bluuebunny/crossref_metadata_2025_split huggingface dataset:
569. Evaluation of a Povidone-Iodine Preparation for Nasal Decolonization of Methicillin-Resistant Staphylococcus aureus
Authors: Abou Ghaddara Hussein , Cadnum Jennifer , Ng Wong Y Karen , Donskey Curtis 
Published: October 2019

Abstract

Background
Mupirocin is commonly used for nasal decolonization of Staphylococcus aureus, but it has limitations including frequent emergence of resistance and non-adherence due to the need for repeated applications. Povidone-iodine is increasingly used as an alternative for nasal decolonization because it has a low propensity for emergence of resistance and rapid in vitro antibacterial activity. However, limited data are available on the microbiological efficacy of povidone-iodine for suppression of nasal S. aureus.

Methods
We compared the effectiveness of a single application or 5 days of twice daily application of a commercial 10% povidone-iodine preparation vs. phosphate-buffered saline for a reduction in nasal MRSA in methicillin-resistant S. aureus (MRSA)-colonized patients (9–11 per treatment group). Nasal swabs were collected for quantitative culture of MRSA before and at 1, 6, 12 and 24 hours after the single application or before each dose for the 5-day regimen. Analysis of variance was used to compare MRSA colony counts in povidone iodine vs. control patients.

Results
The concentrations of MRSA in the nares were similar for povidone-iodine and control group patients prior to treatment. As shown in the figure, the single application of povidone-iodine resulted in a statically significant reduction in nasal MRSA in comparison to controls at 2 and 6 hours after treatment (P10 colonies per swab).

Conclusion
Our findings suggest that single preoperative applications povidone-iodine could be useful for short-term suppression of S. aureus during the perioperative period. Additional studies are needed to evaluate the efficacy of the povidone-iodine preparation for MRSA decolonization when used at more frequent dosing intervals or in combination with chlorhexidine bathing.

Disclosures
All authors: No reported disclosures.
571. Determining the Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening in Antimicrobial Stewardship
Authors: Mergenhagen Kari A , Victor Kaitlyn , Sellick John , Wattengel Bethany A , Sumon Zarchi , Lesse Alan 
Published: October 2019

Abstract

Background
Treatment of suspected Methicillin-resistant Staphylococcus aureus (MRSA) is a cornerstone of many antibiotic regimens; however, some anti-MRSA antibiotics are associated with toxicity. The Veterans Affairs (VA) screens each patient on admission for MRSA nares colonization. The objective of this study was to determine whether MRSA nares screening can be used as a stewardship tool for de-escalation as well as avoidance of anti-MRSA therapy.

Methods
This was a retrospective cohort study across VA medical centers nationwide from January 1, 2007 to January 1, 2018. Data from patients with MRSA nares screening were obtained from the Corporate Data Warehouse. Subsequent clinical cultures within 7 days of the nares swab were evaluated for the presence of MRSA. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated for the entire cohort, as well as subgroups for specific culture sites. Cultures were considered to be from a sterile site if they were from a fluid/aspirate, bone, tissue, or blood taken from the periphery. NPVs and PPVs were calculated for each of these sterile sites.

Results
A total of 447,579 clinical cultures were included in the final analysis. The NPV of MRSA nares screening for ruling out MRSA was 95.7% for all cultures submitted. The sensitivity and specificity for positive clinical cultures were 67.4% and 83%, respectively. The NPV for bloodstream infections (n = 64,128) was 96.2% for intra-abdominal cultures (n = 8,071) was 97.9%, for respiratory cultures (n = 75,242) was 95.3%, for wound cultures (n = 95,832) was 90.4%, and for renal cultures (n = 164,330) was 99.1%. NPVs for sterile sites are as follows: intra-abdominal (n = 7,426) was 98.1%, respiratory (n = 15,583) was 95.2%, wound (n = 51,793) was 91%.

Conclusion
MRSA nares screening has a high NPV and specificity for ruling out potential MRSA infections at a variety of culture sites including bloodstream, intra-abdominal, respiratory, renal, and wounds. MRSA nares screening is a powerful stewardship tool for de-escalation and avoidance of empirical anti-MRSA therapy.

Disclosures
All authors: No reported disclosures.
581. The Epidemiology of Imipenem-Resistant Acinetobacter baumannii Bacteremia in a Pediatric Intensive Care Unit and Carbapenem Use
Authors: Kim Dongsub , Lee Haejeong , Croney Christina M , Sup Park Ki , Jung Park Hyo , Cho Joongbum , Soo Ko Kwan , Kim Jinyeong , Son Sohee , Choi Joon-sik , Choi Soo-Han , Huh Heejae , Ryeon Chung Doo , Yong Lee Nam , Kim Yae-Jean 
Published: October 2019

Abstract

Background
Acinetobacter baumannii (AB) infections cause high mortality and morbidity in intensive care unit patients. There are limited data on the epidemiology of imipenem-resistant A. baumannii (IRAB) amongst pediatric ICU patients.

Methods
A retrospective chart review was performed in patients with AB bacteremia in a pediatric intensive care unit at a tertiary teaching hospital from January 2000 to December 2016. Antimicrobial susceptibility tests, multilocus sequence typing (MLST) and PCR for antimicrobial resistance genes were performed for stored isolates. In addition, antibiotic prescription days of therapy (DOT per 1,000 patient-days) of the pediatric department from January 2001 to December 2016 was analyzed.

Results
Bacteremia episodes occurred in 27 patients. Male patients were 11 (41%) and the median age at the onset of bacteremia was 5.2 years (range, 0–18.6 years). There was a clear shift in antibiogram of AB during the study period. From 2000 to 2003, all isolates were imipenem-sensitive (ISAB, N = 6). From 2005 to 2008, both IRAB (N = 5) and ISAB (N = 4) were isolated. However, since 2009, all the AB isolates were IRAB (N = 12). In 33% (9/27) of patients, first AB was isolated from tracheal aspirate and patients developed bacteremia later (median duration from AB positive tracheal culture to AB positive blood culture, 8 days [range 5–124]). The overall mortality of patients with AB bacteremia was 59.3% (16/27) within 28 days. There was no statistical difference in mortality between ISAB and IRAB groups (50% vs. 71%; P = 0.42). From MLST analysis of 10 available isolates, sequence type 138 was predominant (N = 7). All 10 isolates were positive for OXA-23-like and OXA-51-like carbapenemase. In 2001, carbapenem DOT per 1,000 patient-days was 15.3 and later strikingly raised to 82.5 in 2009 when all the isolates were imipenem resistant. After this IRAB outbreak in PICU, proactive infection control and antimicrobial stewardship were reinforced among multidisciplinary teams in PICU. IRAB outbreak was terminated and carbapenem DOT per 1,000 patient-days was decreased to 51.7 in 2016.

Conclusion
IRAB bacteremia causes serious threat in high-risk pediatric patients in PICU. Proactive infection control measures and antimicrobial stewardship are crucial to manage serious IRAB infection in PICU.

Disclosures
All authors: No reported disclosures.
598. In Vitro Activity of Aztreonam in Combination with Ceftazidime–Avibactam, Amoxicillin–Clavulanate, and Piperacillin–Tazobactam vs. NDM-Producing Escherichia coli and Klebsiella pneumoniae Clinical Isolates
Authors: Walkty Andrew , Karlowsky James 
Published: October 2019

Abstract

Background
There are limited options available for the treatment of infections caused by Enterobacteriaceae that produce an NDM metallo-β-lactamase. The purpose of this study was to compare the in vitro activity of aztreonam in combination with three different β-lactam/β-lactamase inhibitors (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam) vs. NDM-positive Enterobacteriaceae clinical isolates.

Methods
Seven Escherichia coli and three Klebsiella pneumoniae clinical isolates (all NDM-positive by PCR) were included in this study. The in vitro activities of ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam, and aztreonam were determined by disk diffusion as described by CLSI. For synergy testing, disks containing a β-lactamase inhibitor (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin tazobactam) were applied to Mueller–Hinton agar plates inoculated with the test organisms, and the plates were incubated for 1 hour. The disks were then removed and aztreonam disks were dropped on the previous disk sites. The plates were then incubated as per standard CLSI recommendations for disk diffusion testing.

Results
All ten isolates demonstrated phenotypic resistance to aztreonam, amoxicillin-clavulanate, and piperacillin–tazobactam, and eight were resistant to ceftazidime–avibactam (CLSI breakpoints). The zone diameter observed for aztreonam in combination with ceftazidime–avibactam was greater than for either antimicrobial on its own for nine isolates. Seven isolates (70%) had susceptibility to aztreonam restored (zone diameter ≥21 mm) in the presence of avibactam. Aztreonam in combination with amoxicillin-clavulanate demonstrated in increase in zone diameter for all isolates relative to the zone for each antimicrobial alone, but only two (20%) had aztreonam susceptibility restored. Aztreonam susceptibility was not restored for any of the isolates in combination with piperacillin–tazobactam.

Conclusion
Of the three β-lactam/β-lactamase inhibitor-aztreonam combinations evaluated, ceftazidime–avibactam plus aztreonam demonstrated the greatest in vitro activity vs. NDM-producing Enterobacteriaceae.

Disclosures
All authors: No reported disclosures.
615. Daptomycin (DAP) Synergy with β-Lactams in DAP-Resistant (DAP-R) E. faecium (Efm) Is Dependent On PBP5 Sequence and β-Lactam-binding Affinity
Authors: Khan Ayesha , Kebriaei Razieh , Singh, Kavindra V , Murray Barbara E , Rybak Michael J , Arias Cesar A 
Published: October 2019

Abstract

Background
DAP in combination with β-lactams is a viable option to treat recalcitrant DAP-R/tolerant strains of Efm. Ampicillin (AMP), ceftaroline (CPT), and ertapenem (ERT) have the best synergism. Using a DAP tolerant strain (503; DAP MIC 2 µg/mL) of Efm, we previously showed that AMP, CPT, and ERT combined with DAP were effective in reducing bacterial loads and prevented emergence of resistance in a simulated endocardial vegetation model. However, against a DAP-R Efm strain (R497, DAP MIC of 16 µg/mL), CPT, ERT failed to synergize with DAP. Here, we dissect the mechanistic basis of the differing DAP plus β-lactam synergistic effect.

Methods
We performed comparative transcriptional profiling of pbp genes in Efm 503 vs. R497 using qRT–PCR. PBP5 protein levels were assessed by immunoblotting. The β-lactam-binding affinity of PBPs was quantified with bocillin-FL staining and SDS–PAGE. PBP5 sequences of Efm Com15 (AMP and DAP-susceptible strain) and clinical strains S447, 503 and R497 (all with AMP MIC > 256 µg/mL) were compared in silico to identify amino acid (AA) differences in key protein sites which were verified with sequencing

Results
Pbp gene transcripts and PBP5 amounts were similar between 503 vs. R497. Interestingly, bocillin SDS–PAGE showed increased β-lactam binding affinity in PBP5 of 503 compared with that of R497 and S447. PBP5 sequences of S447 and R497 were identical. All three clinical strains had classic mutations (M485A and 466’S) important for high-level AMP-R. However, 503 had additional substitutions in the transpeptidase domain (H408Q, A462V, T546N, T558A, S582G, V586L) and penicillin-binding domain (Q632K, L642P) compared with R497 and S447. The latter AA sequences in 503 are common to AMP-susceptible Efm strains

Conclusion
We uncovered that a “hybrid” pbp5 allele of 503 (DAP-tolerant) correlated with synergism of DAP plus AMP, CPT or ERT and was associated with increased PBP5 β-lactam binding affinity. Lack of synergism of DAP plus CPT or ERT is associated with specific PBP amino acids in the transpeptidase and penicillin-binding domains. Thus, pbp5 alleles are major determinants of the DAP plus β-lactam synergistic effect and could be used as a diagnostic tool to guide therapy in recalcitrant Efm infections

Disclosures
All authors: No reported disclosures.
633. Incidence, Microbial Etiology and Antibiotic Resistance Patterns with Special Reference to Shunt Infections in Neurosurgery at a Tertiary Center in North India
Authors: Gupta Manisha , Dhole Tapan 
Published: October 2019

Abstract

Background
Ventriculoperitoneal (VP) shunt is one of the commonest procedures in neurosurgical practice. A significant problem encountered in shunt procedures is infection, with infection rate ranging from 2 to 27%, often with poor outcome. The objectives of the study were to retrospectively evaluate the infection rate associated with central nervous system (CNS) shunts, assess the frequency of the pathogens as well as their antibiotic sensitivity pattern to aim at suitable prophylaxis.

Methods
Materials and Methods. Retrospective study conducted in the Microbiology Department, SGPGI, Lucknow from December 2017 to August 2018. A total of 168 CSF samples were received with a suspected shunt infection. Samples were analyzed by wet mount, India ink, gram stain and inoculated on blood agar and MacConkey agar. Identification and AST were done by MALDI- TOF system (VITEK-MS) and Vitek 2.0 automated sensitivity system.

Results
During the study period, 37/168(22.02%) CSF were positive by culture. Most frequently isolated pathogen was Acinetobacter baumannii 20/37(54.05%), followed by Staphylococcus aureus 06/37 (16.20%), Enterococcus faecalis 04/37(10.81%) coagulase negative staphylococci- CONS 04/37(10.81%), Klebsiella pneumoniae 2/37 (5.40%)and Escherichia coli 1/37(2.70%). 100% of A. baumannii and E. coli strains were found to be XDR and carbapenem-resistant showing susceptibility to minocycline and colistin only. All strains of K.pneumoniae were MDR. 66.7% S.aureus were MRSA and showed 100% resistance to fluoroquinolone. A similar pattern was seen in CONS. 25% of Enterococci were found to be vancomycin resistant.

Conclusion
Discussion and Conclusion. The antibiotic sensitivity pattern suggests aminoglycosides, colistin and vancomycin to be a better choice of antibiotics either prophylactically/therapeutically, which may result in effective sterilization of the CSF. Infections following VP shunt procedure are secondary to catheter blockage complicating the results of surgery and are associated with high morbidity and mortality rates.

Disclosures
All authors: No reported disclosures.
644. Comparative Evaluation of ETEST® ERV bioMérieux with the CLSI Broth Microdilution Method for Eravacycline MIC Determination
Authors: Sauvonnet Veronique , Fyfe Corey , Halimi Diane , Martelin Roland , Zambardi Gilles 
Published: October 2019

Abstract

Background
Eravacycline (XERAVA™) is a novel, FDA and EMA-approved fully-synthetic fluorocycline antibiotic developed by Tetraphase Pharmaceuticals Inc. for the treatment of complicated intra-abdominal infections (cIAI) including those caused by multidrug-resistant (MDR) pathogens that have been highlighted as urgent public health threats by the US CDC and the WHO.
The new ETEST ERV strip (MIC range 0.002 – 32 µg/mL) has been developed by bioMérieux and calibrated vs. the broth microdilution reference method (BMD) as described by the Clinical and Laboratory Standards Institute (CLSI) to determine the minimal inhibitory concentration (MIC) of eravacycline against Enterobacterales and Enterococci. The aim of the study was to compare ETEST ERV to the CLSI BMD method on a panel of 166 strains comprising 131 Enterobacterales and 35 Enterococci.

Methods
Quality control was performed with the CLSI QC strains E.coli ATCC 25922 and E.faecalis ATCC 29212. The ETEST ERV strip was applied on a Mueller–Hinton agar plate previously seeded with a 0.5 McF bacterial suspension. After incubation for 16–20H at 35°C, the reading was performed using the bacteriostatic mode i.e.,80% of growth. The FDA-approved breakpoints were applied (S≤0.5µg/mL for Enterobacterales and S ≤0.064 µg/mL for Enterococci).

Results
The MIC essential agreement was 99.4% at ±1 dilution for the whole panel and the category agreement was 96.4% with 4.8% Major Errors (1 E. coli, 2 K. pneumoniae, 1 K.aerogenes, 1 C. koseri, 1 E. faecalis), all at ±1 dilution around the single breakpoint. No Very Major Error (VME) was observed.

Conclusion
In this study, the new ETEST ERV strip has been found to be substantially equivalent to the CLI reference method. MIC end-points appear easier to read in comparison to the reference method. With a 15-dilution MIC range and simplicity of use, ETEST ERV could represent a valuable tool for MIC determination and an alternative to the BMD reference method. ETEST ERV will undergo clinical studies to seek IVD FDA clearance and CE marking. For Research Use Only. The performance characteristics of this product have not yet been established.

Disclosures
All authors: No reported disclosures.
654. Evaluation of the Febridx Host Response Point-of-Care Test to Differentiate Viral From Bacterial Etiology in Adults Hospitalized with Acute Respiratory Illness During Influenza Season
Authors: Beard Kate , Chan Cathleen , Mills Samuel , Poole Stephen , Brendish Nathan , Clark Tristan William 
Published: October 2019

Abstract

Background
Antibiotics are overused in patients hospitalized with acute respiratory illness (ARI). Diagnostic uncertainty regarding microbial etiology contributes to this practice and so a host response test that can distinguish between viral and bacterial infection has the potential to reduce unnecessary antibiotic use. The FebriDx is a low cost, rapid, host response POCT that uses fingerpick blood samples to distinguish between viral and bacterial infection but has not been evaluated in hospitalized adults with ARI.

Methods
We took fingerpick blood samples from adult patients with ARI, hospitalized during influenza season, and tested them on the FebriDx. Respiratory samples were tested for viruses on the FilmArray Respiratory Panel (FARP). The FebriDx was evaluated for ease of use, failure rate and accuracy of the results (Viral, Bacterial, Negative).

Results
149 patients were approached and 10 patients declined fingerpick testing. A valid result was obtained from 124/139 (89%) overall. Common user comments included test failure due to difficulty of getting blood to fill the capillary tube and difficulty in interpreting the results lines due to the variability of color change. 111/124 (89%) were tested for viruses by FARP. 69/111 (62%) had viruses detected. Of 69 patients with viruses detected, 41 (59%) had influenza, 12 (17%) rhino/enterovirus and 16 (23%) other viruses. 44/69 (64%) had a viral FebriDx result. For influenza-positive patients 34/41 (83%) had a viral FebriDx result, 1/12(8%) of rhinovirus-positive patients had a viral FebriDx result and 9/16 (56%) of patients with other viruses detected had a viral FebriDx result. These are interim results. Full results for 200 patients will be available at presentation.

Conclusion
The use of the FebriDx POC was associated with a failure rate of ~10% and problems with the interpretation of result lines. FebriDx was not sufficiently accurate in differentiating viral and bacterial infection when using detection of virus by PCR as the definition of viral infection; however, FebriDx had a high PPV for all viral detection and for influenza detection in this cohort and could have utility in hospital emergency departments.

Disclosures
All authors: No reported disclosures.
657. Evaluation of Nanopore-Based 16S Ribosomal RNA (rRNA) Gene Sequencing for the Development of a Rapid Infection Intervention Clinical Service
Authors: Batra Rahul , Baldan R , Cliff P , Patel Amita , Edgeworth Jonathan , Chand M 
Published: October 2019

Abstract

Background
Rapid and accurate identification of bacteria is the basis of appropriate antibiotic treatment and effective clinical decision-making. Next-generation sequencing (NGS) platforms such as Oxford Nanopore Technologies (ONT) holds the promise of a diagnostic revolution by overcoming the limitations of culture-based identification with rapid molecular detection of bacteria. We have developed a pilot to evaluate an ONT 16S rRNA gene assay with the ability to provide real-time analysis and identification of bacterial species. Our aim was to investigate whether long-read sequencing and high-speed analysis can be combined to create a clinically useful, rapid diagnostic tool.

Methods
A collection of bacterial isolates representing pathogenic species received by the clinical laboratory over 1 year was assembled. Sample preparation was as described in the ONT 16S protocol and included bead beating sample disruption, MagNA Pure automated nucleic acid extraction (Roche), and PCR amplification (Thermo). Sequencing was performed on the MinION and GridION X5 platforms. Output was analyzed with ONT’s automated EPI2ME 16S pipeline which assigns reads to taxa using BLAST results and the NCBI 16S Bacterial database.

Results
A total of 155 clinical samples with 139 species were sequenced. 119 species were identified at the species level. For 20 samples, a species in the same genus claimed the majority of reads, with the true species being matched to 3%-41% of reads. The average proportion of reads assigned to the correct species was 62.2%, specifically 67% for non-Enterobacteriaceae and 33% for Enterobacteriaceae. 4 clinical samples (3 Bronchoalveolar lavages (BALs), positive for (1) K. pneumoniae, (2) S. pneumoniae, and (3) S. pneumoniae, S. enterica, and S. typhimurium, and 1 bone positive for P. aeruginosa) were also analyzed with sequencing results matching culture.

Conclusion
Early results show that 16S rRNA sequencing coupled with real-time analysis was able to accelerate pathogen detection and was able to discriminate the majority of species from a relevant clinical collection. Pipeline refinement is required and subsequent confirmatory consensus-based identification may be a helpful adjunct. Nanopore sequencing shows promise as a rapid bacterial pathogen detection platform for clinical service.

Disclosures
All authors: No reported disclosures.
708. In Vitro Activity of Plazomicin vs. Clinical Isolates of Gram-Negative Bacilli, Including Aminoglycoside Nonsusceptible and Multidrug-Resistant Subsets, Recovered from Patients Across Canada as Part of the CANWARD study, 2011–2018
Authors: Walkty Andrew , Adam Heather , Baxter Melanie , Lagace-Wiens Philippe , Karlowsky James , Zhanel George 
Published: October 2019

Abstract

Background
Plazomicin (PLZ) is a next-generation aminoglycoside currently approved by the US FDA for the treatment of complicated urinary tract infections, including pyelonephritis. The purpose of this study was to evaluate the in vitro activity of PLZ against a large collection of Gram-negative bacilli obtained from patients attending Canadian hospitals.

Methods
Annually from 2011 to 2018, sentinel hospitals across Canada submitted blood, respiratory, urine, and wound isolates from patients attending ERs, medical and surgical wards, hospital clinics, and ICUs (CANWARD). Susceptibility testing was performed using broth microdilution (and breakpoints) as described by CLSI (FDA breakpoints used for PLZ).

Results
See table.
S, susceptible; NS, nonsusceptible; ESBL, extended-spectrum β-lactamase; MDR, multidrug-resistant (NS to antimicrobials from three or more classes); n.d., not defined.

Conclusion
PLZ demonstrated excellent in vitro activity vs. E. coli and K. pneumoniae clinical isolates, including aminoglycoside NS, ESBL-positive, and MDR subsets.

Disclosures
All authors: No reported disclosures.