. There were no cases of C.difficile diarrhea. Discontinuations due to treatment-related AEs were lower with DLX (0.3%) compared with VANAZ (2.2%).

Conclusion
Fixed-dose monotherapyDLX was comparable to VANAZ in treatment of ABSSSI in patients with substance abuse based on the Objective Response as well as investigator-assessed outcome. DLX was also comparable to VANAZ in treating patients with SA and MRSA. DLX appears effective and well tolerated in patients with ABSSSI and significant substance abuse.

Disclosures
All authors: No reported disclosures.
475. High Rate of Extended-Spectrum β-Lactamase Producing Gram-Negative Infections and Associated Mortality in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Tufa Tafese B , Beyene Tufa Takele , André Fuchs , Torsten Feldt 
Published: October 2019

Abstract

Background
Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria have become a serious threat to global health. The rapid increase of ESBL-producing bacteria is associated with high mortality due to ineffective antibiotic treatment. To date, regular surveillance of multidrug-resistant (MDR) pathogens is lacking in Ethiopia. For this report, published data regarding ESBL-producing bacteria in different regions of Ethiopia were reviewed systematically. To our knowledge, this is the first systematic review from Ethiopia on ESBL-producing infections and associated mortality in the country.

Methods
A literature search was conducted in PubMed, PubMed Central, and Google Scholar from January 1, 1990 to April 28, 2019, using the following search terms: “ESBL producing Enterobacteriaceae,” “Gram-negative bacteria infection associated mortality,” and “Ethiopia.” Patient mortality associated with infections by ESBL-producing Gram-negative bacteria was recorded.

Results
Fourteen publications qualified for review. Totally, 1,782 Gram-negative bacteria isolated from 5,191 clinical samples were included. The phenotypic pooled rate of ESBL-producing Gram-negatives was estimated to be 52.9(95% CI: 50.5%–55.4%). Among different species, ESBL rates were 65. 7% (262/399) Klebsiella spp., 60.6% (20/33) for Enterobacter spp., 47.8% (22/46) for Citrobacter spp., 47.0% (383/815) for E. coli, 45.7% (85/186) for Salmonella spp., 27.8%(15/54) for Proteus spp., 16.7%(4/24) for P. aeruginosa, 14.3% (3/21) for Acinetobacter spps., and 40.5% (15/37) for others, respectively. ESBL genes were confirmed in three studies. blaCTX-M-1 and blaTEM were the predominately detected genes. Two studies reported mortality associated with Gram-negative infections and 86% (12/14) of the patients infected with ESBL-producing bacteria died.

Conclusion
In this meta-analysis, the pooled phenotypic prevalence of ESBL-producing pathogens is considerably high. Also, the mortality due to ESBL-producers is high but data are scarce. This highlights the need for establishing and upgrading of clinical microbiology laboratories in the country for routine antibiotic susceptibility testing. The capacity to detect ESBL genes is desirable for continuous surveillance of MDR.

Disclosures
All authors: No reported disclosures.
476. Risk Factors of Community-Onset Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Bacteremia in South Korea Using National Health Insurance Claims Data
Authors: Lee Yongseop , Soo Park Yoon , Kim Dokyun , Ah Kim Young , Hee Shin Jong , Uh Young , Seob Shin Kyeong , Hwan Shin Jeong , Hoon Jeong Seok 
Published: October 2019

Abstract

Background
Antibiotic resistance is a significant threat to public health not only in healthcare setting but also in community because antimicrobial-resistant infections can be transmitted in community. Although it is essential to know whether there are particular reasons that caused antibiotic-resistant infection in community, there is lack of evidence regarding risk factors for community-onset extended-spectrum β-lactamase-producing Klebsiella pneumoniae bloodstream infection (ESBL-KP BSI) in South Korea. In the present study, we aimed to reveal risk factors for community-onset ESBL-KP BSI.

Methods
From May 2016 to April 2017, patients with community-onset KP BSI (n = 408) from six sentinel hospitals in South Korea were included. The hospitals are located in different districts throughout South Korea, and had a total of 5,194 beds, ranged from 715 to 1,050 beds per hospital. Admission history and previous usage of antibiotics and medical devices before bacteremia were acquired from National Health Insurance claims data. Risk factors of ESBL-KP BSI were analyzed with a multivariable logistic regression model. PCR and sequencing for the identification of genes encoding ESBLs, and multilocus sequence typing were performed.

Results
Of 408 patient of community-onset KP BSI, 70 (17%) were ESBL-KP BSI patients. ESBL-KP isolates most frequently carried CTX-M-1-group ESBLs (74%, n = 52), followed by CTX-M-9-group ESBLs (16%, n = 11). Most prevalent sequence type (ST) among ESBL-KP isolates was ST48 (14%, n = 10). Among non-ESBL-KP isolates, ST23 was most prevalent (21%, n = 70). Analyzing with multivariate analysis, recent admission to long-term care hospital within 3 months (OR, 5.7; 95% CI, 2.1–15.6; P = 0.001), previous usage of trimethoprim-sulfamethoxazole (OR, 11.5; 95% CI, 2.7–48.6; P = 0.001), expanded-spectrum cephalosporin (OR, 2.2; 95% CI, 1.2–3.9; P = 0.01), and previous use of urinary catheter (OR, 2.3; 95% CI, 1.1–4.5; P = 0.02) were identified as independent risk factors for community-onset ESBL-KP BSI.

Conclusion
Recent admission to long-term care hospital, use of urinary catheter, recent usage of antibiotics were identified as risk factors for community-onset ESBL-KP BSI. Strict antibiotic stewardship and infection control measures in long-term care hospital are needed.

Disclosures
All authors: No reported disclosures.
485. Clinical and Molecular Epidemiology of Carbapenem Non-susceptible Citrobacter sp.
Authors: Babiker Ahmed , Evans Daniel R , Griffifth Marrisa P , Mettus Roberta T , McElheny Christi L , Clarke Lloyd , Harrison Lee , Doi Yohei , Shields Ryan K , Van Tyne Daria 
Published: October 2019

Abstract

Background
Carbapenem non-susceptible Citrobacter sp. (CNSC) are becoming increasingly recognized as healthcare-associated (HA) pathogens, but data on clinical and molecular epidemiology, species diversity and mechanisms of carbapenem resistance are lacking.

Methods
We reviewed patients at University of Pittsburgh Medical Center with CNSC positive cultures from 2000 to 2018. The diversity of CNSC species among a subset of isolates from all UPMC sites was confirmed by 16S rRNA typing, and the presence of carbapenemase enzymes in the same isolates was determined by PCR amplificon. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Significance of epidemiological trends over time was determined by linear regression, and correlation with antibiotic consumption was determined by cross-correlation using STATA v15.

Results
Between 2000 and 2018, 3% (78/2817) of all Citrobacter sp. were CNS. CNSC rates increased from 4% in 2000 to 10% in 2018 (R2 = 0.206, P = 0.05), as did carbapenem consumption (6.5–34.5 DDDs/1000, R2 = 0.831, P < 0.001) (Figure 1). Twenty-one isolates from 19 patients were available for additional analysis. Patients had multiple comorbidities (84%), frequently acquired CNSC in the healthcare setting (84%), were colonized with other organisms (68%), and had high rates of in-hospital mortality/discharge to hospice (47%) (Table 1). C. freundii was the dominant species identified (16/21), followed by C. farmeri (2/21), C. koseri (2/21), and C. werkmanii (1/21). Carbapenemases were identified in 14 isolates, including KPC (n = 12), NDM (n = 2), and OXA-48 (n = 1) (Table 2). Isolates were frequently susceptible to ceftazidime–avibactam (MIC median [IQR]: 2[0.5,8]) 81%) and meropenem-vaborbactam (86%) (MIC median [IQR] 0.12[0.3,0.5]) (Table 2).

Conclusion
CNSC species are diverse, have emerged as an HA pathogen at our center, and cause high rates of mortality. Further studies, including ongoing genome sequencing and analysis, are required to better elucidate CNSC diversity and resistance mechanisms.

Disclosures
All authors: No reported disclosures.
494. Fitness Cost of mcr-1-Mediated Colistin Resistance in Carbapenemase-Producing Klebsiella pneumoniae
Authors: Lin Yi-Tsung , Cheng Yi-Hsiang , Chou Sheng-Hua , Huang Ying-Chi , Chen Liang 
Published: October 2019

Abstract

Background
The emergence of mobile colistin resistance gene mcr-1, a plasmid-borne polymyxin resistance mechanism, in carbapenem-resistant Klebsiella pneumoniae is an alarming concern. However, previous studies showed that the acquisition of mcr-1 was associated with a significant biological fitness cost in K. pneumoniae. We aimed to study the impact of mcr-1 on the biological fitness in clinical carbapenemase-producing K. pneumoniae strains.

Methods
Clinical carbapenemase-producing K. pneumoniae strains were collected consecutively at the Taipei Veterans General Hospital between November 2017 and December 2018. The strain positive for mcr-1 was subjected to whole-genome sequencing to delineate its genomic features. Escherichia coli J53 strain was used as the recipient strain in plasmid conjugation assay and the transconjugants were selected with sodium azide and colistin. Plasmid stability was tested by serial passaging in antibiotic-free LB broth for 28 days. The growth rate was compared between the parental mcr-1-bearing strain and the plasmid-cured strain.

Results
One ST11 strain isolated from a fatal case with bacteremia (KP2509) was found to harbor blaKPC-2, blaOXA-48, and mcr-1. This strain was resistant to colistin (MIC=8 mg/L) and imipenem (MIC≥16 mg/L). Whole-genome sequencing of KP2509 showed that mcr-1, blaKPC-2 and blaOXA-48 were located on an IncHI-FIB type plasmid of 319 Kb, an IncFII type plasmid of 96 Kb, and an IncL type plasmid of 64 Kb, respectively. Conjugation efficiency of mcr-1-bearing plasmid was 2.24 × 10–4, and the colistin MIC of E. coli J53 transconjugant increased from 0.5 to 8 mg/L. The mcr-1-bearing plasmid in KP2509 showed high plasmid stability, and only ~1% were lost after 27-day passages. The resulting plasmid-cured strain (PC-KP2509) was susceptible to colistin (MIC=0.5 mg/L) and had a similar growth rate to that of parental mcr-1-bearing strain KP2509.

Conclusion
We identified an ST11 K. pneumoniae strain carrying blaKPC-2, blaOXA-48, and mcr-1 genes causing a fatal bacteremia. The large mcr-1-bearing plasmid confers a moderate level of colistin resistance but without significant biological fitness cost in carbapenemase-producing K. pneumoniae, which could result in a serious threat clinically.

Disclosures
All authors: No reported disclosures.
495. Risk Factors of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections Among Intensive Care Unit (ICU) Patients in a Tertiary Hospital in the Philippines
Authors: Torio Roderick Oreal , Paras Danielle Nicole T , Abad Cybele Lara R 
Published: October 2019

Abstract

Background
The threat of Carbapenem-Resistant Enterobacteriaceae (CRE) is increasing worldwide, and the epidemiology, risk factors, and outcomes of CRE in the Philippines is unknown.

Methods
We performed a retrospective case–control study of 128 CRE cases and Carbapenem-Susceptible Enterobacteriaceae (CSE) controls matched 1:1 based on site of infection and date of admission among all adult patients in the Intensive Care Unit (ICU) between January 2014 and May 2018 at The Medical City. Predictors of CRE infection among matched cases and controls were determined through multiple conditional logistic regression analysis. In-hospital mortality was analyzed using z-test of two proportions and length of stay among patients with CRE and CSE were compared.

Results
The mean age in both groups was similar at 65.8 (range 23–92) and 64.3 (range 23–98) years, respectively. There were more males among cases than controls [(76/128, 59%) vs. 62/128 (48%)]. Those with CRE were more likely to have a co-morbid illness and an invasive device. Pneumonia was the most common site of CRE infection (40%) followed by the urinary tract (27%). Enterobacter cloacae (54.68%) was the most common organism, followed by Klebsiella pneumoniae (30.46%). On univariate analysis, the use of piperacillin–tazobactam, third or fourth-generation cephalosporins and carbapenems, mechanical ventilation, and acute kidney injury (AKI) increased the risk of developing CRE infections by an OR of 7.5 (CI 1.88–29.95, P = 0.004), 9.32 (CI 1.48–58.59, P = 0.017), and 10.76 (CI 1.69–68.53, P = 0.012), respectively. Those with CRE had a higher in-hospital mortality than the CSE group [(49/79, 38.3%) vs. (33/95, 25.8%); P = 0.032]. Length of hospital stay among CRE cases was also longer with a mean of 43.9 vs. 28 days compared with controls.

Conclusion
In our cohort, older patients w/ comorbidities developed CRE with pneumonia being the most common site of infection. Prior use of broad-spectrum antimicrobials, mechanical ventilation and AKI appeared to increase the risk of CRE infection in the ICU. CRE infection also increased patient mortality and length of hospital stay. Interventions that target these risk factors should be undertaken to help prevent CRE infection.

Disclosures
All authors: No reported disclosures.
512. Healthcare-Acquired (HA) Carbapenemase-Producing Enterobacteriales (CPE) in Southern Ontario, Canada: To Whom Are We Transmitting CPE?
Authors: Jamal Alainna , Coleman Brenda , Johnstone Jennie , Katz Kevin , Muller Matthew P , Patel Samir , Melano Roberto , Rebbapragada Anu , Richardson David , Sarabia Alicia , Mubareka Samira , Poutanen Susan , Zhong Zoe , Kohler Philipp , McGeer Allison 
Published: October 2019

Abstract

Background
Though CPE in Canada are mainly acquired abroad, outbreaks/transmission in Canadian hospitals have been reported. We determined the incidence of HA CPE in southern Ontario, Canada, to inform prevention and control programs.

Methods
Toronto Invasive Bacterial Diseases Network (TIBDN) has performed population-based surveillance for CPE in the Toronto area/Peel region of southern Ontario, Canada, since CPE were first identified in October 2007. Clinical microbiology laboratories report all CPE isolates to TIBDN; annual lab audits are performed. Incidence calculations used first isolates as numerator; denominator (patient-days/fiscal year for Toronto/Peel hospitals) was from the Ontario Ministry of Health and Long-Term Care.

Results
The incidence of HA CPE has risen from 0 in 2007/2008 to 0.45 and 0.28 per 100,000 patient-days for all and clinical cases, respectively, in 2017/2018 (Figure, P < 0.0001). 190/790 (24%) incident cases of CPE colonization/infection in southern Ontario from October 2007 to December 2018 were likely HA (hospitalized in Ontario with no history of hospitalization abroad/high-risk travel). Eighty (25%) were female and the median age was 73 years (IQR 57–83 years). 157 (83%) had no prior travel abroad and 33 (17%) had prior low-risk travel. 122 (64%) had their CPE identified >72 hours post-admission (of which 83 also had ≥1 other prior Ontario hospitalization); 68 (36%) had their CPE identified at admission but had recent prior Ontario hospitalization. HA cases vs. foreign acquisitions were significantly more likely K. pneumoniae (48% vs. 38%, P = 0.02) and Enterobacter spp. (20% vs. 7%, P < 0.0001) and less likely E. coli (20% vs. 48%, P < 0.0001). Genes of HA vs. foreign acquisitions were significantly more likely blaKPC (34% vs. 12%, P < 0.0001) and blaVIM (12% vs. 2%, P < 0.0001) and less likely blaNDM±OXA (38% vs. 56%, P < 0.0001) and blaOXA (13% vs. 27%, P = 0.0001). 36 (19%) HA cases had a negative CPE screen before their first positive CPE test (10/36 (28%) were on admission). The median incidence of HA CPE per 100,000 patient-days at each hospital was 0.44 (IQR 0.15–0.68) (P < 0.0001).

Conclusion
A quarter of CPE cases in southern Ontario were HA and the incidence of HA cases is increasing. Most cases were admitted to >1 Ontario hospital. Strategies to control transmission are critical.

Disclosures
All authors: No reported disclosures.
525. Evaluation of Implementation of Guidelines for Carbapenem-resistant Enterobacteriaceae (CRE) Prevention Using the Consolidated Framework for Implementation Research (CFIR)
Authors: Goedken Cassie , Guihan Marylou , Brown Charnetta R , Ramanathan Swetha , Vivo Amanda , Fitzpatrick Margaret A , Perencevich Eli N , Rubin Michael , Reisinger Heather , Suda Katie J , Evans Martin , Evans Martin , Evans Charlesnika T 
Published: October 2019

Abstract

Background
Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing (CP) CRE are difficult to treat, resulting in a high mortality annually. In 2017, VA released guidelines for CRE/CP-CRE laboratory testing, prevention, and management. We used the Consolidated Framework for Implementation Research (CFIR) to understand factors influencing implementation of the CRE guideline at VA Medical Centers (VAMCs).

Methods
Between 9/17–8/18, 43 semi-structured interviews were conducted with Multi-Drug Resistant Organism Program Coordinators, laboratorians, physicians and infection preventionists from 29 geographically representative VAMCs of varying size and CP-CRE burden. Interviews addressed perceptions of guideline dissemination, laboratory testing, training, patient education, and IT support (e.g., CRE/CP-CRE flag, lab report and template). We analyzed transcripts using a consensus-based mixed deductive-inductive coding approach to identify CFIR constructs, best practices, recommendations/feedback and implementation challenges.

Results
95% of interviewees reported using VA CRE/CP-CRE guidelines, most (79%) with high confidence. Respondent comments (n = 798) were coded using CFIR constructs [Inner Setting (e.g., resources), (48%); Process (e.g., planning), (23%); Intervention Characteristics (e.g., VA guidelines) (17%); Outer Setting (e.g., patient needs) (6%); Characteristics of Individuals (e.g., self-efficacy) (6%)]. Interviewees also described Best Practices (15%) and Feedback/Recommendations (12%) including the need for improved lab testing/reporting, communication, contact isolation, staff training, patient education and cost.

Conclusion
Our results suggest sustained improvement in multiple areas to facilitate guideline implementation to identify, prevent, and manage CRE/CP-CRE are needed. This is critical because CRE/CP-CRE incidence and mortality rates are projected to increase.

Disclosures
All authors: No reported disclosures.