bluuebunny/crossref_metadata_2025_split huggingface dataset:
553. Outbreak of Methicillin-Resistant Staphylococcus aureus Associated with Hepatic Artery Infusion Pumps
Authors: Calero Christopher , Usiak Shauna , Aslam Anoshé , Palazzolo Margaret A , McMillen Tracy , Babady Esther , Guest Rebecca , Lucca Bianchi Anabella , Robilotti Elizabeth , Kamboj Mini 
Published: October 2019

Abstract

Background
Device-related infections account for a fourth of all HAIs. Hepatic artery infusion pump (HAIP) devices are used to deliver chemotherapy directly into the hepatic artery. This device is used primarily in patients with colorectal cancer for the management of unresectable hepatic metastases. We describe the infection rates and outbreak management of MRSA-related infections in newly placed HAIPs.

Methods
In December 2018, a cluster of 3 MRSA cases was identified within 15–26 days of HAIP insertion. From January 1, 2017 to December 31, 2018, patients with culture proven SSIs within 30 days of HAIP placement were identified through the infection control database to establish baseline rates. Procedural denominator data were found by querying CPT procedure codes. EMR was reviewed to extract clinical characteristics. In response to the cluster, healthcare personnel (HCP) were screened for MRSA by PCR and environmental cultures performed. PFGE and whole-genome sequencing (WGS) was performed to compare isolates recovered in culture and SNP analysis performed using the BioNumerics software v7.6.

Results
IIn December 2018, 3/15 patients with HAIP procedures developed MRSA infections within 30 days of the procedures (post-op days: 15,16,26). The baseline 30 day SSI rate for HAIP in 2017 was 1.3% (2/160). No infections, prior to the cluster, in 2017–18 were MRSA related. All patients were male, with a median age of 49 years (range: 45–54). Sixty HCP who provided direct care during the peri and early post-operative period for the 3 cases were screened for MRSA carriage; 2/60 (3.3%) were positive. All 56 environmental cultures were negative for MRSA. WGS of the 3 patient samples showed 2/3 samples were identical (1 SNP difference); confirming common source transmission. Only one HCP isolate was available for WGS and shown to be unrelated to the two patient isolates. Both employees underwent decolonization. Review of HAIP handling did not reveal obvious lapses, but mask use and strict hand hygiene were enforced with HCPs. No further infections have been identified in the 76 procedures since the cluster.

Conclusion
WGS confirmed common source transmission between two newly placed HAIP although the definitive source could not be identified. Surveillance and prevention efforts should extend to all types of vascular access devices.

Disclosures
All authors: No reported disclosures.
579. Machine-Learning Based Models for Prediction of Recurrence-free Catheter Retention After ALT Treatment of CLABSI in a Pediatric Population
Authors: Walker Lorne W , Nowalk Andrew J , Visweswaran Shyam 
Published: October 2019

Abstract

Background
Deciding whether to attempt salvage of an infected central venous catheter (CVC) can be challenging. While line removal is the definitive treatment for central-line associated bloodstream infection (CLABSI), salvage may be attempted with systemic antibiotics and antibiotic lock therapy (ALT). Weighing risk and benefit of CVC salvage is limited by uncertainty in the future viability of salvaged CVCs. If a CVC is likely to require subsequent removal (e.g., due to recurrent infection) salvage may not be beneficial, whereas discarding a viable CVC is also not desirable. Here we describe a machine learning approach to predicting outcomes in CVC salvage.

Methods
Episodes of pediatric CLABSI cleared with ALT were identified by retrospective record review between January 1, 2008 and December 31, 2018 and were defined by a single positive central blood culture of a known pathogen or two matching cultures of a possible contaminant. Clearance was defined as 48-hours of negative cultures and relapse was defined as a matching positive blood culture after clearance. Predictive models [logistic regression (LR), random forest (RF), support vector machine (SVM) and an ensemble combining the three] were used to predict recurrence-free CVC retention (RFCR) at various time points using a training and test set approach.

Results
Overall, 712 instances CLABSI cleared with ALT were identified. Demographic and microbiological data are summarized in Tables 1 and 2. Few (8%) instances recurred in the first 28 days. 58% recurred at any time within the study period. Rates of RFCR were 75%, 43%, 22% and 10% at 28, 91, 182 and 365 days. Machine learning (ML) models varied in their ability to predict RFCR (Table 3). RF models performed best overall, although no model performed well at 91 days.

Conclusion
ML models provide an opportunity to augment clinical decision making by learning patterns from data. In this case, estimating the likelihood of useful line retention in the future could help guide informed decisions on salvage vs. removal of infected CVCs. Limitations include the heterogeneity of clinical data and the use of an outcome capturing both clinical decision making (line removal) and infection recurrence. With further model development and prospective validation, practical machine learning models may prove useful to clinicians.

Disclosures
All authors: No reported disclosures.
585. Shifting Focus Toward Healthcare-Associated Bloodstream Infections: Need for More NICU-Specific NHSN Definitions
Authors: Advani Sonali D , Murray Thomas , Bizzarro Matthew 
Published: October 2019

Abstract

Background
Healthcare-associated bloodstream infections (HABSIs) are a significant cause of mortality and morbidity in the neonatal intensive care unit (NICU) population. Our objectives were to review the epidemiology of HABSIs in our NICU and to examine the applicability of National Healthcare Safety Network (NHSN) definitions to the NICU population.

Methods
We performed a retrospective review of all neonates admitted to the 54-bed level IV NICU at Yale-New Haven Children’s Hospital with a HABSI between January 1, 2013 and December 31, 2018. HABSI was defined as a positive blood culture at >72 hours of life growing an organism not considered a contaminant. Clinical definitions per treating NICU team and NHSN site-specific definitions were compared for source attribution using McNemar’s Chi-square test.

Results
We identified 88 HABSIs with an incidence rate of 0.81 per 1,000 patient-days. Only 13% of these were central line-associated bloodstream infections (CLABSIs). Infants with a HABSI had median birth weight and gestational age of 830 grams and 26 weeks, respectively, with a high percentage requiring mechanical ventilation parenteral nutrition and vascular access (Table 1). Sepsis-related mortality was 24%. The majority of HABSIs were caused by gram-positive and gram-negative bacteria (Figure 1). Most were secondary to necrotizing enterocolitis, pneumonia or a source that was not identified (Table 2). NHSN definitions were less likely to identify a source compared with clinical definitions per NICU treating team (P < 0.001, Table 2). Fifty percent of patients without an identified source of infection by NHSN criteria were identified with a Mucosal Barrier Injury (MBI) organism, likely causing bacteremia from gut translocation.

Conclusion
HABSIs occur in premature babies with comorbidities, and are more prevalent than CLABSIs. Gut translocation with MBI organisms may be an important unidentified source of HABSIs in neonates. With the increasing focus on HABSI prevention, there is a need for better NHSN definitions for source attribution of bloodstream infections in neonates.

Disclosures
All authors: No reported disclosures.
591. Mupirocin and Chlorhexidine Resistance in Staphylococcus aureus Isolated from Children in South Korea
Authors: Na Kim Bi , Mi Kang Hyun , Hee Park Sun , Park Joonhong , Han Kang Jin , Kim Jong-Hyun 
Published: October 2019

Abstract

Background
Increasing prevalence of mupirocin-resistant Staphylococcus aureus have been reported, and chlorhexidine resistance has become an issue. This study aimed to investigate the prevalence of mupirocin and chlorhexidine resistance in both colonized and infection causing Staphylococcus aureus in children, and find factors associated with increased virulence.

Methods
Staphylococcus aureus, isolated from children <18 years old admitted at a single center, were collected prospectively from August 2017 to July 2018. The isolates underwent multilocus sequence typing and were screened for genes causing chlorhexidine resistance (qac A/B), quaternary ammonium resistance (smr), mupirocin resistance (ileS mutation, Mup A, MupB), and Pantone Valentine Leucocidin (pvl) toxin.

Results
During the study period, a total of 49 non-duplicate isolates were included, of which 69.4% (n = 34) were Methicillin-resistant Staphylococcus aureus (MRSA). Of the colonizers (n = 25), the most common sequence type was ST 72 (68.0%), whereas among pathogens (n = 24), ST 72 (29.2%) and ST 89 (29.2%) were most prevalent. Pathogens in this study caused abscess formation (n = 3), sepsis (n = 4), and skin infections such as cellulitis and omphalitis (n = 17). Mupirocin resistance was found in 16.0% among colonizers vs. 45.8% among pathogens (P = 0.023). High-level mupirocin resistance was more common (n = 3/25, 12.0%) than low-level mupirocin resistance (n = 1/25, 4.0%) in colonizers, whereas, pathogens had similar rates of low-level (25.0%) and high-level (n = 20.8%) mupirocin resistance. PVL toxin gene was more frequently found in colonizers than pathogens (64.0% vs. 33.3%, P = 0.032), and all isolates had quaternary ammonium resistance genes. Chlorhexidine resistance gene was found in only 3 MRSA isolates colonized in the nares of preterm infants. All were SCCmec type 4, however, two were ST 72, spa type t1054, which had high -level mupirocin resistance and PVL toxin gene.

Conclusion
A PVL toxin gene-positive MRSA which had genes causing mupirocin and chlorhexidine resistance were found in the nasal carriages of preterm infants. These stains may cause failure of MRSA eradication in hospital settings, using conventional methods of nasal mupirocin application and chlorhexidine bathing.

Disclosures
All authors: No reported disclosures.
605. Identification of a Novel CMY-Variant Enzyme in a Clinical Escherichia coli Strain with Treatment-Emergent Ceftazidime–Avibactam Resistance
Authors: Aitken Samuel L , Aitken Samuel L , Endres Bradley T , Khan Ayesha , Shropshire William C , Borjan Jovan , Bhatti Micah M , Sahasrabhojane Pranoti V , Doi Yohei , Shields Ryan K , Shelburne Samuel A , Shelburne Samuel A 
Published: October 2019

Abstract

Background
Ceftazidime–avibactam (CZA) is a novel β-lactam / β-lactamase inhibitor with in vitro activity against multidrug-resistant Gram-negatives, including those harboring CMY-2 enzymes. Treatment-emergent resistance to CZA has been described in KPC-producing Klebsiella pneumoniae but has not been described in non-carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CRE).

Methods
A patient with an intra-abdominal infection due to a carbapenem-resistant E. coli (ertapenem MIC 16 µg/mL; meropenem MIC 2 µg/mL; CZA MIC 2 µg/mL; carbapenemase negative) was treated with CZA. On day 48 of therapy, a CZA resistant, carbapenem-sensitive E. coli was identified from abdominal drainage (CZA MIC ≥256 µg/mL; meropenem MIC 0.19 µg/mL). Illumina MiSeq whole-genome sequencing (WGS) was performed on both isolates to identify potential resistance mechanisms. The ResFinder database was used to identify known β-lactamase enzymes, and in silico modeling of β-lactamase structure was assessed.

Results
WGS revealed that both isolates were ST410 E. coli, with the sole difference in β-lactam resistance determinants between the two being a novel CMY β-lactamase harbored on an Inc1-type conjugative plasmid in the second isolate. The novel CMY has 4 amino acid substitutions relative to CMY-2: A134E, Q140K, V231S, and N366Y. The V231S substitution is found in CMY-42 and has previously been associated with increased ceftazidime hydrolysis. The remaining three substitutions have not previously been identified. Previous studies have identified that substitutions at position 366 influence the rate of ceftazidime hydrolysis rate. Preliminary protein structure analysis suggests that positions 140 and 366 are in the active site. No other differences in β-lactam resistance determinants were identified between the first and second isolates.

Conclusion
To our knowledge, we have identified the first case of CMY-associated CZA resistance. Given the widespread and transferrable nature of CMY enzymes, this finding raises concern for additional cases of resistance with increasing usage of CZA. Further analysis is needed to identify the mechanism by which this enzyme confers CZA resistance.

Disclosures
Samuel L. Aitken, PharmD, Melinta Therapeutics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
609. Differing Genotypic Contexts Between E. coli and A. baumannii Modulate the Role of blaADC-7 in the Development of Antibiotic Collateral Sensitivity
Authors: McClure Erin , Newman Julia , Krishnan Nikhil , Rutter Joseph , Hujer Andrea M , Adams Mark D , Scott Jacob , Bonomo Robert A 
Published: October 2019

Abstract

Background
Antibiotic resistance is a global health crisis. While persistent drug discovery of novel antibiotics has previously been relied upon to thwart resistance, evolution inevitably perseveres. While genes conferring antibiotic resistance have previously been characterized, it is unclear how varying genetic contexts can change the antibiotic resistance phenotype a given gene confers.

Methods
The DH10B strain of E. coli was transformed with a blaADC-7 plasmid. In 12 evolutionary replicates, the modified E. coli strain and a clinical strain of A. baumannii containing the same resistance gene were passaged daily for 10 days on cefepime gradient agar plates with gradually increasing concentrations of cefepime. MICs of cefepime and a diverse set of 15 other drugs were determined for the parental strains and after the final passage passage. MIC of cefepime after intermediary passages were determined for select replicates. Lastly the blaADC-7 gene after the final passage was sequenced.

Results
At the end of 10 passages, collateral sensitivity in A. baumannii was observed to tigecycline and fosfomycin in 5 and 6 replicates respectively, out of 12 total. 4 out of 12 E. coli replicates displayed collateral sensitivity to minocycline (Figure 1). In the third E. coli replicate, Sanger sequencing revealed a novel S286R mutation in blaADC-7 appearing in passage seven which preceded a several log fold increase in the MIC of cefepime (Figures 2 and 3). No additional mutations were found in the other evolutionary replicates.

Conclusion
Patterns of resistance varied among antibiotics of the same class, (e.g., tetracyclines, fourth-generation cephalosporins) in both E. coli and A. baumannii; however, A. baumannii expressed less widespread collateral resistance than E. coli. A previously undiscovered S286R mutation in blaADC-7 coincided with a pronounced increased in resistance to cefepime. Further studies are required to determine whether this mutation gives rise to a structural change in the protein product. Given that no other mutations were found, resistance to cefepime and subsequent collateral resistance to other antibiotics may have developed due to epigenetic changes or mutations outside the blaADC-7 genes. Indeed, future experiments with whole-genome sequencing may reveal such changes.

Disclosures
All authors: No reported disclosures.
610. Meropenem-vaborbactam (MV) In Vitro Activity Against Carbapenem-Resistant Klebsiella pneumoniae (CRKP) Isolates with Outer Membrane Porin Gene Mutations
Authors: Yasmin Mohamad , Marshall Steven , Jacobs Michael , Rhoads Daniel D , Rojas Laura J , Perez Federico , Bonomo Robert A 
Published: October 2019

Abstract

Background
Vaborbactam is a cyclic boronic acid β-lactamase inhibitor (BLI) developed to potently inhibit Ambler class A&C enzymes, including KPC carbapenemases. Metallo-β-lactamases (MBL) and some Class D oxacillinases (OXA) are not inactivated by vaborbactam. Meropenem-vaborbactam (MV) was recently approved for the treatment of carbapenem-resistant Enterobacteriaceae complicated urinary tract infections. Recent studies have identified outer membrane porin (Ompk35 and -36) mutations in Klebsiella pneumoniae (KP) as a mechanism of decreased susceptibility to MV. We evaluated the activity of MV against a historical cohort of KP clinical isolates with these porin gene mutations.

Methods
WGS of carbapenem-resistant KP clinical isolates was performed and those harboring mutations in Ompk35 or Ompk36 were selected for testing. Strain KP ATCC BAA-1705 was used as a positive control. Meropenem and MV minimum inhibitory concentrations (MIC) were determined by broth microdilution (BMD) in custom 96-well plates (ThermoFisher Scientific) with a constant 8 µg/mL vaborbactam concentration. The MIC of ceftazidime–avibactam (CZA) was determined by standard BMD reference methods and interpreted according to CLSI criteria.

Results
A total of 105 KP isolates with either partial or complete mutations in outer membrane porin genes were included in the analysis. All isolates were resistant to Meropenem. The median MV MIC was 0.03 µg/mL (range, 0.015 to >16 µg/mL). Eleven isolates (10.4%) were resistant to MV. Sixteen additional isolates (16.1%) demonstrated higher than expected MV MICs ranging from 1 to 4 µg/mL. Only 1/11 resistant isolates harbored a gene for MBL production. Gene mutations in blaKPC were not detected. See Table 1 for characteristics of resistant isolates.

Conclusion
Resistance and decreased susceptibility to MV is demonstrated in a historical cohort of KP clinical isolates dating back to 2013. WGS reliably identifies porin variants secondary to gene mutations in Ompk35 and Ompk36 as the underlying mechanism of decreased susceptibility. CZA appears to retain activity against these isolates. Caution should be exercised regarding the empiric use of MV against increasingly resistant KP as a result of non-β-lactamase-mediated mechanisms.

Disclosures
All authors: No reported disclosures.
617. Efficacy of Dimercaptosuccinic Acid (DMSA), a Zinc Chelator, in Combination with Imipenem Against Metallo-β-Lactamase Producing Escherichia coli in a Murine Peritonitis Model
Authors: Cheminet Geoffrey , Nordmann Patrice , Chau Francoise , Kieffer Nicolas , Peoc’h Katell , Massias Laurent , de Lastours Victoire , Fantin Bruno 
Published: October 2019

Abstract

Background
A strategy used by bacterial strains to resist β-lactam antibiotics is the expression of metallo-β-lactamases (MBL) requiring zinc for activity. The use of a zinc chelator may restore carbapenem activity against MBL-producing Enterobacteriaceae. DMSA is a heavy metal chelator approved in humans with a satisfactory safety record. Our objective was to evaluate the activity of DMSA in combination with carbapenems, in vitro and in a fatal murine peritonitis model, against MBL-producing Escherichia coli.

Methods
Isogenic derivatives of wild-type E. coli CFT073 producing the MBL NDM-1, VIM-2, IMP-1, and the serine carbapenemases OXA-48 and KPC-3 were constructed. Minimum inhibitory concentrations (MICs) of imipenem, meropenem, and ertapenem were determined against each strain alone or in combination with DMSA. Mice were infected with E. coli CFT073 or NDM-1 and treated intraperitoneally for 24 hours with imipenem 100 mg/kg every 4 hours, DMSA 200 mg/kg every 4 hours, or both. Mice survival rates and bacterial counts in peritoneal fluid (PF) and spleen were assessed at 24 hours.

Results
In vitro, DMSA in combination with each carbapenem permitted a significant decrease of the MICs against all MBL-producing strains, in a concentration-dependent manner. The maximum effect was found for the NDM-1 strain with a 6- to 8-fold MIC reduction, depending on the carbapenem used. NDM-1 strain became susceptible to carbapenems with concentrations of DMSA ≥6 mM. Increasing zinc concentrations above 1 mg/L (average human plasma concentration) did not alter this effect. No benefit of DMSA was observed against non-MBL strains. In vivo, when used alone, the DMSA regimen was not toxic in uninfected mice and ineffective against NDM-1-infected mice (100% mortality). Combination of imipenem and DMSA significantly reduced bacterial counts in PF and spleen as compared with imipenem alone (P < 0.001), and reduced mortality, although not significantly (11% vs. 37%, respectively, P = 0.12). No benefit of the combination was observed against CFT073.

Conclusion
DMSA is highly effective in vitro in reducing carbapenems MICs against MBL-producing E. coli and appears as a promising strategy in combination with carbapenems for the treatment of NDM-1-related infections.

Disclosures
All authors: No reported disclosures.
619. High Multidrug-Resistant due to TEM and CTX-M-1 Types of Extended-Spectrum β-Lactamase and blaNDM-1 Type Carbapenemase Genes among Clinical Isolates of Gram-Negative Bacilli in Asella, Central Ethiopia
Authors: Tufa Tafese B , André Fuchs , Abdissa Sileshi , Hurissa Zewdu , Martin Orth Hans , Achim Kaasch , Colin Mackenzie , Klaus Pfeffer , Torsten Feldt , Dieter Häussinger 
Published: October 2019

Abstract

Background
Acute infectious diseases and sepsis are among the leading causes of mortality in Ethiopia. The lack of local data concerning causative pathogens and resistance patterns results in suboptimal empirical treatment and unfavorable clinical outcome. The objective of this study was the characterization of bacterial pathogens in hospitalized patients with febrile infections in Central Ethiopia.

Methods
In total, 684 patients ≥1 year of age with fever admitted to the Asella Teaching Hospital from April 2016 to June 2018 were included. Blood and other appropriate clinical specimens were cultured. Susceptibility testing was performed using the Kirby–Bauer method and VITEK2. Confirmation of species identification and identification of resistance genes were conducted using MALDI-ToF and PCR at a microbiology laboratory in Düsseldorf, Germany.

Results
In total, 684 study participants were included; 54% were male and mean age was 26.7 years. Thus, the overall culture positivity rate was 7.5%. Of the 83 cultured organisms, 38(46%) were Gram-negative, 43(52%) Gram-positive, and 2(2%) Candida species. Among the 38 Gram-negative isolates, 16(42%) were E. coli, 15(39%) K. pneumoniae, and 4(11%) P. aeruginosa. Resistance against commonly used antibiotics for Gram-negative at the study site was: piperacillin/tazobactam 48%(13), ampicillin/sulbactam 93% (25), cefotaxime 89%(24), ceftazidime 74%(20), Cefipime 74%(20), meropenem 7%(2), amikacin 4% (1) and gentamicin 56%(15). Of 27 Gram-negative available for resistance-gene detection, blaNDM-1 was detected in one K. pneumoniae isolate and blaNDM-1 plus blaOXA-51 in A. baumannii. 81%(22/27) of the Gram-negative rods were confirmed to contain ESBL-genes as follows: TEM 17(77%), CTX-M-1-group 15(68%), SHV-6(27%) and CTX-M-9-group 2(9%). Among isolated S.aureus, 1(5%) was confirmed to be Methicillin-resistant S. aureus.

Conclusion
We found a high prevalence (81%) of ESBL-producing bacteria and 7.4% carbapenem resistance at the study site. More than half of Gram-negative isolates had two or more mobile resistance genes. These findings warrant the need for local national multidrug-resistant surveillance. Strengthening of antimicrobial stewardship programs is needed in order to face the threat of multidrug-resistant bacteria.

Disclosures
All authors: No reported disclosures.