bluuebunny/crossref_metadata_2025_split huggingface dataset:
541. Factors Associated with the Persistence of Colonization by Multidrug-Resistant Organisms in Cali, Colombia
Authors: Diego Velez Juan , Orrego Marly , Montes Sofia , Tafur Eric , Parra Claudia M , Castro Andres , Milena Ruiz Ana , Guarin† Nora , Rosso Fernando 
Published: October 2019

Abstract

Background
Colonized patients represent a reservoir for transmission to other non-colonized patients for health institutions, so surveillance measures and contact precautions have been taken in the worldwide to mitigate transmission. However, despite the different interventions implemented, factors associated with persistence have not been evaluated in our context. This study aimed to describe the persistence of colonization in patients with multidrug-resistant organisms (MDROs) re-admitted to a health institution.

Methods
A retrospective observational study was conducted. Patients re-admitted with a previous positive rapid test for MDROs, who had received chlorhexidine bathing and contact precautions during hospitalization were included. Samples were obtained from two rectal and one nasal swap. Colonization was defined as MDRO detection in at least one anatomical site, in the absence of symptoms or signs of infection. Persistence was defined as two positive screening for the same MDRO. Laboratory tests were chromID®, CHROMID® CARBA and MacConkey agar. VITEK MS® MALDI-TOF conducted MDROs genus identification, and carbapenem-resistant was evaluated through Sensi-Disc™. Logistic regression was performed to examine any association between persistence and clinical data.

Results
A total of 4,362 screening for MDROs was analyzed form July 2015 to December 2016, and 142 patients were included in the study; the median age was 39 years (IQR=12–62) and 56% were male. The most frequent MDRO was carbapenem-resistant Enterobacteriaceae. There was a statistically significant difference in length of hospitalization (P = 0.003) and ICU (P = 0.035) between non-colonized and persistence of colonization. Factor associated with persistence of colonization included liver disease [OR=3.1; 95% CI: 1.068–9.019; P = 0.037], history of infection in the last year [OR=3.78; 95% CI: 1.036–13.839; P = 0.044], use of permanent urinary catheter [OR=6.48; 95% CI: 1.314–31.975; P = 0.022], history of gastrostomy before hospitalization [OR=5.37; 95% CI: 1.547–18.638; P = 0.008], and use of nasogastric tube [OR=5.14; 95% CI: 1.108–23.861; P = 0.036].

Conclusion
It is necessary to consider the previous history of infection in the last year, and other patient’s comorbidities and conditions as risk factors of persistence to colonization by MDROs.

Disclosures
All authors: No reported disclosures.
546. Seasonal Changes in the Prevalence of Antibiotic-Susceptible Acinetobacter baumannii Results in Increased Multidrug Resistance Rates During Winter Months
Authors: Calix Juan J , Feldman Mario 
Published: October 2019

Abstract

Background
Understanding the seasonal behavior of infections (“seasonality”) caused by Gram-negative pathogens, including Acinetobacter baumannii, is essential for the design of effective healthcare policies; however, the factors mediating seasonality remain elusive.

Methods
Over 2,000 A. baumannii cases identified in the BJC Health System between 2007 and 2017, were retrospectively analyzed according to isolation month, hospital acquisition, anatomical source, and antibiotic susceptibility profile.

Results
Compared with quarter 1 (Q1, December–February), A. baumannii case incidence was similar in Q2 (March–May) but significantly higher in Q3 (June–August) and Q4 (September–November). This seasonality was exhibited by antibiotic-susceptible but not antibiotic-resistant isolates. This was independent of tested antibiotic, anatomic source, or hospital vs. community acquisition.

Conclusion
Seasonality is absent from antibiotic-resistant A. baumannii cases. Selective decrease of antibiotic-susceptible cases in Q1/Q2 results in 50–100% increase in resistance rates compared with Q3/Q4. A. baumannii seasonality is possibly linked to the increased use of antibiotics during winter. As resistance determinants tend to be genetically linked in A. baumannii, pressure from community antibiotics may have the inadvertent effect of selecting for multidrug resistance. This link must be further studied, as it may also explain seasonality in other, more antibiotic-susceptible Gram-negative pathogens.

Disclosures
All authors: No reported disclosures.
554. The Changing Epidemiology of Methicillin-Resistant Staphylococcus aureus Causing Bacteremia in Hiroshima, Japan During 2008–2017
Authors: Kitagawa Hiroki , Hisatsune Junzo , Ohge Hiroki , Sugai Motoyuki 
Published: October 2019

Abstract

Background
Recently, the Japanese intrinsic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone (CA-MRSA/J), classified as sequence type (ST) 8 carrying staphylococcal cassette chromosome mec (SCCmec) type IVl (ST8-IVl), has been identified that causes invasive infections similar to those of USA300 clone. However, epidemiological information regarding epidemic CA-MRSA clones is limited in Japan. This study was performed to investigate the changing epidemiology of MRSA causing bacteremia in Japan.

Methods
We performed whole-genome sequencing of MRSA isolates causing bacteremia at Hiroshima University Hospital between January 2008 and December 2017. MRSA isolates were subjected to multilocus sequence typing, SCCmec typing and were analyzed for virulence factors. Clinical data of patients with MRSA bacteremia were analyzed.

Results
A total of 193 MRSA strains causing bacteremia were identified during the study period. Among these, most belonged to ST764-IIa (30%; 59 of 193) and ST5-IIa (26.9%; 52 of 193). The proportion of ST5-IIa MRSA decreased from 39.6% (42 of 106) in 2008–2012 to 11.5% (10 of 87) in 2013–2017, and that of ST764-IIa MRSA increased from 23.6% (25 of 106) to 39.1% (34 of 87) in the same time period. The proportion of CA-MRSA (MRSA carrying SCCmec type IV or V) increased from 28.3% (30 of 106) in 2008–2012 to 42.5% (37 of 87) in 2013–2017. In CA-MRSA strains, clonal complex (CC) 8-IV MRSA was predominant (76.1%; 51 of 67). Those belonging to CC8-IV MRSA isolates were ST380-IVc (18 of 51), ST8-IVl (CA-MRSA/J; 15 of 51), ST8-IVj (15 of 51), ST8-IVa (2 of 51), and ST4803-IVl (1 of 51). The rate of hospital-onset infections of ST380-IVc, ST8-IVl, and ST8-IVj were 83.3%, 46.7%, and 60%, respectively. In CA-MRSA/J strains, including their variants (e.g., ST4803-IVl), 14 of 16 strains (87.5%) carried genes for toxic shock syndrome toxin (tst-1), enterotoxin C (sec), and enterotoxin L (sel), while none of the ST380-IVc and ST8-IVj MRSA strains carried these genes.

Conclusion
During the study period of 10 years, predominant ST5-IIa MRSA causing hospital-onset infections was replaced by ST764-IIa MRSA. In CA-MRSA clone, ST380-IVc, ST8-IVl (CA-MRSA/J), and ST8-IVj were dominant and have already spread to the healthcare environment.

Disclosures
All authors: No reported disclosures.
563. Association Between Chlorhexidine Gluconate Concentrations and Resistant Bacterial Bioburden on Skin
Authors: Nadimpalli Gita , O’Hara Lyndsay M , Leekha Surbhi , Harris Lisa , Blanco Natalia , Johnson J Kristie , Harris Anthony 
Published: October 2019

Abstract

Background
Little research exists to guide optimal Chlorhexidine gluconate (CHG) bathing practices. We examined the association between CHG concentrations and methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and vancomycin-resistant Enterococcus (VRE) on the skin. Also, we studied whether bioburden is affected by bathing method (2% CHG cloth vs. 4% liquid CHG soap) and time since last CHG bath.

Methods
Patients with MRSA, CRE and VRE at 4 US hospitals were enrolled. Skin swabs (arm, chest) were collected to quantify bioburden and CHG concentrations. Information on bathing method and time since last CHG bath was collected. χ 2 test, Spearman’s correlation, and linear regression were performed.

Results
253 patients were enrolled. On arm skin, MRSA was detected in 17 (19%), CRE on 16 (12%), and VRE on 12 (21%) patients. Detectable CHG levels were observed in 82 (93%) MRSA, 81 (79%) CRE, and 44 (79%) VRE patients. A negative correlation was observed between bioburden and CHG concentration for MRSA (rs = −0.11, P = 0.28) and CRE (rs = −0.02, P = 0.82) while a positive correlation was observed for VRE (rs = 0.15, P = 0.28). On chest skin, MRSA was detected in 25 (28%), CRE on 18 (12%), and VRE on 7 (13%) patients. Detectable CHG levels were observed in 83 (95.4%) MRSA, 78 (72%) CRE, and 43 (77%) VRE patients. MRSA bioburden was negatively correlated with CHG concentration (rs = −0.16, P = 0.12), while a positive correlation was noted for CRE (rs = 0.18, P = 0.06) and VRE (rs =0.24, P = 0.06). There was no significant difference in bacterial bioburden between CHG concentrations (>20 ppm vs. ≤20 ppm) at both skin sites (Table 1). The bioburden did not differ by method of CHG bath. The mean estimates of bacterial bioburden on both skin sites did not show a significant decrease with increase in CHG concentrations and were not affected by time since last bath (Table 2).

Conclusion
Detection of MRSA, CRE and VRE was infrequent irrespective of CHG bathing method and time since last bath. We found inconsistent associations between increasing CHG concentrations and bacterial bioburden. CHG bathing frequency may be optimized for individual patient populations to augment the reduction of bacteria. Additional research to understand the association of CHG skin concentrations and resistant bacterial burden is required.

Disclosures
All authors: No reported disclosures.
593. Burden of Healthcare-Associated Infections among Hospitalized Infants within Community Hospitals
Authors: Akinboyo Ibukunoluwa C , Young Rebecca R , Smith Michael J , Smith Becky A , Lewis Sarah S , Anderson Deverick J 
Published: October 2019

Abstract

Background
Healthcare-associated infections (HAI) remain the leading cause of morbidity and mortality among hospitalized children. Within community hospitals with targeted infection prevention efforts, participation in an infection control network has led to significant decreases in device or procedure-related infections among adult patients. The impact of these interventions has not been assessed in pediatric patients admitted to community hospitals.

Methods
We conducted a retrospective cohort study to describe the burden of HAI among hospitalized infants (< 1 year old) within 53 community hospitals participating in the Duke Infection Control Outreach Network (DICON) from 2013–2018. We determined the frequency of device-related HAI, central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI) and hospital-associated pneumonia or ventilator-associated events (HAP/VAE) using National Healthcare Safety Network (NHSN) definitions; and the burden of HAIs among neonatal intensive care units (NICU) and non-NICU centers. The trend of HAI was analyzed with Spearman’s correlation.

Results
Thirty hospitals reported 150 HAI among 141 infants over the 6-year period. Median (IQR) time to infection was 10 (4, 20) days after admission. Hospitals with a NICU (15) reported more HAI (median 5, (IQR: 3, 12)) than hospitals without a NICU (median 2 (IQR: 1, 2)) (P = 0.031). CLABSI represented 35% of HAI, HAP/VAE were 23% and CAUTI were 12%. The most frequently isolated primary organism for all HAI was Escherichia coli (22 HAI, 15%) which was also isolated in 39% of CAUTI. Methicillin-resistant and methicillin-susceptible Staphylococcus aureus (S. aureus) were the most commonly isolated organisms among CLABSI (17%) and HAP/VAE (33%). Nine centers with ≥4 years of NICU and Central line (CL) use data reported a median (IQR) rate of 1.2 (0, 2.4) CLABSIs/1,000 central line days. There was no change in median CLABSI rate over time (P = 0.47), Figure 1.

Conclusion
CLABSI, most commonly caused by S. aureus, represented the majority of HAI reported from hospitalized infants within community hospitals participating in an infection control network. Further research into device utilization practices may inform future interventions to reduce HAI.

Disclosures
All authors: No reported disclosures.
601. TelA and XpaC Are Novel Mediators of Daptomycin Resistance in Enterococcus faecium
Authors: Tran Truc T , Panesso Diana , Diaz Lorena , Rios Rafael , Arias Cesar A 
Published: October 2019

Abstract

Background
The YycFG system is an essential two-component regulatory system involved in cell wall homeostasis associated with the development of daptomycin (DAP) resistance in E. faecium. Importantly, the standard combination of DAP plus β-lactam is ineffective against strains harboring mutations in yycFG. Transcriptional profiling identified a cluster of two genes (xpaC and telA) that is upregulated in the presence of a YycGS333L substitution. xpaC and telA are annotated as 5-bromo-4-chloroindolyl phosphate hydrolysis and tellurite resistance proteins, respectively. Here, we aimed to determine the contribution of xpaC and telA in DAP resistance.

Methods
Non-polar in-frame deletions of xpaC/telA and complementation of xpaC were performed in clinical strain E. faecium R446RIF. All mutants were characterized by PFGE and sequencing of the open reading frames to confirm the deletion. DAP MIC determination was performed by Etest on Mueller–Hinton agar. Binding of DAP was evaluated using BODIPY-labeled DAP (BDP-DAP). Cell membrane phospholipid microdomains were visualized using 10-N-nonyl acridine orange. All assays were compared with a DAP-susceptible clinical E. faecium strain S447.

Results
R446RIFΔ telA and R446RIFΔ xpaCtelA did not alter DAP MICs in R446RIF (24–32 μg/mL). However, deletion of xpaC alone (R446RIFΔ xpaC) markedly decreased DAP MIC 8 fold (to 4 μg/mL). R446RIFΔ telA and R446RIFΔ xpaCtelA exhibited similar binding of BDP-DAP compared with parental R446RIF. In contrast, R446RIFΔ xpaC exhibited increased binding of the antibiotic molecule to the cell membrane, similar to that of DAP-susceptible S447. Complementation of xpaC restored DAP MIC to 32–48 µg/mL and decrease binding of DAP. NAO staining of S447, R446RIF, R446RIFΔ telA, R446RIFΔ xpaCtelA, and R446RIFΔ xpaC:: xpaC displayed septal and polar distribution. In stark contrast, R446RIFΔ xpaC showed a redistribution of phospholipid microdomains away from the septa.

Conclusion
XpaC is a key contributor to DAP binding and phospholipid architecture of E. faecium but only in the presence of an intact TelA. The xpaC and telA gene cluster is a novel mediator of DAP-resistance in E. faecium via theYycFG system and independent of the LiaFSR system

Disclosures
All authors: No reported disclosures.
618. Fluconazole-Resistant Candida albicans Vaginitis with Cross-Resistance to Azoles: A Case Report
Authors: Akdağ Damla , Pullukçu Hüsnü , Yamazhan Tansu , Yesim Metin Dilek , Reşat Sipahi Oğuz , Ener Beyza , Isikgoz Tasbakan Meltem 
Published: October 2019

Abstract

Background
Local and systemic use of azole derivatives are common in the treatment of vulvovaginal candidiasis. However, there are cases unresponsive to these agents. Herein, we present treatment and follow-up of a patient with fluconazole–itraconazole and voriconazole-resistant recurrent vaginal candidiasis.

Methods
A 37-year-old woman with no comorbidity used topical and oral antifungal/antibacterial medications (including fluconazole and itraconazole) in the treatment of recurrent vulvovaginitis, was hospitalized due to continuous complaints. Intense, white-colored, odorless vaginal discharge was observed on physical examination. Urine and vaginal swab samples were taken for mycological and bacteriological culture. Metronidazole (500 mg 3x1 i.v.) and high dose fluconazole (600 mg/day i.v.) were initiated empirically for the possibility of dose-dependent resistant Candida infection, but there was no clinical response.

Results
Candida albicans was isolated in vaginal swab culture, but response to systemic fluconazole treatment for one week was inadequate. Antifungal susceptibility test was performed by microdilution method according to CLSI M27A3 guidelines and MIC values were reported respectively; fluconazole 4 µg/mL (SDD), itraconazole 1 µg/mL (R), posaconazole 0.06 µg/mL (WT), voriconazole 0.25 µg/mL (SDD), anidulafungin ≤ 0.015 µg/mL (S), amphotericin B 0.06 µg/mL (WT). For the resistance mechanism, point mutation in the ERG11 gene and MDR1 and MDR2 from efflux pumps were investigated and only the G464S mutation was detected in the ERG11 gene. Treatment was switched to IV anidulafungin (200 mg on day 1 followed by 100 mg/day). Clinical response was achieved in the patient whose complaints were reduced, and there was no Candida in the repeated vaginal swab culture taken on day 3 of treatment. The patient was discharged after 2 weeks of treatment. She had no recurrence after 2 years follow-up.

Conclusion
It should be kept in mind that resistant strains may be responsible for recurrent and unresponsive vulvovaginal candidiasis cases. Although there is no case report in which anidulafungin is used for treatment and it should be kept in mind that the anidulafungin is also in the treatment as it is summarized.

Disclosures
All authors: No reported disclosures.
634. Incidence of vanC-Mediated Vancomycin-Resistant Enterococcus Bloodstream Infections at Children’s Hospital of Colorado and Implications for Empiric Enterococcal Therapy
Authors: Dodson Daniel S , MacBrayne Christine , Williams Manon , Parker Sarah 
Published: October 2019

Abstract

Background
The most well-known Enterococcal species, E. faecium and E. faecalis, can harbor high-level vancomycin resistance mediated by acquired vanA and vanB operons. However, other Enterococcal species such as E. gallinarum and E. casseliflavus (VCE), harbor intrinsic low-level vancomycin resistance mediated by an intrinsic vanC operon, and the incidence of these pathogens among pediatric patients is not clear. As the antibiotic resistance pattern of VCE is different than E. faecium and E. faecalis, a high prevalence of VCE may have implications for antibiotic therapy. We describe the incidence and susceptibility of VCE bloodstream infections at a large children’s hospital and compare to E. faecalis and E. faecium.

Methods
Positive blood culture results from 2013 to 2018 were obtained from the Children’s Hospital of Colorado data warehouse. All first-time positive cultures for Enterococcus were analyzed for species, susceptibility, and hospital unit location. First-time positive was defined as being at least 2 weeks after any previous positive Enterococcus blood culture. Susceptibilities were categorized by clinical laboratories standards institute (CLSI) guidelines.

Results
Of 240 positive isolates, 7% were ampicillin susceptible and vancomycin nonsusceptible (resistant or intermediate), vs. 6% that were ampicillin resistant and vancomycin susceptible. An additional 3% of isolates were not susceptible to either antibiotic; all of these were E. faecium. VCE accounted for 12% of our isolates while E. faecalis and E. faecium accounted for 66% and 16%, respectively. All VCE were susceptible to ampicillin, but 52% were nonsusceptible to vancomycin. VCE incidence, ampicillin resistance, and vancomycin nonsusceptibility were most prevalent in our hematology, oncology, and bone marrow transplant (BMT) units.

Conclusion
At our institution, an as yet unspeciated Enterococcus is equally likely to be ampicillin susceptible and vancomycin nonsusceptible as ampicillin resistant and vancomycin susceptible. This is driven by a significant incidence of VCE, especially on our hematology, oncology, and BMT units. Therefore, vancomycin may not provide adequate empiric Enterococcal coverage on these units, and the addition of ampicillin will be recommended.

Disclosures
All authors: No reported disclosures.
661. Ibalizumab Efficacy and Safety Through 48 Weeks of Treatment: Results of an Expanded Access Protocol (TMB-311)
Authors: Emu Brinda , DeJesus Edwin , Berhe Mezgebe , Leider Jason , Creticos Catherine , Weinheimer Steve , Cohen Zvi 
Published: October 2019

Abstract

Background
Ibalizumab (IBA), a humanized monoclonal antibody, is the first CD4-directed post-attachment HIV-1 inhibitor. It was approved by the FDA in March 2018 based on results from the pivotal Phase 3 TMB-301 clinical study.
The TMB-311 expanded access protocol Cohort 2 enrolled treatment-experienced patients with multidrug-resistant (MDR) HIV-1 infection to further evaluate the efficacy, safety and tolerability of IBA in combination with an optimized background regimen (OBR). Here, we report the results through 48 weeks of treatment in these patients.

Methods
Major eligibility criteria included HIV-1 viral load (VL) >1000 copies/mL, resistance to ≥1 antiretroviral (ARV) medication from three different ARV classes and full viral sensitivity to ≥1 ARV agent. Treatment started with IBA 2000 mg intravenously (IV) on Day 0 and then 800 mg IV (maintenance) every 2 weeks thereafter. OBR with ≥1 fully active agent also started at Day 0.

Results
Cohort 2 enrolled 38 patients with a median age of 53 years, mostly male (87%) and white (53%). At Baseline, median VL was 4.7 log10 copies/mL, CD4 cell count was 26 cells/mm3 and overall susceptibility score of 1. A ≥0.5 log10 decrease in VL from Baseline was achieved in 28 of 37 patients (76%) at Day 7. Of 24 patients who completed the Week 24 visit, 11 (46%) had HIV-1 RNA levels <50 copies/mL. Of 17 patients with a VL assessment at Week 48, 8 (47%) achieved <50 copies/mL. Seven patients did not have a Week 48 endpoint because they withdrew from the study to receive commercial IBA. At both time points, the median change in VL from Baseline was -2.6 log10 copies/mL. The most frequently reported treatment-emergent adverse events (TEAEs) were diarrhea (24%), headache (21%), and nausea, cough, rash, and fatigue (16% each). No injection site reactions related to IBA were reported. Most events were mild; 9 patients reported Grade ≥3 TEAEs. Two events were fatal (sepsis and cardiac arrest); neither related to IBA. One event of immune reconstitution inflammatory syndrome was reported and considered possibly related to IBA.

Conclusion
Results from Cohort 2 patients of TMB-311 (IBA + OBR) demonstrate durable viral suppression in this difficult-to-treat patient population and with a safety profile consistent with pivotal Phase 3 study of IBA.

Disclosures
All authors: No reported disclosures.