189. Risk Factors and Outcomes of Hematogenous Vertebral Osteomyelitis in Patients with staphylococcus Aureus Bacteremia: Results from a 20-year Prospective Cohort

Abstract Background Hematogenous vertebral osteomyelitis (HVOM) is a rare, but devastating complication of Staphylococcus aureus bacteremia (SAB). Risk factors and outcomes associated with HVOM among patients with SAB remain incompletely understood. Methods All adult, hospitalized, non-neutropenic patients with SAB were prospectively enrolled from 1995 to 2015. Additional data was subsequently collected on all patients with HVOM. Diagnosis of HVOM was made either radiographically or microbiologically by culture from the infection site. Patients who underwent lumbar puncture or spinal surgery within 30 days prior to the diagnosis of HVOM were excluded. Results Of 2,475 cases of prospectively enrolled patients with SAB, 90 (3.6%) developed HVOM. The most common site of involvement was the lumbar spine (65.6%). MRI was used in the diagnosis of 90% of patients and although only 28.9% underwent bone biopsy, 88.5% of these bone cultures grew S. aureus. Patients with HVOM were more likely to have community-acquired SAB (22.2% vs. 9.9%, P < 0.0001) and persistent bacteremia (47.8% vs. 20.5%, P < 0.0001). Patients with HVOM who required surgical intervention were more likely to have motor deficit (60.9% vs. 21.4%, P = 0.0013) and have associated epidural abscesses (69.6% vs. 44.8%, P = 0.0400). Prolonged antibiotic use for HVOM was common, with 13.3% remaining on therapeutic antibiotics and 16.6% on suppressive therapy at 6 months. This dropped to 2.2% on therapeutic and 15.5% on suppressive therapy at 12 months. All-cause mortality was high in the HVOM cohort at 14.4% at 90-days, increasing to a cumulative 18.9% and 20.0% at 6 and 12-months, respectively. Rates of readmission, recurrent bacteremia, paralysis, and mortality at 6 and 12-months were similar for those who required surgical intervention and those who did not. Demographics, comorbidities, and clinical characteristics of patients with and without hematogenous vertebral osteomyelitis (HVOM) Conclusion HVOM in patients with SAB was associated with high rates of all-cause mortality up to 12 months following date of diagnosis. Patients with community-acquired bacteremia and persistent bacteremia were more likely to develop HVOM. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Download Full-text

181. Demographic and Geographic Epidemiology of Staphylococcus aureus Bacteremia using Geographic Information Systems Mapping and Spatial Statistics

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.383 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S199-S199

Author(s):

Julia Marshall ◽

Vance G Fowler ◽

Felicia Ruffin ◽

Paul Lantos ◽

Christopher Timmins

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Information Systems ◽

Geographic Information Systems ◽

Spatial Statistics ◽

Clinical Characteristics ◽

Geographic Information ◽

Research Support ◽

Material Support ◽

Staphylococcus Aureus Bacteremia

Abstract Background Risk factors for community-associated Staphylococcus aureus bacteremia (SAB) are incompletely understood. We used Geographic Information Systems (GIS) and spatial statistics to analyze demographic and geographic epidemiology of SAB in the community. Methods We used the S. aureus Bacteremia Group Prospective Cohort Study (SABG-PCS) at Duke University Medical Center to obtain demographic and clinical data. We used the American Community Survey and U.S. Census to supply neighborhood variables. Secular trends in demographic and clinical characteristics of SAB patients prospectively enrolled between 1995 and 2015 (n = 2478) were determined using linear regressions. To characterize spatial patterns in Methicillin-resistant S. aureus (MRSA) bacteremia compared to Methicillin-susceptible S. aureus (MSSA) bacteremia, we used GIS mapping and selected a subgroup of patients (n = 667) living in and around Durham County, North Carolina. We then created generalized additive models (GAMs) using this subgroup to detect geographic heterogeneities in probabilities of MRSA infections compared to MSSA infections. Results We found evidence of changing demographic and clinical characteristics of SAB patients over the 21-year period. The proportion of infections acquired in the community increased significantly (p < 0.0001). However, we did not detect spatial heterogeneities of MRSA infections in Durham County. Patient location of residence was not significantly associated with antimicrobial-resistant infections. Patient age and year of hospital admission were the only statistically significant covariates in our spatial models. Conclusion We utilized a novel method to analyze SAB in the community using GIS and spatial statistics. Future research should prioritize community transmission of S. aureus to identify robust risk factors for infection. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant)

Download Full-text

Risk Factors for Recurrent Staphylococcus aureus Bacteremia

Clinical Infectious Diseases ◽

10.1093/cid/ciaa801 ◽

2020 ◽

Author(s):

Seong-Ho Choi ◽

Michael Dagher ◽

Felicia Ruffin ◽

Lawrence P Park ◽

Batu K Sharma-Kuinkel ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Acute Phase ◽

Hemodialysis Patients ◽

Risk Modeling ◽

Single Episode ◽

Staphylococcus Aureus Bacteremia ◽

Multivariate Risk ◽

Persistent Bacteremia ◽

Multiplex Bead

Abstract Background To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB). Methods All SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE). PFGE-indistinguishable pairs from 40 patients underwent whole genome sequencing (WGS). Acute phase plasma from R-SAB and S-SAB patients was matched 1:1 for age, race, sex, and bacterial genotype, and underwent cytokine quantification using 25-analyte multiplex bead array. Results R-SAB occurred in 69 (9.1%) of the 756 study patients. Of the 69 patients, 30 experienced relapse (43.5%) and 39 reinfection (56.5%). Age, race, hemodialysis dependence, presence of foreign body, methicillin-resistant Staphyloccus aureus, and persistent bacteremia were individually associated with likelihood of recurrence. Multivariate risk modeling revealed that black hemodialysis patients were nearly 2 times more likely (odds ratio [OR] = 9.652 [95% confidence interval [CI], 5.402–17.418]) than white hemodialysis patients (OR = 4.53 [95% CI, 1.696–10.879]) to experience R-SAB. WGS confirmed PFGE interpretations in all cases. Median RANTES (regulated on activation, normal T cell expressed and secreted) levels in acute phase plasma from the initial episode of SAB were higher in R-SAB than in matched S-SAB controls (P = .0053, false discovery rate < 0.10). Conclusion This study identified several risk factors for R-SAB. The largest risk for R-SAB is among black hemodialysis patients. Higher RANTES levels in R-SAB compared to matched controls warrants further study.

Download Full-text

167. A Phase 1b, Randomized, Double-blind, Placebo-controlled, Multiple-ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Patients with staphylococcus Aureus Bacteremia Receiving Standard-of-care Antibiotics

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.477 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S213-S213

Author(s):

Jeremy Lim ◽

Nicholas Lewin-Koh ◽

Tom Chu ◽

Sharon M Rymut ◽

Aklile Berhanu ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Healthy Volunteers ◽

Study Drug ◽

Standard Of Care ◽

Research Support ◽

Double Blind ◽

Double Blind Placebo ◽

Staphylococcus Aureus Bacteremia ◽

Phase 1B ◽

Research Grant

Abstract Background New treatment approaches for complicated Staphylococcus aureus bacteremia (SAB) are needed. DSTA4637S is a THIOMABTM antibody-antibiotic conjugate consisting of an engineered human IgG1 monoclonal antibody that binds to wall teichoic acid at the surface of S. aureus, a protease-cleavable linker, and a novel rifamycin class antibiotic, dmDNA31. This Phase 1b study assessed the safety, tolerability, and pharmacokinetics of DSTA4637S in patients with complicated SAB. Methods Multicenter, double-blind, placebo controlled, multiple-ascending dose clinical trial. Patients 18–79 years old with complicated SAB requiring at least 4 weeks of IV anti-staphylococcal standard-of-care (SOC) antibiotics were randomized to receive 4–6 doses of 15, 45, and 100 mg/kg IV DSTA4637S or placebo (6 active:2 placebo) every 7 days in combination with SOC antibiotics. Patients needed ≥ 1 blood culture positive for S. aureus collected within 120 hours prior to randomization. Patients were followed for 120 days after the end of treatment. Results Twenty-five patients with complicated SAB (bone & joint, n=14; endocarditis, n=5; other endovascular, n=5; pneumonia, n=1) were randomized and received 1–6 doses of study drug (19 active:6 placebo). Nine patients (36%) had MRSA. Ten patients completed ≥4 doses of DSTA4637S. The most common treatment-related adverse events were infusion-related reactions (IRRs) (5/19), and abnormal serum color (5/19)/skin discoloration (3/19 (due to dmDNA31). IRRs were not dose-dependent and were reversible with supportive care. Ten of 19 patients (40%) discontinued study drug (9 DSTA4637S,1 placebo); 4/19 (21%) due to IRR. DSTA4637S recipients showed no dose-related changes in laboratory values or vital signs vs. placebo. Observed exposures (Cmax and AUC) were lower in patients immediately after dosing compared to a prior study in healthy volunteers; minimal accumulation occurred. No obvious trends in exploratory bacterial and inflammatory biomarkers were observed between treatment groups. Conclusion DSTA4637S in patients with complicated SAB demonstrated increased IRRs and decreased exposure compared to healthy volunteers, highlighting the importance of Phase I studies of novel treatments in infected SAB patients and not simply healthy controls. Disclosures Jeremy Lim, PharmD, Roche (Employee, Shareholder) Nicholas Lewin-Koh, PhD, Genentech (Employee) Tom Chu, MD, PhD, Genentech (Employee) Sharon M. Rymut, PhD, Genentech (Employee, Shareholder) Aklile Berhanu, PhD, Genentech, Inc. (Employee, Equity interest (Stock/Stock Options)) Montserrat Carrasco-Triguero, PhD, Genentech (Employee) Carrie C. Rosenberger, PhD, Genentech (Employee, Shareholder) Wouter L. Hazenbos, PhD, Genentech (Employee) Loren G. Miller, MD, MPH, genentech (Grant/Research Support) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant) Jose M Miro, MD PhD, GENENTECH (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member) Jessica A. Couch, PhD, Genentech (Employee, Shareholder) Melicent C. Peck, MD, PhD, Genentech (Employee)

Download Full-text

1060. Risk Factors for Recurrent Staphylococcus aureus Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.897 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S317-S317 ◽

Cited By ~ 1

Author(s):

Seong-Ho Choi ◽

Felicia Ruffin ◽

Lawrence Park ◽

Batu K Sharma-Kuinkel ◽

Maria Souli ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

African American ◽

Abscess Formation ◽

First Episode ◽

Spa Typing ◽

Staphylococcus Aureus Bacteremia ◽

Persistent Bacteremia ◽

Independent Risk Factors ◽

African American Race

Abstract Background Recurrent Staphylococcus aureus bacteremia (Re-SAB) occurs in 2–17% of patients with SAB within 3–12 months after resolution of the first episode. The risk factors for Re-SAB are incompletely understood. Methods Re-SAB was defined as a second episode of SAB after the resolution of the first episode occurring at least 14 days from the date of the last positive blood culture of the first episode. Using the SAB Group Prospective Cohort Study (SABG-PCS) data between January 2008 and May 2015, patients with Re-SAB were selected and compared with those without it. Pulsed-field gel electrophoresis (PFGE) was done for the clinical isolates from the Re-SAB group, and spa typing was for those from both groups. Baseline sera from patients with Re-SAB and age/race/gender matched (1:1) control subjects with SAB but without Recurrence underwent Luminex multiplex cytokine array. Results Seventy patients experienced Re-SAB (9.3%) and 686 SAB patients did not. In the Re-SAB group, 156 episodes of SAB were observed. Median time to Re-SAB was 147.5d (IQR, 76–358). Among 65 PFGE-analyzed pairs of isolates from the first and the subsequent episodes, the time to Re-SAB of <300 days was more commonly found in the PFGE-identical pairs than in the PFGE-different pairs (75.6% vs. 33.8%, P = 0.001). In the comparison of clinical factors between 56 Re-SAB patients with available data and 686 without Re-SAB, African American race, dialysis dependence, the presence of foreign body, persistent bacteremia, metastatic abscess formation, and methicillin-resistant S. aureus (MRSA) were more frequently observed in patients with Re-SAB. In a multivariate analysis to identify risk factors for Re-SAB, African American race, dialysis dependence, metastatic abscess formation, and MRSA were independent risk factors. The distribution of spa types between the two group was presented in Figure 1. Conclusion Re-SAB involves a combination of multiple factors of host, microbe, and treatment. Further laboratory investigation for any determinants in host and microbe is required. Disclosures V. G. Fowler Jr., Merck, Cerexa/Actavis, Pfizer, Advanced Liquid Logis, NIH, MedImmune, Basilea, Karius, Contrafect, Regneron, Genentech, Affinergy, Locus, Medical Surface, Inc., Achaogen, Astellas, Arsanis, Bayer, Cubist, Debiopharm, Durata, Grifols, Medicines Co, Novartis: Collaborator, Consultant and Scientific Advisor, Consulting fee, Research grant and Research support.

Download Full-text

187. Vancomycin Plus Ceftaroline Salvage Therapy for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.389 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S201-S202

Author(s):

Wesley D Kufel ◽

Katie A Parsels ◽

Jeffrey Steele ◽

Robert Seabury ◽

Kristopher M Paolino ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Salvage Therapy ◽

Methicillin Resistant Staphylococcus Aureus ◽

Panel Member ◽

Review Panel ◽

Salvage Regimen ◽

Staphylococcus Aureus Bacteremia ◽

All Cause Mortality ◽

Microbiological Cure ◽

Research Grant

Abstract Background The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (pMRSAB) is unclear. Vancomycin plus ceftaroline (V/C) has demonstrated potent in vitro synergistic activity against MRSA; however, clinical data is limited. Thus, we sought to evaluate V/C salvage therapy for pMRSAB. Methods This was a single-center, retrospective cohort study of patients with MRSAB who received V/C salvage therapy between 1/1/2016-3/10/2021. Adult patients were included if blood cultures (BC) were positive for MRSA for ≥ 72 hours, received anti-MRSA monotherapy initially, and subsequently received V/C ≥ 24 hours. Patients were excluded if they received other anti-MRSA antibiotics within 72 hours of V/C initiation. The primary outcome was time to BC clearance following V/C initiation. Secondary outcomes included 90-day all-cause mortality, microbiological cure, 90-day MRSAB recurrence, and length of stay (LOS). Microbiological cure was defined as BC clearance. Results Of 178 patients identified, 20 were evaluated after inclusion and exclusion criteria were applied. Mean (SD) age and Pitt Bacteremia score were 38.5 (14.5) years and 4.2 (3.1), respectively. Most patients were male (70%), intravenous drug users (65%), and admitted to the intensive care unit (65%). The most common source was intravenous drug use (55%) and the majority had infective endocarditis (70%). All patients received infectious disease consultation and median (IQR) vancomycin AUC:MIC was 527 (454, 611). Source control, if possible, was obtained in most patients (55%). Median (IQR) time to bloodstream clearance from first positive BC and from when ceftaroline was initiated was 9.7 (8.4, 10.2) and 2.4 (1.5, 3.1) days, respectively. 90-day all-cause mortality, microbiological cure, and 90-day MRSAB recurrence occurred in 35%, 95%, and 5% of patients, respectively. Median (IQR) LOS was 25 (14.5, 32.0) days. Conclusion To our knowledge, this is the largest cohort to evaluate V/C for pMRSAB. Patients were medically complex; however, median time to MRSAB clearance following ceftaroline initiation was < 2.5 days and microbiological cure was obtained in nearly all patients. V/C may represent a potential salvage regimen for pMRSAB. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, Pharm.D., Paratek Pharmaceuticals (Advisor or Review Panel member)

Download Full-text

1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

Download Full-text

Staphylococcus aureus Keratitis: Incidence, Pathophysiology, Risk Factors and Novel Strategies for Treatment

Journal of Clinical Medicine ◽

10.3390/jcm10040758 ◽

2021 ◽

Vol 10 (4) ◽

pp. 758

Author(s):

Jason W. Lee ◽

Tobi Somerville ◽

Stephen B. Kaye ◽

Vito Romano

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Clinical Characteristics ◽

Surgical Intervention ◽

Current Evidence ◽

Bacterial Keratitis ◽

Novel Therapies ◽

Causative Pathogen ◽

Novel Treatments

Bacterial keratitis is a devastating condition that can rapidly progress to serious complications if not treated promptly. Certain causative microorganisms such as Staphylococcus aureus and Pseudomonas aeruginosa are notorious for their resistance to antibiotics. Resistant bacterial keratitis results in poorer outcomes such as scarring and the need for surgical intervention. Thorough understanding of the causative pathogen and its virulence factors is vital for the discovery of novel treatments to avoid further antibiotic resistance. While much has been previously reported on P. aeruginosa, S. aureus has been less extensively studied. This review aims to give a brief overview of S. aureus epidemiology, pathophysiology and clinical characteristics as well as summarise the current evidence for potential novel therapies.

Download Full-text

Risk Factors for Methicillin-Resistance among Patients with Staphylococcus aureus Bacteremia at the Time of Hospital Admission

The American Journal of the Medical Sciences ◽

10.1097/00000441-200203000-00001 ◽

2002 ◽

Vol 323 (3) ◽

pp. 117-123 ◽

Cited By ~ 56

Author(s):

Nilton A. Rezende ◽

Henry M. Blumberg ◽

Susan M. Ray ◽

Brian S. Metzger ◽

Nina M. Larsen ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Hospital Admission ◽

Methicillin Resistance ◽

Staphylococcus Aureus Bacteremia

Download Full-text

Interleukin (IL)-1β and IL-10 Host Responses in Patients With Staphylococcus aureus Bacteremia Determined by Antimicrobial Therapy

Clinical Infectious Diseases ◽

10.1093/cid/ciz686 ◽

2019 ◽

Vol 70 (12) ◽

pp. 2634-2640 ◽

Cited By ~ 7

Author(s):

Cecilia F Volk ◽

Sarah Burgdorf ◽

Graham Edwardson ◽

Victor Nizet ◽

George Sakoulas ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Therapy ◽

Ex Vivo ◽

Host Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Treatment Groups ◽

Staphylococcus Aureus Bacteremia ◽

Medical Centers ◽

Persistent Bacteremia

Abstract Background Patient interleukin (IL)-1β and IL-10 responses early in Staphylococcus aureus bacteremia (SaB) are associated with bacteremia duration and mortality. We hypothesized that these responses vary depending on antimicrobial therapy, with particular interest in whether the superiority of β-lactams links to key cytokine pathways. Methods Three medical centers included 59 patients with SaB (47 methicillin-resistant S. aureus [MRSA], 12 methicillin-sensitive S. aureus [MSSA]) from 2015–2017. In the first 48 hours, patients were treated with either a β-lactam (n = 24), including oxacillin, cefazolin, or ceftaroline, or a glyco-/lipopeptide (n = 35), that is, vancomycin or daptomycin. Patient sera from days 1, 3, and 7 were assayed for IL-1β and IL-10 by enzyme-linked immunosorbent assay and compared using the Mann-Whitney U test. Results On presentation, IL-10 was elevated in mortality (P = .008) and persistent bacteremia (P = .034), while no difference occurred in IL-1β. Regarding treatment groups, IL-1β and IL-10 were similar prior to receiving antibiotic. Patients treated with β-lactam had higher IL-1β on days 3 (median +5.6 pg/mL; P = .007) and 7 (+10.9 pg/mL; P = .016). Ex vivo, addition of the IL-1 receptor antagonist anakinra to whole blood reduced staphylococcal killing, supporting an IL-1β functional significance in SaB clearance. β-lactam–treated patients had sharper declines in IL-10 than vancomycin or daptomycin –treated patients over 7 days. Conclusions These data underscore the importance of β-lactams for SaB, including consideration that the adjunctive role of β-lactams for MRSA in select patients helps elicit favorable host cytokine responses.

Download Full-text

746. Characteristics of Respiratory Syncytial Virus (RSV) Infection Among Hospitalized Adults, United States, 2014–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.753 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S268-S268 ◽

Cited By ~ 1

Author(s):

Lindsay Kim ◽

Bryanna Cikesh ◽

Pam Daily Kirley ◽

Evan J Anderson ◽

Seth Eckel ◽

...

Keyword(s):

Risk Factors ◽

Respiratory Syncytial Virus ◽

Case Series ◽

Chronic Obstructive ◽

Medical Conditions ◽

Research Support ◽

Catchment Population ◽

Icd Codes ◽

Syncytial Virus ◽

Research Grant

Abstract Background Respiratory syncytial virus (RSV) vaccines are in clinical development for older adults. We described RSV infections among adults requiring hospitalization and risk factors for severe outcomes using a population-based platform, the Influenza Hospitalization Surveillance Network (FluSurv-NET). Methods Surveillance occurred October 1–April 30 (2014–2017) at sites located in seven states (California, Georgia, Michigan, Minnesota, New York, Oregon, and Tennessee) covering an annual catchment population of up to 13 million adults ≥18 years. Laboratory-confirmed RSV cases were identified using hospital and state public health laboratories, hospital infection preventionists, and/or reportable condition databases. Medical charts were reviewed for demographic and clinical data. International Classification of Diseases (ICD) discharge codes were abstracted. Odds ratios (Oregon) and 95% confidence intervals (CIs) were determined to assess risk factors for ICU hospitalization and deaths. Results A total of 2,326 hospitalized RSV cases were identified. Over half were ≥65 years (62%, n = 1,438/2,326), female (59%, n = 1,362/2,326), white (70%, n = 1,301/1,855), and had ≥3 underlying medical conditions (52%, n = 1,204/2,326). 20% (n = 398/2,000) were hospitalized in the ICU (median length of stay, 3 days; interquartile range, 1–6 days), and 5% (n = 96/2,001) died in the hospital. Congestive heart failure (CHF; OR: 1.4, 95% CI: 1.1–1.8) and chronic obstructive pulmonary disease (COPD; OR: 1.3, 95% CI: 1.1–1.7) were associated with ICU admission, while age ≥80 years (OR: 4.1, 95% CI: 1.8–12.1) and CHF (OR: 2.4, 95% CI: 1.6–3.6) were associated with in-hospital deaths. RSV-specific ICD codes were listed in the first 9 positions in only 44% (879/1,987) of cases. Conclusion To our knowledge, this is the largest US case series of RSV-infected hospitalized adults. Most cases were ≥65 years and had multiple underlying medical conditions. Older age, CHF, and COPD were associated with the most severe outcomes. Few cases had RSV-specific ICD codes, suggesting that administrative data underestimate adult RSV-related hospitalizations. Continued surveillance is needed to understand the epidemiology of RSV among adults as vaccine products move toward licensure. Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

Download Full-text