bluuebunny/crossref_metadata_2025 huggingface dataset:
409. Using the Host Response to Reduce Unnecessary Antibiotic Use in Outpatient Acute Respiratory Infections
Authors: Sambursky Robert , Bell Annie
Published: October 2019

Background

Acute respiratory tract infections (ARI) often resolve without antibiotics. Yet, antibiotics are prescribed in 60–98% of cases despite lack of confirmed bacterial etiology. Antigen, culture and molecular testing identify pathogens; however, do not differentiate colonization from invasive infection. Since antibiotics are often prescribed despite the low prevalence of confirmed bacterial infection in patients with ARI, we analyzed the impact of adding host response biomarkers to the clinical and microbiological evaluation of outpatients with ARI.

Methods

A secondary analysis was performed using data from su suspected ARI cohorts derived from two clinical studies. A clinical reference algorithm, which included bacterial culture, respiratory PCR panels for viral and atypical pathogens, procalcitonin, CBC, serology, and Myxovirus resistance protein A (MxA), was used to define invasive infection based on pathogen detection plus host response and classify infections that may benefit from antibiotics. Antibiotics were considered “warranted” if patients exhibited a bacterial-specific host response, with or without bacterial pathogen detection, and a detected bacterial pathogen without a host response was deemed to be colonization and “at risk for antibiotics.” The percentage requiring antibiotics was calculated by dividing the number of patients with a host response for bacteria by the total number of patients at risk for receiving antibiotics (warranted + at risk). A Chi-square test was performed to determine the difference between patients likely to be treated with antibiotics, bacteria detected with or without host response and bacteria detected with a host response.

Results

Each dataset (Self, n = 205) and (Shapiro, n = 220) was analyzed separately and pooled (n = 445). Upon enrollment, 15% (Self) and 55% (Shapiro) were febrile. A pathogen was detected in 67% (Self) vs. 82% (Shapiro) subjects. Reduction in antibiotic prescription was calculated to be 35–44%, (P < 0.001–0.004), when host response was evaluated in addition to bacterial pathogen detection. Results presented in Table 1.

Conclusion

Host response may aid in differentiating viral infection and bacterial colonization from invasive bacterial infections requiring antibiotics.

Disclosures

All authors: No reported disclosures.
411. Does an Early Cytokine Response During Ebola Virus Disease Improve the Duration of Survival in Rhesus Macaques?
Authors: Blair Paul W , Martins Karen A O , Maryam Keshtkar-Jahromi , Kortepeter Mark G , Michael Keebaugh , Downs Isaac L , Cardile Anthony P
Published: October 2019

Background

Ebola virus disease results in a severe cytokine release resulting in organ failure and disseminated intravascular coagulation, often leading to death. An early post-exposure immune response may improve outcomes but that remains poorly characterized. Therefore, we evaluated select serum cytokine markers of immune activation in nonhuman primates (NHPs) for their association with duration of survival.

Methods

This was a post-hoc analysis of an interventional supportive care NHP study in which 13 rhesus macaques were inoculated intramuscularly with a target dose of 1000 PFU Zaire ebolavirus (Kikwit). We measured cytokines with a Luminex MAGPIX panel at baseline and daily starting day 3 post-exposure until euthanasia. Based on human clinical data, 10 cytokines and proteins were included in our analysis: IL-1ra, IL-6, IL-10, GM-CSF, MCP-1, MIP-1α, MIP-1β, IFN-γ, TNF-α, and C-reactive protein levels. After NHPs were divided into two groups by k-means clustering, we developed Kaplan–Meier curves for time to death (Figure 1). We visually explored Pearson’s correlation and kinetics of serum cytokines and log10viral load (Figure 1; Figure 2). We fitted cox regression models with each cytokine to evaluate the risk of early disease for each cytokine log10 level or log2-fold change. We performed a sensitivity analysis for MIP-1β centering the data at dpe 0.

Results

Among NHPs with temperature data, 83% (N = 10) developed fevers (>3 SD baseline) from dpe 3 to 4.The macrophage markerMIP-1β was associated with an increased risk of early death (per log10pg/mL increase, HR= 52.83 at dpe 3, adjusted P = 0.045). Surprisingly, this association was also observed at dpe 0 (HR= 36.88 at dpe 0, adjusted P = 0.044). Other cytokine levels or changes were not associated with an increased hazard of death.

Conclusion

Our findings did not support a role for early systemic cytokine release in improving survival. However, elevated baseline levels of the MIP-1β may predispose NHPs to early death from EVD. This finding could represent a target for therapeutic strategies and should be further researched.

Disclosures

All authors: No reported disclosures.
446. Epidemiology of Necrotizing Fasciitis in Korea: A Nationwide Study Using Claims Data
Authors: Kyoung Choi Hee , Seo GiHyeon , Han Euna
Published: October 2019

Background

Necrotizing fasciitis (NF) is a rare but fatal infectious disease that causes economic burdens on patient and the healthcare system. We investigated the incidence of necrotizing fasciitis (NF) and the seasonal variation of necrotizing fasciitis in Korea.

Methods

We analyzed a nationwide claims database from the Korean Health Insurance Review and Assessment Service from 2011 to 2017. For case definition, we used two different methods. First, patients who hospitalized with NF diagnosis code and received surgical intervention (NF code method) were defined as NF. Second, patients hospitalized with sepsis codes accompanying surgical intervention codes were defined as NF (sepsis code method). The annual incidence rate per 100,000 population of NF was calculated using the number of identified NF cases as numerator and age- and sex-specific midyear population as the denominator. Poisson regression models were used to assess the relationship of crude incidence rates to year, age, and sex. A multivariate Poisson regression model was used to investigate variations in trends in the monthly NF cases.

Results

The overall average annual incidence rate of NF during 2012–2017 was 0.86/100,000 by NF code method and 1.47/100,000 by the sepsis code method. The incidence of NF increased with age and 2.5 times higher in males than females across all age groups. Two-thirds of episodes occurred in diabetes patients. The incidence of NF occurred the most during summer. A multivariate Poisson regression model using national meteorological variables suggested that higher mean temperature of and larger numbers of NF cases during a prior month increased NF cases.

Conclusion

The possibility of NF should be suspected for the cases for an elderly man with diabetes in summer. From a national management perspective, the prior information on the number of NF incidences and the mean temperature can help predict NF outbreak.

Disclosures

All authors: No reported disclosures.
452. Antibiotic Duration, but Not Size, Impacts Clinical Cure of Limited Skin and Soft-Tissue Infection After Incision and Drainage
Authors: Lake Jason G , Fritz Stephanie
Published: October 2019

Background

Incision and drainage (I&D) is the most common treatment for skin abscesses. A recent randomized clinical trial (RCT) of outpatients with limited (≤5 cm) skin abscesses demonstrated antibiotic therapy with clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) was superior to I&D alone. We performed a subgroup analysis to measure the effect of antibiotic duration and abscess size on clinical cure at 7–10 days after antibiotic completion.

Methods

Participants with complete data regarding adherence to the 10-day treatment were included. Demographic and baseline clinical features were compared using t-test, Pearson’s chi-square or Fisher’s exact test, or a non-parametric equivalent where appropriate. Largest abscess dimension (cm) was dichotomized by median size. The effect of antibiotic duration, abscess size (≤ median vs. >median) and covariates on clinical cure were measured using logistic regression. Breslow-Day Test for Homogeneity was used to assess the interaction between treatment and abscess size.

Results

Of 786 participants in the intention-to-treat analysis, complete adherence data were available for 680 (87%) participants. Of these, 463 (68%) received either antibiotic: 421 (91%) completed 10 days of therapy, 29 (6.3%) ≤7 days and 20 (4.3%) ≤5 days. Only antibiotic treatment duration was associated with clinical cure (table). Odds of clinical cure were 1.7 (95% CI: 1.5, 2.0) times higher for each additional day of treatment. Median abscess size was 2.5 cm (range: 0.2–5); 364 participants had abscesses ≤ median vs. 316 >median. Assessed continuously, abscess size was not associated with cure within antibiotic groups (table) or between placebo and treatment groups (OR 0.94, 95% CI: 0.58–1.5). Stratifying on size, no significant interaction was observed with antibiotic treatment (Breslow-Day P = 0.13).

Conclusion

Adherence to the treatment protocol was high. These data suggest that longer courses of antibiotic therapy in conjunction with I&D are associated with successful treatment of limited skin abscesses. Size was not associated with clinical cure. Prospective RCTs to determine the optimal length of treatment are needed.

Disclosures

All authors: No reported disclosures.
460. Ceftriaxone vs. Standard of Care for Definitive Treatment of Methicillin-Susceptible Staphylococcus aureus Infections
Authors: Snawerdt Jessica , Withers Sarah , Schrank John
Published: October 2019

Background

β-Lactam antibiotics, specifically nafcillin, oxacillin, and cefazolin, have proven efficacy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Outpatient antimicrobial therapy (OPAT) with these agents is limited due to side effects and multiple doses required per day. Ceftriaxone, a third-generation cephalosporin, has a favorable profile for OPAT. Limited evidence supporting ceftriaxone therapy for MSSA infections prevents its widespread use.

Methods

A multi-center, retrospective cohort study comparing patients who received cefazolin or nafcillin to patients who received ceftriaxone for treatment of microbiologically proven MSSA infections was conducted from February 2016 to February 2018. The primary outcome of interest was a clinical success, defined as the absence of infection-related readmission, worsening infection, or recurrent infection within 90 days. Secondary outcomes included the rate of adverse reactions, length of stay, and impact of Infectious Diseases (ID) consult.

Results

66 patients treated with ceftriaxone and 156 patients treated with cefazolin or nafcillin were included. Skin and soft tissue and bone and joint were the most common infections in the ceftriaxone group, whereas bacteremia was most common in the nafcillin and cefazolin group. There were significant differences in baseline age (61 years vs. 59 years; P = 0.036) and intravenous drug use (1 patient vs. 25 patients; P = 0.002) between groups. As shown in Table 1, there were significantly lower rates of clinical success with ceftriaxone compared with standard of care as a composite of all infection sites (78.8% vs. 91%; P = 0.012). No statistically significant differences were seen in safety outcomes or ID consultation. Length of stay was significantly longer in the nafcillin and cefazolin group (5.2 days vs. 12.8 days; P ≤ 0.0001).

Conclusion

The results of this study indicate that patients treated with ceftriaxone for MSSA infections had significantly lower rates of clinical success compared with standard of care antibiotics. Nafcillin or cefazolin should remain as first-line agents for treatment of bone and joint infections and skin and soft-tissue infections due to MSSA.

Disclosures

All authors: No reported disclosures.
474. Battling Addiction: Impact of Intravenous Drug Use on Invasive Skin and Soft Tissue Management
Authors: Ivey Alison , Holt Shannon
Published: October 2019

Background

Although skin and soft-tissue infections (SSTIs) remain a common cause of hospitalization for intravenous drug users (IVDU), little has been done to identify whether there should be differences in the SSTI management of IVDU vs. nonusers. The objective of this study was to evaluate the impact of documented intravenous drug abuse on the overall management of invasive SSTIs in hospitalized patients.

Methods

This retrospective cohort study randomly selected 100 IVDU and 100 nonusers (controls) hospitalized for an SSTI over 18 months in a community teaching hospital. Patients eligible for inclusion were 18–60 years old and treated with IV inpatient antibiotics for at least 48 hours. Pregnant women, transfers from an outside hospital, and diabetic foot infections were excluded. The primary endpoint was hospital length of stay (LOS). Secondary endpoints included: percentage prescribed empiric combination antibiotic therapy, percentage prescribed an anti-pseudomonal agent, inpatient and total antibiotic duration of therapy (DOT), 30-day readmission rates, and 30-day emergency department (ED) visit rates.

Results

The study population was predominantly male (66%), Caucasian (72%), and had a mean age of 40 years old (18–59). IVDU were more likely to have complications (18% vs. 6%) and polymicrobial infections (19% vs. 2%), Mean hospital length of stay was 9.0 days for IVDU compared with 4.8 days for controls (P < 0.001). There was no difference in empiric combination therapy (48% vs. 37%; P = 0.115) or empiric exposure to an anti-pseudomonal agent (38% vs. 30%; P = 0.232). Mean duration of inpatient antibiotic DOT was longer in IVDU (7.5 days vs. 4.3 days; P < 0.001), but total antibiotic DOT was similar between groups (16.0 days vs. 13.8 days; P = 0.141). Thirty-day ED visits were higher for IVDU (16% vs. 5%; P = 0.009); however, there was no difference in 30-day readmission (14% vs. 16%; P = 0.692).

Conclusion

Documented IV drug abuse resulted in a significant increase in the length of stay in hospitalized adults with SSTIs requiring IV antibiotics. Exposure to combination therapy and anti-pseudomonal agents did not differ between the groups as would be expected. In the future stewardship initiatives are needed to increase adherence to SSTI guideline recommendations for empiric therapy.

Disclosures

All authors: No reported disclosures.
479. Associated Factors for Extended-Spectrum β-Lactamase Infection Among Patients with Solid or Hematological Malignancy
Authors: Martinez-Valencia Alvaro J , Gomez Martinez Brian J , Montañez Ayala Anita , Garcia Katherine , Sánchez Pedraza Ricardo , Paola Jiménez Cetina Leydy , Cuervo Sonia , César Gómez Rincón Julio
Published: October 2019

Background

Cancer patients are susceptible to infections due to immunodeficiency, frequent invasive interventions-devices, chemotherapy and antibiotics exposure. Infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae increase morbidity and mortality. The objective was to identify clinical factors associated with ESBL in infected patients with cancer at the Instituto Nacional de Cancerología.

Methods

A case–control study was conducted from 2013 to 2015. Cases were infected patients with ESBL-producer Enterobacteriaceae. Controls (matched for date and ward) with non-ESBL-producer Enterobacteriaceae were included. Data were extracted from electronic medical records at index culture: clinical and admission data, Charlson index, immunosuppressive, radio and chemotherapy, neutropenia, invasive devices, surgical procedures and antimicrobial therapy. Microorganisms were identified by the automatized system. Conditional logistic regression and backward stepwise was used to identify predictors of ESBL isolation.

Results

A total of 265 patients with ESBL producer Enterobacteriaceae and 445 non-ESBL producers were identified, mean age 59, 61% male, 48% admitted as outpatients, 73% with solid tumors, 38% with Charlson index ≥4. E.coli and Klebsiella spp. represented 90% of microorganisms. Factor associated with ESBL producer Enterobacteriaceae were hospitalization ≥7 days (OR: 1,59; CI 1.11–2,29), hospitalization the previous year (OR: 4.02; CI 2,68–6,02), immunosuppressive therapy (OR: 2.07; CI 1,05–4.05), Β-lactam therapy the last month (OR: 1.54; CI 1.05–2.26), invasive devices (OR: 1.58; CI 1.10–2.27), active neoplasia (OR: 2,22; CI1.05–4.68), neutropenia (OR: 2.03; CI:1.26–3.27) and absence of chemotherapy during last 3 months (OR: 1.91; CI1.29–2.82). Discriminatory capacity was acceptable (AUC: 0.71).

Conclusion

The presence of ESBL-producer Enterobacteriaceae in oncologic patients is associated with health care, hospital admission and length of stay, invasive devices and exposure to antibiotics. The magnitude of associated factors are weak and do not completely allow the identification of cancer patients infected with ESBL-producer Enterobacteriaceae.

Disclosures

All authors: No reported disclosures.
502. Klebsiella variicola Infections in Service Members Who Sustained Trauma in Iraq and Afghanistan
Authors: Kiley John L , Mende Katrin , Beckius Miriam , Kaiser Susan , Carson M Leigh , Lu Dan , Whitman Timothy , Petfield Joseph , Tribble David , Blyth Dana M , Blyth Dana M
Published: October 2019

Background

Recent work has argued that genus Klebsiella is best divided into 3 clades: K. pneumoniae (Kp), K. quasipneumoniae (Kq), and K. variicola (Kv). Kv has drawn attention from reports of higher mortality and virulence. We evaluated a previously defined group of military trauma patients with Klebsiella infections for the presence of Kv, described clinical and isolate characteristics, and compared Kv and Kp groups.

Methods

All initial and serial (≥7 days from prior isolate) infecting Kp isolates (identified by clinical laboratories without the ability to speciate Kq and Kv) were collected from the Trauma Infectious Disease Outcomes Study (6/09–12/14). Additionally, a previously defined group of colonizing isolates linked to the infecting isolates and a selection of random colonizers were included from groin swabs. DNA extraction and PCR targeting Kv per published methods was performed. Antimicrobial susceptibilities were determined using the BD Phoenix Automated Microbiology System and CLSI criteria. Multidrug resistance was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of ESBL or KPC.

Results

Of 237 archived Kp isolates (from 122 patients), 10 (4%) were identified as Kv by PCR (from 8 [7%] patients). The Kv sources were 4 from blood (40%), 1 intra-abdominal (10%) and 5 from groin (50%). Six (3%) isolates were identified as Kq (4 from groin and 2 from respiratory specimens). The Kv and Kp patients were all males, with a median age of 25 (IQR 21–46) and 23 (IQR 21–28), length of hospital stay of 24 days (IQR: 5–106) and 53 days (IQR 36–74), and Injury Severity Score of 21 (IQR: 10–50) and 38 (IQR: 30–45), respectively. There were no deaths in the Kv group compared with 4 with Kp. Infecting Kv isolates were more likely to be from blood compared with Kp (80% vs. 17%, P = 0.04). No infecting Kv isolates were multidrug-resistant compared with 70% of infecting Kp isolates (P < 0.01).

Conclusion

Kv represented 4% of the previously identified Kp isolates in this population. Patient characteristics were similar in both groups. While Kv was less resistant than Kp, it was more likely to be associated with invasive disease in this group.

Disclosures

All authors: No reported disclosures.
514. Shedding of Multidrug-Resistant Gram-Negative Bacilli by Colonized Patients during Procedures and Patient Care Activities
Authors: Alhmidi Heba , Cadnum Jennifer , Jencson Annette , Bonomo Robert A , Wilson Brigid , Mayer Jeanmarie , Samore Matthew H , Donskey Curtis
Published: October 2019

Background

Contaminated environmental surfaces contribute to transmission of healthcare-associated pathogens such as multidrug-resistant gram-negative bacilli. We hypothesized that medical procedures and patient care activities facilitate environmental dissemination of multidrug-resistant gram-negative bacilli in hospitalized patients.

Methods

We conducted a cohort study of hospitalized patients in contact precautions for carriage of extended-spectrum β-lactamase (ESBL)-producing or carbapenem-resistant gram-negative bacilli (CR-GNB) to determine the frequency of environmental shedding during procedures and care activities. Perirectal, wound, and skin were cultured for the gram-negative bacilli of interest. Prior to each procedure or activity, surfaces in the room and portable equipment used for procedures were disinfected. After procedures, high-touch surfaces and portable equipment were cultured; negative control cultures were collected after 1 hour in the absence of a procedure.

Results

Of 60 participants, 38 (63%) were in contact precautions for ESBL-producing gram-negative bacilli and 22 (37%) for CR-GNB. Thirty-four (57%) participants had positive perirectal, wound, or skin cultures. Contamination of surfaces with the colonizing multidrug-resistant gram-negative bacilli occurred frequently during procedures and activities such as wound care, assistance with meals, and urinary catheter or colostomy care (11% to 29% of procedures/activities), whereas contamination was rare in the absence of a procedure (1%). Contamination was recovered from 6 of 56 (10%) portable devices used for procedures.

Conclusion

Environmental shedding of multidrug-resistant gram-negative bacilli occurs frequently during medical and non-medical procedures in hospitalized patients. Our results suggest that there is a need for effective strategies to disinfect surfaces and equipment after procedures.

Disclosures

All authors: No reported disclosures.
516. Social Network Analysis to Study MDRO Transmission in VA Community Living Centers and Spinal Cord Injury Units
Authors: Bondar Svetlana , Ewers Tola , Vivo Amanda , Gutkowski Marissa , Evans Charlesnika T , Perencevich Eli N , Crnich Christopher
Published: October 2019

Background

Residents of VA Community Living Centers (CLC) and Spinal Cord Injury units (SCI) are commonly colonized or infected with multidrug-resistant organisms (MDROs). The mechanisms by which MDROs are spread between residents in CLC/SCI settings remain poorly understood. Our objective was to develop methods to better understand how MDROs are spread in VA CLCs/SCIs.

Methods

Preliminary data from two of the four VA medical centers participating in an ongoing study are included in these analyses. A structured sociometric survey was employed to collect data on interactions between residents, staff and environmental surfaces in study units. UCINET was used to construct a sociogram and calculate network characteristics (density, centrality) using responses to the surveys administered in one of the participating facilities.

Results

A total of 136 surveys were completed by 49 staff and 45 residents at the two VA sites. Staff reported more interactions with residents than with other staff. Residents reported more interactions with staff than with other residents, the latter tending to only occur during group activities. Sociograms generated from preliminary surveys collected at one site suggest a four-core-person social network pattern connecting two staff with two specific residents and showed that the dining room was the group setting most frequently visited by residents. Mobile computers, blood pressure cuffs/thermometers and glucometers were the equipment used most heavily during resident care activities (figure). Challenges in identifying contact patterns include recall bias and inability of some residents to identify names of individuals with whom they interacted. Residents were still able to reliably identify staff roles.

Conclusion

This preliminary work shows heterogeneous contact patterns between persons and surfaces in VA CLCs/SCIs. Characterizing this heterogeneity and its influence on MDRO spread via this type of social network analysis is feasible in the VA CLC/SCI setting, albeit with some limitations. Next steps in our studies include adding data from two additional sites and using observation techniques supplemented with microbiological sampling of targeted environmental surfaces to further understand potential transmission patterns.

Disclosures

All authors: No reported disclosures.
526. Significant Reduction of Hospital Onset Carbapenem-Resistant Enterobacteriaceae Utilizing Infection Prevention Strategies: It takes a Village!
Authors: Alexander Kinta , Brown Sean , Lorin Scott , Koll Brian , Mazo Dana , Ehni Jordan , Javaid Waleed
Published: October 2019

Background

Carbapenem-resistant Enterobacteriaceae (CRE) is a Gram-negative bacteria and is considered one of the major challenges in healthcare worldwide. CRE has a high mortality rate, and the majority produce carbapenemase enzymes, which can be easily spread to other bacteria and patients. An inner-city hospital had a substantial decrease in CRE associated infections/colonization after the implementation of a multi-disciplinary process championed by hospital leadership and Infection Prevention (IP).

Methods

A quasi-experimental study of patients with hospital-onset CRE-positive cultures over Thirty-eight months was conducted. The pre-intervention period was from January 2015 to July 2016 and the post intervention period was from August 2016 to February 2018. The intervention comprised of a CRE prevention and control (CPC) bundle. The bundle comprised of hand hygiene, strict contact precautions, appropriate surveillance cultures and the cleaning of a patient’s environment and equipment with bleach. Hospital leadership implemented the CPC bundle during daily huddles with IP and department leaders with real-time identification and resolution of any barriers. The diligence of cleaning and disinfection was monitored using a transparent, easily cleanable and environmentally stable solution that fluoresces when exposed to UV light. The solution was used to mark standardized high touch surfaces and shared equipment in CRE patient rooms prior to terminal cleaning. These surfaces were evaluated with a UV light and used as an opportunity to educate staff on common cleaning oversight.

Results

Prior to implementation of the CPC bundle, there were 24 cases of CRE with a baseline rate of 2.40. After introducing the CPC bundle, there were 8 cases of CRE with a rate of 0.83 (P = 0.006). The CPC bundle was associated with a reduction in CRE cases by 67%.

Conclusion

A hospital-wide approach between multiple departments is critical for the success of CRE prevention and control. This study provides further evidence that a multi-faceted approach to monitoring compliance with the CPC bundle can help reduce the transmission of CRE. This approach can decrease the burden on the healthcare system and improve patient outcomes.

Disclosures

All authors: No reported disclosures.
530. Sequential Screening of High-Risk Patients for Carbapenemase-Producing Enterobacteriaceae Colonization
Authors: Brodkin Elizabeth , Short Katy , Purych Dale
Published: October 2019

Background

Early identification of patients colonized with carbapenemase-producing Enterobacteriaceae (CPE) facilitates the implementation of appropriate infection control measures and reduces nosocomial transmission. Sequential screening for CPE colonization of close contacts of known cases to confirm initial negative results is recommended. Fraser Health (FH) expanded sequential screening to patients with recent exposure to other risk factors following the identification of CPE in patients who initially screened negative.

Methods

FH screens patients for CPE who report healthcare outside of Canada or travel to endemic countries within the previous 12 months. Patients remain on contact precautions and are re-screened 7 and 21 days after the last known exposure date. We reviewed CPE cases with foreign healthcare or travel to endemic countries who screened negative on admission but subsequently screened positive within 30 days. Patients without confirmation of colonization through a rectal screen or possible exposure to a current nosocomial source were excluded. Whole-genome sequencing results were examined to confirm foreign healthcare or travel as the likely source of acquisition. Medical records were reviewed to obtain patient history and clinical details.

Results

Between November 2015 and January 2019, 21 patients had a positive CPE screen within 30 days of a negative screen, with no known CPE exposures during that time. The median time between the last date of known exposure and positive CPE screen was 20 days (range: 7–77 days). Twelve (57%) cases were hospitalized outside of Canada, 8 (38%) reported other foreign healthcare encounters, and 1 (5%) had no reported healthcare outside of Canada but had traveled to an endemic country. Sixteen (71%) cases received antibiotics prior to the positive CPE screen.

Conclusion

Patients with unrecognized CPE colonization are a source for nosocomial transmission. Patients screening negative for CPE with recent exposure to risk factors other than contact with a known case may screen positive at a later date. This may be due to higher colonization levels or antibiotic selection pressures. Consideration should be given to sequential CPE screening of high-risk patients based on the last day of exposure.

Disclosures

All authors: No reported disclosures.
531. Practical and Evidence-Based Considerations for Implementation of Bacterial Whole-Genome Sequencing Within Longitudinal Infection Control Practice
Authors: Chen Donald S , Quinn Moira , Sussner Rita M , Wang Guiqing , Fallon John T , Chanza Melissa , Doty Alan J , Ashworth Judy L , Kelleher Steven W , Holler Devon J , Fortunato-habib Mary M , Loving Joshua , Abdolahi Amir , Carmona Juan J , Gross Brian D
Published: October 2019

Background

Whole-genome sequencing (WGS) of bacteria is becoming a routine tool within microbiology, yet its utility to help guide infection control (IC) practice longitudinally is underexplored. As with any technology adopted in the hospital, the integration of WGS into IC practice must be carefully managed and considered. We qualitatively report an evidence-based implementation workflow that considers WGS to help proactively guide IC professionals during investigation of infectious outbreaks.

Methods

We built upon lessons learned in an ongoing surveillance effort at a tertiary care hospital—utilizing retrospective WGS data within the Philips IntelliSpace Epidemiology system—to understand facilitators and barriers to the use of bacterial WGS longitudinally to inform IC workflow. Our team established a 9-month workgroup to study the practical aspects of implementing WGS in routine IC practice. From expert opinion collected via the workgroup, in addition to evidence from the literature, a workflow guidance document and checklist were codified. New ideas included incorporating education to promote the establishment of an IC triage process.

Results

Facilitators to implementation included ability to display genomic relatedness alongside relevant patient data to enable clinical actionability, ability to pivot time and resources rapidly when infections are a pseudo outbreak (false positive) or missed outbreak (false negative), opportunities for nuanced staff education, and willingness to be a first-of-kind adopter. Barriers were communication of genomic concepts to IC professionals and relevant institutional stakeholders, maintaining sharable notes of active investigations to promote data-sharing practices, and timing and review of relevant interventions into the facility workflow. Strategies to address these issues are considered.

Conclusion

This study provides a novel framework for adaptation of existing IC workflow strategies to leverage the utility of bacterial WGS, and it presents a schema to effectively engage relevant stakeholders, based on an analysis of the unique challenges inherent within IC practice. It also offers an innovative model for the development and implementation of IC workflows to account for, and adapt to, site-specific conditions.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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.