bluuebunny/crossref_metadata_2025 huggingface dataset:
163. Enhancing the Immunogenicity of a Novel, Low-cost Ebola Vaccine
Authors: Stampfer Samuel D , Jin Rui , Yang Chinglai
Published: January 2021

Background

Ebolaviruses cause viral hemorrhagic fever with high mortality rates. Nearly all Ebola vaccines in development use Ebola glycoprotein (GP) as the immunizing antigen. GP is present on the viral membrane and functions in cell entry by binding the cellular receptor and mediating membrane fusion; antibodies to GP induce protective immunity. Ebola also produces sGP: a smaller, secreted form of GP containing the receptor-binding domain; it is also able to induce protective immunity. sGP naturally refolds after thermal denaturation and thus may be more stable than GP, and may also be more cost effective as it is produced easily in high quantities. sGP is a homodimer that is covalently linked by a cysteine near its C-terminus. In this work, we explored how modifications to sGP that affect its ability to dimerize also alter its immunogenicity.

Methods

sGP mutants were generated in the pCAGGS mammalian expression plasmid, and injected into mice as a DNA vaccine. Mouse sera was tested by ELISA against sGP and GP proteins, and in a neutralization assay against GP-typed pseudovirions.

Results

We generated 4 different mutants of sGP that had altered abilities to form inter-protomer disulfide bonds. All had a mutated or deleted cysteine at position 306; two had disulfide-bonding restored by introduction of an engineered inter-protomer disulfide bond. Mice were immunized with a DNA vaccine encoding either an sGP mutant or wild-type sGP, and sera were collected. We found that sera from sGP mutants with reduced interprotomer disulfide bonds had significantly higher antibody titers to sGP and GP than sera from our wild-type sGP and engineered-disulfide sGP immunized mice. Antibody titers were similar between sGP and GP; these titers correlated with neutralization ability.

Relative binding to sGP & GP (by ELISA OD) & relative % neutralization of pseudovirions at 1:10 dilution

Conclusion

Immunogenicity of Ebola sGP was enhanced significantly when mutations were introduced to reduce its ability to covalently dimerize. Immunogenicity correlated with induction of neutralizing antibodies, implying that our mutants may outperform wild-type sGP when used as a vaccine in vivo. This work helps paves the way for an alternative Ebola vaccine that has the potential to be more cost-effective and heat-stable than the currently-licensed vaccine.

Disclosures

Samuel D. Stampfer, MD/PhD, Gilead (Shareholder)
164. in Vitro Antibacterial Activity of Cefiderocol Against Non-fermenter Clinical Strains Collected in North America and Europe from Multinational Surveillance Studies SIDERO-WT-2014–2018
Authors: Ukai Yuuta , Nakamura Rio , Oota Merime , Hackel Meredith , Echols Roger , Takemura Miki , Yamano Yoshinori , Sahm Daniel F
Published: January 2021

Background

Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa, Acinetobacter baumannii-complex (ABC), Stenotrophomonas maltophilia, and Burkholderia cepacia-complex (BCC), are recognized as difficult-to-treat organisms due to acquired and intrinsic antimicrobial resistance. This study evaluated the in vitro activity of cefiderocol (CFDC), a novel parenteral siderophore cephalosporin, and comparator agents against NFGNB clinical isolates collected in 2014–2018 as part of the multinational SIDERO-WT surveillance program.

Methods

12,293 non-fermenter clinical isolates, including 5310 from North America and 6983 from Europe, were tested for antimicrobial susceptibility. Minimum inhibitory concentrations (MICs) were determined for CFDC, cefepime (FEP), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), meropenem-vaborbactam (MVB), meropenem (MEM), ciprofloxacin (CIP), colistin (CST), and trimethoprim-sulfamethoxazole (SXT) by broth microdilution according to Clinical Laboratory and Standards Institute (CLSI) guidelines. MICs for aztreonam-avibactam (ATM/AVI; ATM in the presence of 4 μg/mL AVI), MVB, and SXT were determined only for SIDERO-WT 2018 strains. As per CLSI guidelines, CFDC was tested in iron-depleted media, and carbapenem-non-susceptible (CarbNS) isolates were defined as non-susceptible to MEM.

Results

CFDC demonstrated in vitro activity with MIC90s of 0.25–2 µg/mL against clinical isolates of P. aeruginosa, ABC, S. maltophilia, and BCC, including CarbNS subsets. MIC90s of CFDC against CarbNS P. aeruginosa (N=1416), CarbNS ABC (N=2274), S. maltophilia (N=1565), and CarbNS BCC (N=80) were 1, 2, 0.5, and 2 μg/mL, respectively, which were the lowest among the tested compounds (Table). The MIC90 differences between all isolates and CarbNS subsets were ≤2-fold for P. aeruginosa and ABC, showing that CFDC is active against CarbNS subsets as well as carbapenem-susceptible isolates. However, an 8-fold MIC90 difference between all isolates and CarbNS subsets was observed for BCC.

Conclusion

In 4 years of consecutive multinational surveillance studies, CFDC was the most active agent among antimicrobials tested against a wide range of NFGNB, including CarbNS strains.

Disclosures

Yuuta Ukai, MSc, Shionogi & Co., Ltd. (Employee) Rio Nakamura, BSc, Shionogi & Co., Ltd. (Employee) Merime Oota, BSc, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
170. Acute Flaccid Myelitis: Patient Characteristics and Prospective Follow-up Study at Children’s National Hospital, 2013–2019
Authors: Yonts Alexandra B , Harik Nada , Doslea Alyssa , Murnick Jonathan , Carpenter Jessica , Wells Elizabeth , DeBiasi Roberta L
Published: January 2021

Background

Acute Flaccid Myelitis (AFM), diagnosed almost exclusively in children, is characterized by sudden onset flaccid weakness in one or more extremities with distinct gray matter spinal cord lesions on magnetic resonance imaging (MRI), with or without cerebrospinal fluid (CSF) pleocytosis. Outbreaks of AFM have occurred biennially since 2014. Although the definitive causative agent(s) remain unknown, current data support an association with Enteroviruses D68 and A71. Treatment is supportive and long-term prognosis is variable, with many children having persistent motor deficits.

Methods

In this prospective cohort study, we identified patients with clinical and radiographic presentation consistent with AFM at Children’s National Hospital (CNH) from 2013–2019. Medical records and MRIs of identified patients were then reviewed by members of the multidisciplinary CNH AFM Task Force to identify those meeting diagnostic criteria for AFM. Identified patients had follow-up arranged in the multidisciplinary AFM clinic for exam, functional motor assessment and quality of life questionnaires (Peds QL, PROMIS and NeuroQoL).

Results

Since 2013, we identified 22 patients meeting criteria for AFM at CNH. The average age of our patients was 7.25 years (range 6 months to 16 years); almost 2/3 of patients had CSF pleocytosis. Half of patients presented with initial neurologic complaint of single limb weakness. Other presenting neurological symptoms included ataxia, bilateral lower extremity weakness and ophthalmoplegia. A potential infectious cause was identified in the CSF, blood, nasopharynx or stool of 9 patients. As of November 2019, 7 of 21 patients have had follow-up evaluation; 1 had no improvement, 4 had partial improvement but with persistent motor deficits, and 2 had complete resolution. Two patients/families have completed quality of life questionnaires to date.

CNH AFM Patient Characteristics and Results

Conclusion

Similar to other centers, the majority of CNH AFM patients with follow-up to date have persistent and significant long term motor deficits. Assessment of quality of life is an important aspect that has not yet been formally assessed in other studies and will provide useful information regarding the experience of these patients and help identify goals for optimizing care in the future.

Disclosures

All Authors: No reported disclosures
177. Safety of Measles and Pertussis-containing Vaccines in School-age Children Previously Diagnosed with Autism Spectrum Disorders
Authors: Zerbo Ousseny , Modaressi Sharareh , Goddard Kristin , Lewis Ned , Fireman Bruce , Jackson Lisa , Irving Stephanie , Daley Matthew F , Gethaun Darios , Qian Lei , Donahue James , Klein Nicola P
Published: January 2021

Background

Some parents, especially those of children with autism spectrum disorders (ASD), are uncertain about the safety of childhood immunization. We compared rates of fever, febrile seizure and emergency room (ER) visits following measles and pertussis-containing vaccines recommended between ages 4–6 years among children with and without ASD.

Methods

The study included children who were born between 1995–2012, aged 4–7 years at vaccination, and members of six integrated healthcare delivery systems within the Vaccine Safety Datalink. Children with ASD were defined based on receipt of two separate International Classification of Diseases (ICD)-9 or 10 codes. Outcomes (fever, febrile seizures, and ER visits) were identified in electronic health records. To minimize confounding by unmeasured factors related both to avoidance of vaccination and to outcomes of interest, we compared rates of each outcome between children with and without ASD, in risk and control intervals, by estimating the difference-in-differences on a log scale (i.e. the ratio of rate ratios) using logistic regressions. We also conducted risk interval analyses comparing rates of outcomes in risk intervals and control intervals within each group.

Results

The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles or pertussis-containing vaccination, there were no differences in association between the two groups for fever or ER visits (Table). There were no febrile seizures identified among children with ASD. Within the ASD group, rates of fever, seizure or ER visits did not differ significantly between the risk and control intervals after vaccination. However, among the non-ASD group, measles and pertussis-containing vaccines were associated with higher rates of fever and seizure in risk intervals compared to controls intervals. Pertussis-containing vaccines were associated with increased risk of ER visits in risk interval compared to control interval (Table).

Conclusion

We found no difference in the risk of fever, and ER visits comparing children with autism to children without autism after measles or pertussis-containing vaccines. The study provides some reassurance that these vaccines are not less safe in children with ASD.

Disclosures

Lei Qian, PhD, GlaxoSmithKlein (Research Grant or Support) Nicola P. Klein, MD, PhD, GSK group of companies (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Protein Science (now SP) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)
183. chlamydia Trachomatis Seroprevalence with a pgp3 Serologic Assay and Association with Pelvic Inflammatory Disease Among Women, United States, 2013–2016
Authors: Anyalechi Gloria E , Danavall Damien , Raphael Brian H , Bowden Katherine E , Hong Jaeyoung , Gwyn Sarah , Martin Diana , Kersh Ellen , Kirkcaldy Robert D
Published: January 2021

Background

Chlamydia trachomatis (CT) causes pelvic inflammatory disease (PID) and other sequelae; however, these associations are not fully characterized. CT serologic assays including Pgp3 ELISA may detect prior CT infection and may better elucidate these associations. We used a serologic Pgp3 multiplex bead array assay (Pgp3MBA) to measure CT seroprevalence in reproductive-age US women and assess the association with PID.

Methods

We performed CT Pgp3MBA on sera collected from women 18–39 years old during the 2013–2016 cycles of the National Health and Nutrition Examination Survey (NHANES) who had available urine CT nucleic acid amplification test results. Weighted Pgp3MBA CT seroprevalence and 95% confidence intervals (95% CI) were calculated. We also determined weighted prevalence ratios (PRs) and 95% CIs of self-reported lifetime PID among women with and without detectable Pgp3MBA and other characteristics to estimate these US national statistics.

Results

Among 2,339 women, 1,725 (73.7%) had available sera. Of these women, 1,425 (or 93.4% of those with data) were sexually experienced and had a CT seroprevalence of 35.9% (95% CI 33.4–38.4). When weighted for US women, CT seroprevalence was 30.5% (95% CI 26.6–34.4%), ranging from 16.9% (95% CI 11.0–22.8%) among non-Hispanic Asian women to 70.2% (95% CI 62.4–78.0%) among non-Hispanic black women.

PID was reported by 4.2% (95% CI 3.1–5.2) of 1,413 sexually-experienced women with PID data or an estimated 3.8% (95% CI 2.6–5.0) of US women. Among US women, estimated PID varied by Pgp3MBA status; 7.3% (95% CI 4.3–10.2) of Pgp3MBA-positive women were estimated to report PID versus 2.3% (95% CI 1.3–3.4) of Pgp3MBA-negative women (PR 3.1; 95% CI 1.7–5.9). PID prevalence did not vary by age, nor self-reported recent sexually transmitted disease among US women, but was higher among non-Hispanic black women compared to non-Hispanic white women (PR 2.2; 95% CI 1.4–3.5).

Conclusion

Nearly one-third of US women have had CT by Pgp3MBA, with differences by race/ethnicity. Women with prior CT had three times the reported PID prevalence of women without CT. Further serologic research may refine the population-level impact of CT prevention activities, such as recommended annual CT screening, on PID incidence, particularly among non-Hispanic black women.

Disclosures

All Authors: No reported disclosures
186. A Systematic Literature Review on the Economic Burden of Illness in Gonorrhea
Authors: Martin Amber , Mitrani-Gold Fanny S , Turner Monica , Schiller Emma , Joshi Ashish V
Published: January 2021

Background

In 2016, the World Health Organization estimated the global incidence of gonorrhea (GC) to be 86.9 million, and the reported incidence of GC in 2017 was 145.8 cases per 100,000 females and 212.8 cases per 100,000 males in the US. GC therefore represents a significant global healthcare burden; as the infection can be recurrent, overall costs can accumulate. We undertook a systematic literature review (SLR) to examine the economic burden of illness for GC in key countries.

Methods

Systematic searches were conducted in MEDLINE, EMBASE, and Cochrane databases to identify English-language articles published from January 1, 2009–December 1, 2019 reporting data on the economic burden of uncomplicated urogenital GC (uuGC) in the US, the UK, Germany, Japan and China. The SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (2009). Articles were evaluated for eligibility using population, intervention, comparison, outcome, study design and time period criteria (Table). Dual-independent screening was used at both the abstract and full-text levels; data were captured by a single reviewer with validation by a second reviewer.

Table. PICOS-T Study Selection Criteria

Results

The SLR identified 27 eligible articles (Figure), of which 17 studies (16 US, 1 UK) reported the economic burden of uuGC. The studies primarily reported cost data, with a subset reporting limited resource use. Lifetime costs for uuGC, when elaborated upon, considered the potential for pelvic inflammatory disease among women, and epididymitis in men, as well as lifetime medical costs associated with human immunodeficiency virus. Among the 16 studies reporting costs, the total estimated lifetime cost of uuGC in the US reached as high as $162.1 million. Costs varied vastly based on sex, with one study reporting lifetime estimates up to $163,433 for men but $7,534,692 for women in 2005. Nine studies described costs per patient/infection and found average costs ranging from $26.92–$438.46, though most fell in the range of $79–$354.

Figure. PRISMA flow diagram of study inclusion and exclusion

Conclusion

We identified a large body of evidence detailing the economic burden of GC. The cost burden varied by sex and was higher for females. However, the vast majority of the evidence came from the US, highlighting the need for more global research.

Disclosures

Amber Martin, BS, Evidera (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Monica Turner, MPH, Evidera (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Emma Schiller, BA, Evidera (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)
188. The Role of Bone Pathology in the Management of Residual Osteomyelitis After Amputation for Diabetic Foot Infections
Authors: Lee Eugene , Pupaibool Jakrapun , Certain Laura
Published: January 2021

Background

Diabetic foot osteomyelitis is a common infection often treated by a combination of antibiotic therapy and limb-sparing amputation. During amputation, IDSA guidelines recommend histopathological analysis of the proximal resection margin, but there are few studies evaluating the prognostic value of such analysis. We did a retrospective cohort study to evaluate whether histopathologic findings predict the clinical outcomes of further proximal amputation or death.

Methods

We conducted a retrospective cohort study at a VA hospital reviewing 84 patients. We evaluated patients who had a diagnosis of diabetes mellitus with diabetic foot osteomyelitis who were treated with limb-sparing amputations. All cases that were included had adequate histopathological description of the proximal margin of the amputation site. We also collected relevant clinical data including comorbidities, labs, culture data and pre-op and post-op antibiotics. The primary outcome was defined as the need for further proximal resection at the amputation site within six months of the original amputation or death from all causes within three months of the original amputation. Categorical variables were compared using Fischer’s exact test or the Chi-Square test. Continuous variables were compared using the t-test.

Results

We found a statistically significant difference (p=0.0003) of the primary outcome with 10 of 19 (53%) patients with positive margins needing further surgical resection and 1 of 19 (5%) patients dying. Of the patients with negative margins, 9 of 55 (14%) patients needed further surgery and none died.

Conclusion

Our study showed that patients with residual osteomyelitis at the proximal margin were more likely to need further proximal amputation or die. We did not have adequate power to assess whether extended antibiotic therapy improved outcomes for patients with positive margins, but there was no suggestion that it did. Further research will be needed to elucidate what the ideal duration of antibiotic therapy is for residual osteomyelitis after amputation for diabetic foot osteomyelitis.

Disclosures

All Authors: No reported disclosures
190. Osteomyelitis Following Mandibular Reconstruction with Free Fibula Flap: A Cohort Study of an Emerging and Complex Bone and Joint Infection
Authors: javaux Clément , Daveau Clémentine , Bettinger Clothilde , Bourlet jérôme , Dupieux-Chabert Céline , craighero Fabien , Fuchsmann Carine , Céruse Philippe , Sigaux Nicolas , Ferry Tristan , Valour Florent
Published: January 2021

Background

Free fibular flap (FFF) mandible reconstruction is at high risk of complications due to patient comorbidities, microvascular surgery after neck irradiation and intrabuccal exposure. We aimed to describe clinical and microbiological features, management and outcome of osteomyelitis following mandibular reconstruction with FFF.

Methods

Patients referred to our reference center for an osteomyelitis following FFF reconstruction of the mandible were included in a retrospective cohort. Microbiology was described based on gold-standard samples. Risk factors for treatment failure (infection persistence or relapse, need for additional surgery for septic reason, infection-related death) were assessed by logistic regression and Kaplan-Meier survival curve analysis.

Results

48 patients (age, 60.5 [IQR, 52.4–66.6]; 30 males; 62.5%; modified Charlson comorbidity index, 4 [3–5]) were included. Indications for FFF mandible reconstruction were mostly carcinoma (n=27; 56.3%) and osteoradionecrosis (n=12; 25.0%), with 44 (82.9%) previous neck irradiation. FFF osteomyelitis were mostly early (≤ 3 months post-surgery; n=43; 89.6%). Main symptoms were local inflammation (n=28; 59.6%), ununion or sinus tract (n=28; 59.6%), bone or device exposure (n=21; 44.7%), and were associated with radiological signs for infection in 33 (75.0%) cases. Microbiological documentation highlighted Enterobacteriaceae (n=25; 61.0%), Streptococcus spp. (n=22; 53.7%), S. aureus (n=10; 24.4%), anaerobes (n=10, 24.4%), Enterococcus spp. (n=9; 22.0%) and non-fermenting Gram negative bacilli (GNB; n=8; 19.5%). Thirty-nine (81.3%) required surgery, consisting in debridement with implant retention in 25 (64.1%) cases, associated with a 93 (64–128) day course of antibiotherapy. After a follow-up of 18 (11–31) months, 24 (50.0%) treatment failure were observed. An early ID-specialist referral was the only significant predictor of favorable outcome (OR, 0.167; p=0.005). Non-fermenting GNB infections tended to be associated with a higher risk of failure (OR, 8.4; p=0.058).

Probability of treatment failure of osteomyelitis following FFF mandible reconstruction according to ID-referral (A), CRP level 2 weeks after surgery (B) and presence of non-fermenting GNB

Conclusion

Osteomyelitis following mandibular reconstruction with FFF represent difficult-to-treat infections. Our results advocate for a multidisciplinary management, including an early ID-specialist referral.

Disclosures

All Authors: No reported disclosures
191. oral versus Intravenous Antibiotic Treatment in Skin and Soft Tissue Infections as a Consequence of Intravenous Drug Use: A Retrospective Study to Demonstrate Noninferiority
Authors: Andrzejewski Aryn M , Viehman J Alex
Published: January 2021

Background

Skin and soft tissue infections (SSTIs) are among the most prevalent infectious complications of intravenous drug use (IVDU). Given its polymicrobial nature, studies focusing on SSTIs in the general population may not be generalizable this group. We completed a retrospective chart review to better characterize the safety and efficacy of oral versus intravenous (IV) antibiotics for the treatment SSTIs in IVDU.

Methods

We reviewed patients admitted with bacterial SSTIs and IVDU from January 01, 2012 to December 31, 2019 based on ICD-10 codes. SSTIs complicated by bacteremia, endocarditis, bone or joint involvement on index admission were excluded. Patients who received < 48 hours of IV antibiotics were considered oral therapy, otherwise they were considered IV therapy. Patient comorbidities, incision and drainage (I&D) status, substance use, microbiology and antimicrobial data were reviewed.

Results

Of 231 eligible patients, 84 received oral therapy. There was no statistical difference in patient characteristics between the two therapy groups. Streptococcus anginosus group were the most common organisms found (33%) followed by Staphylococcus aureus (31%). There was no statistical difference between rates of readmission (p=0.87), recurrent primary site infection (p=1.00), repeat debridement (p=0.08) or occurrence of deep-seated infections within 90 days of treatment completion. No morality was observed. The oral group had shorter length of stay (3 vs. 5 days, p < 0.001) and shorter total duration of antibiotics (10 vs. 13 days, p < 0.001). Overall, 90% of those with abscess underwent I&D, which did not differ between therapy groups. Time to I&D was shorter (0 vs. 1 day, p=0.005) in the oral group. Patients who did not receive and I&D were more likely to be readmitted within 90 days (p=0.025).

Conclusion

In SSTIs related to IVDU, oral antibiotic therapy was noninferior to IV in terms of mortality, readmission, and deep-seated infection rates within 90 days of treatment completion and had a decreased length of stay and total treatment duration. A delay in I&D led to increased length of stay and lack of I&D increased readmission rate. Therefore, a prompt I&D may allow a safe and effective early transition to oral therapy in SSTIs related to IVDU.

Disclosures

All Authors: No reported disclosures
193. quality Improvement Initiative for Non-purulent Cellulitis Management in Urgent care setting: provider-level Performance Feedback
Authors: Reddy Laya , Goicoechea Miguel , Kozak Thomas , Bagsic Samantha
Published: January 2021

Background

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a common cause of skin and soft-tissue infections (SSTIs). This has resulted in an 88% increase in MRSA-directed antibiotic use in emergency departments. However, the majority of cellulitis presents as non-purulent due to Group A streptococci. An unintended consequence is that many with non-purulent cellulitis receive sub-optimal antibiotics and unnecessary diagnostics. Clinical guidelines at our institution recommend beta-lactam antibiotics and discourage empiric MRSA coverage for non-purulent cellulitis. The aim of this study is to use an audit-feedback intervention to optimize urgent care providers management of mild/moderate non-purulent cellulitis.

Methods

We identified all consecutive patients presenting to our urgent care with a diagnosis of lower extremity non-purulent cellulitis using ICD coding. We conducted a prospective pre and post-intervention study from 10/2018-3/2019 and 11/2019-4/2020 respectively. Intervention included review of practice guidelines with providers and feedback from pre-intervention phase. To assess individual practitioners’ prescribing habits, a comprehensive scoring system focused on empiric antibiotic selection, antibiotic duration, and diagnostics was combined with patient demographics. Scores classified non-purulent SSTI treatment as follows: 0–2 = good, 2.5–5 = fair, and >5.5 = poor (Figure 1).

Figure 1: Provider Cellulitis Management Scoring Sheet

Results

There was statistically significant provider score improvement in the post-intervention phase with greater percentage of good cases (40% to 69%) and no poor cases (Figure 2). For IV antibiotics for mild and moderate cellulitis, there was decreased use of overly broad antibiotics (Figure 3). Antibiotic duration of greater than 7 days decreased from 68% to 52%. Combination antibiotic therapy decreased from 12% to 4%. There was also a statistically significant decrease in use of wound cultures but no change in ultrasound use.

Figure 2: Overall Provider Scores

Figure 3: IV Antibiotic Use

Conclusion

Audit-feedback intervention was effective for improving antibiotic usage and decreasing treatment duration. Providing physicians with data on their practice patterns relative to those of their peers and clinical practice guidelines can improve management of non-purulent cellulitis.

Disclosures

All Authors: No reported disclosures
194. Combinatorial Polyfunctionality Analysis of Antigen-specific T-cell Subsets (COMPASS) as a Predictor for Clinically Significant CMV Infection in the Letermovir Era
Authors: Zamora Danniel , Duke Elizabeth , Xie Hu , Edmison Bradley , Akoto Brenda , Kiener Richard , Stevens-Ayers Terry , Wagner Ralf , Mielcarek Marco , Schiffer Joshua , De Rosa Stephen , Boeckh Michael
Published: January 2021

Background

Increased CMV reactivation is observed following discontinuation of letermovir prophylaxis after hematopoietic cellular transplantation (HCT) and decreased CMV-specific polyfunctional T-cell immunity has been proposed as a possible mechanism (BBMT 2020;26:S68). COMPASS is a novel analytical tool that integrates polyfunctional T-cell cytokine responses into a single score value (Nat Biotechnol 2015;33:610). We employed COMPASS for the first time in the HCT setting to determine if CMV-specific immunodeficiency is associated with late CMV events in a prospective cohort of allogeneic HCT recipients receiving either letermovir or preemptive therapy.

Methods

Peripheral blood mononuclear cells were collected 3 months post-HCT and assessed with a 13-color intracellular cytokine staining (ICS) assay that includes 5 functional markers. Intermediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) were used to stimulate polyfunctional T-cell responses that were defined using COMPASS generated polyfunctionality scores (PFS). CMV DNAemia was monitored by weekly plasma PCR and patients who reactivated were treated with preemptive therapy per institutional standards. Cumulative incidence of clinically significant CMV infection (cs-CMV; ≥500 IU/mL or CMV disease) by day 270 was assessed. Univariable and multivariable Cox regression were used to estimate the association of polyfunctional T-cell responses (upper quartile versus lower 3 quartiles) with cs-CMV infection by day 270 post-HCT.

Results

56 letermovir recipients and 93 preemptive controls were evaluated. Time to first clinically significant CMV (cs-CMV) infection after HCT and among day 100 survivors in both groups is shown in Figure 1. COMPASS PFS at 3 months were significantly lower in letermovir recipients (Figure 2). After adjusting for CMV infection before day 100, CD4 and CD8 PFS to IE-1 and pp65 below the upper quartile were associated with higher risk of late cs-CMV infection, with IE-1 CD8 PFS reaching statistical significance (Figure 3).

Conclusion

Our findings demonstrate that COMPASS is a valuable tool to evaluate multiple, T-cell cytokine responses to CMV in HCT recipients. COMPASS appears to be useful to identify patients at risk for late cs-CMV infection.

Disclosures

Elizabeth Duke, MD, Merck (Grant/Research Support) Michael Boeckh, MD PhD, AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)
197. Dengue Virus Infection Among Renal Transplant Recipients in Singapore: A 15-year Single Center Retrospective Review
Authors: Xuan Sophie Tan Seine , Ho Quan Yao , Thangaraju Sobhana , Tan Thuan Tong , Kee Terence , Shimin Jasmine Chung
Published: January 2021

Background

Dengue is a mosquito-borne viral infection endemic in Singapore. Its clinical course in the immunocompetent host is well characterised but its impact in renal transplantation is not well described. We aim to characterise the clinical presentation and outcomes of dengue virus infection in renal transplant recipients treated at a tertiary center in Singapore.

Methods

We conducted a 15 year retrospective review of dengue in renal transplant patients treated at Singapore General Hospital between January 2005 to October 2019. The diagnosis of dengue was made if there were a compatible clinical syndrome and a positive dengue diagnostic assay, either Dengue NS1 antigen, IgM or PCR.

Results

Thirty-two renal transplant patients were diagnosed with dengue, 18 (56.3%) were deceased donor recipients. The median age at time of diagnosis was 53 [IQR 42,61] years; 16 (50%) were males. The median time to diagnosis of dengue was 95.5 [IQR 15.0,95.5] months from transplant; and the median duration of clinical illness was 7 [IQR 5,7] days. The most common clinical symptoms were fever (84.4%), myalgia (40.6%), gastrointestinal symptoms (37.5%) and headache (25.0%). Based on the WHO 2009 dengue classification, 20 (62.5%) had dengue without warning signs, 9 (28.1%) had dengue with warning signs, and 3 (9.4%) had severe dengue; 19 (59.3%) had graft dysfunction and 1 (3.1%) required dialysis. Of the patients who had graft dysfunction, 18 (94.7%) had recovery of graft function at time of dengue resolution. Dengue mortality rate was 3.1%. There were 2 possible cases of donor derived dengue infections, occurring within 2 weeks of deceased donor transplantation.

Conclusion

Dengue in renal transplant is usually community acquired; donor derived infections are uncommon. The clinical presentation of dengue is similar to the immunocompetent host, however graft dysfunction is common and fluid management in this population is important. Severe dengue is less common.

Disclosures

All Authors: No reported disclosures
314. A Retrospective Review of Dalbavancin Utilization at an Academic Medical Center
Authors: Napoli Emma , Badwal Jasmin K , Kirkpatrick Emily R , Pinilla Ruth Serrano , Wang Chen-Pin , Javeri Heta
Published: January 2021

Background

Dalbavancin is a novel long-acting lipoglycopeptide with increasing utilization for management of bone and joint infections as a two-dose regimen. The purpose of this study is to describe the patient characteristics, evaluate clinical outcomes, and calculate inpatient hospital days saved with use of dalbavancin as outpatient parenteral antimicrobial therapy (OPAT).

Methods

A retrospective review of patients treated with dalbavancin at University Hospital was conducted from Aug 2019- March 2020. Patients ≥ 17 yrs of age with plan to receive at least 1 dose of dalbavancin were included. All patients were initially evaluated by, and had clinic follow up with, an infectious disease physician. Information on baseline demographics, infection characteristics, treatments, and outcomes were recorded from the EMR.

Results

42 patients met the study criteria. 62% were males with a median age of 49 yrs. 67% of patients had diabetes and 12% had a documented history of intravenous drug use. The most common indication was osteomyelitis (71%). S. aureus was the most commonly isolated organism in monomicrobial infections (MRSA 24%, MSSA 9.5%) and often a component of polymicrobial infections (33%). 90.5% of patients were adherent to their prescribed therapy; 1 patient missed both doses and 3 only received 1 of their recommended doses. Adverse effects were mild and noted in only 4 patients. 24 patients (57%) received concomitant antibiotics. 45% of patients achieved a cure with another 12% were classified as improved but requiring further antibiotics. 31% (N=13) had failure of therapy of which, 69% (N=9) did not achieve prior source control. 5 patients were lost to follow up. Our health system saved 160 inpatient days through dalbavancin use.

Conclusion

Dalbavancin treatment had a high adherence rate with minimal adverse effects and achieved a positive outcome in 57% of patients. Of patients that failed, the majority did not have appropriate source control. Dalbavancin use has the potential to save inpatient days while offering a more convenient option for treatment. However, further studies should be conducted to evaluate its efficacy in comparison to standard of care therapy at our institution.

Disclosures

All Authors: No reported disclosures
325. Invasive and Non-Invasive Osteomyelitis Caused by Group B Streptococcus Infection Among Veterans
Authors: Bej Taissa A , Wilson Brigid , Banks Richard , Briggs Janet , Song Sunah , Perez Federico , Jump Robin
Published: January 2021

Background

Epidemiological studies that assess invasive Group B Streptococcus (GBS) infections may not capture cases of osteomyelitis diagnosed using non-invasive cultures in combination with imaging, laboratory tests, and clinical assessment. Here, we compare GBS osteomyelitis among individuals diagnosed using invasive and non-invasive cultures.

Methods

Using the Veterans Health Administration corporate data warehouse, we studied a national retrospective cohort review of Veterans diagnosed with GBS osteomyelitis between 2008 – 2017. Invasive cases were defined as an International Classification of Disease (ICD) code for osteomyelitis accompanied by a blood or bone culture positive for GBS within 2 weeks. Non-invasive cases were defined as an ICD code for osteomyelitis and a non-invasive culture positive for GBS from a concordant site within 2 weeks. We compared demographics, comorbid conditions, mortality, and time to below- or above-knee amputation among patients with invasive and non-invasive GBS osteomyelitis.

Results

We identified 1167 cases of invasive osteomyelitis among 1077 patients and 692 cases of non-invasive osteomyelitis among 644 patients. Most patients were male (98%) with an average age of 63.2 years (± standard deviation (SD) 10.1 years). The Charlson Comorbidity Index (CCI) was similar among patients with invasive and non-invasive disease (3.85 ± SD 2.3 and 3.83 ± SD2.4, respectively). Among those with lower extremity osteomyelitis, 11% of invasive cases had an amputation at 30 days while 2% of non-invasive cases had an amputation in the same time frame (Figure 1). Mortality was similar among those with invasive and non-invasive GBS osteomyelitis at 30-days (1% and 1%, respectively) and at 1-year (11% and 9%, respectively) (Figure 2).

Figure 1: Time to Amputation

Figure 2: Survival

Conclusion

Over 1/3 of the cases of osteomyelitis caused by GBS do not meet the case definition for invasive disease. Whether diagnosed using invasive or non-invasive microbiological cultures, survival outcomes for people with GBS osteomyelitis were similar. These findings suggest that non-invasive GBS osteomyelitis is as clinically important as invasive GBS osteomyelitis and that the rates of GBS osteomyelitis may be higher than previously reported.

Disclosures

Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Robin Jump, MD, PhD, Accelerate (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)
328. Outcomes in Spinal Cord Injury Patients with Stage 3 and 4 Pressure Injuries at a Veterans’ Affairs Hospital
Authors: Koh Shannon J , Van Beest Dominique , Kargel Jennifer , Wang Jijia , Bedimo Roger , Cutrell James B , Tan Wei-Han
Published: January 2021

Background

Pressure injuries (PI) and the complication of PI-related osteomyelitis (PIrOM), are a significant source of morbidity and mortality in spinal cord injury (SCI) patients. This study describes the epidemiology, healthcare utilization, and outcomes of SCI patients with PI at a large Veterans’ Affairs (VA) hospital.

Methods

We retrospectively reviewed all SCI patients with stage 3 or 4 PI in the pelvic area admitted to the VA North Texas SCI unit from 1/1/2013 to 12/31/2018. We abstracted demographic, diagnostic testing, treatment, and outcomes data from PI-related admissions for wound care from the electronic medical record. A composite definition categorizing the diagnosis of PIrOM was created (table 1). Two-sample t test and Fisher’s exact test were used to compare variables between flap patients (FP, those who received at least one flap surgery) and non-flap patients (NFP, those without any flap surgery).

Table 1. Composite Definition for Pressure Injury-related Osteomyelitis

Results

A total of 78 patients, accounting for 113 hospitalizations, and 138 unique PI, were identified (table 2). Patients had a mean age of 59 years at index admission and male predominance (97%). Of the 138 PI, 49% were ischial and 88% were stage 4. There were 27 FP and 51 NFP. The mean Charlson Comorbidity Index was 4.9 overall and significantly higher in the NFP vs. FP (5.2 vs. 4.3, p=0.05). Diagnostics included at least one imaging study in 76% (n=86) of hospitalizations and a bone biopsy in 45% (n=51). Bone biopsy cultures were commonly polymicrobial (47%, n=24), with anaerobes, Staphylococcus aureus, and Streptococcus species being the most predominant organisms. A diagnosis of definite, probable, or possible PIrOM was made in 14%, 16%, and 41% of hospitalizations, respectively (table 3). Healthcare utilization was high, with a mean length of antibiotic therapy of 54 days and mean length of stay of 122 days per hospitalization. The rates of healed PI overall at discharge and at 1 year were 27% and 39%, and 12% and 40% in the NFP group. The 1-year mortality for NFP was 22%, while all FP were alive at one year.

Table 2. Demographics and Comorbidities in SCI Patients with Stage 3 and 4 Pressure Injury

Table 3. Healthcare Utilization, Osteomyelitis Classification, and Outcomes in PI-related Hospitalizations

Conclusion

Despite significantly high healthcare utilization, VA SCI patients with stage 3 and 4 PI had very poor wound outcomes and high mortality, particularly in NFP. Evidence-based, high value care paradigms are needed for this population and disease state.

Disclosures

Roger Bedimo, MD, Gilead Sciences (Consultant)Merck & Co. (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Research Grant or Support)
330. Risk Factors for Acute Kidney Injury after the Use of Antibiotic Loaded Bone Cement in Orthopedic Surgery – a Retrospective Case-control Study
Authors: Schulz Lucas , Georgieva Darina , Haleem Ambar
Published: January 2021

Background

As the number of joint replacement surgeries continues to rise, so does the number of joint infections. Many patients end up needing the implantation of antibiotic loaded bone cement (ALBC) to treat their infection. The use of localized high dose vancomycin, tobramycin, and gentamicin may be linked to acute kidney injury (AKI) in certain patients. Our hypothesis is that patients who developed AKI after receiving a joint spacer had a predisposition to AKI due to other comorbidities, high antibiotic doses in ALBC, immunosuppression, or the use of other nephrotoxic drugs pre-op. These patients may need close monitoring of their renal function and serum antibiotic levels after surgery.

Methods

We performed a chart review of 428 patients who underwent an orthopedic surgery that involved insertion of ALBC at our institution between 2015 and 2018. We excluded patients under age 18, those who had antibiotic irrigation only, trauma patients, non-arthroplasty surgeries (such as fractures and debridement of deep wounds), and patients with missing data for 30 days after the surgery. We identified 57 patients who fit our inclusion criteria and received a bone cement spacer or beads to treat an infection of the hip, knee, shoulder, or ankle. We matched patients who had AKI to 2 patients who did not have AKI. Matching was based on age (± 5 years), joint operated on, and antibiotics used.

Results

15 patients showed an elevated serum creatinine level of over 1.2 within 30 days of surgery. 86.7% of these patients were male, their average age was 64.1 ± 6.2 years old, 40% had hip surgery, 46.7% knee surgery, 6.7% ankle, and 6.7% shoulder. All received vancomycin and tobramycin in Palacos bone cement. Compared to their case-control matches, these patients had more frequent use of immunosuppressive medication, a history of malignancy, a history of previous kidney disease, and obesity. The use of combined intravenous vancomycin and piperacillin-tazobactam post-operatively may also be linked to higher rates of AKI.

Conclusion

Immunosuppression, obesity, male gender, and history of kidney injury and cancer are factors associated with AKI after ALBC spacer implantation. Further analysis and study are needed to identify potential causation between ALBC use and AKI.

Disclosures

All Authors: No reported disclosures
331. Septic arthritis: when is the joint clean enough?
Authors: Young Heather , Aragon Deborah , Miller Whitney , Iams Dane , Mauffrey Cyril
Published: January 2021

Background

Septic arthritis is an orthopedic emergency that requires debridement. Previous authors reported that patients with inflammatory arthropathy, diabetes, infection with S. aureus, involvement of a large joint, and synovial fluid WBC >85,000 are associated with >1 debridements. The purpose of this study was to determine factors associated with 1 vs >1 debridements.

Methods

This is a retrospective cohort of adult patients hospitalized at Denver Health Medical Center with large joint septic arthritis between 7/1/2012 and 4/13/20. Patients with implanted orthopedic material, osteomyelitis, and recurrent septic arthritis were excluded. Septic arthritis was defined as a patient presenting with acute arthritis and positive culture OR negative culture and no other etiology. Both electronic capture and manual chart review were performed. Descriptive statistics were used to characterize the population. Statistical analyses included bivariate and multivariate analyses.

Results

Forty-four cases were included (26 knee [59.1%], 4 hip [9.1%], 6 elbow [13.6%], and 8 shoulder [18.2%]. The median age was 55.7 years (41.3–64.1], and 79.5% were male. The most common organisms were S. aureus (n=20, 45.5%) and beta-hemolytic Streptococcus (n=10, 22.7%). Three patients had no surgical debridement, 21 had 1 debridement, and 20 had >1 debridements.

As compared to those who had 1 debridement, those with >1 debridements were more likely to be male (95% vs 61.9%, p=0.02) and to have a higher synovial fluid leukocyte count (102,761 vs 49,154, p=0.001), CRP at admission (162.5 vs 97.7, p=0.039), and WBC the day prior to debridement (13.4 vs 9.8, p=0.007). Intra-operative purulence trended to association with >1 debridements. Pre- to post-operative changes in opiate use, temperature, and ability to work with physical therapy were not associated with 1 vs >1 debridements. Both higher synovial fluid leukocyte counts and CRP value at admission were independently associated with >1 debridements (OR 2.31, p=0.015; OR 1.01, p=0.036 respectively).

Conclusion

Patients with higher synovial fluid leukocytes and CRP at admission were more likely to have >1 debridements. Additional studies with functional outcome scores are necessary to determine if >1 debridements are associated with better clinical outcomes.

Disclosures

All Authors: No reported disclosures
334. Treatment Duration of Antibiotics for Sacral Osteomyelitis After Skin Flap Procedure
Authors: Frye Emily , Linneman Travis W , Moenster Ryan P
Published: January 2021

Background

Patients with spinal cord injuries frequently develop sacral osteomyelitis. Optimal treatment often involves intravenous antibiotics and skin flap closure of the ulcer; however, best practices for the duration of antibiotic therapy pre- and post-procedure are unknown.

Methods

This was a retrospective, cohort study of spinal cord injury patients at the VA St. Louis undergoing a skin flap procedure from 1 October 2014 to 31 March 2019. Patients aged 18 to 89 years with a documented spinal cord injury and receiving treatment for sacral osteomyelitis with antibiotics and skin flap placement were considered for inclusion. The primary outcome was to determine if there was a difference in antibiotic treatment duration, both pre-procedure and post-procedure, between those that failed combination therapy and those patients for which the treatment was successful. Treatment failure was defined as documentation of no resolution of sacral osteomyelitis after treatment, re-initiation of antibiotics for sacral osteomyelitis of the same area, documented flap break-down, or an unplanned flap-related procedure within 1 year of completion of antibiotic therapy.

Results

Twelve patients were identified for inclusion. Baseline characteristics were similar between groups; 5/8 patients successfully treated received vancomycin, compared to 4/4 patients that failed therapy. Overall, 75% (8/12) had a successful treatment outcome at 12 months. In qualifying patients, average days of pre-procedure and post-procedure antibiotics were similar between patients who achieved success and those who failed (45.5 vs. 44.3 days pre-procedure, respectively (p >0.05) and 39 vs. 43 days post-procedure (p >0.05), respectively). When evaluated by weeks of therapy, no statistically significant differences were noted in treatment success rates between those treated for less than 6 weeks versus those treated for longer (66.6% [2/3] vs. 63.6% [6/9], p >0.05).

Conclusion

No difference in pre- or post-flap procedure antibiotic duration was observed in patients who failed therapy compared to those who were successfully treated.

Disclosures

All Authors: No reported disclosures