bluuebunny/crossref_metadata_2025_split huggingface dataset:
551. Burden of Illness in Carbapenem-Resistant Acinetobacter baumannii Infections in US Hospitals (2014 to 2018)
Authors: Pogue Jason M , Kanakamedala Hemanth , Zhou Yun , Cai Bin 
Published: October 2019

Abstract

Background
Infections caused by Acinetobacter baumannii present a challenge for treating physicians due to the high level of antimicrobial resistance. The current analysis compared the burden of illness in patients infected with carbapenem-resistant (CR) vs. -susceptible (CS) strains of A. baumannii.

Methods
Hospitalized adult patients with microbiologically confirmed A. baumannii infections (defined as a positive culture and receipt of antibiotics between 2 days prior to 3 days after the culture) included in the Premier Healthcare Database were retrospectively evaluated. Patient characteristics including demographics, comorbidities, time of infection onset and site of infection were assessed. Comparative outcomes between CR and CS patients assessed included in-hospital mortality, length of hospital stay (LOS), ICU LOS, and discharge status. Outcomes were also stratified by site of infection.

Results
A total of 3,471 patients admitted between January 1, 2014 and June 30, 2018 were included. Patients with CR strains of A. baumannii were older (62 vs. 59 years), more likely to have Charlson Comorbidity Index ≥3 (63.4% vs. 56.1%), more likely admitted from a healthcare origin (30.3% vs. 11.4%) and less likely to have the onset of infection within first 48 hours of hospitalization (58% vs. 69%) than those with CS strains. CR patients had increased inpatient mortality compared with CS patients (16.3% vs. 11.0%), driven primarily by patients with bloodstream infections (42.6% vs. 12.4%, respectively, P < 0.001). CR patients had a non-significantly increased median overall LOS from the onset of infection (9 vs. 8 days, P = 0.068), were more likely to be admitted to the ICU, and were significantly less likely to be discharged home (16% vs. 47%, P < 0.001). Hospitalization charges were considerably higher for CR patients (table). Readmission rates were high among CR patients and were similar to patients with CS infections.

Conclusion
Patients with CR strains of A. baumannii face a greater burden of illness compared with CS patients, experiencing increased mortality, ICU admission and LOS, and incur higher hospitalization charges. Furthermore, CR patients were less likely to be discharged home after admission.

Disclosures
All authors: No reported disclosures.
567. Does Universal Nasal Decolonization with an Alcohol-Based Nasal Antiseptic Reduce Infection Risk and Cost?
Authors: Arden Scott 
Published: October 2019

Abstract

Background
Nasal decolonization with mupirocin to reduce infection risk, has been associated with mupirocin-resistant Staphylococcus aureus (SA). A community hospital identified two patients colonized with methicillin and mupirocin-resistant SA (MRSA), one scheduled for surgery, one for inpatient IV antibiotic therapy. Instead of mupirocin, an alcohol based nasal antiseptic was applied to these patients twice daily for 5 days, resulting in a negative MRSA nasal screening test in both patients. Neither patient developed an infection during or after treatment. Building on this success, a plan was made to assess the impact of universal nasal decolonization to replace screening and contact precautions for MRSA colonized patients, and to reduce surgical site infections (SSI).

Methods
A 12-month project using a before and after design, was initiated in April 2018. The project involved twice daily application of alcohol-based nasal antiseptic for all inpatients, and preoperatively for all surgical patients in addition to existing preoperative chlorhexidine bathing. No other practice change was made during this period. Assessment of impact was planned by comparing the incidence of MRSA bacteremia and SSI at baseline (2017) and after project implementation, in addition to costs avoided with reduction of nasal screening and CP.

Results
Compared with baseline, between April 2018 and March 2019, there was a decrease in MRSA bacteremia from 3/1,000 patient-days to 0/1,000 patient-days, a reduction in CP from 3.78 to 1.53/1,000 patient-days, a reduction in nasal screens from 3,874 to 605, and a reduction of all-cause (Gram-negative and Gram-positive) SSI after all surgical procedures from 3/4,313 procedures to 0/4,872 procedures. After accounting for the cost of the nasal antiseptic, the reduction in gowns, gloves and nasal screening tests resulted in $104,099.91costs avoided.

Conclusion
House-wide application of alcohol-based nasal antiseptic in place of screening and contact precautions, resulted in a reduced incidence of both MRSA bacteremia and SSI for all types of surgical procedures, in addition to significant costs avoided.

Disclosures
All authors: No reported disclosures.
590. Reduction of Endotracheal Colonization by Gram-Negative Bacilli in a Neonatal Intensive Care Unit Through Use of a Novel Drain Cover
Authors: Buck Melissa , Antunes Michael , Kingham Brewster , Polson Shawn W , Eppes Stephen C 
Published: October 2019

Abstract

Background
Splash and aerosolization from sink drains are a source of contamination, particularly by Gram-negative bacilli (GNB), in healthcare facilities. Neonatal Intensive Care Unit (NICU) outbreaks of infection due to GNB have been attributed to NICU sinks. Recent studies found that a dome-shaped drain cover placed in sinks in an adult ICU prevented dispersal of sink drain bacteria to the environment and hands of healthcare providers. Our NICU routinely performs weekly surveillance cultures of all endotracheal tubes (ETT) and has previously reported a correlation of ETT colonizing organisms with bacteria isolated from blood in late onset sepsis. Our objective was to determine whether the use of a drain cover in every sink in a level III 72 bed NICU could lead to a decrease in the isolation of GNB in the ETTs of hospitalized infants.

Methods
All 34 sink drains and basins in an open layout NICU were cultured. Drain covers were then installed and replaced on a routine basis. Weekly endotracheal tube cultures were performed for all intubated infants.

Results
Prior to implementation of drain covers, the most common GNBs cultured from ETTs were, in order, E. cloacae, Klebsiella spp., Acinetobacter spp., and S. maltophilia. The most common organisms isolated from sinks were, in order, P. aeruginosa, Acinetobacter spp. and S. maltophilia. An unusual species, Acinetobacter ursingii, was common in both sinks and endotracheal tubes. Before and after the implementation of drain covers, the median time to first isolation of a GNB was 14 and 17 days, respectively. Prior to draining cover implementation, there were 31 new GNB isolates during 700 ventilator days (rate of 44.3/1000 ventilator days) among infants with any positive ETT cultures. Post drain cover there were 26 new GNB isolates during 900 ventilator days (rate of 28.9/1000 ventilator days). There was a shift in microbial species isolated from ETTs with Klebsiella spp. and S. marcescens predominating after implementation of drain covers.

Conclusion
The use of a novel drain cover in the sinks in a NICU can reduce the frequency of GNB colonizing the ETTs of patients and can lengthen the time to first positivity. Mitigating sinks as a reservoir for GNB may reduce the likelihood of these bacteria infecting a vulnerable population.

Disclosures
All authors: No reported disclosures.
596. Distinct, Segregated Daptomycin-Susceptible and Daptomycin-Nonsusceptible Staphylococcus aureus Populations Associated with Tricuspid-Valve Infective Endocarditis
Authors: Miller Christopher R , Dey Somrita , Smolenski Paula , Kulkarni Pushkar S , Sakoulas George , Monk Jonathan M , Szubin Richard , David. Berti Andrew 
Published: October 2019

Abstract

Background
Loss of daptomycin susceptibility in Staphylococcus aureus is often associated with sequestered foci of infection, driven by selection pressure from both administered antibiotics and host defense peptides. Susceptibility testing of the organism cultured from blood is assumed to parallel that of the infectious foci, such as heart valves. We studied a case of tricuspid valve endocarditis where one leaflet yielded exclusively daptomycin-nonsusceptible S. aureus and another leaflet yielded purely daptomycin-susceptible S. aureus. We examined the responses of the two populations to different anti-staphylococcal therapies to identify regimens effective against both isolates.

Methods
Both isolates were whole-genome-sequenced using Illumina technologies. The presence of heterogeneous daptomycin-resistant subpopulations was assessed by dilution plating and population analysis profiling. One compartment pharmacokinetic/pharmacodynamic modeling was used to simulate different potential antistaphylococcal pharmacotherapies against each isolate. Hemolysin activity was evaluated as a surrogate for accessory gene regulator function.

Results
The daptomycin-susceptible isolate did not demonstrate heteroresistance while the daptomycin-resistant population was uniformly daptomycin nonsusceptible. The daptomycin non-susceptible isolate demonstrated regrowth by 72 hours of simulated treatment with vancomycin (2 g Q12H) or daptomycin (10 mg/kg daily). Adding cefazolin (2 g Q8H) to vancomycin or daptomycin prevented regrowth at 72 hours. The daptomycin-resistant isolate was deficient in hemolysin production suggesting agr dysfunction. Comparative sequencing identified daptomycin-resistant isolate mutations in mprF, purR and agrA.

Conclusion
This case underscores the complex dynamics of the emergence of S. aureus resistance to daptomycin in vivo. Our pharmacokinetic modeling supports combination therapy in the treatment of endovascular MRSA infection. Reduced hemolytic activity supports the hypothesis that agr modulation is associated with persistent infection and/or treatment failure. Ongoing studies will identify features of distinct bacterial populations that promote ecological succession during infection at a sequestered anatomical site.

Disclosures
All authors: No reported disclosures.
608. Emerging Methicillin Resistance Mechanism in mec Gene-Negative Staphylococci not Detected by Reference Methods
Authors: Durand Geraldine , Dupieux-Chabert Celine , Gustave Claude-Alexandre , Bes Michèle , Fruiquière Berangere , Fulchiron Corine , Munoz Lorette , Rivat Sarah , Ranc Anne-gaelle , Vandenesch Francois , Laurent Frederic , Tristan Anne , Martins-Simoes Patricia 
Published: October 2019

Abstract

Background
B-lactam resistance in Staphylococci is mediated by mec genes usually diagnosed by disc diffusion Cefoxitin test (DDFOX) and PCR testing. Here, we report methicillin-resistant Staphylococcus lugdunensis and Staphylococcus aureus strains lacking mec gene misdiagnosed by reference methods. Since the strains are not B-lactamase hyperproducers we investigated the molecular basis of the methicillin resistance.

Methods
We tested 2 S. lugdunensis isolates (SL1, SL2) collected from distinct blood cultures of the same patient and 2 S. aureus isolates (SA1, SA2): (i) by DDFOX, (ii) for Oxacillin MIC by agar dilution (AD), (iii) by VITEK®2 (bioMérieux) for Oxacillin MIC (V2 OXA) and Cefoxitin Screen Test (V2 OXSF), (iv) for mecA, B, C genes by PCR and (v) by whole-genome sequencing (WGS).

Results
The 4 isolates were methicillin susceptible by DD FOX and mec negative. However, all the isolates displayed variable results for V2 OXA MIC (0.5 to ≥4 mg/L) and for V2 OXSF (POSITIVE, NEGATIVE). For SL1 and SL2 isolates, the V2 OXSF growth curve atypical pattern has led to investigating the OXSF wells. The plates inoculated with the broth extracted from the OXSF well showed 2 colony morphotypes (small “P” and regular “G”) for both isolates. The small colonies (SL1P, SL2P) were Oxacillin resistant (V2 OXA MIC≥4; AD MIC = 4) and V2 OXSF POSITIVE whereas the regular colonies (SL1G, SL2G) were Oxacillin susceptible (V2 OXA MIC = 2; AD MIC = 0.5) and V2 OXSF NEGATIVE. The 4 morphotypes were cefoxitin susceptible by DDFOX and mec negative. Interestingly, WGS revealed a GdpP truncation in the N-terminal domain only found in S. lugdunensis small colonies (SL1P, SL2P) phenotypically resistant to Oxacillin. GdpP is a cyclic diadenosine monophosphate phosphodiesterase enzyme which function is the hydrolysis of a signaling nucleotide.

Conclusion
We described mec negative S. lugdunensis and S. aureus strains expressing heterogeneous methicillin resistance detected by the VITEK2 OXSF test. S. lugdunensis subpopulation of small colonies resistant to oxacillin is associated with a truncation of GdpP protein previously described in S. aureus. Interestingly GdpP loss of function in Staphylococci is associated with a reduced growth and may arise as a result of the selective pressure of exposure to B Lactams.

Disclosures
All authors: No reported disclosures.
611. Fosfomycin Resistance of Multidrug-Resistant Escherichia coli and Mechanisms of Fosfomycin Resistance
Authors: Seok Hyeri , Hoon Jeon Ji , Kyoung Choi Hee , Suk Choi Won , Won Park Dae , Mi Wi Yu , Soo Ko Kwan , Ran Peck Kyong 
Published: October 2019

Abstract

Background
Fosfomycin is one of the antibiotics that may be a candidate for the next-generation antimicrobial agents againt multidrug-resistant bacteria. To date, it is known that the resistance rate is not high for Escherichia coli. However, it is necessary to update the fosfomycin resistance rates in E. coli according to the studies that extended spectrum β-lactamase (ESBL) producing E. coli strains are highly resistance to fosfomycin. We evaluated the resistance rate of fosfomycin, the resistant mechanism of fosfomycin in E. coli, and the activity of fosfomycin against susceptible and resistant strains of E. coli.

Methods
A total of 283 clinical isolates was collected from patients with Escherichia coli species during the period of January 2018 to June 2018, in three tertiary hospitals of Republic of Korea. In vitro antimicrobial susceptibility tests were performed in all E. coli isolates using the broth microdilution method according to the Clinical and Laboratory Standard Institute (CLSI). Multilocus sequence typing (MLST) of the Oxford scheme was conducted to determine the genotypes of E. coli isolated. Fosfomycin genes were investigated for all fosfomycin-resistant E. coli strains.

Results
The overall resistance rate to fosfomycin was 10.2%, compared with 53.4%, 46.3%, 41.3%, 31.1%, 10.6%, 2.5%, and 2.1% for ciprofloxacin, cefixime, cefepime, piperacillin/tazobactam, colistin, ertapenem, and amikacin, respectively. The 29 fosfomycin-resistant isolates did not show a clonal pattern on the phylogenetic tree. MurA and glp genes were identified in all strains. FosA3 were identified in two strains and uhp gene were identified in 4 strains. In time-kill curve studies, fosfomycin was more bactericidal than cefixime against all sensitive E. coli strain. Morever, fosfomycin was more bactericidal than piperacillin/tazobactam against ESBL-producing E. coli strain.

Conclusion
The resistant rate of fosfomycin to E. coli is still low. Fosfomycin was active against E. coli including ESBL producing strains.

Disclosures
All authors: No reported disclosures.
635. Genomic Evolution and Progression of Antimicrobial Resistance in a Series of Extensively Drug-Resistant Pseudomonas aeruginosa (XDR-Pa) Isolates from a Cystic Fibrosis Lung Transplant Recipient
Authors: Yasmin Mohamad , Adams Mark D , Marshall Steven , Abbo Lilian , Benjamino Jacquelynn , Krishnan Nikhil , Rojas Laura J , Scott Jacob , Jacobs Michael , Rhoads Daniel D , Perez-Cardona Armando , Martinez Octavio , Perez Federico , Bonomo Robert A 
Published: October 2019

Abstract

Background
Chronic respiratory infection due to extensively drug-resistant Pseudomonas aeruginosa (XDR-Pa) is a significant cause of mortality in cystic fibrosis (CF) patients. The CF respiratory anatomy, chronic antibiotic use, and PA colonization creates a milieu for high evolutionary pressure and genetic diversity. We sought to explore the progression of antibiotic resistance and genome evolution of XDR-Pa in a longitudinal series of isolates collected from an18-year-old CF patient who underwent lung transplantation.

Methods
Consecutive respiratory isolates were collected from December 2016 to March 2018. Standard disk diffusion methods were used to evaluate antimicrobial susceptibility. Whole-genome sequencing (WGS) data were obtained on an Illumina NextSeq and assembled. Variants were identified using the GATK HaplotypeCaller and their functional impact was determined using snpEff. Maximum likelihood phylogenetic trees were constructed using MEGA and BEAST. Panther was used to test for enrichment of Gene Ontology functional categories among mutated genes.

Results
Phylogenetic analysis of complete genome sequences showed that 18 isolates formed a monophyletic group. Analysis using BEAST showed that genomes shared a common ancestor that was present prior to transplant. Over 300 single nucleotide variants and small insertion-deletion mutations were found, in comparison with a reconstruction of the ancestral sequence (Figure 1). Shared patterns of antibiotic susceptibility profiles were largely concordant with phylogenetic clustering and trended toward a decrease in susceptibility over time. Two different frameshift mutations in the DNA mismatch repair gene mutL were found in 15 genomes and these exhibited an increased rate of transition to transversion mutations, consistent with a hypermutator phenotype.

Conclusion
WGS of XDR-Pa identified variations in antibiotic resistance and virulence genes. Changes in mutL likely accelerated the accumulation of mutations. Multiple related sub-groups of strains appear to have been circulating prior to transplant and continued to diverge during the treatment period. Correlating antibiotic pressure, susceptibility profiles, and WGS in XDR-Pa from a single patient reveals the clinical impact of genomic evolution in CF.

Disclosures
All authors: No reported disclosures.
638. Comparative Genomics of Mycoplasma pneumoniae Isolated From Children with Pneumonia: South Korea, 2010–2016
Authors: Lee Hoan J , Kee Lee Joon , Young Choi Yun , Young Park Ji , Seong Moon-Woo , Hwa Choi Eun 
Published: October 2019

Abstract

Background
This study applied high-throughput whole-genome sequencing (WGS) technologies to investigate the comparative genomics of 30 M. pneumoniae strains isolated from children with pneumonia in South Korea during two epidemics from 2010 to 2016 in comparison with a global collection of 48 Mycoplasma pneumoniae strains which includes seven countries ranging from 1944 to 2017.

Methods
A total number of 30 M. pneumoniae strains were selected for whole-genome sequence analysis from two epidemics, 2010–2012 and 2014–2016. Next-generation sequencing (NGS) of all M. pneumoniae strains was performed using the Illumina MiSeq desktop sequencer. Comparative genomic analysis was performed using BLAST Ring Image Generator (BRIG), MAUVE, MAFFT, CLC Phylogeny Module, SnpEff, and Pathosystems Resource Integration Center (PATRIC).

Results
The 30 Korean strains had approximately 40% GC content and ranged from 815,686 to 818,669 base pairs, coding for a total of 809 to 828 genes. Overall, BRIG revealed 99% to>99% similarity among strains. The genomic similarity dropped to approximately 95% in the P1 type 2 strains when aligned to the reference M129 genome, which corresponded to the region of the p1 gene. MAUVE detected four subtype-specific of which were all hypothetical proteins except for one tRNA insertion in all P1 type 1 strains. eBURST analysis demonstrated two clonal complexes which are accordant with the known P1 typing, with higher diversity among P1 type 2 strains. The phylogenetic tree constructed with 78 genomes including 48 genomes outside Korea, formed three clusters, in which the sequence type 3 strains from Korea were divided into two P1 type 1 clusters.

Conclusion
The comparative genomics of the 78 M. pneumoniae strains including 30 strains from Korea by WGS reveals structural diversity and phylogenetic associations, even though the similarity across the strains was very high.

Disclosures
All authors: No reported disclosures.
642. Higher Diagnostic Accuracy with Ultrasensitive Detection of Helicobacter pylori Stool Antigen Using Single-Molecule Counting Technology
Authors: Katzenbach Phoebe , Dave Gipshu , Mukherjee Ali , Sandlund Johanna , Estis Joel , Nolan Niamh , Banaei Niaz , Noland Brian 
Published: October 2019

Abstract

Background
Current diagnostic methods for Helicobacter pylori infection include fecal antigen tests, 13C-urea breath test, and gastric biopsy. The breath test is limited by poor specificity and the fecal antigen tests by poor sensitivity. We have developed a prototype assay for detection of H. pylori antigen in human stool, powered by ultrasensitive Single Molecule Counting technology, and compared the analytical performance to a commercially available enzyme-linked immunoassay (EIA) antigen test.

Methods
The Singulex Clarity H. pylori antigen assay incubates diluted stool with capture and fluorescent-labeled detection antibodies. After incubation and wash steps, fluorescent molecules are eluted and single-molecule fluorescence measured by detected events (DE′). Analytical performance was compared with a commercial EIA (Premier Platinum HpSA® Plus, Meridian Bioscience, Inc.) using serial dilutions of H. pylori control (~37,500–1.7 ng/mL) and high positive stool (signal to noise ratio >2). Clinical performance was evaluated using two cohorts, one had 10 EIA-negative and 10 EIA-positive samples and the other 13 high positives (> 0.500 at 450/630) and 5 low positives near the EIA cutoff (0.100–0.500 at 450/630). One sample was excluded due to discordant EIA results, and three to reader flags.

Results
The lower limit of detection of the Clarity H. pylori assay was 1.7 ng/mL and the EIA 1,250 ng/mL (IFU: LOD 4.67 ng/mL). A high positive stool sample was detectable by the Clarity H. pylori assay diluted 1:10,000,000 and by the EIA 1:10,000. The Clarity H. pylori assay showed a 729-fold increase in lower limit of detection and 1,000-fold increase in endogenous antigen lower limit of detection compared with the EIA. Clarity signal ranged from 46–665 DE’ for EIA-negative samples and 487,484–576,747 DE’ for EIA-positive samples.

Conclusion
The Singulex Clarity H. pylori antigen assay may have orders of magnitude higher analytical sensitivity than the commercial EIA and demonstrated 100% positive agreement and 100% negative agreement on detection of H. pylori antigen in human stool samples. The ultrasensitive Clarity H. pylori assay has the potential for high sensitivity and specificity to improve current diagnostic options for H. pylori infection; however, additional multicenter studies are required.

Disclosures
All authors: No reported disclosures.