Staphylococcus aureus bacteremia (SAB), including right-sided infective endocarditis (NCT03138733). We reported molecular characteristics of methicillin-resistant S. aureus (MRSA) along with the clinical outcomes.A Phase 3 clinical trial evaluated ceftobiprole (BPR) for the treatment of spa, and SCCmec types.94 patients had MRSA isolated from baseline blood cultures, 90 of which were available for molecular characterization. Susceptibility testing used the CLSI broth microdilution method. Total genomic DNA was extracted and sequenced. Assembled genomes were used to determine multilocus sequence typing (MLST), clonal complex (CC), A total of 10 CC were present within the 90 isolates. 71 (78.9%) MRSA fell into 3 predominant clones: CC8, CC22, and CC5 (Table). Among CC8 , 4 ST8-like  from USA (3) and Ukraine (1) were presumptively designated as USA300, whereas 12 ST239  from Bulgaria (1), Georgia (1), Russia (1), Serbia (2), and Ukraine (7) were designated as the Hungarian clone. Other ST8-like MRSA  from Ukraine (15), Russia (2), Spain (1), and Argentina (1) were identified as USA300LAV. Nineteen  MRSA belonged to CC22/ST22. Fifteen  MRSA were CC5, and included ST5 and related single- (ST225 and ST2704) or double-locus (ST1827) variants. CC5 MRSA were designated as USA100  or USA800 . Other strains were represented by 7 CC, including those associated with livestock infections. Overall, clinical responses (CR) and microbiological eradication (ME) were similar between treatment arms (Table). CR and ME rates were higher in the BPR arm among patients infected with CC5 strains, whereas these rates in the comparator arm were higher in patients infected with CC22 and other CC types.This global SAB trial included patients with MRSA strains belonging to pandemic lineages and those causing infections in United States hospitals. This strain set includes clones previously associated with hospital- and community-acquired infections as well as strains associated with livestock infections. In general, CR and ME were comparable between the 2 study arms with small differences in outcomes by CC type.Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Leonard R. Duncan, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support John H. Kimbrough, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options Mark E. Jones, PhD, Astellas Pharma Global Development, Inc: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Marc Engelhardt, MD, Astellas Pharma Global Development, Inc.: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


Multiple combinations of COVID-19 vaccine regimens have been used in Canada throughout the SARS-CoV-2 immunization campaign. Studies evaluating the humoral immune response following COVID-19 vaccination in community dwelling older adults remain limited. This study assessed COVID-19 vaccine elicited antibody responses in older adult populations, alongside factors that influence antibody responses.Community dwelling adults aged 50 to 87 years (mean=65) were enrolled (n=612). Detection of index SARS-CoV-2 anti-spike IgG (anti-S-IgG) concentration and surrogate neutralization were performed on dried blood spot samples via two multiplex assays . Anti-S-IgG concentration and surrogate neutralization were quantified following mRNA  or viral vector (ChAdOx1-S [ChAd]) vaccination. Vaccine groups were compared using one-way ANOVA and Tukey-Kramer multiple comparisons tests. Multivariable regression analyses evaluated influences of demographic and clinical factors on humoral immune responses.P=0.009) post dose three. Three dose mixed vaccination with ChAd, m-1273 and BNT resulted in comparable anti-S-IgG concentration to three dose m-1273 at four months post dose three. Three doses of either m-1273 or mixed mRNA containing vaccines was associated with significantly higher surrogate neutralization compared with three BNT doses at four months  post dose three. No significant difference in anti-S-IgG concentration was observed in four dose vaccination regimens. SARS-CoV-2 infection, health status of excellent or very good, and m-1273 containing vaccine regimens positively influenced the antibody response.Three doses of m-1273 resulted in significantly higher anti-S-IgG compared with three BNT doses at four months (geometric mean concentration; 10167 AU/mL vs. 5412 AU/mL, Immunization schedules including a minimum of one m-1273 dose elicited the strongest and most durable antibody responses compared with BNT only containing regimens. There is no established correlate of protection for COVID-19, and as such this data should be interpreted alongside vaccine effectiveness studies. Omicron and XBB specific antibody responses will be compared.Sofia R. Bartlett, PhD, Abbvie: Advisor/Consultant|Abbvie: Grant/Research Support|Cepheid: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support Theodore Steiner, MD, FRCPC, Edesa: Grant/Research Support|Ferring: Advisor/Consultant|Ferring: Grant/Research Support|Qu Biologics: Advisor/Consultant|Qu Biologics: Stocks/Bonds|Seres: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support


The bivalent mRNA COVID-19 vaccine booster dose, composed of mRNA from ancestral and Omicron BA.4/BA.5 strains, was recommended for adolescents aged ≥12 years on September 1, 2022, and for children aged 5–11 years on October 12, 2022. However, data demonstrating the effectiveness of bivalent boosters among children and adolescents are limited. During Omicron variant sublineage predominance, September 4, 2022 – February 4, 2023, we conducted a multicenter prospective cohort study at 7 sites in the United States to assess vaccine effectiveness (VE) of bivalent COVID-19 vaccine boosters against laboratory-confirmed SARS-CoV-2 virus infection among children aged 5–17 years.Participants collected weekly nasal swabs, irrespective of symptoms, and at onset of symptoms if present outside of their weekly swab cadence. Vaccination status was captured from periodic surveys (self-report), supplemented with queries from the state immunization information systems, and abstraction of electronic medical records system, when available. All respiratory swabs were tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction. Symptomatic infection was defined as ≥2 COVID-like illness symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios of infections comparing participants with receipt of a bivalent booster to participants without , adjusting for age, sex, race/ethnicity, underlying health conditions, prior infection status, geographic site, and local virus prevalence.Among 3,331 participants aged 5-17 years, adjusted VE against infection was 51% (95% CI: 29–66%). When stratified by age, adjusted VE was 48% (95% CI: 15-68%) for 5-11 year old participants and 55% (95% CI: 17-76%) for 12-17 year old participants. Against symptomatic infection, adjusted VE among 5-17 year old participants was 51% (95% CI: 14-72%).These results demonstrate that the COVID-19 bivalent booster reduces risk of SARS-CoV-2 infection and symptomatic illness among children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.Helen Y. Chu, MD, MPH, Abbvie: Advisor/Consultant|Ellume: Advisor/Consultant|Ellume: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Vir: Advisor/Consultant Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Emily T. Martin, PhD, MPH, Merck: Grant/Research Support Arnold Monto, MD, Roche: Advisor/Consultant|Roche: Honoraria


Burkholderia species can cause chronic and often severe respiratory tract infections in cystic fibrosis (CF) patients. The treatment of infections Burkholderia isolates is complicated by low cell permeability to most antimicrobial agents, presence of beta-lactamases and expression of efflux systems. We evaluated the activity of meropenem-vaborbactam (MEV) and comparator agents tested against Burkholderia spp. isolates collected during a surveillance study.Burkholderia spp. isolates were received as part of a global surveillance program from 2014 to 2022. Isolates were identified using MALDI-TOF MS and included B. cenocepacia (11), B. cepacia species complex , B. gladioli (28) and B. multivorans (21). Isolates were susceptibility (S) tested by reference broth microdilution methods and CLSI interpretative criteria was applied for comparator agents for BCC isolates. Meropenem (MEM) alone breakpoints published by CLSI for BCC or EUCAST for Pseudomonas aeruginosa breakpoints were applied for MEV for comparison purposes.A total of 328 50/90, 1/2 mg/L) inhibited 95.1% of the BCC isolates at ≤4 mg/L and 97.0% at ≤8 mg/L. Trimethoprim-sulfamethoxazole (T/S), MEM and ceftazidime (CAZ) were active against 87.7%, 86.9% and 84.3% of the BCC isolates, respectively and levofloxacin and minocycline inhibited 63.4% and 82.5% of BCC isolates, respectively. Against B. multivorans (21), MEV  inhibited 95.2% of the isolates at ≤4 mg/L or ≤8 mg/L while MEM inhibited 71.4% of the isolates at ≤4 mg/L and 95.2% of the isolates at ≤8 mg/L. T/S and CAZ were active against 71.4% and 81.0% of the B. multivorans isolates. T/S MEV, MEM and CAZ were active against all 11 B. cenocepacia isolates. MEM and MEV  exhibited the same activity against 28 B. gladioli isolates.MEV (MICBurkholderia spp. isolates can lead to respiratory failure which is the primary cause of mortality and morbidity in CF patients. Despite the elevated susceptibility rates for the therapies of choice for these isolates, T/S, CAZ and MEM resistant isolates have been reported. MEV demonstrated good activity against BCC isolates that are commonly recovered from CF patients.Chronic pulmonary infections caused by Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Dee Shortridge, PhD, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Kelley Fedler, BS, Melinta: Grant/Research Support|Paratek: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support


Annual influenza vaccine is universally recommended for high-risk adults, but effectiveness varies between 19-60% in the general population by season and is markedly lower for specific high-risk groups, underscoring the need for novel prophylactic interventions. Though abundant in vaccine effectiveness studies, direct evidence quantifying influenza risk in vaccinated high-risk adults is limited. We aimed to estimate incidence of post-vaccination medically attended influenza-like Illness (ILI) and subsequent hospitalization among adults with chronic diseases and immunosuppression.U.S. adults who received an influenza vaccine in influenza seasons 2015-2019 were identified using Optum commercial claims database (inpatient and outpatient). Known risk factors for influenza were assessed prior to vaccination, while medically attended ILI and subsequent hospitalization (within 30 days) were ascertained post-vaccination. Incidence rates and 95% confidence intervals (CI) were estimated for individual patient risk subgroup during the study period while maintaining sample independence across years. Relative risks were calculated using all vaccinated with or without risk as control.Among 5,195,160 vaccinated adults , annual incidence of medically attended ILI was 2.04 [95% CI 2.03-2.06] per 100 person-years and 0.25 [0.25-0.26] per 100 person-years for ILI-related hospitalization. ILI-related hospitalization risk was the highest for immunocompromised transplant patients , late-stage kidney disease (RR: 5.4-7.4), and severe chronic lung disease (RR: 4.6-5.4), with likelihood of hospitalization after ILI up to 51.3%. More than half of ILI-related hospitalizations were in individuals with chronic obstructive pulmonary disorder, heart failure, or late-stage kidney disease.Immunocompromised and individuals with severe chronic cardiopulmonary or renal disease retained the highest residual risk of ILI-related hospitalization despite vaccination. Additional prophylactic intervention complementing vaccination could potentially offer enhanced protection for these patients.Natalia Zemlianskaia, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Amanda Zheutlin, PhD, Janssen Pharmaceuticals: Employee Yoshihiko Murata, MD, PhD, Gilead Sciences: Current employee of Gilead Sciences|Gilead Sciences: Stocks/Bonds|Merck Research Laboratories: Listed as co inventor in a patent|Merck Research Laboratories: Former employee of Merck Research Laboratories|ViiV Healthcare: Former employee of ViiV Healthcare Jyotsna Bhattacharya, MD, FAAP, Janssen Pharmaceuticals: Current Employee|Janssen Pharmaceuticals: Stocks/Bonds Geoffroy Coteur, PhD, Janssen Pharmaceutica: Honoraria|Janssen Pharmaceutica: Stocks/Bonds Gabriela Ispas, PhD, Janssen Pharmaceuticals: Current Employee|Janssen Pharmaceuticals: Stocks/Bonds Jorge Villacian, MD, Janssen Pharmaceuticals: Current Employee|Janssen Pharmaceuticals: Stocks/Bonds Jason Chien, MD, MS, Janssen Biopharma: Stocks/Bonds David Hong, MD, Janssen: Former employee|Janssen: Stocks/Bonds|Spero Therapeutics: Employee Jennings Xu, BA, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Breno Neri, PhD, Janssen R&D: Full time employment|Janssen R&D: Stocks/Bonds Khaled Sarsour, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Tripthi Kamath, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Xinggang lIU, MD, PhD, Janssen Pharmaceuticals: Current employee|Janssen Pharmaceuticals: Stocks/Bonds


Prior studies demonstrated the vaccine effectiveness and safety of mRNA COVID-19 vaccines, but additional data is needed regarding the effects of timing and number of doses on disease severity. This study determined predicted protection against severe COVID-19 by number of vaccine doses.We enrolled adults hospitalized with acute respiratory infection (ARI) and/or related diagnoses at two Emory University hospitals from May 2021 – Aug 2022. This analysis included COVID-19 positive patients among unvaccinated and 2 or 3 doses of an mRNA vaccine. Vaccinations ≤ 14 days prior to admission were excluded. Medical and social histories were obtained from interviews, medical records, and the state vaccine registry. We used stepwise logistic regression to determine dose-specific odds ratios (OR) against severe outcomes (pneumonia (PNA), length of hospital stay (LOS) ≥ 4 days, ICU admission, mechanical ventilation, and death). Analysis was performed using SAS v9.4 software.Of the 1,677 total enrollments, 850 were positive for COVID-19. Another 168 were excluded due to lack of vaccine records or other vaccine dosages, 682 were eligible for analysis. Compared to those unvaccinated, vaccinated participants were older, male, and unemployed or on disability. Those with three doses obtained a higher education level than unvaccinated participants. Individuals with comorbidities – specifically blood disorders, chronic kidney disease, and immunocompromised – were more often vaccinated. When controlling for race, age, and employment, the odds of PNA ) and ICU admission ) were less for those with two doses than those with none; whereas those with three mRNA doses had less odds of having PNA  and LOS ≥ 4 days ). Predicted protection against severe outcomes persisted 6 months from last dose for PNA, LOS ≥ 4 days, and ICU admission (Table 1).Among COVID-19 positive adults hospitalized with ARIs, both two and three doses of a COVID-19 mRNA vaccine predicted protection against severe COVID-19 outcomes, with durability lasting more than 6 months. Future studies should explore the role of additional boosters and vaccine regimens in the prevention of severe COVID-19.Laura A. Puzniak, PhD. MPH, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Srinivas Valluri, PhD, Pfizer Inc: Pfizer Employee and hold Pfizer stocks/options|Pfizer Inc: Ownership Interest|Pfizer Inc: Stocks/Bonds Timothy L. Wiemken, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support


Mycobacterium abscessus (MAB) is a highly drug-resistant nontuberculous mycobacterium (NTM) that is an important cause of pulmonary disease (PD). Treatment is limited by the lack of active oral drugs and frequent adverse reactions. EBO is a novel oral, boron-containing antimicrobial that inhibits bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis. It has demonstrated encouraging in vitro and in vivo efficacy against MAB in small, limited preclinical studies and is currently in clinical development for the treatment of other NTM-PD. This study evaluated EBO minimal inhibitory concentrations (MIC) against a larger number of recent MAB isolates.MAB isolates collected in 2021 from the United States (n=122) from respiratory sources and in 2019-2022 from Europe (n=25) from respiratory and other sources were tested by broth microdilution according to Clinical and Laboratory Standards Institute guidelines using frozen microtiter panels manufactured by ThermoFisher against EBO and a panel of 13 antimicrobials with anti-MAB activity. MIC values were determined after 4-5 days of incubation; if an isolate was susceptible to clarithromycin (CLR) at day 5, it was reread at day 14 to assess for inducible macrolide resistance. Descriptive analyses were done on the MIC values.abscessus, 6 were bolletii, and 40 were massiliense. EBO MIC50/MIC90 for all isolates were 0.06/0.12 mg/L. MICs ranged from 0.03 - 0.25 mg/L and were consistent across subspecies (Table 1). MIC ranges, MIC50, and MIC90 values for all agents are summarized in Table 2. 95 isolates (64.6%) were CLR-resistant, consisting of 73 isolates with inducible and 22 with constitutive resistance. The EBO MIC50/MIC90 values for either CLR-resistant or amikacin (AMK)-resistant isolates remained 0.06/0.12 mg/L.Of the 147 MAB isolates, 101 were subspecies in vitro activity against MAB with MICs from 0.03-0.25 mg/L with similar activity against all subspecies. EBO MICs remained low against MAB isolates that were resistant to other agents, including CLR and AMK. These data demonstrate EBO’s promising in vitro activity versus MAB regardless of subspecies or resistance to current agents and support clinical evaluation of EBO as a therapeutic option for MAB disease.EBO demonstrated potent Tiffany Keepers White, PhD, AN2 Therapeutics: Employee|AN2 Therapeutics: Stocks/Bonds Charles L. Daley, MD, AN2: Advisor/Consultant|AN2: Grant/Research Support|Aztrazeneca: Advisor/Consultant|Beyond Air: Grant/Research Support|Bill and Melinda Gates Foundation: Data Monitoring Committee|Bugworks: Grant/Research Support|Genentech: Advisor/Consultant|Hyfe: Advisor/Consultant|Insmedd: Advisor/Consultant|Insmedd: Grant/Research Support|Juvabis: Grant/Research Support|Lilly: Data Monitoring Committee|MannKind: Advisor/Consultant|Matinas: Advisor/Consultant|Otsuka: Data Monitoring Committee|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Pfizer: Advisor/Consultant|Spero: Advisor/Consultant|Zambon: Advisor/Consultant


Correction: BMC Psychiatry 23:733 (2023)10.1186/s12888-023-05249-yFollowing publication of the original article , the autThe incorrect caption is: Percentage distribution of CKD stages (n = 261). CKD: chronic renal failureThe correct caption is: Percentage distribution of CKD stages (n = 261). CKD: chronic kidney disease.The original article  has been


Staphylococcus aureus (MRSA) biofilms can be resilient to the human immune system and antibiotics, a challenge augmented by acquired antimicrobial resistance. Phage therapy is being evaluated for biofilm-associated infections.Methicillin-resistant Here, model phages SaMD07ø1 and SaRB105030ø5 were evaluated against their hosts SaMD07 and SaRB105030, respectively, grown as biofilms in 96-well plates, as biofilms on glass beads and planktonically. Trypticase soy broth (TSB) and phosphate buffered saline (PBS) were evaluated as testing media . Biofilms were incubated with phages in the presence of media containing tetrazolium dye in 96-well plates and assessed for hold times  over 48 hours (h) using a Biolog Omnilog® system and by assessing colony forming units (CFUs). Subsequently, using the beads biofilm assay in TSB medium performed on the Omnilog® (BBTO) , test phage SaMD22ø1 was evaluated in quintuplicate against biofilms formed by MRSA isolates IDRL-6130, IDRL-6927, IDRL-6987, IDRL-7381, IDRL-7542 and IDRL-10947, all recovered from periprosthetic joint infection. Test phage K was evaluated against GFP-labelled MRSA AH1263 using BBTO method and simultaneously by fluorescence microscopy.A comparison of result of testing of biofilms in wells and on beads and against planktonic bacteria is shown in Figure 3. Phage SaMD07ø1 showed no growth at 4 h; whereas phage SaRB105030ø5 showed ∼1-log decrease in CFUs at 4 h and ∼3-log decrease in CFUs at 8 h . BBTO hold-times of 37, 28 and 15 h were observed for phages SaMD07ø1, SaRB105030ø5 and phage K respectively. Phage SaMD22ø1 had an average hold time of 9 h and showed hold times >6 hours for all isolates tested . Microscopic inspection showed eradication of GFP-labelled MRSA biofilm by phage K .The solid blue line indicates a hold time of 8 hours.The authors are thankful to Dr. Alexander Horswill at University of Colorado for providing the GFP-labelled MRSA strain.In conclusion, BBTO is a promising method for testing biofilm phage susceptibility although clinical correlation and testing of larger numbers of phage and bacterial isolates are needed.Joseph Fackler, n/a, Adaptive Phage Therapeutics, Inc: Employee|Adaptive Phage Therapeutics, Inc: Stocks/Bonds John M. Sowers, n/a, Adaptive Phage Therapeutics: Employee|Adaptive Phage Therapeutics: Stocks/Bonds Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant


Babesiosis is a tick-borne disease frequently encountered in the region of New England in the US, with increasing incidence and complications ranging from hemolysis to end-organ damage and death. Immunocompromised (IC) patients and patients with impaired splenic function are at increased risk of complications and relapse.This was a multicenter, retrospective study cohort of adult patients diagnosed with babesiosis from 03/2015 – 03/2023 at two institutions. Patient demographics, diagnostic testing, treatment, and outcomes were obtained from the electronic medical record. We aimed to investigate how patient risk factors, complications, length of therapy, and frequency of relapse inform clinical decisions in IC patients.Borrelia spp. 54 patients (95%) received initial treatment with combinations of azithromycin , atovaquone , clindamycin , and quinine  with a median duration of 24.5 days [IQR 11-46]). Median treatment duration was shorter in those who were asplenic only  compared to those IC with splenic function  and those who were IC and asplenic . 3 patients did not receive treatment against Babesia. Prior to therapy discontinuation, 37 (65%) of patients had a documented negative smear, and 12 (21%) were PCR negative. 3 cases (5%) experienced a relapse, with 1 patient remaining PCR positive before treatment discontinuation. 4 patients (7%) died within 90 days of babesia diagnosis, with 1 death (2%) secondary to babesiosis [Table 1].We identified 57 IC or asplenic/hyposplenic patients with babesiosis. Median age was 66 (IQR 60–76) and 40 (70%) were male. 45 patients (79%) were IC, 21 (37%) were asplenic, and 9 (16%) were both. The initial diagnostic test was a peripheral blood smear in 38 (67%). 25 (35%) were also co-infected with Our analysis demonstrates a low relapse and babesiosis-related mortality rate in this cohort, where IC patients typically receive a prolonged treatment course. Parasitemia detection by blood smear continues to be the initial test to determine disease severity and clearance of parasitemia. Further studies are warranted to determine the optimal length of therapy and criteria for therapy cessation, including the role of PCR.Courtney E. Harris, MD, Dynamed: Advisor/Consultant Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Astellas: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Fujifilm: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support


Hand hygiene reliability is a top priority in healthcare. Infection Prevention and Control (IPC) programs often rely on clinical personnel to audit hand hygiene performance. Interrater reliability among auditors is critical to ensuring data validity. We evaluated whether spaced education, which increases long-term knowledge retention, could be integrated into auditor competency assessment.113 trained hand hygiene auditors were enrolled in a 13-month online spaced-education platform to assess their mastery of knowledge needed for the role. We delivered 46 unique questions  followed by rationale; we retired questions after 3 correct answers. A 10-item survey consisting of 9 Likert-scale questions and one free-text comment was emailed to gauge participant satisfaction with the competency program. Frequencies and percentages were used to summarize Likert responses, and themes were elicited from comments.From November 2021 to December 2022, a total of 12,120 questions were attempted, and 32 of 113 auditors (28%) completed the competency. Auditors answered 70% of questions correctly on the first attempt and 83% on the final attempt. 30 of 113 auditors (27%) responded to the survey. The majority agreed the number and complexity of questions were appropriate . 87% reported the platform easy to navigate, 63% reported the spaced-education model worked, and 77% agreed adequate time was provided for completion. 30% of respondents reported the individual competition as enjoyable. Time and effort required for completion was the most common theme identified among auditor comments; several respondents recommended fewer questions at a narrower spacing interval over a shorter time frame due to competing work demands; 5 individuals expressed a preference for an annual computer-based module.A spaced education competency program improved hand hygiene auditor knowledge in the short term. Completion rate was low and participants expressed a desire for fewer questions over a shorter time frame. This study offers insight into ways to optimize spaced education as a potential tool for hand hygiene competency assessment.Ana M. Vaughan-Malloy, MD, MPH, Asana: Stocks/Bonds|Aurora: Stocks/Bonds|Ayr Wellness: Stocks/Bonds|Bionano Genomics: Stocks/Bonds|Butterfly Network: Stocks/Bonds|Canopy Growth: Stocks/Bonds|Cresco Labs: Stocks/Bonds|CRISPR Therapeutics: Stocks/Bonds|Cronos Group: Stocks/Bonds|Curaleaf Holdings: Stocks/Bonds|Editas Medicine: Stocks/Bonds|Green Thumb Industries: Stocks/Bonds|High Tide: Stocks/Bonds|Iovance Biotherapeutics: Stocks/Bonds|Jushi Holdings: Stocks/Bonds|Moderna: Stocks/Bonds|Organigram Holdings: Stocks/Bonds|Pacific Biosciences of California: Stocks/Bonds|Personalis: Stocks/Bonds|Pfizer: Stocks/Bonds|SNDL Inc: Stocks/Bonds|Terrascend: Stocks/Bonds|Tilray Brands: Stocks/Bonds|Trulieve: Stocks/Bonds


Cabotegravir + rilpivirine (CAB+RPV) injections, the first complete long-acting (LA) antiretroviral therapy (ART) regimen, was approved by the FDA in January 2021 for ART-experienced people with HIV (PWH) who are virologically suppressed (VL < 50 copies/mL). Among individuals virologically non-suppressed (VL ≥ 30 copies/mL) at initiation, high rates of virologic suppression were observed in the demonstration project at Ward 86 for CAB+RPV LA. We observed CAB+RPV LA real-world utilization and effectiveness over the first 2 years of availability in the United States (US) in individuals with VL ≥ 50 copies/mL at initiation in the OPERA® Cohort.All ART-experienced adults with VL ≥ 50 copies/mL at initiation who received their first CAB+RPV LA injection between 21Jan2021 and 28Feb2023 were followed until 25Mar2023. Discontinuation (ART switch or 2 consecutive missed doses) and confirmed virologic failure  were described, for all individuals with VL ≥ 50 copies/mL and for the subset with VL ≥ 200 copies/mL.Of 1843 ART-experienced PWH with ≥ 1 CAB+RPV injections, 229 (12%) had a VL ≥ 50 copies/mL at initiation. At baseline, they were a median of 41  years of age, 31% female, 57% Black and 20% Hispanic. Injections started a median of 9  years after HIV diagnosis with a median viral load of 2.1  log copies/mL and median CD4 count of 579  cells/μL (Table 1). Over a median of 6.1  months of follow-up, 83% were still on CAB+RPV LA at study end. Among the 80% with ≥ 1 VL over follow-up, 94% had a VL < 200 copies/mL and 75% had a VL < 50 copies/mL at study end. CVF was observed in 7 (4%) individuals (Table 2). Similarly for the subset of 93 individuals with a VL ≥ 200 copies/mL at initiation, 90% and 74% had a VL < 200 or < 50 copies/mL at study end, respectively, when follow-up VLs were available (Table 2).In a large, diverse cohort of real-world, routine clinical care in the US, CAB+RPV LA injections were observed in individuals with viral loads ≥ 50 copies/mL at initiation. Most of these individuals were able to suppress to VL < 50 copies/mL and maintain suppression through study end.Ricky K. Hsu, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Michael Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Jennifer S. Fusco, BS, Epividian, Inc.: Salary|Epividian, Inc.: Ownership Interest|Epividian, Inc.: Stocks/Bonds Laurence Brunet, PhD, Epividian, Inc.: Salary|Epividian, Inc.: Stocks/Bonds Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Full Time Employee Vani Vannappagari, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Jean A. van Wyk, MBChB, MFPM, ViiV Healthcare Ltd: Stocks/Bonds Michael B. Wohlfeiler, JD, MD, AAHIVS, ViiV Healthcare: Serves as a PI on clinical trials, but does not receive personal compensation for this work  Gregory P. Fusco, MD, MPH, Epividian, Inc.: Board Member|Epividian, Inc.: Ownership Interest|Epividian, Inc.: Stocks/Bonds


CAB+RPV LA is the only complete long-acting regimen for treatment of virologically suppressed PWH. Administered monthly or every 2 months by a healthcare provider, CAB+RPV LA may alleviate adherence challenges with daily oral therapy. The ABOVE study evaluated real-world adherence and persistence to CAB+RPV LA versus remaining on oral ART regimens.ABOVE was a retrospective US cohort study using Symphony Health Solutions Integrated Dataverse administrative claims database from 01/01/2020 to 12/31/2022. PWH ≥12 years of age on stable guideline-recommended oral ART were categorized into those initiating CAB+RPV LA and those remaining on oral ART. Index date was defined as first injection between 01/01/2021 and 6/30/2022 (CAB+RPV LA cohort) or imputed for the oral ART cohort. PWH were required to have ≥6 months of follow-up after index. Standardized mortality ratio (SMR) weights were generated based on propensity scores to balance baseline characteristics between cohorts. Adherence (proportion of days covered (PDC) ≥0.9 over 6-months following index) and persistence to the index regimen (days from index to the earliest of treatment discontinuation or end of follow-up) were compared. Logistic regression model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for adherence.393,484 PWH were identified during the study period. After applying eligibility criteria, 130,362 in the oral ART cohort (N=950 after weighting) and 947 in the CAB+RPV LA cohort comprised the analysis sample. Key baseline characteristics were balanced post SMR weighting (Table 1). Majority of CAB+RPV LA dosing was every two months only (50%) or switched from monthly to every two months (33%). A higher proportion of PWH in the CAB+RPV LA cohort were adherent  and had higher persistence  compared with the oral ART cohort (Table 2). PWH in the CAB+RPV LA cohort had significantly higher adjusted odds of being adherent compared to the oral ART cohort .These data demonstrate that, among US PWH on stable oral ART, switching to long-acting ART resulted in significantly higher adherence and persistence, a critical aspect of long-term success of HIV treatment, compared with remaining on oral ART.Cindy Garris, MS, GSK: Stocks/Bonds|ViiV Healthcare: Employee Raj Desai, PhD, Analysis Group, Inc: Employment|ViiV Healthcare: Grant/Research Support Rose Chang, ScD, Analysis Group, Inc.: Employee|ViiV Healthcare: Grant/Research Support Louise Clear, MPH, Analysis Group, Inc.: Employment|ViiV Healthcare: Grant/Research Support Zhuo Chen, MPH, Analysis Group, Inc.: Employment|ViiV Healthcare: Grant/Research Support Daisy Liu, MS, Analysis Group, Inc.: Employment|ViiV Healthcare: Grant/Research Support Maral DerSarkissian, PhD, Analysis Group, Inc: Employment|ViiV Healthcare: Grant/Research Support Paula Teichner, PharmD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employment Edgar T. Overton, MD, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds


Acinetobacter baumannii infections. We sought to characterize SUL and DUR adsorption and transmembrane clearance (CLTM) in an ex vivo CRRT model.Optimal dosing of antibiotics in patients on CRRT is complicated by factors that can influence drug adsorption and clearance including filter type, CRRT mode, effluent rate (ER), and the drug’s properties itself. SUL-DUR is a novel combination antibiotic under development for management of TM was determined in hemofiltration (CVVH) and hemodialysis (CVVHD) modes using the Prismaflex M100 and HF1400 hemofilter sets. One liter of heparinized bovine blood was allowed to circulate in the Prismaflex CRRT system for 10 minutes. SUL and DUR were then added to achieve a plasma concentration of 30 mg/L, the average maximum concentration achieved in humans following SUL-DUR 1g/1g q6h as a 3h infusion. Pre-filter blood, post-filter blood and effluent samples were collected at 0, 10, 30, and 60 minutes to determine SUL and DUR concentrations. Combinations of filters, modes, and replacement fluid were tested in triplicate at effluent rates of 1, 2 and 3 L/h. The sieving coefficient (SC) for CVVH and the saturation coefficient (SA) for CVVHD were calculated to determine CLTM. Adsorption was measured through a closed loop system bypassing effluent elimination. Multiple linear regression was used to determine SUL and DUR CLTM as a function of ER, filter, and mode.CLTM for both drugs based on the equations: SUL CLTM (L/h) = -0.0123 + (1 x ER), R2 = 0.998; DUR CLTM (L/h) = 0.0346 + (0.91 x ER), R2 = 0.958.SUL and DUR adsorption was minimal at 10% for both drugs. Mean ± standard deviation initial SUL and DUR concentrations were 28.6 ± 2.5 and 27.4 ± 1.9 mg/L, respectively. The overall mean SC/SA across different modes, filters, and ERs was 1.0 and 0.9 for SUL and DUR, respectively. Multiple linear regression demonstrated that the ER was the primary driver (p< 0.001) of CLTM and devise dosing recommendations for SUL-DUR for patients requiring CRRT.SUL and DUR were efficiently cleared by both CVVH and CVVHD through M100 and HF1400 filters. The clearance of both drugs during CRRT was dependent primarily on the ER. When incorporated into established population pharmacokinetic models, these data can be used to estimate CLXiaoyi Ye, MD, Sanofi Genzyme: Honoraria David P. Nicolau, PharmD, Allergan: Advisor/Consultant|Allergan: Grant/Research Support|Cepheid: Advisor/Consultant|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Tetraphase: Advisor/Consultant|Tetraphase: Grant/Research Support|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support|Wockhardt: Advisor/Consultant|Wockhardt: Grant/Research Support Joseph L. Kuti, PharmD, bioMeriuex Inc.: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Merck & Co, Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|Shionogi Inc: Grant/Research Support|Shionogi Inc: Honoraria


Rapid and accurate diagnosis of acute respiratory infection (ARI) in children is crucial for proper patient management, and nucleic acid amplification tests are the gold standard. Nasal swabs are preferred for surveillance studies due to their ease of use, mainly in children. Our study compares the performance of two sample-to-answer (STA) platforms for detecting multiple viruses in self-collected nasal swabs from symptomatic children.Between January 2023 and March 2023, self-collected nasal swabs in UTM from children and staff with ARI symptoms were collected as part of an ongoing school-based surveillance study in a large Missouri school district. Samples were tested on the QIAstat-Dx Respiratory SARS-CoV-2 Panel and the fully automated Hologic Panther Fusion system, which can detect a total of 21 respiratory viruses. Percent Agreement analysis was performed to compare the performance of each platform.Of 200 samples collected, QIAstat detected viruses in 111 samples (55.5%) and Hologic in 115 samples (57.5%). Both assays showed high overall agreement (90%), with a PPA (Positive percentage agreement) of 89%, an NPA (Negative percentage agreement) of 94%. Parainfluenza (PIV) showed 100% PPA and NPA followed by adenovirus (Adv)  and rhinovirus (RV) (PPA: 92% and NPA: 94%). Human metapneumovirus (hMPV) had the lowest PPA (47%) but a high NPA (99%) (Table 1). The median CT values for QIAstat and Hologic were 28.8 (IQR 23.65 - 32.5) and 29.3 (IQR 24.2 – 34.5), respectively. QIAstat missed 19 detections, including hMPV , coronavirus NL63 , and RV , with a corresponding median Ct of 39.1 (IQR 34.5 – 41.2) on Hologic. Hologic missed 12 detections, with RV being the most common target , and a corresponding median Ct of 32.9 (IQR: 30.3-35.5) on QIAstat.QIAstat and Hologic exhibit comparable performance  for detecting viral respiratory pathogens from self-collected nasal swabs. Viral detections missed by QIAstat assay had low viral loads, while targets missed by Hologic assay had moderate viral load; additional investigation is needed. Our findings suggest that both STA platforms are suitable for diagnosing respiratory viral infections in self-collected nasal swabs in school-setting.Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support


Different kinetic models such as zero-order, first-order, Higuchi and Korsmeyer–Peppas were studied to evaluate the influence of CS/CMC ionic interactions on the ability to improve the release rate of poorly soluble drugs.Simvastatin (SIM) is a potent lipid-lowering drug used to control hyper-cholesterolemia and prevent cardiovascular diseases. SIM presents low oral bioavailability (5%) because of its low aqueous solubility. In this work, polyelectrolyte complexes (PEC) are developed with different chitosan (CS) and carboxymethylcellulose (CMC) ratios that will allow for an increase in the SIM dissolution rate (2.54-fold) in simulated intestinal medium (pH 4.5). Scanning Electron Microscopy (SEM) images revealed highly porous structures. The changes between both complexes, PEC-SIM:CS:CMC (1:1:2) and (1:2:1), were related to the relaxation of the polymer chains upon absorption of the dissolution medium. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRPD) studies were used to evaluate the polymer/polymer and drug/polymer interactions on the different PEC-SIM:CS:CMC ratios. In addition, the PEC-SIM:CS:CMC (1:2:1) complex exhibited a high ratio of protonated amino groups (NH Th. Thr2 ofc chains . The pre–45 min) ,22. 3+) from the CS chains and the anionic groups (COO−) from the CMC chains. In addition, the presence of free amino groups (NH3+) was shown to be dependent on the CS and CMC ratios within the interpenetration network. High CMC ratios in PEC-SIM:CS:CMC (1:1:2) increase the number of anionic groups (COO−), which produces a dense structure with high polymer/polymer interactions, resulting in a more sustained SIM release profile, avoiding side effects such as hepatotoxicity. The elaboration and characterization of different polyelectrolyte complexes, PEC-SIM:CS:CMC (1:1:1), PEC-SIM:CS:CMC (1:1:2) and PEC-SIM:CS:CMC (1:2:1), were carried out. These complexes displayed different CS/CMC interactions that were correlated with different SIM release rates at pH 4.5. SEM studies showed different changes in the surface morphology of the interpolymeric network related to the CS amount within the CS/CMC interpolymeric complexes. These complexes exhibited a high swelling process within the CS/CMC, which was confirmed via FTIR, DSC and XRPD studies. The different polyelectrolyte complexes studied showed different interactions between the protonated amino groups (NHp < 0.05) at 15 and 60 min compared to SIM-RM. The expansion of the CS interpolymeric chains and the increase in intramolecular hydrogen bonds promote hydration and improve the SIM dissolution rate. Finally, the first-order and Korsmeyer–Peppas models were the best fitting models for PEC-SIM:CS:CMC (1:2:1) because of its fast release kinetics. These polyelectrolyte complexes with a large number of free protonated amino groups (NH3+) have great potential to improve the dissolution profiles of poorly soluble drugs. These polyelectrolyte complexes with high CS ratios could produce similar decreases in the crystallinity of other poorly soluble drugs and increase their wettability on the network surface due to their ionic interactions with the dissolution medium, resulting in improved drug dissolution.Dissolution studies (at pH 4.5) indicated that high CS proportions in PEC-SIM:CS:CMC (1:2:1) produced significant improvements (


COVID-19 vaccines in pregnancy may protect young infants from severe illness via maternally-derived IgG. Transplacental transfer of maternal IgG is thought to be decreased in infants with low-birth weight (LBW). The impact of maternal COVID-19 vaccine in this population is unknown. We aimed to evaluate anti-Spike (S) IgG transfer in LBW versus normal birthweight (NBW) infants.th percentile) birthweight.In this prospective cohort study among individuals with a singleton pregnancy without detectable anti-nucleocapsid IgG who received at least 2 doses of an mRNA COVID-19 vaccine prior to delivery, we tested paired maternal and cord samples for anti-S IgG. We used linear regression to evaluate associations between LBW (birthweight < 2500 grams), timing of vaccine dose, and anti-S IgG. We included as covariates timing of last vaccine dose, gestational age at delivery, number of doses prior to delivery, and small for gestational age  and 1260 BAU/mL  for LBW and NBW infants, respectively. Median cord anti-S IgG was 4585 BAU/mL  and 1734 BAU/mL  for LBW and NBW infants, respectively . After adjustment for covariates including vaccine dose timing, there was no difference between cord anti-S IgG concentrations of LBW and NBW infants . As time between last dose and delivery increased, cord anti-S IgG concentrations significantly decreased . In contrast, cord:maternal IgG ratios significantly increased with greater time between last vaccine dose and delivery .Figure 3Maternal IgG levels may be more important predictors than infant birthweight for SARS-CoV-2 cord IgG concentrations. Policy regarding timing of COVID-19 vaccine during pregnancy should consider pregnancies at risk for LBW infants.Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Mindy Pike, PhD, Merck: Grant/Research Support Alexander L. Greninger, MD, PhD, Cepheid: central contracts|Hologic: central contracts|Janssen: central contracts|Novavax: central contracts|Pfizer: central contracts Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant


Asymptomatic bacteriuria (ASB) is common in patients with urinary catheters and unneeded urine cultures (UC) can lead to misidentification of CAUTI. We evaluated the long-term effectiveness of restricting UC utilization on the incidence of inpatient CAUTI and if the COVID pandemic influenced CAUTI rates.A UTI evaluation panel was implemented at our academic medical center in April 2015 requiring clinician documentation of UTI symptoms or criteria supporting UC in the absence of symptoms or pyuria. UC was performed reflexively if the following were present: documented symptoms, pyuria ( > 10WBC), and no contamination ( > 100 squamous cells) . UC in at risk patients without symptoms or pyuria were performed. CAUTI data was collected using NHSN methodology with 2014 CAUTI rates recalculated using 2015 definitions. Three periods were compared: Pre-implementation (1/2014-3/2015), post-implementation (4/2015-3/2020) and COVID (4/2020-6/2022). NHSN SIR and SUR were compared where available (4/2015-3/2020 vs. 4/2020-6/2022). Poisson regression was used to model rate of infection per month. A generalizing estimating equation was used for interrupting time series model to compare rates of infection.Urine culture rates decreased in both post and COVID periods and catheter days decreased in the post but not COVID period (Table 1). CAUTI rates per 1000 CD decreased 40% between pre- and post-intervention (p=0.0001) and were unchanged during COVID, (p=0.61) although the slope of change did alter from decreasing to increasing . Quarterly SURs decreased during COVID while the institutional SIR increased non-significantly.Figure 2:Our intervention decreased urine cultures and CAUTI. There was a non-statistically significant increase in CAUTI during the COVID pandemic with the direction of rate of change going from negative to positive. This may have been due to diversion of resources from infection prevention programs. Catheter use decreased throughout; this may have impacted the metrics which used CD as a denominator  as both showed non-significant increases during COVID.Trevor C. Van Schooneveld, MD, FSHEA, FACP, AN2 Therapeutics: Grant/Research Support|Biomeriuex: Advisor/Consultant|Biomeriuex: Grant/Research Support|Insmed: Grant/Research Support|Thermo-Fischer: Honoraria Mark E. Rupp, MD, 3M: Advisor/Consultant|Citius: Advisor/Consultant|contrafect: Grant/Research Support|Teleflex: Advisor/Consultant


Bacille Calmette Guerin (BCG) vaccine’s protective effect against tuberculosis (TB) is established. BCG vaccine also has off-target effects, perhaps due to long-lasting trained immunity. BCG provides unanticipated beneficial effects against other infectious/non-infectious diseases, including respiratory infections, diabetes mellitus, dementia, and cancer. We aimed to determine if there was differential mortality over a lifetime in those receiving BCG versus placebo. We analyzed all cause and infectious diseases (ID) mortality in a longitudinal cohort study of American Indians and Alaska Natives (AI/AN) enrolled in a BCG efficacy clinical trial.2963 AI/AN participants were enrolled median age 7.6 years (range 0.1-20) in a saline placebo-controlled BCG trial between 1935-8 in five US geographic regions, with prospective follow up through 1948. Retrospective data collection was completed from 1992-8. Mortality data was supplemented by National Death Index search in 2006, pending 2023. Demographics, medical and mortality history were collected blinded to vaccine arm. Differences in mortality were analyzed by vaccine, demographic and death characteristics via bivariate association using chi-square, t-test and logistic regression with STATA.1540 BCG, 1423 placebo participants enrolled. At 71 years from the trial start, 1600/2963 (54.0%) participants were deceased; 1171 (73.2%) to non-ID, 94 (5.9%) TB, 217 (13.6%) other infections, and 118 (7.3%) were unknown. Median age at death was similar . BCG vaccinated participants had a 31% decreased odds of death vs. placebo for ID not-TB  and 74% decreased odds of death due to TB . Adjusted logistic regression analysis showed BCG decreased odds of all cause death by 14% (p = 0.04). Male sex (OR 1.77) and living in Arizona (OR 2.53) or Wyoming (2.24) were associated with increased all cause mortality (p< 0.001).In this cohort, BCG vaccine conferred a mortality benefit against TB but also other infections. Male sex and certain geographic regions were associated with higher odds of death. These findings suggest that childhood vaccination with BCG vaccine may reduce mortality beyond preventing TB deaths.Lee Harrison, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Naomi E. Aronson, MD, british medical journal: Honoraria|British Medical Journal: honoraria for writing chapter for Best Evidence|Elsevier: royallties serve as textbook editor|Elsevier: Royalties as text editor|UpTo Date: royalties for writing chapters|UpToDate: royalties for writing chapters|Wellcome Foundation: Honoraria|Wellcome Foundation: program advisory board|Wellcome Trust: Honoraria|Wellcome Trust: program advisory board Naomi E. Aronson, MD, british medical journal: Honoraria|British Medical Journal: honoraria for writing chapter for Best Evidence|Elsevier: royallties serve as textbook editor|Elsevier: Royalties as text editor|UpTo Date: royalties for writing chapters|UpToDate: royalties for writing chapters|Wellcome Foundation: Honoraria|Wellcome Foundation: program advisory board|Wellcome Trust: Honoraria|Wellcome Trust: program advisory board


Lactobacillus crispatus), and a substantial increase in BV-associated bacteria (BVAB), particularly Gardnerella vaginalis. We investigated the vaginal microbiota to identify changes prior to, during, and immediately after incident BV (iBV).Bacterial vaginosis (BV) is the most common vaginal infection among reproductive-aged women worldwide. It is associated with multiple adverse obstetric and gynecologic outcomes, yet its etiology remains unknown. BV is characterized by a decrease in protective lactobacilli  were enrolled and followed for iBV using twice-daily self-collected vaginal specimens. 16S rRNA gene sequencing was performed on specimens collected during the 14 days prior to BV (pre-BV), during BV (Nugent score 7-10), and days post-BV among cases. A similar number of specimens from age, race, and menstrual cycle day matched controls maintaining normal vaginal microbiota were also sequenced. qPCR was also performed on all specimens to determine total bacterial burden and inferred absolute abundance (IAA) of key vaginal bacteria, particularly G. vaginalis during BV . There was a significant decrease in the IAA of L. crispatus during BV , whereas L. iners IAA increased in post-BV .Vaginal specimens from 5 BV cases (n=169) and 5 matched controls  were analyzed. Overall, a significantly higher bacterial burden was observed in specimens from BV cases compared to matched controls . In BV cases, specimens collected on the day of BV had a significantly lower bacterial burden than specimens collected pre- and post-BV . When comparing changes in the IAA of our vaginal bacteria of interest, we observed significantly higher amounts of Comparing qPCR and inferred absolute abundance (IAA) between vaginal specimens collected from women with incident BV (cases) and healthy controls maintaining normal vaginal microbiota.A, B. qPCR derived total bacterial burden between vaginal specimens from incident BV cases and healthy controls. C- E. inferred absolute abundance (IAA) of G. vaginalis, L. crispatus, and L. iners between vaginal specimens from incident BV cases and healthy controls. A, C. Mann Whitney test; B, D, E. Kruskal-Wallis test *p≤ 0.05, **p≤ 0.01, ***p≤ 0.001, ****p≤ 0.0001.G. vaginalis while protective L. crispatus decreased, and L iners increased after BV. We anticipate expanding this analysis to include additional key BVAB.These preliminary results support the hypothesis that a sequence of changes in the abundance of key vaginal bacteria occur prior to BV. During BV, we observed an increase in Christina A. Muzny, MD, MSPH, Abbott Molecular: Grant/Research Support|Abbott Molecular: Honoraria|BioNTech: Advisor/Consultant|Cepheid: Advisor/Consultant|Cepheid: Honoraria|Elsevier: Honoraria|Gilead: Grant/Research Support|Lupin Pharmaceuticals: Grant/Research Support|Roche: Honoraria|Scynexis: Advisor/Consultant|Scynexis: Honoraria|Visby Medical: Honoraria


EBONI and PILLAR are Phase IV implementation science trials evaluating the integration of long-acting injectable Cabotegravir for PrEP (CAB LA) into standard of care at 37 clinics across the U.S. EBONI enrolls Black cisgender/transgender women and PILLAR enrolls men who have sex with men (MSM)/transgender men. We report CAB LA implementation plans among staff study participants (SSPs).Of 105 SSPs from 20 EBONI sites, 65 (62%) from 14 activated clinics completed baseline surveys starting in August 2022. Eighty-six (100%) SSPs from all 17 PILLAR clinic sites completed surveys from April-October 2022. Various clinic types were selected to enroll diverse populations. Survey domains included SSPs’ perceptions of implementing CAB LA, plans for integration, and estimation of resources needed for integration were collected.Table 1 presents notable gender and racial differences among SSPs across the studies. Table 2 reveals similar SSPs’ experience with PrEP and injections within the two studies. A high proportion of SSPs  felt extremely positive or positive about implementing CAB LA. The majority of SSPs in EBONI (74%) than in PILLAR (53%) perceived implementation would be very easy or easy.Regarding CAB LA integration plans, compared to EBONI, SSPs in PILLAR reported being able to manage more CAB LA patients per week; having more staff prepared to give injections; having a specific person to follow up with no-shows; planning to have providers track patients; and planning to offer drop-in injection options (Table 3). However, more SSPs in EBONI reported plans to create roles to coordinate the CAB LA program.Various appointment reminder tools are in place and used in similarly high proportions across both studies. However, a higher proportion of SSPs in PILLAR reported using email and postal reminders.Healthcare staff were positive about integrating CAB LA into care. Sites serving MSM and transgender men had more detailed implementation plans in place than those serving cisgender and transgender women. Sites serving women may need additional support to develop their plans to build staff and clinic capacity. To address the gaps identified in clinic planning, an equity-centered implementation strategy should be employed.William M. Valenti, MD, FIDSA, Gilead: Grant/Research Support|ViiV Healthcare: Grant/Research Support John Phoenix, MSN, APRN, FNP-C, Gilead: Grant/Research Support|Gilead: Speaker Bureau|Huntridge Family Clinic: Ownership Interest|Napo Pharmaceuticals: Speaker Bureau|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Speaker Bureau Rupa R. Patel, MD MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Roche: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Zandraetta Tims-Cook, MD, ViiV Healthcare: Speaker Nanlesta Pilgrim, PhD, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Amber Haley, PhD, ViiV Healthcare: Former Employment Kenneth Sutton, MA, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Alison Gaudion, PhD, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Deanna Merrill, PharmD, MBA, AAHIVP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Rimgaile Urbaityte, MSc, GSK: Employment|GSK: Stocks/Bonds Bo Li, PhD, GSK: Employment|GSK: Stocks/Bonds David Andrae, PhD, Evidera: Employment Abigail Herbst, MPH, Evidera: Empoyment|ViiV Healthcare: Grant/Research Support Harmony Garges, MD, GSK: Stocks/Bonds|Medexus Pharmacy: Board Member|ViiV Healthcare: Empoyment Maggie Czarnogorski, MD MPH, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds


Periprosthetic joint infection (PJI) is a devastating complication following joint replacement, associated with morbidity and mortality. Here, we established a clinically representative murine model of knee arthroplasty and determined the ideal bacterial inoculum that would result in PJI without causing significant limb compromise.Staphylococcus aureus Xen36, ranging from 29 to 14,000 colony forming units (CFU) (Table 1). Mice were sacrificed at 3 weeks, or earlier if necessary due to infectious sequelae, and the joint tissue, tibia, femur, and prosthesis quantitatively cultured.A titanium tibial prosthesis designed for the murine knee was 3D printed and surgically implanted into the proximal tibia  of 38 C57BL/6 mice. The prosthesis is designed to osseointegrate into the tibia and has a smooth articular surface to allow for immediate weight bearing and range of motion. At the time of surgery, the arthroplasty was inoculated with five inocula of All mice inoculated with 181 to 14,000 CFU developed PJI as did 90% inoculated with 29 CFU. Bacterial loads from joint tissues and tibial prostheses are shown in Table 1. All mice inoculated with 14,000 and 760 CFU had overt findings of infection  requiring early euthanasia (Table 2). Mice inoculated with 640 CFU had swelling, redness, and small sores in first 3 days, and 1 death, but otherwise appeared well; only 2/9 had a visible abscess at 3-week sacrifice. 2/10 mice receiving 181 CFU had small sores that resolved in the first week; all limbs functioned well prior to sacrifice. Mice receiving 29 CFU had no external evidence of infection, however 9/10 had purulence within the joint at sacrifice.S. aureus PJI. An inoculum of 181 CFU resulted in universal infection without significantly compromising the limb. The ability of this model to create PJI without overt infectious sequela will allow for evaluation of therapeutics, including those locally delivered.This study demonstrates that inoculum size directly impacts clinical manifestations of infection in a murine model of Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant Nicholas Bedard, MD, Stryker: Advisor/Consultant


In March 2023, the Clinical and Laboratory Standards Institute (CLSI) lowered the Enterobacterales susceptible (S)/resistant breakpoints for amikacin from ≤16/≥64 mg/L to ≤4/≥16 mg/L and gentamicin and tobramycin from ≤4/≥16 mg/L to ≤2/≥8 mg/L. As aminoglycosides are frequently used to treat infections caused by multidrug-resistant (MDR) and carbapenem-resistant Enterobacterales (CRE), we evaluated the activity of plazomicin and the impact of CLSI breakpoint changes on the susceptibility rates of Enterobacterales collected from US medical centers.5,725 Enterobacterales isolates were consecutively collected (1/patient) from 36 US medical centers in 2020–2022 and susceptibility tested by broth microdilution against amikacin, gentamicin, tobramycin, and plazomicin. Susceptibility rates were calculated using both current CLSI/USFDA breakpoints and the recently revised CLSI breakpoints. Aminoglycoside-nonsusceptible isolates were screened for genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methyltransferases (16RMT).Plazomicin was active against 96.3% of isolates and retained potent activity against MDR (93.1%S) and CRE (92.1%S) isolates. The highest variations in susceptibility rates due to breakpoint changes were observed with amikacin, especially among MDR  and CRE (77.8%S to 61.9%S). Against all Enterobacterales, amikacin susceptibility rates decreased from 99.6%S to 95.0%S; susceptibility to gentamicin and tobramycin decreased 0.8% and 2.6%, respectively. Gentamicin and tobramycin showed limited activity against MDR and CRE with both 2022 and 2023 breakpoints. AME-encoding genes were observed in 474 (8.3% of isolates) and 16RMT was found in 7 isolates (0.1%). Plazomicin was active against 97.3% of AME producers.Amikacin’s spectrum of activity against CRE and MDR Enterobacterales was drastically reduced when interpretative criteria based on PK/PD parameters currently used to establish breakpoints to other antimicrobials were applied. Plazomicin is markedly more active than amikacin, gentamicin, or tobramycin against CRE and MDR Enterobacterales causing infections in US medical centers.Helio S. Sader, MD, PhD, FIDSA, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support S J Ryan Arends, PhD, Cipla: Grant/Research Support|GSK: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


This study compared outcomes among COVID-19 patients (pts) treated with the monoclonal antibody (mAb) sotrovimab matched to untreated pts.Administrative claims  were used to identify pts (≥ 12 years) diagnosed with COVID-19 (ICD-10: U0.7.1) in an ambulatory setting in the US (26 May 2021–5 April 2022). The sotrovimab cohort included pts meeting sotrovimab’s Emergency Use Authorization (EUA) criteria and receiving sotrovimab ≤ 10 days from diagnosis (index date = day of infusion). The untreated cohort included pts with no evidence of early/prophylaxis mAb or antiviral treatments (index date imputed based on the time distribution between diagnosis and sotrovimab infusion for their matched counterpart from the sotrovimab cohort). Pts were required to be continuously enrolled for ≥ 12 months pre-index and ≥ 29 days post-index (excluding death). Exact matching and propensity-score matching (EM/PSM) methods were used to construct 1:2 matched cohorts of sotrovimab-treated and untreated patients . Outcomes evaluated in the 29-day post-index period were all-cause hospitalization, all-cause hospitalization and/or mortality, all-cause mortality, intensive care unit (ICU) admission, and maximum level of respiratory support.A total of 34,160 sotrovimab pts were matched to 68,320 untreated pts . The 29-day hospitalization and/or mortality rates were 4.0%  and 5.2%  in the sotrovimab and untreated cohorts, respectively (p < 0.0001). Patients in the sotrovimab cohort had statistically significantly lower rates of all-cause hospitalization, all-cause mortality, ICU admission, and respiratory support as compared with patients in the untreated cohort (Table).*Obtained from conditional logistic regression models (binary outcomes). All models adjusted for malignancy. ECMO, extracorporeal membrane oxygenation; ICU, intensive care unitSotrovimab demonstrated effectiveness in preventing severe outcomes  as compared with untreated pts during the period in which Delta and early Omicron variants were predominant.Christopher F. Bell, MS, GSK: Employee|GSK: Stocks/Bonds Tasneem Lokhandwala, PhD, GSK: Funding to conduct study|Vir Biotechnology, Inc: Funding to conduct study Daniel C. Gibbons, PhD, GSK: Employee|GSK: Stocks/Bonds Myriam Drysdale, PhD, GSK: Employee|GSK: Stocks/Bonds Jane Wang, MS, GSK: Funding to conduct study|Vir Biotechnology, Inc: Funding to conduct study Emily Lloyd, MSc, GSK: Employee|GSK: Stocks/Bonds


Maternal vaccination is a promising strategy to prevent COVID-19 in early infancy, yet the amount of protection that maternally derived vaccine specific SARS-CoV-2 binding and neutralizing antibodies provide to infants in the first six months of life is not well characterized.Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of an mRNA COVID-19 vaccine  were followed prospectively from birth up to 6 months. At delivery, anti-Spike IgG and pseudovirus neutralizing antibody (Nab) levels were measured. Between September 2021 and December 2022, at pre-specified timepoints, COVID-19 infection was determined by verified maternal report. The risk reduction for COVID-19 in infants by antibody titers at delivery was estimated using a calendar-time Cox regression model after adjusting for maternal age, booster status, and recency of last dose. The relative vaccine effectiveness (VE) of 3 vs 2 maternal vaccine doses for COVID-19 in infants < 6 months was estimated in separate models.Infants in the boosted group (n=181) had higher anti-Spike IgG and pseudovirus Nab titers at delivery compared with the primary series group (n=260) . A 10-fold increase in anti-Spike IgG measured at delivery was associated with a 69.2%  reduction in the infant’s risk of acquiring COVID-19 in the first 6 months. Similarly, having a pseudovirus Nab response above an IC50 of 20 at delivery was associated with a 96.2%  reduction in the infant’s risk of acquiring COVID-19 in the first 6 months. The relative VE of 3 vs 2 doses against infant COVID-19 was 65%  when accounting for changes in anti-Spike IgG levels, and 83%  when accounting for pseudovirus Nab levels.Higher SARS-CoV-2 IgG Spike and pseudovirus Nab titers at delivery are associated with a substantially reduced risk of COVID-19 infection for infants in the first 6 months of life. Until infants are age-eligible for COVID-19 vaccination, maternal vaccination provides transplacentally transferred passive binding and neutralizing SARS-CoV-2 antibodies that protect against infection during early infancy.Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support Lalitha Parameswaran, MD, MPH, Pfizer: Grant/Research Support Richard M. Novak, MD, Moderna: Advisor/Consultant Rebecca C. Brady, MD, AztraZeneca: Grant/Research Support|PATH: Grant/Research Support|Pfizer: Grant/Research Support Bryan J. Berube, PhD, HDT Bio Corp.: Author on patents|HDT Bio Corp.: Salary|HDT Bio Corp.: Ownership Interest Barbra A. Richardson, PhD, Gilead Sciences: Advisor/Consultant Kathy M. Neuzil, MD, MPH, NIH: Grant/Research Support|Pfizer: Grant/Research Support Elizabeth R. Brown, ScD, Merck: Advisor/Consultant


Current data on infectious complications of chimeric antigen receptor (CAR) T-cell therapy are limited to single center retrospective cohort studies. Presented here is a subset of patients from a multicenter retrospective cohort study including recipients of CAR T-cell therapy at Duke University, University of North Carolina at Chapel Hill, and Stanford University.In a retrospective cohort of 66 patients who received CD19 CAR T-cell therapy Duke University between January 1, 2018 and August 31, 2021 rates and characteristics of bacterial, viral, and fungal infections within the first year after CAR T-cell infusion are described. Demographic, baseline clinical, and outcome variables are compared between patients who developed infection and those who did not.Forty-nine total infections occurred in 29 (43.9%) patients within 1 year of CAR T-cell infusion. Patients who developed infection were more likely to have an underlying malignancy other than diffuse large B-cell lymphoma , and to have developed immune effector cell-associated neurotoxicity syndrome . Viral  and bacterial  pathogens predominated and infections most often involved the bloodstream  and lung .There were no statistically significant differences between rates of bacterial and viral infection based on time since CAR T-cell infusion (≤30 days vs 30 – 90 days vs >90 days), though fungal infections only occurred after 90 days in patients with relapse of their underlying disease.Infectious complications after CAR T-cell therapy are common within the first year of infusion. Bacterial and viral infections predominate while fungal infections are rare and occurred only in patients with relapsed disease.Melody Smith, MD, MS, BMS: Advisor/Consultant Krista Rowe-Nichols, RN, MSN, AOCNS, Bristol Myers Squibb: Advisor/Consultant|Kite Pharmaceuticals: Advisor/Consultant|Kite Pharmaceuticals: Speaker Bureau Christopher Kelsey, MD, Colgate-Palmolive: Expert Testimony|Johnson and Johnson: Expert Testimony Taewoong Choi, MD, Janssen biotech: Honoraria Matthew McKinney, MD, ADC Therapeutics: Advisor/Consultant|ADC Therapeutics: Honoraria|Beigene: Grant/Research Support|Beigene: Honoraria|Epizyme: Advisor/Consultant|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|Genentech: Honoraria|Gilead/Kite: Advisor/Consultant|Gilead/Kite: Honoraria|Incyte: Grant/Research Support|Novartis: Advisor/Consultant|Seagen, Inc.: Advisor/Consultant|Takeda: Advisor/Consultant|TG therapeutics: Advisor/Consultant


P. aeruginosa (PSA) and A. baumannii-calcoaceticus complex (ABC) as part of the SENTRY Antimicrobial Surveillance Program.Cefiderocol (CFDC) is a siderophore-conjugated cephalosporin with activity against Gram-negative bacteria. CFDC and comparator activities were evaluated against resistant and molecularly characterized Acinetobacter spp. (979 ABC) were consecutively collected from 64 US sites in 2020–2022. Susceptibility testing was performed by broth microdilution and CFDC testing used iron-depleted media. FDA and CLSI breakpoints were used for CFDC. CLSI criteria were applied to comparators, except for imipenem-relebactam . Isolates with a resistance phenotype to ≥ 3 classes were defined as multidrug resistant (MDR). ABC and PSA with imipenem and/or meropenem (MER) MICs ≥ 4 μg/mL or ceftazidime (CAZ) and/or cefepime MICs ≥ 16 μg/mL were subjected to genome sequencing for screening of acquired carbapenemase genes.3,384 PSA and 1,186 50/90, 0.12/0.5 μg/mL) that did meet the MIC screening criteria and against those that did not . CFDC also had similar MIC50 values (0.12 μg/mL) against the MDR and carbapenemase-positive PSA populations, whereas other agents had compromised activity. 47.3% (463/979) of ABC met the MIC screening criteria, while 37.1% (363/979) had an MDR phenotype, and 28.4% carried carbapenemase genes. In general, CFDC, IMR, meropenem-vaborbactam, colistin (COL), MER, ceftazidime, and CAZ had activity against ABC that did not meet the MIC screening criteria, but only CFDC  and COL were active against the resistant ABC subsets.31.3%  and 14.7%  of PSA met the MIC screening criteria for molecular characterization and showed an MDR phenotype, respectively (Table). Carbapenemase genes were detected in 10 PSA (< 1%). CFDC had similar MICs against PSA (MICMany PSA had a MDR phenotype but acquired carbapenemase genes remained rare in this subset. Resistance and presence of carbapenemase genes were high in ABC. CFDC showed potent activity against PSA and ABC subsets in US hospitals, including across resistant and molecularly characterized subsets, where treatment options are limited.Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Cory Hubler, BS, AbbVie: Grant/Research Support|Shionogi: Grant/Research Support Valerie Kantro, BA, AbbVie: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Dee Shortridge, PhD, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Helio S. Sader, MD, PhD, FIDSA, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


Legionella pneumonia (LP) is an uncommon, yet severe pneumonia in cancer patients, but its clinical features are scarcely studied in contemporary cohorts. Therefore, this study aimed to characterize the clinical manifestations, therapy, and outcomes of LP in contemporary cancer patients.Legionella urine antigen and/or culture from sputum, tracheal aspirate, or bronchoalveolar lavage. Species identification was achieved by Matrix-assisted laser desorption ionization–time-of-flight mass spectrometry or 16S rRNA. Independent predictors of 30-day mortality after LP diagnosis were determined using multivariable logistic regression analysis.We identified cancer patients with LP at MD Anderson Cancer Center in 2009-2021. LP was diagnosed using Table 1.We identified 64 LP patients; of which 47 (73%) were caused by Legionella pneumophila and 17 (27%) by Legionella non-pneumophila . Most patients (66%) had hematological malignancy, and 31% had a history of hematopoietic stem cell transplantation (HSCT). Lymphopenia (< 1000 cells/µl) was common (75%). Twenty patients (31%) had lung coinfections, especially those with a history of HSCT . A total of 30 co-pathogens were isolated, with Gram-negative bacteria, cytomegalovirus, and respiratory viruses  being the most common co-pathogens . Twenty-five patients (39%) had hyponatremia and 17 (27%) had acute kidney injury. Most patients (64%) had bilateral lung involvement. All but one patient received appropriate antibiotics at the onset of LP. Thirty-day mortality of LP was 23% (Table 1). Independent predictors of 30-day mortality were hyponatremia , bilateral lung involvement , and Sequential Organ Failure Assessment (SOFA) score ≥5 .Dimitrios P. Kontoyiannis, MD, MS, ScD, PhD, AbbVie: Board Member|Astellas: Grant/Research Support|Cidara: Board Member|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Scynexis/MSGERC: Board Member


Pseudomonas aeruginosa producing serine- and metallo-β-lactamases. Cefepime-taniborbactam (FTB) was superior to meropenem (MEM) for the primary composite endpoint of microbiologic and clinical success at test of cure (TOC) in adults with cUTI in the CERTAIN-1 study (NCT03840148). We assessed outcomes in subsets defined by baseline pathogen resistance phenotype and genotype.Taniborbactam is an investigational β-lactamase inhibitor that restores cefepime (FEP) activity against FEP-, carbapenem-, and multidrug-resistant Enterobacterales and P. aeruginosa at ≥105 CFU/mL in urine at study entry against which at least 1 study drug had activity ). Phenotypic subsets included FEP-, multidrug-, and/or carbapenem resistance. Genotypic subsets included carriage of ESBL, extended-spectrum AmpC, plasmidic AmpC, and/or carbapenemase genes.Composite, microbiologic and clinical responses at TOC were assessed in the extended microbiologic intent-to-treat (microITT) population . FTB achieved composite success in 7/8 patients with carbapenem-resistant Enterobacterales and in 8/9 patients with Enterobacterales producing a carbapenemase . FTB achieved composite success in 8/16 patients  with FTB demonstrated efficacy in cUTI patients infected with cefepime-, multidrug-, and carbapenem-resistant pathogens and pathogens carrying ESBL, AmpC, and carbapenemase genes. Rates of success at TOC in each resistance subset were similar to or higher than those overall. These results are consistent with the ability of taniborbactam to restore cefepime activity against cefepime-, multidrug-, and carbapenem-resistant gram-negative pathogens producing serine and metallo-β-lactamases in nonclinical studies.Greg Moeck, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder Leanne Gasink, MD, MSCE, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|CSL Behring: Advisor/Consultant|CSL Behring: Consulting fees|Everest Medicines: Grant/Research Support|Evopint Biosciences: Advisor/Consultant|Evopint Biosciences: Consulting fees|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|LBG Consulting, LLC: Principal|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Consulting fees|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Consulting fees|Vera Therapeutics: Advisor/Consultant|Vera Therapeutics: Consulting fees Mary Beth Dorr, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Merck and Co.: Shareholder|Pfizer: Shareholder|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder Hongzi Chen, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee|Venatorx Pharmaceuticals, Inc.: Stocks/Bonds Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Florian Wagenlehner, MD, Achaogen: Advisory Board member, study participation|Astellas: Honoraria|AstraZeneca: Honoraria|AstraZeneca: Advisory Board member|Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Bionorica: Honoraria|Bionorica: Meeting/travel support, study participation|Deutsches Zentrum für Infektionsforschung (DZIF): Study participation|Enteris BioPharma: Study participation|Everest Medicines: Grant/Research Support|German S3 guideline Urinary tract infections: Board Member|Glaxo Smith Kline: Advisor/Consultant|Glaxo Smith Kline: Honoraria|Glaxo Smith Kline: Consulting fees, meeting/travel support, advisory board member, principal investigator in a GSK-sponsored study|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Guidelines European Association of Urology: Infections in Urology: Board Member|Helperby Therapeutics: Study participation|Janssen: Honoraria|Janssen: Advisory Board member|Klosterfrau: Honoraria|LeoPharma: Advisory Board member|MerLion: Advisory Board member|MIP Pharma: Honoraria|MSD: Advisory Board member|OM Pharma/Vifor Pharma: Advisory Board member, study participation|OM-Pharma: Honoraria|Pfizer: Honoraria|Pfizer: Advisory Board member|RosenPharma: Advisory Board member|Shionogi: Advisory Board member, study participation|Speaker research group German research foundation (DFG) Bacterial Renal Infections and Defense (FOR 5427): Study participation|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Consulting fees|University Hospital Giessen and Marburg GmbH, and Justus Liebig University, Germany: Employee|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Consulting fees, Advisory Board member Tim Henkel, MD, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Employee, consulting fees, shareholder Paul McGovern, MD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Paratek Pharmaceuticals: Shareholder|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder


Clostridioides difficile infection (rCDI) substantially diminishes patients’ health-related quality of life (HRQL). The gut microbiome is known to play an important role in rCDI, but little is known about its relationship with HRQL. In this study, we assessed the relationship between the gut microbiome and HRQL in patients with rCDI from REBYOTA’s  phase 3 PUNCH CD3 trial (NCT03244644).Recurrence of C. difficile Quality of Life Survey (Cdiff32) via its total score and physical, mental, and social domain scores .HRQL and relative abundance  of gut microbiota at the class level were collected at baseline and weeks 1, 4, and 8. The Microbiome Health Index , defined as (Bacteroidia + Clostridia) / (Gammaproteobacteria + Bacilli), was analyzed using log transformation and as a binary indicator with MHI > 7.2 indicating a healthy microbiome. HRQL was measured using the disease-specific Correlations between microbiota data  and Cdiff32 scores were estimated. Associations of Cdiff32 scores with microbiota data and MHI > 7.2 were estimated using mixed effects analyses adjusted for baseline patient characteristics. Analyses used all available data . P-values were adjusted for multiple testing via the Benjamini-Hochberg procedure; correlations were interpreted as moderate if ≥ 0.3 and large if ≥ 0.5 .Table 1). Significant associations of microbial relative abundances and log MHI with all Cdiff32 scores were found in mixed effects analyses  (Table 2). MHI > 7.2  was associated with an improvement of 14.2 to 18.4 points in Cdiff32 scores (vs. MHI ≤ 7.2).A total of 176 out of 262 (67.2%) patients had Cdiff32 and microbiota data  in PUNCH CD3. All four Cdiff32 scores correlated positively with log MHI (∼0.6), Clostridia (∼0.5) and Bacteroidia (∼0.3), and negatively with Gammaproteobacteria (∼−0.5) and Bacilli (∼−0.3) (Our study found moderate to large and statistically significant associations between a healthy gut microbiome and improved HRQL in patients with rCDI.Paul Feuerstadt, MD, FACG, AGAF, Ferring/Rebiotix Pharmaceuticals: Advisor/Consultant|Ferring/Rebiotix Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Seres Therapeutics: Advisor/Consultant|Seres Therapeutics: Grant/Research Support|Takeda Pharmaceuticals: Advisor/Consultant Ken Blount, PhD, Ferring Pharmaceuticals: Employee Amy Guo, PhD, Ferring Pharmaceuticals: Employee Min Yang, MD, PhD, Analysis Group, Inc.: I am an employee of Analysis Group, Inc., which has received consulting fees from Ferring for the conduct of this study. Viviana García-Horton, PhD, Analysis Group, Inc.: I am an employee of Analysis Group, Inc., which has received consulting fees from Ferring for the conduct of this study. Mirko Fillbrunn, PhD, Analysis Group, Inc.: I am an employee of Analysis Group, Inc., which has received consulting fees from Ferring for the conduct of this study. Glenn S. Tillotson, PhD, Dynavax: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Peggy Lillis Foundation: Honoraria|Spero Therapeutics: Advisor/Consultant Yipeng Gao, PhD, Merck and Co.: Grant/Research Support Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|Ferring: Advisor/Consultant|Paratek: Grant/Research Support


Older individuals have high rates of seasonal influenza-related hospitalizations and deaths. For this population, enhanced vaccines have been designed to mitigate the effect of age-related immunosenescence by providing higher immunogenicity and increased relative vaccine effectiveness (rVE) compared with standard vaccines. The objective of this review is to assess the assumptions taken in published cost-effectiveness analyses (CEA) and analyze the results and decision-making implications on enhanced influenza vaccines for older adults (65yrs+).A targeted literature review was performed to identify economic evaluations of two enhanced vaccines in older individuals: adjuvanted trivalent/quadrivalent vaccine (aTIV/aQIV) and high-dose trivalent/quadrivalent vaccine (HD-TIV/HD-QIV). PubMed was searched for publications in March 2023, limited to studies from the past 10 years and prioritizing English-language publications. Papers describing CEAs were prioritized for inclusion. Congress presentations that included CEA were included based on expert knowledge and ability to retrieve poster and/or oral presentations.31 CEAs comparing enhanced vaccines to standard-dose trivalent/quadrivalent vaccines (SD-TIV/SD-QIV) were analyzed, 15 comparing HD-TIV/HD-QIV with SD-TIV/SD-QIV and 17 comparing aTIV/aQIV with SD-TIV/SD-QIV. Enhanced vaccines were consistently cost-effective vs SD-TIV/SD-QIVs, despite diversity of model types, vaccine acquisition price, rVE estimate used, influenza-associated costs, and study perspective used. CEA results were inconsistent when the enhanced vaccines were compared with each other. The key driver of the latter was the different rVE approaches considered. While observational studies on vaccine effectiveness used in CEAs suggest effectiveness comparability between aTIV/aQIV and HD-TIV/HD-QIV, most studies show a lower acquisition price for aTIV/aQIV.Enhanced vaccines for older adults are more efficient compared to standard-dose vaccines. The adjuvanted influenza vaccine could reduce overall costs compared to high-dose vaccine if it has a lower acquisition price.David Fisman, CSL Seqirus: Advisor/Consultant Norberto Giglio, CSL Seqirus Inc.: Advisor/Consultant Sergio Márquez-Peláez, MD, CSL Seqirus Inc.: Advisor/Consultant Van Nguyen, PhD, CSL Seqirus Inc.: Advisor/Consultant|CSL Seqirus Inc.: Advisor/Consultant|CSL Seqirus Inc.: Honoraria Maarten Postma, PhD, CSL Seqirus Inc.: Advisor/Consultant|CSL Seqirus Inc.: Advisor/Consultant|CSL Seqirus Inc.: Honoraria Andrea Pugliese, PhD, CSL Seqirus Inc.: Advisor/Consultant Jesús Ruiz-Aragón, MD, CSL Seqirus Inc.: Advisor/Consultant Analia urueña, n/a, CSL Seqirus Inc.: Advisor/Consultant|CSL Seqirus Inc.: Advisor/Consultant Joaquin F. Mould-Quevedo, PhD, CSL Seqirus Inc.: Employee|CSL Seqirus Inc.: Employee|CSL Seqirus Inc.: Stocks/Bonds|CSL Seqirus Inc.: Stocks/Bonds


Photosynthetic organisms, including plants and algae, possess a remarkable ability to harness carbon dioxide and solar energy, enabling them to produce a vast array of complex compounds such as phenolic acids , terpeneTaparia et al., developed modular CRISPR/Cas9 constructs for the model diatom Phaeodactylum tricornutum that allow the multiplexed targeting and creation of marker-free genome-edited lines. The system was used to knock out StLDP, the gene encoding Stramenopile-type lipid droplet protein essential for lipid droplet biogenesis . Li et al. produced carotenoids in rice (Oryza sativa) endosperm by overexpressing rice GOLDEN2-LIKE (OsGLK) transcription factor and OsGLK with three other carotenogenic genes, tHMG1 (truncated Saccharomyces cerevisiae 3-hydroxy-3-methylglutaryl-CoA reductase), ZmPSY1 (Zea mays L. phytoene synthase), and PaCrtI (Pantoea ananatis phytoene desaturase), to improve the nutritional composition of rice . In perennial herbs, Wang et al. identified physiological/biochemical indicators, such as enzyme activities of glutamine synthetase (GS), glutamate synthase (GLS), glutamate dehydrogenase (GDH), peroxidase (POD), and catalase (CAT), were related to biomass accumulation in Salvia miltiorrhiza .This Research Topic includes eight original research and two review articles, with a special focus on the metabolic engineering of valuable biomaterials in plants and algae. ogenesis Figure 1Z-YD: Funding acquisition, Resources, Visualization, Writing – original draft, Writing – review & editing. WB: Writing – review & editing. GK: Writing – review & editing. IK-G: Writing – review & editing. X-HY: Writing – review & editing. AZ: Writing – review & editing. KZ: Writing – review & editing.