bluuebunny/crossref_metadata_2025_split huggingface dataset:
359. TLR7 Gene Polymorphisms Influence Development of Hepatic Fibrosis in HCV/HIV Coinfection
Authors: Sherman Kenneth , Meeds Heidi L , Abdel-hameed Enass A , Rouster Susan D , M. Shata M Tarek 
Published: October 2019

Abstract

Background
Hepatic fibrosis in individuals with HCV/HIV coinfection or HCV mono-infection may be modulated by a variety of host factors. In this study, we investigated the role of gene polymorphisms of putative genes that might influence fibrosis progression including MICA (rs2596542), interferon-stimulated gene OAS2 (rs1293762) and the pathogen recognition receptors TLR7 (rs179009) and TLR9 (rs187084). Effect on a cytokine panel was evaluated.

Methods
Longitudinal samples were obtained from subjects enrolled in the NCI Multicenter Hemophilia Cohort Study. Within the cohort, a subset of subjects were included based upon presence or absence of the CCR5 delta-32 mutation which was previously shown to influence the rate of fibrosis progression. Hepatic fibrosis change was determined using the serum-derived Enhanced Liver Fibrosis (ELF) Index. Four putative genes with polymorphisms that have been previously associated with the development or progression of hepatic fibrosis were evaluated using Taqman SNP genotyping assays. Cytokine assays were performed using Luminex chipsets. Samples were analyzed using Statistix 10.0 using ANOVA and least square regression models.

Results
58 unique subjects were evaluated. The mean age was 38 years, and all were male. 74% were HIV infected and 97% were HCV infected (76.8% coinfection). Controlling for the effect of CCR5, only the TLR7 A -> G polymorphism was predictive of change in the ELF Index. There was no statistically significant predictive difference between genotypes in the other three polymorphisms. Subjects with the TLR7 A allele (n = 47) had an average increase in ELF of 0.79 units, while the G allele (n = 11) had an increase in ELF of 2.1 units (P = 0.008). A regression model identified TLR7 as a key factor in ELF change, as well as HCV/HIV coinfection. Interferon alfa-2 levels were highly associated (increased, P = 0.0007) with the TLR7 A -> G polymorphism, while RANTES levels were inversely associated (decreased, P = 0.0443) with it.

Conclusion
Of the gene polymorphisms investigated, only TLR7 (rs179009) is an independent predictor of development of hepatic fibrosis in HCV/HIV coinfected subjects. The mechanism may involve modulation of inflammatory response pathways.

Disclosures
All authors: No reported disclosures.
384. Denosumab-Related Osteonecrosis of the Jaw: an Emergent and Potentially Complex Bone and Joint Infection
Authors: Bricca Romain , Valour Florent , Anne Conrad , Braun Evelyne , Jaby Philippe , Bachelet Jean-Thomas , Breton Pierre , Gleizal Arnaud , Laurent Frederic , Chidiac Christian , Ferry Tristan 
Published: October 2019

Abstract

Background
Osteonecrosis of the jaw is a known complication of antiresorptive treatment, like bisphosphonate. More recently, denosumab was validated as a treatment in the osteoporosis and bone metastasis. Its mechanism is different from bisphosphonate but induces also a decrease of bone resorption and a risk of osteonecrosis of the jaw. In case of treatment failure by a dental surgeon or in complex cases, patients could be addressed to a bone and joint infection (BJI) reference center. The aim of this study was to analyze microbiology, as well as surgical and medical care of patients who present denosumab-related osteonecrosis of the jaw (DRONJ) and who were treated in a bone and join reference center.

Methods
All patients managed in our BJI reference center between January 2013 and December 2018 for a DRONJ were included in our retrospective observational monocentric cohort.

Results
Twelve patients (median age 71; ratio M/W 0.7) with a DRONJ (metastatic cancer, n = 10 (83%)) in grade 3 (n = 5), 2 (n = 4), 1 (n = 3) were included. Only 3 patients (25%) had a dental health control before initiating the treatment by denosumab and 7 patients (58%) had a dental surgical procedure done before the DRONJ. Eleven patients had a bone exposure, treated at least with a scaling and mucosal closure at the same time. All infections with bacterial cultures (n = 11 (91%)) were polymicrobial, including 8 (72%) with Streptococcus spp; 8 (72%) with anaerobia including 2 (18%) with Actinomyces; 5 (45%) with Staphylococcus spp; 5 (45%) with enterobacteria; 3 (27%) with Candida spp; 2 (17%) with a non-fermentative Gram-negative bacilli and 7 (64%) with others bacteria. All patients (n = 12) received a betalactam, 8 (66%) a lincosamide or a synergistin, 5 (41%) an antifungal, 5 (41%) metronidazole, 4 (33%) a fluoroquinolone, 3 (25%) a glycopeptide and 2 (17%) other antibiotics. The median follow-up was 6 months. Eight patients were cured after a medico-surgical care and a median duration of antibiotics of 97 days (including 28.5 days in intravenous). 2 patients required a suppressive antibiotic treatment, 1 relapsed at a distance of the treatment and 1 died from some other causes.

Conclusion
DRONJ is a potential complex BJI, for which some patients could benefit from medical care in a BJI reference center.

Disclosures
All authors: No reported disclosures.
386. Blue Light Reduces Cutibacterium (Propionibacterium) Acnes Bacterial Burden: Orthopedic Shoulder Infection Prevention Strategy?
Authors: Bhargava Swati , Boyle Kathleen , Diletti Sara , Nodzo Scott , Crane John , Duquin Thomas 
Published: October 2019

Abstract

Background
Cutibacterium acnes (C. acnes) is a common shoulder periprosthetic joint infection (PJI). Blue light (BL) is effectively used in the dermatologic clinical setting against acne vulgaris caused by C. acnes. Photodynamic therapy (PDT) is the use of light source and photosensitizer (PS) to enhance antimicrobial activity. We studied the effect of PDT using BL and PS in vitro on shoulder PJI isolates of C. acnes.

Methods
19 strains were grown in thioglycollate medium and diluted in sterile normal saline (NS) to a turbidity of 0.5 McFarland standard; OD600 of 0.1 to 0.15. 250 µL with PS added were placed in 96-well plates at 37ºC, exposed to BL (415 nm) placed 1 cm above for 0 to 60 minutes at 15-minute intervals. Susceptibility to BL alone, and BL with PSs such as riboflavin (R, Vit B2), fluorescein (F) or demeclocycline (tetracycline antibiotic, “D”) were studied. After serial 10-fold dilution with NS, 3 µL of each well were spotted onto Brucella Blood Agar plates and incubated anaerobically for 48 hours. Eradication was defined as below the limit of detection. Definitions include Sensitive (S) if 3-log decrease in bacterial density or eradication at any time point, Weakly Sensitive (WS) with 1- to 3-log decrease and Resistant (R) with no decrease.

Results
Based on BL alone, (n = 19). 68% strains were S, 32% were resistant. BL+ R (10 μg/mL) effect in 25% (n = 3) and exerted a protective effect against 33% (n = 4). BL+ F (1 μg/mL) potentiated in 67%. BL+ D (0.1–1.5 μg/mL) in 83% of strains tested. The most resistant strain was eradicated using BL + D at an increased concentration of demeclocycline (2.5 μg/mL).

Conclusion
F and D enhanced the potential for eradication compared with BL exposure alone. R was a photo-protectant to BL for select strains. Prior studies have hypothesized endogenous intracellular porphyrins excited by BL causing energy transfer and production of highly cytotoxic reactive oxygen species causing bacterial death. Future clinical research evaluating the use of preoperative PS and surgical site exposure to BL as a preventative PJI strategy are needed. Our research shows that BL with the addition of PS significantly reduces the bacterial burden of clinically relevant PJI shoulder isolates of C. acnes in an in vitro model.

Disclosures
All authors: No reported disclosures.
393. Changing Trends, Risk Factors, and Treatment Challenges in Staphylococcus aureus Septic Arthritis
Authors: Gobao Valerie , Alfishawy Mostafa , Shah Neel , Byers Karin , Yassin Mohamed , Urish Kenneth 
Published: October 2019

Abstract

Background
Staphylococcus aureus is a common organism in native septic arthritis. It is traditionally believed to be self-limited with rapid and aggressive debridement and appropriate antibiotic selection. The incidence of S. aureus septic arthritis is increasing, and further characterization is needed to improve diagnosis and treatment. For patients presenting with native S. aureus septic arthritis, we evaluated the reliability of methicillin-resistant S. aureus (MRSA) screening as a predictor to rule out MRSA septic arthritis, the risk factors associated with this disease, and the treatment and surgical outcomes.

Methods
A retrospective case–control study of patients diagnosed with septic arthritis in the UPMC health system (Pittsburgh, PA) between 2012 and 2016 was completed. The primary outcomes of interest were surgical intervention and the need to alter antibiotic treatment. Patient demographics, characteristics, and outcomes were recorded.

Results
A total of 215 cases of septic arthritis were identified, and 64% (n = 138) had S. aureus cultured. In this set, 36% (50/138) of these patients were identified with MRSA. Of the patients diagnosed with MRSA septic arthritis, 50% screened prior to admission had a positive result (8/16) and 48% screened during admission had a positive result (14/29). Compared with septic arthritis with other organisms, risk factors associated with S. aureus included history of intravenous drug use (OR: 4.3, CI: 1.7 to 10.8, P = 0.002) and being immunocompetent (OR: 0.3, CI: 0.1 to 0.6, P = 0.002). These infections were associated with concurrent infections of the spine (OR: 5.7, CI: 2.1 to 15.1, P = 0.0005). As compared with other organisms, there was a high probability of switching antibiotics during treatment (OR: 3.7, CI: 1.1 to 13.0, P = 0.04) and relapse of infection (OR: 4.2, CI: 1.2 to 14.6, P = 0.02).

Conclusion
S. aureus septic arthritis is associated with intravenous drug use, and not with immunosuppression. A negative MRSA screen does not rule out this organism. Concurrent spine infections are common. There is a high likelihood of infection relapse and that antibiotics will need to be altered during treatment. With the opioid epidemic, the incidence is likely to increase further. More work is needed to improve diagnosis and overcome treatment challenges.

Disclosures
All authors: No reported disclosures.
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.