bluuebunny/crossref_metadata_2025 huggingface dataset:
395. Safety and Tolerability of Rifampin in Staphylococcal Orthopedic Infections
Authors: Miller Andy O , Kapadia Milan , Carli Alberto V , Brause Barry , Henry Michael
Published: October 2019

Background

Rifampin is part of optimal combination antimicrobial therapy for staphylococcal foreign-body infections, including periprosthetic joint infections (PJI) in cases of retained prostheses. However, rifampin can have important drug interactions, can cause hepatotoxicity and other organ toxicity, and can induce treatment-limiting side effects. Although rifampin safety and tolerability is well-described in tuberculosis patients, its use in orthopedic infections is poorly described. We therefore analyzed the safety and tolerability of rifampin in patients with staphylococcal hip and knee PJIs treated with implant retention.

Methods

A retrospective institutional PJI database was queried to identify all staphylococcal PJI cases treated with implant retention, from 2008 to 2016. Patient demographics, comorbidities, and antibiotic treatment course were collected. The Chi-square or Fisher’s exact test was used for comparisons between rifampin-tolerant (RT) and -intolerant (RI) subgroups.

Results

80 patients were included, of which 75 (94%) began rifampin. Of the 75 who received rifampin, 23% (17/75) were RI. The median duration of rifampin for RT was 3.0 months (range 1–60) and 0.75 months for RI (range 0.1–3). Reasons for RI included allergies (N = 6), GI toxicity (N = 5), increased liver function tests (N = 2), leukopenia (N = 2), acute kidney injury (N = 1), exacerbated epilepsy (possibly due to low phenytoin; N = 1), and vasculitis (N = 1). Patient age, sex, and Charlson comorbidity index did not predict rifampin intolerance. In 5/80 (6%) patients who never received rifampin, reasons included liver disease, drug interactions, and rifampin resistance. Overall, 27% (22/80) could not be adequately treated with rifampin.

Conclusion

In this study cohort of PJI patients, contraindications to rifampin initiation were infrequent, but discontinuation due to intolerance, allergy, or toxicity occurred in nearly a quarter of patients. Drug-drug interactions can preclude its use, or may cause important medication switches in critical areas such as anticoagulation, epilepsy treatment, and HIV care. Research into the anti-staphylococcal efficacy and safety of alternative rifamycins (such as rifabutin and rifapentine) in patients with staphylococcal hardware infections is warranted.

Disclosures

All authors: No reported disclosures.
407. The Effect of Streptococcus pneumoniae Pneumonia on Atherosclerosis
Authors: Bazaz Rohit , Francis Sheila , Dockrell David
Published: October 2019

Background

Clinical studies consistently find an increase in the risk of acute coronary syndrome (ACS) in the weeks following pneumonia, although the mechanisms underlying this finding are unknown. ACS most commonly occurs as a result of thrombosis at the site of ruptured atherosclerotic plaques. We hypothesized that the systemic inflammatory response to pneumococcal pneumonia leads to acute localized inflammatory changes within established atherosclerotic plaques, favoring plaque instability and rupture, thereby resulting in ACS.

Methods

Male ApoE-/- mice, a well-established model of atherosclerosis, were fed an atherogenic diet for 7–8 weeks before intranasal infection with Streptococcus pneumoniae or mock infection. Mice were sacrificed 2 or 8 weeks post-infection. Formalin-fixed, paraffin-embedded aortic sinus plaque sections were analyzed to assess markers of plaque vulnerability to rupture. To characterise post-pneumonic plaque macrophage phenotype, aortic sinus plaque cryosections 2 weeks post pneumonia/mock infection were immunostained for MAC-3 to identify macrophage-rich areas. These plaque regions were collected using laser capture microdissection and RNA extracted for microarray analysis.

Results

S. pneumoniae infection was associated with increased aortic sinus atherosclerotic plaque macrophage content (18.1 vs. 8.0%; P < 0.05) at 2 weeks post infection, but no significant difference in aortic sinus plaque burden, plaque smooth muscle or collagen content. There was no significant difference in any of these plaque vulnerability markers at 8 weeks post infection. Microarray analysis of laser capture micro-dissected plaque macrophages identified downregulation of the expression of three genes coding for specific E3 ubiquitin ligases following pneumonia. Pathway analysis identified a significant perturbation in the ubiquitin proteasome system pathway as a result.

Conclusion

In this murine model, pneumococcal pneumonia resulted in increased atherosclerotic plaque macrophage content, a marker of plaque instability, at 2 weeks post infection. Pneumonia may therefore lead to an increased propensity for atherosclerotic plaques to rupture soon after pneumonia, due to infiltration of macrophages into the plaque.

Disclosures

All authors: No reported disclosures.
457. Cutibacterium (Propionibacterium) acnes Infection Rate and Optimization of Surgical Culture Duration
Authors: Cueva Carlos Christian , Odrobina Robert , Pupaibool Jakrapun , Fisher Mark
Published: October 2019

Background

Cutibacterium acnes is part of the normal skin and gastrointestinal tract flora that is increasingly recognized as a causative organism of surgical infections. Distinguishing between infection and contamination is difficult. The standard culture duration for C. acnes has not been determined. As a slow-growing organism, a prolonged incubation of 10–14 days is adopted in many laboratories. Ideally, only samples with high pretest probability for infection should be worked up this way, otherwise resources are overutilized with likely no benefits and potential harms to patients. We conduct a study to assess the optimal incubation duration for C. acnes.

Methods

We retrospectively reviewed microbiologic and clinical data of patients who underwent surgical procedures at the Veterans Affairs (VA) Hospital and the University of Utah Hospital in Salt Lake City, Utah, between 2015 and 2018 for which prolonged incubation of surgical samples was requested. Samples that grew C. acnes were divided into three groups (infection, contaminant, indeterminate) based on the quantity of growth and the number of positive samples (Figure 1). Samples in the “indeterminate” group were re-classified into the other two groups based on clinical criteria (Figure 2). Time to culture positivity (TTP) was calculated for each group.

Results

741 patients contributed to a total of 909 surgical cases. There were 2,401 samples collected resulting in 4,408 bacterial cultures. C. acnes grew in 131 cases (14.41%). Fifty-five cases (44%) fulfilled the criteria for true infections and 70 cases (56%) were contaminants. 6 cases were lost to follow-up. The mean TTP of the infection and the contamination groups were 5.60 + 0.76 days and 8.67 + 0.81 days, respectively. The TTP of C. acnes from specimens of true surgical infections was significantly shorter than that of contaminants by the mean of 3.07 days (95% CI: -4.22 to -1.92); P < 0.001.

Conclusion

Using our microbiological and clinical criteria to differentiate infections and contaminations, this study provides evidence that surgical sample cultures should be held no longer than 7 days to limit the effect of contaminated C. acnes on cultures and reduce unnecessary antimicrobial use.

Disclosures

All authors: No reported disclosures.
472. Rethinking the Role of Clindamycin for Toxin-Mediated Illnesses
Authors: Saldarriaga Perez Carolina , Nuibe Andrew M
Published: October 2019

Background

Treatment of toxin-mediated diseases such as toxic shock syndrome (TSS) and Staphylococcus scalded skin syndrome (SSSS) typically includes adjunctive clindamycin to halt bacterial exotoxin production. However, there is emerging clindamycin resistance in Staphylococcus aureus and Streptococcus pyogenes. We compared pathogen susceptibilities, clinical features, and outcomes of patients with toxin-mediated diseases to evaluate the role of adjunctive clindamycin in a contemporary setting.

Methods

Epic was queried for patients < 18 years of age admitted to Inova Fairfax Hospital from January 1, 2009 to December 31, 2018. Patients were identified by ICD-9 and ICD-10 codes for TSS and SSSS and validated by manual chart review. TSS cases were classified as possible, probable, or confirmed, and SSSS cases were classified as probable or confirmed. Early antimicrobial use was defined as administration within the first 3 days of admission. Clindamycin, aminoglycosides, tetracyclines, and linezolid were considered antimicrobial agents with anti-toxin effect.

Results

There were 32 cases of TSS, 38 cases of SSSS, and 1 case of bullous impetigo. S.aureus (30) and S.pyogenes (8) were the most common pathogens recovered with 1 case of MRSA. Vancomycin was given to 40 patients. 45% of S.aureus isolates were clindamycin resistant; no S.pyogenes isolates were clindamycin resistant. Fifty-eight patients received early anti-toxin agents: 51 received clindamycin, 4 received clindamycin and doxycycline, 1 received clindamycin and gentamicin, 1 received doxycycline, and 1 received gentamicin. 13 did not receive any early anti-toxin agent. 42% of patients who received early clindamycin had a clindamycin-resistant S. aureus. The presenting features, number of TSS and SSSS cases, need for intensive care, median length of stay, and 30-day readmissions did not significantly differ based on early anti-toxin agent use or based on clindamycin susceptibility. There were no deaths.

Conclusion

Withholding anti-toxin agents early in the course of illness or giving clindamycin to a resistant organism in toxin-mediated diseases did not adversely affect patient outcomes or mortality. Opportunities remain to decrease the use of empiric vancomycin and re-evaluate the role of clindamycin for toxin-mediated diseases.

Disclosures

All authors: No reported disclosures.
505. Making of a “Super-Duper Bug”: Plasmid-Mediated Resistance Accumulation in a Carbapenemase-Producing Klebsiella quasipneumoniae from Patients and the Environment
Authors: Mathers Amy J , Sheppard Anna , Stoesser Nicole , Crook Derrick , Barry Katie E , Eyre David , Vegesana Kasi B , Parikh Hardik
Published: October 2019

Background

Carbapenemase-producing Enterobacteriaceae can form a reservoir in hospital wastewater biofilms. Klebsiella quasipneumoniae is increasingly recognized as an emerging nosocomial threat, frequently carrying antimicrobial resistance (AMR) genes on plasmids. The dynamics of AMR gene and plasmid gain/loss over time in this species remain unclear.

Methods

Klebsiella pneumoniae carbapenemase producing-K. quasipneumoniae (KPC-Kq) isolates from patients and wastewater sites from drains and toilets were sequenced (Illumina). Sequence assemblies (SPAdes) were probed in silico for AMR genes and plasmid Incompatibility types (using AMRFinder and PlasmidFinder databases, respectively). For related isolates (<100 SNV) cultured from the same sites longitudinally, we compared the accumulation of AMR genes in patients and environmental reservoirs over time.

Results

From 2009 to 2016 there were a total of 15 KPC-Kq isolates from 8 patients and 17 environmental isolates from 11 rooms. The mean number of resistance genes identified in patients and environmental isolates were 15 and 14, respectively (P = NS), with five resistance genes carried by all isolates including blaKPC. There was an average of 4.4 unique incompatibility types from patients and 4.0 from the environment (P = NS). For the longitudinal subset, there were 17 related isolates from two patients and two sink drains. One hospitalized patient with repeated antimicrobial exposure had a KPC-Kq initial isolate with 3 plasmid types and 13 AMR genes and died one year later with a KPC-Kq isolated from blood with 11 plasmid types and 25 AMR genes. The other patient was primarily an outpatient with little antimicrobial exposure. His KPC-Kq lost 1 plasmid and 3 AMR genes over 15 months. One KPC-Kq strain in the environment lost 3 plasmid types and 8 AMR genes over 4 months; the other was unchanged over 5 months.

Conclusion

KPC-Kq has been seen in both patients and the environment for several years at our institution. Sequencing of longitudinal isolates revealed that under antimicrobial pressure a patient KPC-Kq accumulated multiple plasmids and AMR genes. This same accumulation was not witnessed environmental sites over time although the numbers are small and will require confirmatory work.

Disclosures

All authors: No reported disclosures.
529. Halting Multi-Modal Transmission of a Novel Carbapenemase-Producing Enterobacteriaceae Outbreak
Authors: Sickbert-Bennett Emily , Schultz Kate , Teal Lisa , DiBiase Lauren , Weber David J
Published: October 2019

Background

In January 2018, the first case of anOXA-48 carbapenem-resistant Klebsiella pneumoniae (OXA-48 CRKP) was identified in a North Carolina hospital in a patient arriving from Eastern Europe. Over the next year across multiple inpatient adult units, 14 patients had clinical isolates and 2 patients had positive rectal surveillance screens for OXA-48 CRKP.

Methods

Investigation activities to characterize the OXA-48 CRKP epidemiology included: >1000 rectal colonization screens of epidemiologically linked patients, chart reviews of infected and colonized patients, hand hygiene and environmental cleaning observations on affected units, environmental sampling to include endoscopes, sinks and toilets, and molecular analyses (pulsed-field gel electrophoresis and whole-genome sequencing).

Results

Molecular analyses confirmed a clonal outbreak. All environmental cultures including endoscope cultures performed were negative for OXA-48 CRKP. All cases were explained by at least one of three mechanisms: (1) time/space overlap on same unit (presumed lack of hand hygiene or contamination of shared patient equipment), (2) patient housed in room where previously infected patient was housed (presumed inadequate terminal disinfection/contaminated environment), or (3) a single upper gastrointestinal endoscope. Interventions included surveillance to identify and isolate colonized patients, discharge room cleaning of OXA-48 CRKP patients enhanced by ultraviolet light disinfection, curtain laundering, and discarding unused patient supplies, and monitoring and feedback for compliance with hand hygiene, cleaning, and use of personal protective equipment. A single endoscope used between multiple OXA-48 CRKP patients with no other known transmission link was quarantined upon identification, sterilized with ethylene oxide, and ultimately placed out of service.

Conclusion

A clonal outbreak of a novel carbapenemase-producing Enterobacteriaceae likely spread via multiple modes of transmission. The investigation was complicated by infrequent identification of colonization among patients epidemiologically linked to known cases. Multiple interventions based on epidemiological links were necessary to halt hospital-wide transmission.

Disclosures

All authors: No reported disclosures.
560. Relating Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Isolates to Transmission Dynamics and Efficacy of Control Interventions
Authors: Blumberg Seth , Porco Travis , Shopsin Bo , Phillips Michael
Published: October 2019

Background

Methicillin-resistant staphylococcus aureus (MRSA) colonization of hospitalized patients is associated with higher readmission rates and increased morbidity. Depending on the mechanisms of transmission, numerous potential control interventions exist to reduce the burden of disease. However, given the preponderance of asymptomatic colonization, it is challenging to quantify the relative importance of different transmission mechanisms and assess control efficacy. By identifying clusters of transmission, whole-genome sequencing (WGS) provides an opportunity to overcome these challenges.

Methods

We sought to apply cluster analysis techniques to WGS data for MRSA, in order to assess MRSA prevalence, transmissibility, the degree of transmission heterogeneity and the potential effectiveness of control. Our model builds upon previous work that showed a direct relationship between the size distribution of infection clusters, the effective reproduction number (R) and the dispersion parameter (k). To demonstrate its functionality, our model was applied to existing WGS data for MRSA isolates collected during a 12 month period in the East of England (DOI: 10.1126/scitranslmed.aak9745)

Results

The effective reproduction number for the East of England data is 0.29 (95% CI: 0.24–0.36). The dispersion parameter is 0.09 (0.03–0.33) reflecting a high degree of transmission heterogeneity. This implies all transmission is caused by just 12% of the cases. Targeted control of these cases could have decreased overall burden of MRSA colonization by 29% during the time period of the study.

Conclusion

The high degree of transmission heterogeneity seen in MRSA transmission suggests that the risk for infection is variable.This observation motivates the need for more detailed mechanistic modeling of hospital-based MRSA transmission that integrates patients-specific factors, movement data and genome sequencing. Such models could be used to forecast which patients are at greatest risk for either acquiring or transmitting MRSA, thereby improving targeted control.

Disclosures

All authors: No reported disclosures.
565. Implementation of a Staphylococcus aureus Screening and Decolonization Program in a Multisite Urban Healthcare System
Authors: King-Morrieson Tamara , Stachel Anna , Phillips Michael , Aguero-Rosenfeld Maria E , Inglima Kenneth , Hochman Sarah
Published: October 2019

Background

Staphylococcus aureus infection confers high mortality. S. aureus-colonized hospitalized patients are more likely to develop invasive infection and can transmit S. aureus to other patients in the absence of symptoms. Our health system has a baseline S. aureus colonization rate of 21% (MSSA and MRSA combined). To reduce risk of invasive S. aureus infection in our patients, we implemented an inpatient S. aureus screening and decolonization program.

Methods

Interventions include universal S. aureus screening and targeted decolonization for all patients on the Medicine and Pediatrics inpatient services. Adult patients are screened at admission and change in the level of care; pediatric patients are screened weekly. S. aureus screening began incrementally by unit between 2016 and 2017, and extended to transplant units in 2018. All cultures are processed in the hospital microbiology lab for identification of MRSA and MSSA. S. aureus decolonization (mupirocin ointment in nares twice daily, chlorhexidine 2% wipes below the chin daily for 5 days) began in 2017 for patients with a central venous catheter, in intensive care unit or multibedded room. Decolonization was extended to all S. aureus-colonized patients beginning in June 2018, with involvement of a dedicated clinical nurse specialist. We compared compliance with screening and decolonization and the secondary outcome of MRSA bacteremia in the 6 month period before and after the addition of the clinical nurse specialist.

Results

21.5% of screened patients were colonized with S. aureus (82.4% MSSA, 17.6% MRSA). Screening compliance improved from 39.4% of eligible patients (N = 1805) to 52.1% (N = 2024) and decolonization increased from 18.6% of colonized patients to 41.2% comparing January-June 2018 with July-December 2018. The MRSA bacteremia rate fell from 0.2/1,000 patient-days in the first half of 2018 to 0.1/1,000 patient-days in the second half of 2018.

Conclusion

A system-wide program that includes S. aureus screening and decolonization of hospitalized patients found that 21% of patients had S. aureus colonization. Screening and decolonization compliance increased with the introduction of a dedicated clinical nurse specialist, and the MRSA bloodstream infection rate fell.

Disclosures

All authors: No reported disclosures.
570. Impact of Discontinuation of Methicillin-Resistant Staphylococcus aureus Contact Precautions on Bloodstream Infection Rates at an Academic Medical Center
Authors: Navalkele Bhagyashri D , Fletcher Sheila , Truhett Nora , Hester Xiaoming , Martin Sanjosa , Smith Elizabeth , Galloway Regina , Stempak Lisa , Allard Cynthia , Hayes Willis , Parham Jason
Published: October 2019

Background

Contact precautions (CP) in methicillin-resistant Staphylococcus aureus (MRSA) patients along with hand hygiene has been considered a gold standard to prevent transmission. The actual impact of these measures in reducing MRSA infections is still controversial. At our institution, we evaluated the impact of discontinuation of MRSA CP on hospital-onset (HO) and community-onset (CO) MRSA bloodstream (BSI) rates. We also analyzed consequential cost savings.

Methods

The University of Mississippi Medical Center is a 700+ bed academic facility located in Jackson, MS. Patients admitted to any inpatient units with diagnoses or history of MRSA infection or colonization were subjected to CP during their stay. In July 2018, we discontinued MRSA CP across all inpatient units (except neonatal intensive care unit). HO MRSA BSI rate was calculated per National Healthcare Safety Network (NHSN) laboratory-identified event. CO MRSA BSI was reported per NHSN admission prevalence rate. One-way Analysis of Variance (ANOVA) was performed to compare pre-and post-intervention data.

Results

There was a rise in HO MRSA BSI rate after discontinuation of CP (July 2018-March 2019) in comparison to the 9-month pre-intervention period (October 2017-June 2018); however, the difference was not statistically significant (1.79/10,000 patient-days vs. 1.2/10,000 patient-days; P = 0.056). Similarly, CO MRSA BSI prevalence rate did not show a statistically significant difference between pre- and post-intervention period (0.103 vs. 0.08; P = 0.584).The total annualized cost savings on personal protective equipment (PPE) was an estimated $193,398 post-intervention. Hand hygiene (HH) compliance was higher in post-intervention compared with pre-intervention period (83% vs. 78%, P = 0.0007).

Conclusion

At our institute, discontinuation of MRSA CP was associated with an insignificant rise in HO MRSA BSI rates. No impact was observed on CO MRSA BSI prevalence. We had a 34% reduction in PPE expenditure. We observed an increase in HH compliance post-discontinuation of CP, but it did not reduce MRSA BSI rates. Further studies are needed to evaluate the impact of bundling hand hygiene practices with other horizontal strategies (prevention bundles, chlorhexidine bathing, environmental disinfection practices) in prevention of MRSA infections.

Disclosures

All authors: No reported disclosures.
572. Relationship Between Chlorhexidine Gluconate (CHG) Skin Concentrations and Microbial Skin Colonization among Medical Intensive Care Unit (MICU) Patients
Authors: Rhee Yoona , Hayden Mary K , Simms Andrew T , Yelin Rachel D , Lolans Karen , Bell Pamela B , Schoeny Michael , Baker Arthur W , Baker Meghan A , Gohil Shruti K , Rhee Chanu , Talati Naasha J , Warren David K , Welbel Sharon F , Dangana Thelma E , Majalca Thelma , Bravo Heilen , Cass Candice , Nelson Alicia , Tolomeo Pam C , Wolf Robert , Lin Michael Y
Published: October 2019

Background

CHG bathing is used to suppress patients’ microbial skin colonization, in order to prevent infections and transmission of multidrug-resistant organisms. Prior work has suggested that microbial growth is inhibited when CHG skin concentrations exceed threshold levels.

Methods

We conducted 6 single-day surveys from January 2018 to February 2019 in 7 academic hospital MICUs with established CHG patient bathing. Adult patients were eligible to have skin swabbed from adjacent 25 cm2 areas on the neck, axilla, and inguinal region for culture and CHG concentration determination. CHG skin concentrations were measured by a semi-quantitative colorimetric assay. Selective media were used to isolate targeted microorganisms (Table 1). Species were confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry; antibiotic susceptibility was determined by MicroScan (Beckman Coulter). We modeled the relationship between CHG skin concentrations (log2-transformed) and microorganism recovery (yes/no as primary outcome) using multilevel models controlling for clustering of body sites within patients and within ICUs, assessing slope and threshold effects.

Results

We enrolled 736/759 (97%) patients and sampled 2176 skin sites. Gram-positive bacteria were detected most frequently (Table 1). The adjusted odds of identifying gram-positive organisms decreased linearly as CHG skin levels increased (Figure 1a), without evidence of a threshold effect. We also found significant negative linear slopes without evidence of threshold effects for other pathogens tested (Table 2; Figure 1), with the exception of gram-negative bacteria and vancomycin-resistant enterococci. When modeling quantitative culture results (colony-forming units) for gram-positive organisms as a continuous outcome variable, a similar relationship was found.

Conclusion

Higher concentrations of CHG were associated with less frequent recovery of gram-positive bacteria and Candida species on the skin of MICU patients who were bathed routinely with CHG. For microbial inhibition, we did not identify a threshold concentration of CHG on the skin; rather, increasing CHG skin concentrations led to additional gains in inhibition. For infection prevention, aiming for high CHG skin levels may be beneficial.

Disclosures

All authors: No reported disclosures.
573. Enterococcal Bacteremia in a Tertiary Care Center in Mexico: A Retrospective Analysis Focus on Vancomycin-Resistant E. faecium and Ampicillin-Resistant E. faecalis
Authors: Lopez Luis Bruno A , Lambraño-Castillo Darwin , Ortiz-Brizuela Edgar , Ramirez-Fontes Andrea , Estrella Tovar-Calderon Yanet , Javier Leal-Vega Francisco , Bobadilla-Del-Valle Miriam , SIFUENTES-OSORNIO JOSE , Ponce de Leon Alfredo
Published: October 2019

Background

The primary pathogens in genera enterococcus are E. faecalis and E. faecium, increasing acquired resistance to glycopeptides and β lactamic has done the management more challenging. We aimed to describe the risk factors for acquisition of bacteremia for vancomycin-resistant E. faecium (VRE) and ampicillin-resistant E. faecalis (ARE) and the 30-day mortality in comparison to susceptible enterococcal bloodstream infection (BSI)

Methods

From 2007- 2017 medical records of all BSI for E. faecalis and E. faecium were evaluated. Risk factor for acquisition of VRE and ARE as well as the significant variables associated with 30-day mortality for enterococcal BSI were determined by univariate and multivariate analysis. The molecular mechanism of VRE was performed by PCR

Results

There were 192 patients with E. faecium BSI of which 107(56%) patients had VRE BSI with 94% VRE strains expressing vanA gene. The index bacteremic episodes were classified as nosocomial o healthcare associated in 99%, 102(95%) had hospitalization 1 year before and 101(94%) history of use of antibiotics 3 months earlier, the multivariate analysis showed duration of the previous hospitalization >10 days (OR, 80.18; 95% CI, 1.81–634), use of central venous catheter [OR, 11.15; 95% CI, 2.48–50.2), and endotracheal cannula [OR, 17.91; 95% CI, 1.22–262) as significant associated variables. The mortality for VRE was greater than susceptible E. faecium (60% vs. 24%, P < 0.001). The only factors for 30-day mortality for E. faecium BSI in the multivariate analysis was APACHE ll score [OR,1.45; 95% CI, 1.26–1.66) and patients with chemotherapy of cancer. (OR, 3.52; 95% CI, 1.09–11.39). 147 patients had E. faecalis BSI of which 18 (11%) patients had ARE, we did not find relevant clinical differences of ARE in comparison with ampicillin-susceptible E. faecalis, neither in risk factors for acquisition of ARE nor 30-day mortality [7(39%) vs. 38(29%), P = 0.58] in uni and multivariate analysis

Conclusion

Our evaluation showed in a period of 10 years that VRE expressing vanA gene had a strong association with patients with previous nosocomial exposure. Severely ill patients and cancer patients on chemotherapy during the bacteremic episode were the variables more associated with 30-day mortality. ARE is yet of low prevalence and less known, constant surveillance about it is warranted

Disclosures

All authors: No reported disclosures.
576. A Multicenter Epidemiology Study on Risk Factors of Vancomycin-Resistant Enterococcus Infections in China: Results from the China Antimicrobial Surveillance Network (CHINET) in 2016
Authors: Lin Dongfang , Guo Yan , Yang Yang , Zhu Demei , Hu Fupin
Published: October 2019

Background

Bacterial resistance in China had been increasing in prevalence. Vancomycin-resistant enterococcus (VRE) different from other bacteria had lower isolated rate and apparent regional variations. In this study, we identified the characteristics of VRE infections in Chinese patients based on the China Antimicrobial Surveillance Network (CHINET) in 2016.

Methods

This case–control study was conducted in 97 VRE patients and 95 Vancomycin-susceptible Enterococcus (VSE) patients from 20 medical centers. Demographics, disease characteristics, therapeutic measure, as well as laboratory data were obtained from medical records for analysis. Descriptive statistics, simple and multivariate logistic regression were performed to explore the risk factors of VRE infection.

Results

The mean age of patients in the case and control groups was 75.0 years and 65.0 years, respectively. In the case group, 52 patients developed urinary tract infections, accounting for 53.6%, followed by bloodstream infections (19.6%) and abdominal infections (5.2%). And the cases of Enterococcus faecium, Enterococcus faecalis and other enterococci infections were 70 (72.2%), 7 (7.2%), and 20 (20.6%), respectively. Moreover, the proportion of vancomycin usage before infection was 20.6%. The result of resistance analysis showed VRE patients’ other dug resistance rate was higher than VSE ones. Compared with VSE patients, VRE patients had received more urinary intubation, indwelling venous catheter, and dialysis. Additionally, the proportions of combination with stroke (8.3% vs. 2.1%), multiple organ failure (8.3% vs. 3.2%), and other infection (59.8% vs. 40.0%) were higher in the case group. What’s more, 44 (45.4%) VRE patients had been treated in intensive care unit, while 21 (22.1%) cases in the control group. Multivariate logistic regression showed that receiving indwelling venous catheter was independent risk factor for VRE infection (OR=3.342, 95% CI: 1.379~8.099). For prognosis, VRE patients had a lower effective rate (67.4% vs. 83.7%), higher hospital expense (￥94991 vs. ￥38248), and longer hospital stay (26.0 days vs. 21.0 days).

Conclusion

Indwelling venous catheter may increase the VRE infection risk and Linezolid or Fosfomycin could still be used for infection treatment in VRE patients.

Disclosures

All authors: No reported disclosures.
587. Risk Factors for Nosocomial Methicillin-Resistant Staphylococcus aureus (MRSA) Colonization in a Neonatal Intensive Care Unit (NICU): A Case–Control Study
Authors: Balamohan Archana , Beachy Joanna , Kohn Nina , Rubin Lorry G
Published: October 2019

Background

Staphylococcus aureus (SA) is a leading cause of nosocomial infection in NICUs. Colonization is a prerequisite for most SA infections. Previously recognized risk factors for colonization include the length of stay (LOS), multiple gestation, low birth weight, Caesarean delivery and multibed location. The objective of this study was to determine risk factors for MRSA colonization in a Level IV NICU independent of LOS and gestational age (GA) in the context of a circulating MRSA clone.

Methods

Weekly MRSA colonization cultures were performed from April 2017 through March 2018. Case–control study. Cases: Infants with newly acquired MRSA colonization and at least one previous negative culture. Controls: Infants with negative surveillance cultures, matched 1:1 with cases by GA and LOS. Factors compared: (a) neonatal demographics; (b) maternal factors; (c) neonatal factors since admission including antimicrobial therapy; (d) neonatal factors during the week prior to MRSA acquisition, including bed location, number of location changes, presence of central line, respiratory support, NICU census, ATP surface bioburden testing pass rate, MRSA colonization pressure.

Results

50 case infants were matched with controls. Forty-five of the 50 isolates were mupirocin-resistant and related by pulse-field gel electrophoresis On matched univariable analysis, the following were significantly associated with a risk for MRSA acquisition: (1) Bed location in the acute area (P = 0.03), (2) The requirement of any level of respiratory support during the week prior to MRSA detection (P = 0.04), (3) Higher ATP pass rate during the week of and week prior (P = 0.01), (4) Higher MRSA colonization pressure during the prior week (P = 0.002), (5) Not having a hearing test during the time between the previous negative culture and MRSA acquisition (P = 0.01). A multivariable conditional logistic regression model (that excluded ATP pass rate) found that only colonization pressure was associated with acquisition of MRSA colonization.

Conclusion

Independent of LOS and GA, MRSA colonization pressure, ATP pass rate and higher patient acuity, reflected by location within the acute area and requiring respiratory support, are significantly associated with MRSA acquisition in the NICU; only colonization pressure remained associated in a multivariable model.

Disclosures

All authors: No reported disclosures.
592. Assessment of Time Spent in the Room by Nurses and Nursing Assistants on a Pediatric Ward by Patient Isolation Status and Demographics
Authors: Simonsen Kari , High Robin , Fortini Mary , Hegemann Lindsay , Beedle Susan , Phipps Amber
Published: October 2019

Background

Published reports have raised concern that RNs spend less time in hospital rooms of patients requiring isolation precautions. Other patient-related factors including race/ethnicity, primary language, and socio-economic factors reportedly influence the mean time spent in the room by RNs and certified nursing assistants (CNAs). At a children’s hospital the automated hand hygiene monitoring system (AHHMS) has motion sensors that detect patient room entry and exit and sensors that detect hand hygiene events. Time spent in patient rooms by RNs and CNAs was examined using AHHMS data captured for patients on a 24-bed pediatric hospital ward for multiple patient characteristics to evaluate factors influencing the duration of visits.

Methods

RNs and CNAs routinely wore badges with infrared signal technology to monitor hand hygiene compliance, generating time-stamped data for room entries and exits, identified by user job category. Over a 30 day period, April 2016, RN and CNA time in the room was compared by patient characteristics including: length of stay, white yes/no, Hispanic yes/no, interpreter needed yes/no, and isolation status of contact-droplet, contact, or none. Mean minutes spent in the room for RNs and CNAs were evaluated with a random-effects linear model and gamma distribution.

Results

Admissions for 220 patients occurred in the 24 rooms during the evaluation period; 88 RNs and 28 CNAs completed 18,641 time-stamped room entries and exits. The natural log of patient length of stay (hours) was significantly associated with increased RN and CNA minutes spent in the room (P < 0.001). Interpreter required was not associated with time in the room (P = 0.72), nor was race (P = 0.60), nor was Hispanic ethnicity (P = 0.81). There were no significant differences in time spent in the room for contact, contact-droplet, and no isolation (P = 0.92).

Conclusion

Data derived from infrared signal AHHMS badges can provide insight into RN and CNA care patterns. Isolation status and patient demographics were unrelated to mean RN and CNA time in the room. Patient length of stay was the only predictor of increased nursing time spent providing direct patient care. These results contrast with previous reports demonstrating fewer nursing interactions based on patient demographics or isolation.

Disclosures

All authors: No reported disclosures.
599. LiaF is an Activator of the LiaR-Mediated Response Against Daptomycin and Antimicrobial Peptides in Multidrug-Resistant Enterococcus faecalis (Efs)
Authors: Ortiz-Velez Laura C , Rincon Sandra L , Degani Jesse , Shamoo Yousif , Tran Truc T , Arias Cesar A , Panesso Diana
Published: October 2019

Background

Daptomycin (DAP) is a key first-line agent for the treatment of vancomycin-resistant enterococcal infections. Resistance to DAP in enterococci is regulated by the liaFSR three-component regulatory system that consists of a histidine kinase sensor (LiaS), a response regulator (LiaR) and a transmembrane protein of unknown function (LiaF). Previous studies indicate that deletion of isoleucine in position 177 of LiaF results in DAP tolerance and is sufficient to change membrane architecture. Here, we dissect the role of LiaF in DAP resistance

Methods

We generated three liaF mutants in OG1RF, a DAP-susceptible laboratory strain of Efs (DAP MIC = 2 µg/mL): (i) a non-polar, C-terminal truncation of liaF (OG1RFliaF∆152), (ii) a null liaF mutant with a premature stop-codon (OG1RFliaF*11), and (iii) an isoleucine deletion at position 177 (OG1RFliaF177). We determined DAP MIC by Etest and characterized the localization of anionic phospholipids microdomains using 10-nonyl-acridine-orange (NAO). The expression of the liaXYZ (the main target of LiaR) and liaFSR clusters were evaluated by qRT-PCR and relative expression ratios (Log2 fold change) were calculated by normalizing to gyrB expression. We assessed activation of LiaFSR by evaluating surface exposure of LiaX by ELISA. We used the bacterial adenylate cyclase two-hybrid system (BACTH) to evaluate the protein-protein interaction between LiaF and LiaS.

Results

Full deletion of liaF or the C-terminal truncation of LiaF did not have any effect on DAP MICs, membrane architecture or a significant increase in LiaX surface exposure compared with parental strain OG1RF. In contrast, deletion of the codon encoding isoleucine in position 177 of LiaF caused a major increase (8-fold) in LiaX exposure and redistribution of anionic phospholipid microdomains away from the septum without changes in the actual DAP MIC. Transcriptional analyses indicated upregulation (>2 log2-fold) in the liaXYZ gene cluster indicating activation of the stress response. We also observed a positive interaction between LiaF and LiaS.

Conclusion

LiaF is likely a key activator of the LiaFSR stress response and the critical regulatory domain appears to be located in a stretch of four isoleucines toward the C-terminal of the protein.

Disclosures

All authors: No reported disclosures.
628. Integrated Surveillance for Antimicrobial-Resistance in Salmonella From Clinical and Retail Meat Sources—Pennsylvania, 2015–2017
Authors: M’ikanatha Nkuchia M , Kline Kelly E , Boktor Sameh W , Yin Xin , Dettinger Lisa , Tewari Deepanker , Tate Heather
Published: October 2019

Background

Antimicrobial resistance (AMR) in foodborne pathogens of animal origin, including nontyphoidal Salmonella (NTS), is a public health concern. Pennsylvania conducts integrated surveillance for AMR in NTS from human and animal sources in collaboration with the FDA and CDC National Antimicrobial Resistant Monitoring System (NARMS).

Methods

We reviewed pulsed-field gel electrophoresis (PFGE), antimicrobial susceptibility (SST) and whole-genome sequencing (WGS) data for isolates from animal and food sources, including 96 NTS from 2,520 meat samples (poultry, ground beef and pork chops) purchased during 2015–2017 from randomly selected retail outlets in Pennsylvania. SST to 15 antimicrobial agents was done on 109 NTS clinical isolates that had similar PFGE patterns to meat isolates. SST and WGS were used to characterize all isolates from meat and two clinical isolates from 2017.

Results

28 (29.2%) and 17 (17.7%) NTS isolated from meat sources were resistant to ≥3 and ≥5 antibiotics classes, respectively. Resistance to ceftriaxone rose from 12% (3/25) in 2015 to 27% (10/37) in 2016 and resistance to amoxicillin/clavulanate also increased. Plasmid-mediated bla CMY-2 β-lactam resistance genes that hydrolyze extended-spectrum cephalosporins (ESC) increased from 12% in 2015 (3/25) to 18.9% (7/37) in 2016. Four blaCTX-M-65 genes that confer resistance to extended-spectrum β-lactamases (ESBLs) were identified in 2016 (n = 3) and 2017. Of the 109 clinical isolates, 25.7% demonstrated resistance to ≥3 and 11% to ≥5 antibiotics classes, respectively. No clinical isolates were resistant to ceftriaxone in 2015, 12.5% (6/48) and 24.3% (9/37) were resistant in 2016 and 2017, respectively. Resistance to amoxicillin/clavulanate was demonstrated in 8.3% (4/48) of isolates in 2016 (figure). Two clinical isolates carried blaCTX-M-65 ESB Ls genes and were resistant to eight antimicrobial agents (ACSSuTCxNalCot. Phenotype).

Conclusion

NTS (≥25%) from animal and human sources were multidrug-resistant and harbored CMY-2 and CTX-M-65 genes. Dissemination of genes that confer resistance to ESBLs and ESCs in NTS undermines recommended treatment for severe infections and underscores the need for One-Health surveillance and antimicrobial stewardship efforts.

Disclosures

All authors: No reported disclosures.
659. Evaluation of a Rapid Diagnostic Assay for Early Detection of Bacteriuria
Authors: Christian Robbie Lee Anne , Donskey Curtis , Navas Maria
Published: October 2019

Background

Patients with suspected urinary tract infection (UTI) are often prescribed an empiric antibiotic treatment due to delays in obtaining results of urine cultures. The BacterioScan System measures the turbidity of incubating urine specimens to provide a qualitative determination of bacteriuria at a density of >5 × 104 colony-forming units (CFU)/mL within approximately 3 hours. We examined the utility of the BacterioScan assay in predicting bacteriuria and assessed the potential impact of this test to reduce the number of urine cultures processed.

Methods

Urine samples received for culture in the microbiology laboratory of the Cleveland VA Medical Center were collected daily between September 2018 and December 2018. For each specimen, we performed a bacterioscan diagnostic test and compared it with the result of the traditional culture and urinalysis if available. Urinary cultures were categorized into 4 groups as defined in Figure 1. We compared the sensitivity and specificity of the bacterioscan vs. urinalysis (leukocyte esterase and/or pyuria) results.

Results

120 urine samples were tested. As shown in Table 1, the BacterioScan had better sensitivity and specificity than the urinalysis for detection of positive urine cultures. The use of the BacterioScan to rule out UTI could have accurately spared 69 of 120 (57.5%) samples from traditional culture and prevented 26 of 120 (21.6%) from possible misinterpretation as infection due to reporting of growth. BacterioScan resulted in 4 of 31 (12.9%) false negatives, but all occurred when positive cultures were due to viridans streptococci or uropathogens in numbers below 100,000 CFU.ml.

Conclusion

The BacterioScan system is a rapid diagnostic test that provides early information on urine culture results that could help to avoid overuse of empirical antimicrobials in patients with suspected UTI and decrease the workload of the Microbiology Laboratory.

Disclosures

All authors: No reported disclosures.
676. Health-Related Quality of Life (HRQoL) as Measured by the 12-Item Medical Outcomes Study Short-Form (SF-12) Among Adults With Community-Acquired Bacterial Pneumonia (CABP) Who Received Either Lefamulin (LEF) or Moxifloxacin (MOX) in Two Phase 3 Randomized, Double-Blind, Double-Dummy Clinical Trials (LEAP 1 and 2)
Authors: Lodise Thomas , Colman Sam , Alexander Elizabeth , Stein Daniel , Fitts David , Goldberg Lisa , Schranz Jennifer
Published: October 2019

Background

Interest in patient health experience as part of a benefit–risk assessment for new drug approvals is increasing. Patient-centeredness, a key metric in the 2010 Affordable Care Act, is also a growing area of focus in healthcare. LEF, a new antibiotic in development for treating adults with CABP, was noninferior to MOX based on clinical response endpoints in LEAP 1 and 2. HRQoL was prospectively incorporated and evaluated in both studies via SF-12, a well-known survey that measures general health status in 8 domains (physical function, role limitations due to physical problems, bodily pain, general health, vitality, social function, role limitations due to emotional problems, and mental health).

Methods

An exploratory analysis evaluated HRQoL in patients who received LEF or MOX in LEAP 1 (IV-PO treatment) and LEAP 2 (PO-only treatment). SF-12 was measured at baseline (BL) and test-of-cure (TOC; 5–10 days after last study drug dose). SF-12 outcomes assessed included the 8 domains, physical component summary (PCS), and mental component summary (MCS) scores. SF-12 scores were normalized to the 2009 US population reference mean (SD) of 50 (10). A 3-point change on any scale represents a clinically meaningful difference.

Results

Analysis included 1,215 patients (LEF n = 607; MOX n = 608). At BL, all mean SF-12 scores in both treatment groups were well below the US reference mean, indicating a low HRQoL level, consistent with the acute illness of the study population (figure). Clinically meaningful and significant improvements from BL to TOC were observed in all domain, PCS, and MCS scores in both groups. Mean scores were close to the reference mean, indicating an average HRQoL level. No significant differences in mean score improvements from BL to TOC were seen for LEF vs. MOX. SF-12 score improvements at TOC across predefined subgroups (age, sex, number of comorbidities, study, and PORT risk class) were comparable between treatment groups.

Conclusion

Our data indicate that adults with CABP experienced HRQoL improvements with LEF that were comparable with MOX, and treatment with either agent resulted in return to normal HRQoL. When combined with overall study results, these data suggest LEF as a potential alternative to MOX for treatment of adults with CABP.

Disclosures

All authors: No reported disclosures.