Pseudomonas aeruginosa (PA) is an important nosocomial pathogen. In 2023, tobramycin (TM) susceptibility breakpoints for PA were lowered (from ≤4 to ≤1 µg/mL) by the Clinical and Laboratory Standards Institute (CLSI). The purpose of this study was to evaluate whether this change will result in an increase in the proportion of PA clinical isolates that are considered multidrug-resistant (MDR).PA clinical isolates were obtained from patients evaluated at hospitals across Canada (January 2016 to December 2021) as part of an ongoing national surveillance study (CANWARD). Susceptibility testing was carried out using custom broth microdilution panels. MICs were interpreted using current (2023) CLSI breakpoints, with the exception of TM (interpreted using the 2022 and 2023 breakpoints). MDR PA were defined as isolates testing not susceptible at least three of the following: ceftazidime, ciprofloxacin, meropenem, piperacillin-tazobactam, and TM (assessed with both the 2022 and 2023 CLSI breakpoints).1649 PA isolates were included in this study. The proportion of isolates testing susceptible to TM using the 2022 (S ≤4 µg/mL) and 2023 (S ≤1 µg/mL) CLSI breakpoints were 93.6% and 84.8%, respectively. Overall, 21.6% (356/1649) and 22.7% (374/1649) of PA isolates were MDR, using the 2022 and 2023 CLSI breakpoints. Below, the in vitro activities of common antipseudomonal antimicrobials versus PA isolates from this study  are presented.In this dataset, the proportion of MDR PA isolates was minimally altered by a recent change to the CLSI TM susceptibility breakpoints. A reduction in the proportion of PA isolates that were susceptible to TM using the new breakpoints was most pronounced for the MDR subset.George Zhanel, PhD, Avir: Grant/Research Support|Iterum: Grant/Research Support|Merck: Grant/Research Support|Orimed: Grant/Research Support|Paladin Labs: Grant/Research Support|Pfizer: Grant/Research Support|Verity: Grant/Research Support|Zambon: Grant/Research Support


Staphylococcus aureus (methicillin-resistant [MRSA] and methicillin-susceptible [MSSA]), Streptococcus pyogenes (SP), Enterococcus faecalis (EF), and Gram-negative organisms, including Escherichia coli (EC) and Pseudomonas aeruginosa (PSA). In this study, the in vitro susceptibilities of DLX and comparator fluoroquinolones (FQ), levofloxacin (LEV), moxifloxacin (MOX), and ciprofloxacin (CIP) were determined for US clinical isolates.Delafloxacin (DLX) is a broad-spectrum fluoroquinolone antibacterial approved in the USA in 2017 for treatment of acute bacterial skin and skin structure infection (ABSSSI). DLX is indicated to treat ABSSSI caused by multiple pathogens, including Isolates from SSSI were consecutively collected at 77 US medical centers participating in the SENTRY Surveillance Program (2017–2022). Sites submitted 1 isolate per patient per infection episode. Isolate identification was determined at each site and confirmed using MALDI-TOF MS at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology. FDA interpretative criteria were used for DLX; CLSI (2023) criteria were applied to comparators. MOX was tested against Gram-positive and CIP against Gram negative species.The most common organisms were SA , including 4,967 MSSA and 3,573 MRSA (58%), PSA , EC (n=840), and SP (n=781). Susceptibilities (%S) by year to DLX, LEV, and MOX are shown in the Table. For MRSA, %S to DLX increased from 81.0% to 87.0% over 6 years, while LEV declined from 36.5% to 34.7% and MOX from 36.8% to 34.7%. SP %S to all FQ was stable at 99.7–100%. EF %S to DLX increased from 64.6% to 80.3% with smaller increases for LEV (5%) and MOX (3%). EC %S to DLX increased from 59.4% to 74.4%, and also increased for LEV (66.7% to 75.2%) and CIP (61.8 to 76.0%). PSA %S to DLX increased from 64.9% to 73.7%, as did %S to LEV (69.5% to 74.7%). The PSA %S to CIP declined slightly from 82.5% to 79.8%.An increase in %S to FQs was observed for most ABSSSI pathogens, including EC, EF, and PSA. MRSA %S to DLX increased from 2017 to 2022, while %S to LEV and MOX declined. The decreased use of FQs may have led to improved susceptibility for DLX and as such it may be a good treatment option for ABSSSI.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 Dee Shortridge, PhD, Melinta: 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 Mike Huband, BS, Melinta: 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


Correction: BMC Women’s Health (2022) 22:1 10.1186/s12905-022-01609-0‘College of Medicine, King Abdullah Bin Abdul Aziz Hospital, Princess Nourah Bint Abdul Rahman University, Riyadh, Saudi Arabia.’ but should have been ‘Department of Clinical sciences, College of Medicine, Princess Nourah bint Abdul Rahman University, King Abdullah Bin Abdulaziz University Hospital, Riyadh, Saudi Arabia.’Following publication of the original article [1], in this article the affiliation details for Reem Alharbi were incorrectly given as The original article has been corrected.


Children with underlying medical conditions are at higher risk for developing severe influenza illness. Annual influenza vaccination is recommended for all children ≥ 6 months and can protect against severe influenza. Limited studies have examined if vaccine effectiveness (VE) against influenza illness differs in children with underlying conditions compared to those without.We used a test-negative design to assess VE against laboratory-confirmed influenza-associated ED visits or hospitalizations in children 6 months-17 years of age with and without underlying conditions. Children were enrolled at 7 medical centers within NVSN, a prospective respiratory viral surveillance platform in 7 states, during each influenza season from 2015-2016 through 2019-2020. Influenza vaccination was assessed using documentation from state registries or providers. Underlying conditions were abstracted from medical records. We estimated VE by comparing the odds of vaccination ≥ 14 days prior to symptom onset in case patients with influenza compared to test-negative control patients with non-influenza respiratory illness. VE was adjusted for age, study site, and calendar time.A total of 15,739 children were included . Among cases, 48% had an underlying condition, and about half (51%) of those conditions were respiratory (Table). Cases with underlying conditions were more likely to be hospitalized (53%) compared to cases without (26%). Among patients with underlying conditions, 38% of cases and 56% of controls were vaccinated . Overall  VE was 48%  among children with underlying conditions and 57%  among children without. VE against hospitalization was 46%  among children with underlying medical conditions and 59%  among children without.Vaccination reduced the odds of influenza illness in children with and without underlying conditions. VE was similar in children regardless of presence of conditions. Vaccination was sub-optimal in children with and without underlying conditions and continued efforts are needed to improve vaccination uptake in all children ≥ 6 months.Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support John V. Williams, MD, Merck: Grant/Research Support|Quidel: Board Member 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 Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant 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 Geoffrey A. Weinberg, MD, Merck & Co: Honoraria Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support


E. coli BSI.Several randomized controlled trials (RCT) have shown that short-course (∼7 days) antibiotic treatment is non-inferior to longer antibiotic courses (∼14 days) in patients with uncomplicated bloodstream infection (BSI) with mostly susceptible Gram-negative bacteria. Here, we evaluate short-course therapy in ceftriaxone-resistant E. coli BSI at 14 United States hospitals between November 2020 and April 2021, each patient with ceftriaxone-R E. coli BSI, and the next consecutive patient with a ceftriaxone-S E. coli BSI was included. Patients who received 5-8 days (“short”) or 9-21 days (“long”) of antibiotics were included in this analysis. Patients who died before day 9 were excluded. Primary outcome was a Desirability of Outcome Ranking  based on disposition at day 30 after collection of the index blood culture. Ceftriaxone susceptibility was centrally determined using broth microdilution for all bacterial isolates.In a prospective cohort of 300 patients with Desirability of outcome ranking (DOOR) categoriesOf 300 patients in the original cohort, 227 were included; 44 patients  received short , and 183 patients  received long duration . Age , sex , and Charlson comorbidity index  were similar between groups. Notably, almost all patients  with solid organ or stem cell transplant were in the long duration group. The median Pitt bacteremia score was 2 (IQR 1-3) in the short duration group vs. 1 (IQR 0-3) in the long duration group (Wilcoxon Rank Sum p=0.07). DOOR outcomes were similar in both groups . Numerically more patients in the ceftriaxone-resistant group on short treatment were in category 3; 4/20 (20%) vs 5/87 (6%) in the long duration group. These 4 patients all had unsuccessful discharge combined with renal failure (n=2), and/or lack of clinical response (n=3).Desirability of outcome ranking (DOOR) analysesShown are the percentages of patients in each group with a specific DOOR category outcome.E. coli BSI. Further studies are needed to determine whether short-course therapy is appropriate for ceftriaxone-R E. coli BSI.Short duration of therapy was less frequently used than long duration of therapy in this prospective cohort of Yohei Doi, MD, PHD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Owen Albin, MD, Charles River Laboratories: Advisor/Consultant|Shionogi: Advisor/Consultant Elie Saade, MD, MPH, FIDSA, Envision Pharma: Speaker, Presenter|Johnson and Johnson: Speaker, Travel, Lodging|Protein Sciences Corp: Grant/Research Support|Sanofi Pasteur: Speaker, Travel and Lodging Loren G. Miller, MD MPH, ContraFect: Grant/Research Support|GSK: Grant/Research Support|Medline: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBiome: Grant/Research Support Martin Krsak, MD, MSc, FASAM, AbbVie: Grant/Research Support|Melinta: Honoraria W. Charles Huskins, MD, MSc, ADMA Biologics: Advisor/Consultant|Bristol Myers Squibb: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds|Zimmer Biomet: 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 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 David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant


CYP2C19; however, such information is limited for the pediatric population.Voriconazole pharmacokinetics (PK) are known to be affected by genetic polymorphisms of drug-metabolizing enzymes such as CYP2C19 genotypes was assessed by whole genome genotyping and defined as follows: *1/*1, *1/*17: normal metabolizer [NM], *1/*2, *1/*3: intermediate metabolizer [IM], and *2/*2, *2/*3, *3/*3: poor metabolizer [PM]. Population PK analysis was performed using Phoenix NLME (v8.3.0). The voriconazole serum concentration profile was described by a two-compartment model with first-order absorption, mixed linear and nonlinear (Michaelis-Menten) elimination, and allometric scaling, as described in previous reports. Covariates were examined using a stepwise method and included to the model when the objective function [-2LL (log-likelihood)] by the maximum likelihood method decreased significantly .This was a single-center population PK study. Information regarding patient background, laboratory test data, voriconazole serum concentration, voriconazole dosing status, and concurrent medications were extracted from electronic medical records. CYP2C19 genotypes were NM in 22 patients, IM in 27 patients, and PM in 11 patients. Underlying diseases included 40 patients with malignancy (66.7%), 18 patients with inborn errors of immunity (30.0%), and 2 patients with other comorbidities. Among the CYP2C19 phenotypes, PM was predicted to show complete inhibition  = 100%; Vmax= 0). The estimated parameters of Vmax,inh were +0.8 higher in patients with γ-GTP Grade 2 or higher compared with those with Grade 1 or lower. The increase in Vmax,inh was shown to be caused by an increase in C-reactive protein (CRP); the estimated parameters of Vmax,inh were +2.7 higher when CRP was 2.0 mg/dL or higher.Voriconazole concentration data were available from 60 patients with a median age of 5.3 years. In total, 526 measurements were available for population PK analysis. The phenotypes predicted from CYP2C19 genetic polymorphisms (PM), γ-GTP, and CRP affect Vmax,inh of voriconazole in Japanese children with malignancy or inborn errors in immunityKensuke Shoji, MD, PhD, AstraZeneca K.K.: Honoraria|Gilead Sciences, Inc.: Honoraria|KYORIN Pharmaceutical Co.,Ltd.: Honoraria|Meiji Seika Pharma Co., Ltd.: Honoraria|Nippon Becton Dickinson Company, Ltd.: Honoraria|Novartis Pharma Co., Ltd.: Honoraria|Viatrs, Inc: Honoraria Motohiro Kato, MD, PhD, Amgen: Honoraria|Bayer: Honoraria|Chugai Pharm: Honoraria|CSL Behring: Honoraria|Daiichi Sankyo: Grant/Research Support|Konica Minolta REALM: Honoraria|Kyowa KIRIN: Honoraria|Maruho: Honoraria|Nippon Shinyaku: Honoraria|Novartis: Honoraria|Ohara Pharma: Honoraria|Riken Genesis: Honoraria|Sanofi: Honoraria|Sumitomo Pharma: Honoraria|Takeda Pharma: Honoraria Toshinao Kawai, MD, PhD, Novartis Pharmaceuticals: Honoraria|Takeda Pharmaceutical Company: Advisor/Consultant|Takeda Pharmaceutical Company: Honoraria Hidefumi Nakamura, MD, PhD, Asahi Kasei Corporation: Stocks/Bonds|Bristol Myers Squibb Company: Honoraria|Chugai Pharmaceutical Co., Ltd.: Honoraria|Daiichi Sankyo Company, Ltd.: Advisor/Consultant|Pfizer Global Supply Japan Inc.: Advisor/Consultant|Pfizer R&D Japan G.K.: Advisor/Consultant|Sato Pharmaceutical Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Honoraria|Taisho Pharmaceutical Holdings Co., Ltd: Advisor/Consultant Isao Miyairi, MD, PhD, Astrazeneca: Honoraria|Mitsubishi-Tanabe: Honoraria|Pfeizer: Honoraria|Sanofi: Advisor/Consultant|Shionogi: Honoraria Taisei Mushiroda, PhD, Zenyaku Kogyo Company, Limited: Grant/Research Support


Clostridioides difficile infection (rCDI) in adults. As the first FDA-approved microbiota product, this new agent may pose challenges in administration, particularly with Infectious Disease (ID) or other specialties not typically providing rectally administered therapies. As part of an ongoing real-world study of RBL, the purpose of this study is to develop and report a simple protocol for the administration of RBL in clinical practice.Fecal Microbiota, live-jslm (RBL) is a rectally administered, pre-packaged, live biotherapeutic approved in November 2022 for the prevention of recurrence of We reviewed electronic health records, administration records and internal databases for patients receiving RBL since February 2023. Records were reviewed for patient demographics, setting of care, time from order to treatment, logistics from order to administration and payor details.Six rCDI patients  have received RBL; 1 treated in an ID practice and the other 5 in GI practices. Following insurance approval and scheduling of the patient, RBL was ordered from the distributor and shipped to the practices in a 150mL pre-packaged frozen suspension. RBL was thawed for 24 hours and administered within 5 days. Average time from order to treatment was 18±5 days. Administration of RBL was performed by registered nurses or licensed vocational nurses. Reported RBL administration time was 5 minutes, with an additional 15 minutes for observation. Medicare (MCR) was the most common payor (71%) with traditional MCR (n=3), MCR Advantage (n=2), and one commercially insured. There have been no payor denials. Criteria for approval differed slightly between payors, but all required at least 1 prior episode of CDI. All plans required prior authorization except traditional MCR. Reimbursement was adequate for both the medication and instillation protocols.Early experience with RBL administration found more treatment by GI than ID physician practices. Authorizations were granted as expected with the administration and visit surprisingly brief and simple. RBL holds promise as a feasible office-based therapy for prevention of rCDI.Jonathan A. Rosenberg, MD, Aimmune: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant Timothy E. Ritter, MD, Abbvie: Advisor/Consultant|Ardelyx: Advisor/Consultant|Arena: Advisor/Consultant|Boehringer Ingelheim: Advisor/Consultant|Bristol Myers Squibb/Celgene: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Ferring: Advisor/Consultant|Ferring: Data Adjudication Committee|Genetech/Roche: Advisor/Consultant|Gilead: Advisor/Consultant|Intercept: Advisor/Consultant|Iterative Scopes: Expert Testimony|Iterative Scopes: Ownership Interest|Janssen: Advisor/Consultant|Nestle/Seres: Advisor/Consultant|Pfizer: Advisor/Consultant|Prometheus: Advisor/Consultant|Rebiotix: Data Adjudication Committee|Sanofi: Advisor/Consultant|Takeda Pharmaceuticals: Advisor/Consultant Lucinda J. Van Anglen, PharmD, ADMA Biologics, Inc.: Grant/Research Support|Ferring Pharmaceuticals: Grant/Research Support|Novartis: Grant/Research Support|Octapharma: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support Amy Guo, PhD, Ferring Pharmaceuticals: Employee Mielad Moosapanah, PharmD, 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. Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|Ferring: Advisor/Consultant|Paratek: Grant/Research Support


CAB+RPV LA is the first complete long-acting regimen for virologically suppressed people with HIV (PWH) and demonstrated non-inferiority to standard of care antiretroviral regimens in the Phase 3/3b trials FLAIR, ATLAS, ATLAS-2M, and SOLAR. Implementation of a provider administered regimen poses new delivery challenges and real-world evidence is essential to understand utilization and clinical outcomes. The BEYOND study describes the demographics and month 6 (M6) clinical outcomes of patients initiating CAB+RPV LA in the US.BEYOND is a 2-year observational real-world study of utilization, outcomes, and experience of people with HIV (PWH) initiating CAB+RPV LA (monthly or every 2 months) across 30 US sites. Healthcare providers (HCPs) completed an electronic case report form (eCRF) at baseline and M6 to capture demographics, medical and treatment history, and clinical outcomes.A total of 308 PWH (Table 1) were enrolled between Sep 2021- Jul 2022 and initiated on CAB+RPV LA. As of the data cut-off for this analysis (Jan 2023), 248 PWH had reached M6 of which 25 were reported as having discontinued CAB+RPV LA. The most common HCP reported primary reason for initiating CAB+RPV LA was patient request (41%). At M6, of the 803 injections given after the first injections, 667 (83%) occurred within +/-7 days of the target treatment date and 136 (17%) were outside the target treatment window (median 4 days outside). Of 1087 total injections expected, 44 (4%) were missed; of these, 3 (7%) used oral CAB+RPV and 19 (44%) used other oral regimens to cover missed injections. Of 189 PWH with viral load data available at both baseline and M6 (Table 2), 181 (96%) had viral loads of < 50 copies/mL. Confirmed virologic failure (CVF) occurred in 4 (1.6%), including 1 who had missed injections. Resistance was reported in 2 PWH. Discontinuations due to drug intolerance/injection site reactions were reported in 6 PWH.The M6 results from real world initiation of CAB+RPV LA in the US are consistent with the Phase 3/3b clinical trials with high rates of virologic suppression, low rates of CVFs and treatment emergent resistance, and low rates of discontinuation due to drug intolerance.Gary I. Sinclair, MD, Abbvie: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Thera: Advisor/Consultant|Thera: Grant/Research Support|Thera: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Michael Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Alexandra Dretler, MD, Gilead: Stocks/Bonds|Johnson and Johnson: Stocks/Bonds|Pfizer: Stocks/Bonds Stefan Schneider, MD, ViiV Healthcare: Grant/Research Support Catherine K. Schubert, PharmD, GSK: Stocks/Bonds|ViiV Healthcare: Employee of ViiV Healthcare Deanna Merrill, PharmD, MBA, AAHIVP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Cindy Garris, MS, GSK: Stocks/Bonds|ViiV Healthcare: Employee


Urinary tract infections (UTIs) are the most common bacterial infections in women. Antibiotics (ABX) are available to treat uncomplicated UTI (uUTI), but 10–30% of patients experience treatment failure (TF). We assessed uUTI-related healthcare costs among uUTI patients with/without oral ABX TF in the United States (US).Figure 1). Eligible patients were female, ≥ 18 years, with a uUTI diagnosis identified in an outpatient setting, ≥ 1 oral ABX prescription within ± 5 days of diagnosis, and ≥ 1 year pre- and post-index follow-up. ABX prescription claim was designated index date.This retrospective cohort study used Optum’s de-identified Clinformatics Data Mart Database from October 1, 2015 to September 30, 2021 : ≥ 1 additional oral ABX prescription(s); intravenous ABX; or a primary diagnosis of UTI in an acute care setting (emergency room or inpatient). uUTI-related costs (US$) were assessed during the follow-up period.Figure 2]).In total, 238,335 patients were identified, of whom 29,333 (12.3%) had evidence of TF. Total uUTI-related costs were higher for patients with TF vs those without . By contrast, outpatient hospital visits accounted for < 20% of all outpatient costs for patients without TF; in these patients, office costs were the greatest contributor (31.9%).uUTI-related outpatient costs were higher for patients with vs without TF . Patients with TF had higher outpatient costs across all categories, with outpatient hospital visits contributing 45.6% of costs . Mean (SD) pharmacy costs for patients with vs without TF were $28 ($26) and $13 ($16), respectively (p < 0.0001).Patients with ABX TF for uUTI had significantly higher costs  than patients without TF. This finding highlights the importance of appropriate empiric ABX selection to reduce the likelihood of TF in uUTI and its economic impact.Meg Franklin, PharmaD, PhD, Franklin Pharmaceutical Consulting: Owner and President|Franklin Pharmaceutical Consulting: Ownership Interest|GSK: Grant/Research Support|PRECISIONheor: Contractor Maia R. Emden, BA, GSK: Grant/Research Support|PRECISIONheor: Employee Sharon Kautz, BS, GSK: Grant/Research Support|PRECISIONheor: Employee Anh Thy H. Nguyen, MSPH, GSK: Grant/Research Support|PRECISIONheor: Employee Naomi C. Sacks, PhD, GSK: Grant/Research Support|PRECISIONheor: Employee Shinyoung Ju, MS, GSK: Employee|GSK: Stocks/Bonds Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds Ashish V. Joshi, PhD, GSK: Employee|GSK: Stocks/Bonds Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds


Respiratory viruses are a substantial cause of hospitalization in infants and young children; less is known about their contribution to ARI-associated hospitalizations in children ≥ 5 years of age.We conducted prospective, active surveillance among children ages 5–17 years hospitalized for acute respiratory illness (ARI) at 7 pediatric medical institutions comprising the New Vaccine Surveillance Network (NVSN) during December 1, 2016 through April 1, 2020. Children hospitalized for fever and/or respiratory symptoms were consented for enrollment. Demographic and clinical data were collected through parent/guardian interviews and chart abstraction. Mid-turbinate nasal and/or throat specimens were collected and tested using molecular methods for respiratory syncytial virus (RSV), influenza, parainfluenza viruses 1–4 (PIV), human metapneumovirus (HMPV), rhinovirus/enterovirus (RV/EV), adenovirus (AdV), and seasonal coronaviruses (CoV).Of 6,992 eligible children, 4,011 (57%) were enrolled and 3,953 (99%) had respiratory specimens obtained. Median age of enrolled children was 8.9 years , 55% were male, 38% were non-Hispanic White, and 76% had ≥ 1 underlying medical condition (Table). Respiratory viruses were detected in 54% of patients hospitalized with ARI: RV/EV occurred most frequently (32%), followed by influenza (11%) and RSV (5%) . Respiratory virus coinfections were detected in 133 (3%) patients. Common symptoms reported included cough, congestion/runny nose, and fever, and a majority of children experienced dyspnea and wheezing. Median length of hospitalization was 2 days ; 687 (17%) patients were admitted to an intensive care unit, of whom 119 (17%) required intubation.Figure. Detection and seasonality of respiratory viruses in hospitalized children 5–17 years, 2016–2020Respiratory viruses were detected in more than half of ARI-related hospitalizations in children aged ≥ 5 years. This multi-center, multi-year, pre-pandemic assessment provides baseline data to evaluate for possible changing epidemiology of respiratory viruses after the onset of the COVID-19 pandemic.Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria 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 Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support John V. Williams, MD, Merck: Grant/Research Support|Quidel: Board Member Geoffrey A. Weinberg, MD, Merck & Co: Honoraria 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 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 Pedro A. Piedra, MD, Ark Bioscience: Advisor/Consultant|Ark Bioscience: Grant/Research Support|GSK: Grant/Research Support|Icosavax: Advisor/Consultant|Icosavax: Grant/Research Support|Mapp Biologics: Grant/Research Support|Meissa Vaccines: Grant/Research Support|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Novavax: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Takeda: Advisor/Consultant Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support


Widespread CHG bathing to prevent infection has raised concerns about potential skin microbiome perturbations and depletion of commensal microbiota.A prospective repeated measures cross-over study in NH residents/hospital patients evaluated the impact of CHG vs routine soap bathing on the nose/skin microbiome. Participants underwent serial visits during distinct CHG and routine soap phases  involving nares, axilla, groin, and finger/hand swabs processed for MDROs, CHG concentration (skin sites only), and bacterial 16S rRNA V1-3 gene sequencing (Illumina MiSeq). Sequences were processed with DADA2 and analyzed with PhyloSeq and Vegan packages in R to calculate microbial diversity and composition.We enrolled 30 participants . Mean age was 62y, 52% female. Mean CHG concentration was 1736 µg/mL (range: 0-20000) during CHG visits vs 17.5 µg/mL (range: 0-1250) during routine soap visits. MDRO prevalence was lower during CHG visits  vs routine soap visits . 555 samples from 30 participants were adequate for microbiome analyses.CHG did not affect overall alpha diversity of microbial communities on skin , but proteobacteria were notably higher in NH vs hospital participants (P< 0.001). Because gram-negative bacteria often exhibit higher MICs to CHG than gram-positive bacteria, we assessed whether CHG concentration in NHs was associated with greater relative abundance of proteobacteria using generalized linear mixed models clustered by person. In NHs, CHG concentration was not associated with relative abundance of skin proteobacteria, although body mass index ≥30  and stool/urine incontinence were . Compared to the axilla, the groin had 35% higher relative abundance of proteobacteria (P< 0.001); fingers/hand samples had 9% lower (P=0.01).Nose/Skin Taxonomic Diversity Not Impacted by CHG BathingTimeline and alpha diversity using the Shannon Diversity Index of axilla, groin, finger/hand, and nares samples during CHG versus routine soap bathing phases. Each dot represents a sample. There were no significant differences in alpha diversity between CHG and routine soap phases.CHG bathing reduced MDRO prevalence but did not impact skin or nasal microbial alpha diversity in hospital or NH participants. Overall, NH residents had notably higher relative abundance of skin proteobacteria vs hospital patients. This finding was not associated with CHG concentration. Rather, proteobacteria appeared enriched in NH residents with obesity or incontinence.Gabrielle Gussin, MS, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product|Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Raveena D. Singh, MA, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product|Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Raheeb Saavedra, AS, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product|Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Connie Nguyen, n/a, Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Robert Pedroza, BS, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product Chase Berman, BS, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product Susan S. Huang, MD MPH, Medline Industries, Inc: Conducted studies whereby participating nursing homes and hospital patients received cleaning & antiseptic products|Xttrium Laboratories: Conducted studies where participating nursing homes and hospital patients received antiseptic products


PCR testing of clinical specimens has been associated with false-positive test results. Detection of CMV DNA by PCR in saliva and urine has been used to identify neonates with congenital CMV infection, but the frequency of false-positive PCR results is not fully known. Our objective is to describe the frequency of "false-positive" saliva and urine CMV PCR tests when performed as screening for congenital CMV infection.From 2018 to 2023, neonates were screened for CMV infection if they had abnormal clinical, laboratory, or radiographic findings, referred on the newborn hearing screen, and since 2019, on admission to the 9 neonatal intensive care units (NICU) of the Nationwide Children’s Hospital neonatal network, Columbus, OH. Pertinent demographic, clinical, audiologic, laboratory, and radiographic data were obtained and managed using REDCap. Infants who had an initial positive PCR screening test for CMV but subsequent negative PCR tests were identified.During the 6 year study period, 139 infants were diagnosed with congenital CMV infection. An additional 28 (17%) neonates tested positive for CMV DNA in saliva (n=26) or urine (n=2) but subsequent tests of urine specimens were negative for CMV. Most of the infants were tested as part of universal NICU screening (n=22), 5 had symptomatic disease, 3 referred on the newborn hearing screen, and 1 had thrombocytopenia. The infants were tested at a median (IQR) age of 3 (2-6) days. Their median (IQR) birth weight and gestational age were 2458 (1865-3360) grams and 37 (33-39) weeks, respectively. Four infants had their dried blood spot tested for CMV by PCR and were negative. 17 (77%) of 22 infants had known maternal milk exposure in the neonatal period.Neonatal saliva and/or urine screening for congenital CMV infection was associated with a “false-positive” test result in 17% of neonates who tested positive for CMV DNA by PCR. These results suggest that confirmation of a diagnosis of congenital CMV infection by PCR requires testing of multiple specimens with one of them being urine.Asuncion Mejias, MD, PhD, MsCS, Astra-Zeneca: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant Alexandra Katherine Medoro, MD, Merck: Grant/Research Support Amy Leber, PhD, Biomeriux: Grant/Research Support|BioRad: Advisor/Consultant|Cephied: Grant/Research Support|Diasorin: Grant/Research Support


In this work, the 6 CFU of P. aeruginosa. Biofilms were allowed to form over 2 days, after which e-bandages with Tegaderm™ or Tegaderm only were placed on the wound beds. Specifically, mice were randomized to one of three experimental groups (n = 7-8): 1) Tegaderm only (control); 2) non-polarized e-bandage; 3) polarized e-bandage using a wearable potentiostat. After 48 hours, animals were sacrificed and 10 mm skin biopsies containing the wound and surrounding tissue were harvested for bacterial quantification. Histopathology was performed on H&E-stained sections of wound beds from each treatment group. Blood was screened with an inflammatory cytokine panel. Wound healing  and purulence  were assessed in pre- and post-treatment wounds.5 mm skin wounds were created on the dorsal surface of Swiss-Webster mice and infected with 1010 biofilm CFUs/g (p < 0.0001) vs non-polarized controls, and 2.18 log10 CFU/g reduction (p < 0.0001) vs Tegaderm only controls . Compared to Tegaderm only, purulence reduction and wound healing were significantly higher for both non-polarized  and polarized treatment  groups, but were not significantly different from each other. Histopathology and blood inflammation panel testing showed no significant differences between groups.48 hours of polarized e-bandage treatment resulted in a mean reduction of 1.86 logP. aeruginosa in wound biofilms, representing a potential antibiotic-free strategy for the treatment of recalcitrant wound infections.An HOCl-producing e-bandage reduced Audrey N. Schuetz, MD, Merck: Advisor/Consultant 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


The publishers apologize for the error.The first author’s name is spelled incorrectly. The correct name is: Alexander Tschantz. The correct citation is: Tschantz A, Millidge B, Seth AK, Buckley CL (2023) Hybrid predictive coding: Inferring, fast and slow. PLoS Comput Biol 19(8): e1011280.


Staphylococcus aureus in clinical trials. We have developed a novel injectable scaffold-based vaccine for PJI. In this study, we evaluated vaccine immune response and bacterial burden in a murine model of PJI.There are currently no vaccines available to prevent periprosthetic joint infection (PJI) and existing vaccine platforms have failed against S. aureus-derived pathogen-associated molecular patterns (PAMPs) as described previously .Vaccines consisting of mesoporous silica rods (scaffold) and demethylated CpG (adjuvant) were prepared using S. aureus Xen29, a bioluminescent strain. Infected mice without vaccination (“Unvaccinated”) and without infection (“Uninfected”) also underwent implant insertion (n=5). Mice underwent bioluminescent imaging, collection of sera and tissue, and euthanasia with implant harvest on Day 49.Mice were either unvaccinated or vaccinated by subcutaneous scaffold injection containing different amounts of PAMP antigen: 7.5, 30, or 150 units (n=5-8 per group). Mice received a second scaffold injection on Day 14 (same dose as Day 0) as booster. Sera was collected on Day 28. For a challenge study, mice vaccinated on Days 0 and 14 with scaffold loaded with 30 U of PAMPs (“Vaccinated”) underwent implantation of a stainless-steel wire in the distal femur protruding into the joint space on Day 35 (n=8). The implant was inoculated with 1000 CFU S. aureus antibodies in a dose-dependent manner. Vaccination with Xen29 PAMPs resulted in antibodies with cross-reactivity against other S. aureus strains . Vaccinated mice had increased CD4+ and CD8+ T cells in the adjacent draining lymph node. Vaccination induced higher IgG1 and IgG2b whereas infection only increased IgG2b . Vaccinated animals had bioluminescent similar to uninfected animals by Day 45 . Vaccinated animals had significantly less implant bacteria than unvaccinated animals and 25% of vaccinated animals did not have any detectable bacteria at euthanasia .Vaccination increased anti-S. aureus antibody production in an antigen dose-dependent manner and decreased bacterial burden in a murine model of PJI.Scaffold-based vaccination increased generalized anti-David Mooney, Ph.D., Advanced Healthcare Materials: Board Member|Agnovos: Stocks/Bonds|Attivare: Stocks/Bonds|Boston Scientific: Advisor/Consultant|Cartesian Therapeutics: Advisor/Consultant|IVIVA: Stocks/Bonds|Johnson & Johnson: Advisor/Consultant|Journal of Biomedical Materials Research: Board Member|Lightning Bio: Stocks/Bonds|Lyell: Stocks/Bonds|Medicenna: Advisor/Consultant|Norvartis: Advisor/Consultant|Norvartis: Grant/Research Support|Norvartis: IP Royalties|Revela: Stocks/Bonds|Samyang: Advisor/Consultant


The COVID-19 pandemic greatly impacted the lives of people across the globe. We sought to understand how the pandemic was perceived by and impacted the care of people living with chronic respiratory diseases, such as bronchiectasis and nontuberculous mycobacterial (NTM) infections.We conducted a prospective online survey of adults with chronic lung disease collecting data on demographics, health status, and the impact of the COVID-19 pandemic on treatment, healthcare access and utilization. Participants were enrolled between 9/2021 and 3/2023. We recruited from outpatient bronchiectasis treatment centers and online forums. Patients completed a self-screening survey to verify meeting eligibility criteria . Baseline survey data were analyzed by viral variant wave [Delta (9/2021-12/2021) and Omicron (1/2022-3/2023)] and COVID-19 avoidance was compared by political party.Of 1,027 screened, 627 (61%) were eligible. Of those, 305 (49%) completed the baseline survey and were included. Participants were median age 67, mostly female , and 263 (89%) lived in the United States. 285 (93%) had bronchiectasis and 260 (85%) had NTM infection. Overall, 178 (58%) reported extreme concern about COVID-19. Of 254 (85%) patients reporting available telehealth, 235 (93%) reported a telehealth visit. In-person healthcare avoidance lessened or was similar comparing Delta to Omicron waves, e.g. avoidance of doctor visits , procedures , and lab tests . Participant level of concern about their lung disease remained high 98% to 95% across Delta and Omicron waves (p=0.08), while the proportion of those infected increased with Omicron (Table 2). When stratified by political party, Democrats were more likely to take social distancing precautions and take vaccine than those identifying as Republican (Table 3).Bronchiectasis and NTM patients reported a high level of concern about COVID-19 and many avoided in-person healthcare during the pandemic, which could impact disease progression. Most individuals took social distancing precautions, but levels varied by political party. This study was funded by Insmed Incorporated in accordance with fair market value.Emily Henkle, PhD, MPH, AN2 Therapeutics: Advisor/Consultant|MannKind: Advisor/Consultant Kevin L. Winthrop, MD, MPH, AN2: Advisor/Consultant|AN2: Grant/Research Support|Insmed: Advisor/Consultant|Insmed: Grant/Research Support|Insmed: This study was funded by Insmed Inc.|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Red Hill Biopharma: Advisor/Consultant|Red Hill Biopharma: Board Member|Red Hill Biopharma: Grant/Research Support|Renovion: Advisor/Consultant|Renovion: Grant/Research Support|Spero: Advisor/Consultant|Spero: Grant/Research Support


Rates of annual flu vaccine receipt among college students remains significantly lower than the 2030 Healthy People target of > 70%. College students are at increased risk of contracting influenza due to close living and dining conditions, and illness due to influenza can have a negative impact on school attendance and academic achievement. This study assessed the extent to which vaccine hesitancy and logistical factors impacted college students’ ability to receive a flu vaccine.This study consisted of three surveys administered through REDCap. During the 2021-22 and 2022-23 flu seasons, we administered a baseline survey to assess intention to receive a flu vaccine and logistical barriers that students face in receiving a flu vaccine. We also assessed vaccine hesitancy using a modified Parental Attitudes about Childhood Vaccines (PACV) questionnaire. One month later, we administered a follow-up survey to assess whether students had received a flu vaccine and to rank the importance of several factors in their decision-making.Sociodemographic information of respondents to the baseline survey.We had a total of 156 participants in the baseline survey and 97 participants in the follow-up survey. Sociodemographic information can be seen in Table 1. There was a self-reported flu vaccination rate of 63.9%. Only 4.5% of participants scored ≥50 for their adapted PACV survey, indicating that a small proportion of students are flu vaccine hesitant. Individuals who self-reported that they typically receive a flu vaccine yearly had statistically significantly (p < 0.0001) lower adapted PACV scores (11.0[9.5]) compared to individuals who self-reported that they do not typically receive a flu vaccine annually or have only received the vaccines needed to enter school (31.3[21.3]). Among individuals who did not receive a flu vaccine, the top three concerns were easiness of forgetting (78.6%), inconvenience (57.2%), and lack of time (49.9%).Understanding undergraduate barriers to receiving flu vaccines is critical in designing interventions that increase flu vaccine uptake in this population. Our study found that logistical barriers, rather than vaccine hesitancy, was the limiting factor in preventing college students from receiving flu vaccines.Tina Q. Tan, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Iliad: Advisor/Consultant|Merck: Advisor/Consultant|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support Ravi Jhaveri, MD, AbbVie: Grant/Research Support|AliOS: Grant/Research Support|AstraZeneca: Advisor/Consultant|Gilead: Grant/Research Support|MedImmune: Advisor/Consultant|Merck: Grant/Research Support|Saol Therapeutics: Advisor/Consultant|Seqirus: Advisor/Consultant


Adherence to daily oral antiretroviral therapy is important for sustaining HIV suppression. B/F/TAF Studies 1489, 1490, 4458, 1844 and 4030 demonstrated the noninferior efficacy of B/F/TAF versus DTG + 2 nucleoside reverse transcriptase inhibitors (NRTIs). We retrospectively assessed drug adherence and effect on virologic outcomes.(Table) plus placebo; as a result, all received multiple tablets. Participants with ≥ 1 returned pill bottle and ≥ 1 on-treatment HIV-1 RNA measurement were included in the analysis. Adherence was calculated by pill count; virologic outcome was assessed by last on-treatment HIV-1 RNA.All studies were double-blind, placebo-controlled, and enrolled treatment-naïve  or virologically suppressed  adults. Participants were randomized 1:1 to receive B/F/TAF or DTG + 2 NRTIs P ≤ 0.002, Figure). Similar results were observed at W144 in 2 studies  with additional follow-up data. Nine participants with low adherence had HIV-1 RNA ≥ 50 copies/mL at their last visit through W48: 3 subsequently resuppressed , 5 discontinued  and 1 was lost to follow-up (B/F/TAF).Altogether, 2,622 participants were included . The proportions of participants with high (≥ 95%), intermediate (≥ 85%‒< 95%) or low (< 85%) adherence were similar between the 2 groups; few had low adherence . Overall, 98.5%  in the B/F/TAF group and 98.2%  in the DTG + 2 NRTI group had virologic suppression (HIV-1 RNA < 50 copies/mL) at last on-treatment visit through W48. In the B/F/TAF group, virologic suppression was similar in those with high and intermediate adherence versus those with low adherence; however, in the DTG + 2 NRTI group, virologic suppression was significantly higher in those with high and intermediate adherence compared with low adherence (Overall, most participants receiving either placebo-controlled B/F/TAF or DTG + 2 NRTIs demonstrated ≥ 85% adherence. In those with suboptimal adherence, B/F/TAF treatment maintained high levels of virologic suppression, while those with suboptimal DTG + 2 NRTI adherence had reduced virologic suppression.Kristen Andreatta, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds Paul E. Sax, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Grant/Research Support David Alain Wohl, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Advisor/Consultant|Janssen: Honoraria|Theratech: Advisor/Consultant|Theratech: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Michelle L. D’Antoni, PhD, Gilead: Employment|Gilead: Stocks/Bonds Hailin Huang, PhD, Gilead: Employment Jason Hindman, PharmD, MBA, Gilead: Employment|Gilead: Stocks/Bonds Christian Callebaut, PhD, Gilead: Employment Hal Martin, MD, Gilead: Employment


The RAPIDS GN trial, a prospective randomized controlled trial, showed that rapid blood culture antibiotic susceptibility testing (AST) led to faster antibiotic therapy changes compared to standard of care (SOC) testing for Gram negative bacteremia  73:e39-e46). A secondary analysis of the data was conducted to assess impact of rapid testing on appropriateness of antibiotic spectrum by pathogen and resistance profile.Empiric treatment (0 to 2 h post randomization) among subjects with antibiotic-susceptible isolates of monomicrobial, on-panel Gram negative species (N = 320). For this analysis subjects from both SOC and rapid testing groups were included. Black: Excluded from treatment definition if subjects received no antibiotics, antibiotics without susceptibility results reported, or only an aminoglycoside, azithromycin, penicillin, rifaximin, or atovaquone.Antibiotic treatment appropriateness for antibiotic-susceptible Escherichia coli, and Klebsiella and Proteus isolates (N= 240) by time after randomization and treatment arm. Black: Excluded from treatment definition if subjects received no antibiotics, antibiotics without susceptibility results reported, or only an aminoglycoside, azithromycin, penicillin, rifaximin, or atovaquone. AXDX, rapid susceptibility testing group.rd generation cephalosporin non-susceptible or carbapenem-resistant isolates.Subjects enrolled in the RAPIDS GN trial who had blood cultures with monomicrobial Gram negative bacilli that were “on-panel” for the rapid test were included. Antibiotics administered from randomization (0 h) through 52 h were evaluated. Antibiotic therapy was classified based on SOC AST as: undertreatment (antibiotic to which the blood isolate was resistant), appropriate treatment (narrowest spectrum antibiotic to which the blood isolate was susceptible), and overtreatment [overly broad-spectrum antibiotic(s) based on blood isolate AST]. Antibiotic-resistant isolates were defined as 3Antibiotic treatment appropriateness for antibiotic-resistant  Escherichia coli, and Klebsiella and Proteus isolates (N= 50) by time after randomization and treatment arm. Black: Excluded from treatment definition if subjects received no antibiotics, antibiotics without susceptibility results reported, or only an aminoglycoside, azithromycin, penicillin, rifaximin, or atovaquone. AXDX, rapid susceptibility testing group.Escherichia coli, and Klebsiella and Proteus species than for other species . Among 290 E. coli, Klebsiella and Proteus isolates, treatment appropriateness improved with time after randomization in both SOC and rapid testing groups. The proportion with appropriate treatment was higher in the rapid testing group than the SOC group at all time points after 24 h post-randomization and differed by resistance. Overtreatment was common for susceptible isolates while undertreatment was common for resistant isolates . Among resistant isolates, by 52 h post-randomization undertreatment decreased to 15% in the rapid testing group but only 35% in the SOC group .388/448 (87%) subjects were included . Among susceptible isolates, between 0 through 2 h post-randomization (before AST results), overtreatment was more common for E. coli, Klebsiella, and Proteus bacteremia. These findings can inform antibiotic stewardship and design of future blood culture diagnostic trials.In the RAPIDS GN trial, rapid AST had the greatest benefit on management of antibiotic-resistant Ritu Banerjee, MD, Ph.D, bioMerieux: Grant/Research Support|bioMerieux: company is providing partial support for an ongoing trial unrelated to submitted abstract Sarah B. Doernberg, MD, MAS, Basilea: Clinical events committee/adjudication committee participation|F2G: Grant/Research Support|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Janssen/J+J: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clinical events committee/adjudication committee participation 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


RSV infection diagnosis in hospitalized adults is based primarily on PCR testing of nasopharyngeal (NP) swabs. Adding sputum is known to increase diagnostic yield, and saliva has been successfully used for viral respiratory infection diagnosis, however, no study has evaluated the synergistic effect of adding both sample types concurrentlyWe sought to define the increase in RSV prevalence when diagnosed by PCR of NP swab plus sputum and/or saliva versus NP swab PCR alone in adult patients hospitalized with acute respiratory illness (ARI) over two seasons, overall and by subgroup. First season overall findings were previously presented at ID week; this analysis adds season 2 data, allowing for subgroup analyses.This was a prospective cohort study of patients aged ≥40 years and hospitalized for ARI in four hospitals in Louisville, Kentucky during two seasons: 27Dec2021–01Apr2022 and 22Aug2022–03Mar2023. NP swab, saliva, and sputum specimens were obtained, and PCR tested with Luminex ARIES platform. RSV prevalence was calculated for diagnosis by NP swab alone, and NP swab plus sputum and/or saliva. Increase in RSV diagnosis with additional sample testing was compared for the whole cohort, for those with all three specimen types obtained, and by age, sex, and immune status.We enrolled 2,798 patients and collected NP swabs in 100%, saliva in 99%, and sputum in 31% of patients. Among all patients, 133 (4.8%) had RSV diagnosed by any specimen versus 80 (2.9%) diagnosed by NP swab alone, consistent with an 66% increase in prevalence . Among 856 patients with three specimens obtained, 62 (7.2%) patients were diagnosed by any specimen, versus 37 (4.3%) patients with RSV diagnosed by NP swab alone. RSV detection trended higher among men (2.00), middle-aged adults , and immunocompromised persons (1.78) (Table 1).Table 1Increase in RSV detection associated with testing additional specimen types beyond NP swab for specific populationsRSV infections were frequently detected in saliva and sputum samples. Standard-of-care PCR testing of NP swabs for RSV underestimates RSV prevalence in adult patients hospitalized with ARI. Hospitalized RSV ARI burden estimates in adults based solely on NP swab RT-PCR should be adjusted for underestimation.Ruth Carrico, PhD, DNP, APRN, Moderna: COVID-19 vaccine|Pfizer: Grant/Research Support|Pfizer: PCV20|Pfizer: Meningococcal and Pneumococcal vaccines; Paxlovid|Sanofi: Speaker; influenza vaccine|Seqirus: Influenza vaccine|Valneva: Travel vaccines Ashley M. Wilde, PharmD, BCIDP, Pfizer: Grant/Research Support Robin Hubler, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds Negar Aliabadi, MD, MS, Pfizer: Employee Bradford J. Gessner, M.D, M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Elizabeth Begier, M.D, M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds


Syphilis rates in the United Stated (U.S.) have increased steadily for over a decade. Despite over 75 years as the drug of choice for syphilis treatment, controversy persists on optimal duration of therapy with benzathine penicillin G (BPG) for persons with early syphilis, particularly for persons co-infected with HIV. Given the ongoing national shortages of BPG, optimizing duration of therapy is an urgent concern.> 4-fold decline in RPR titer measured at 6 months. Intention to treat (ITT) and per protocol analyses were performed and were similar. ITT analyses are presented here.We conducted a multicenter RCT comparing a single intramuscular (IM) injection of BPG, 2.4 million units to BPG administered for three successive weeks for treatment of early syphilis in persons with and without HIV. The primary outcome of the study was a > 4-fold decline in RPR titer) at 6 months was 76%  0.68-0.82) in the single dose group and did not differ significantly from the three-dose group . There were no treatment failures (> 4-fold increase in RPR titer). Among persons with and without HIV there was no significant difference in RPR response at 6 months: 76% in the single-dose group vs. 71% in the 3-dose group (95% CI 0.05-0.17). Most participants experienced mild to moderate local injection site pain and tenderness.A total of 249 persons with early syphilis were enrolled at 10 participating sites. Most (97%) participants were were categorized as male sex, black race (62%), and 153 (64%) were living with HIV. The syphilis stage distribution was 19% primary, 47% secondary, and 33% early latent and did not differ significantly by HIV status. Serologic response (Treatment of persons with early syphilis with more than a single dose of 2.4 million units of BPG offers no therapeutic benefit irrespective of HIV infection status and was associated with increased rates of injection site discomfort.Edward W. Hook, III, FIDSA, GARPD (Global Antibiotic Resistance Program: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|VISBY Diagnostics: Advisor/Consultant Candice J. McNeil, MD, MPH, BARDA/GSK: Grant/Research Support|Becton Dickinson: Grant/Research Support|Cepheid: Grant/Research Support|Gilead: Grant/Research Support|Hologic: Grant/Research Support|Lupin: study product Julia C. Dombrowski, MD, MPH, Hologic: Grant/Research Support|Mayne Pharmaceuticals: Grant/Research Support


Cefiderocol (CFDC) is a siderophore cephalosporin that hijacks the iron transport system of Gram-negative bacteria to facilitate cell entry and reach its target. CFDC remains stable to hydrolysis in the presence of serine β-lactamases  and metallo-β-lactamases (MBL). CFDC and comparator activities were analyzed against Enterobacterales (ENT), including molecularly characterized isolates, as part of the US SENTRY Antimicrobial Surveillance Program.E. coli, K. pneumoniae, and P. mirabilis with ceftriaxone, ceftazidime, or aztreonam MIC ≥ 2 μg/mL plus any ENT displaying an MIC ≥ 2 μg/mL for imipenem  or meropenem (MER) were subjected to genome sequencing and screening of β-lactamase genes.11,884 ENT were collected from 33 sites in the USA in 2020–2022. Susceptibility (S) testing was performed by broth microdilution. CFDC testing utilized iron-depleted media. CLSI breakpoints were used. 50/90, 0.5/4 μg/mL; 97.6%S) and CZA  were the most active agents against carbapenem-nonS isolates, whereas IMR  and MEV  had suboptimal activity. CFDC , IMR , MEV , and CZA  were active (98.7–100%S) against the KPC subset. CFDC  was also active against ENT carrying MBL genes, whereas CFDC  and CZA  were active against isolates carrying blaOXA-48–like.CFDC (99.8%S), imipenem-relebactam , meropenem-vaborbactam , and ceftazidime-avibactam  were active against carbapenem-susceptible ENT that carried ESBL and/or AmpC genes (Table). CFDC (MICblaKPC, where approved β-lactam/β-lactamase inhibitor combinations showed limited activity. These data emphasize CFDC as an important option for the treatment of infections caused by ENT and resistant subsets.CFDC activity against ENT was consistent, regardless of isolate phenotypes or genotypes, including against isolates carrying carbapenemase genes other than 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 John H. Kimbrough, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Pfizer: 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


Clostridioides difficile infection (CDI). In this post hoc subgroup analysis, the durability of fecal microbiota, live-jslm , the first microbiota-based LBP approved by the US Food and Drug Administration for the prevention of recurrent CDI (rCDI) in adults following antibiotic treatment for rCDI, was investigated in a subset of participants who received systemic antibiotics for indications other than CDI following RBL treatment in a phase 2 open-label trial (NCT02589847).Live biotherapeutic products (LBPs) are adjunctive therapies to prevent recurrence of PUNCH Open Label participants were ≥ 18 years old with either ≥ 2 rCDI episodes treated with standard-of-care antibiotic therapy after a primary CDI episode, or ≥ 2 severe CDI episodes requiring hospitalization. Participants in this analysis all received 2 doses of RBL rectally administered approximately 7 days apart. We report outcomes at various timepoints for participants who were successfully treated with RBL and subsequently received non-CDI systemic antibiotics.A total of 43 participants were included in the analysis; the mean age was 65.9 years, most were male (67.4%), and most (97.7%) had ≥ 3 rCDI episodes before RBL. Most participants were treated with antibiotic monotherapy , received 1 course of treatment , and did not receive CDI prophylaxis . The median time to antibiotic exposure after the second dose of RBL was 155 days , and the median duration of treatment per antibiotic course was 8 days . Urinary system infections were the most common indication for antibiotic treatment . Among evaluable participants who received systemic antibiotics within 8 weeks, 6 months, 12 months, and 24 months of RBL administration, 91.6% (11/12), 95.7% (22/23), 90.6% (29/32), and 83.3% (30/36) remained CDI recurrence-free, respectively. A total of 86% (37/43) of participants were recurrence-free at their last evaluable timepoint.In this post hoc analysis, RBL remained effective in preventing CDI recurrence in patients with multiple episodes of rCDI after subsequent systemic antibiotic exposure.Kelly R. Reveles, PharmD, PhD, Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Honoraria Anne J. Gonzales-Luna, PharmD, BCIDP, Cidara Therapeutics: Grant/Research Support|Ferring Pharmaceuticals: Personal Fees|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support Yoav Golan, MD, Ferring Pharmaceuticals: Advisor/Consultant|Pfizer: Honoraria|Seres Therapeutics: Advisor/Consultant|Vedanta Bioscience: Advisor/Consultant Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support Beth Guthmueller, AS, Rebiotix Inc., a Ferring Company: Employee Xing Tan, PharmD, Ferring Pharmaceuticals: Employee Monique Bidell, PharmD, Ferring Pharmaceuticals: Employee Victoria Pokhilko, PhD, Ferring Pharmaceuticals: Employee Carl Crawford, MD, Ferring Pharmaceuticals: Advisor/Consultant Andrew M. Skinner, MD, Academy for Continued Healthcare Learning: Honoraria|American Society of Healthcare Pharmacists: Honoraria|Ferring Pharmaceuticals: Honoraria|MJH Life Sciences: Honoraria


Clinical implementation of whole genome sequencing (WGS) has been identified as the optimal approach to identify transmission of multidrug-resistant (MDR) organisms in the healthcare setting. Although WGS capabilities are becoming more common in clinical laboratories, analysis and interpretation of results is still a barrier to implementation. The purpose of this study was to evaluate cloud-based automated analytic pipelines to aid with WGS analysis of MDR gram-negative organisms as part of outbreak investigations.Enterobacterales (n: 142), Acinetobacter baumannii complex (n: 14) and Pseudomonas aeruginosa (n:29) isolates were WGS on Illumina sequencing platforms. The FASTQ files were uploaded to AREScloud  and to EPISEQ CS (bioMérieux) for whole genome or core genome multi-locus sequence typing (wgMLST/cgMLST) with dendrogram creation. Results were compared to traditional 7 gene MLST schema. Ease-of-use and additional tools were compared between pipelines.A convenience set of MDR AREScloud and EPISEQ CS generated similar dendrograms for all organisms evaluated . EPISEQ CS provided preset similarity thresholds based on percent relatedness to define clusters simplifying outbreak analysis, whereas AREScloud allowed users to define allelic difference cutoffs. Although the wgMLST/cgMLST clusters aligned with traditional MLST types, not all isolates assigned to a similar MLST were identified as part of a related cluster demonstrating increased resolution of wgMLST and cgMLST phylogenetic assessments. Table 1 compares the features between the two pipelines.Dendrogram generated for Escherichia coli (EPISEQ CS)Dendrogram generated for Escherichia coli (AREScloud)Comparison of features between EPISEQ CS and AREScloud for phylogenetic analysisBoth cloud-based tools perform comparably for assessing phylogenetic relatedness compared to traditional MLST. Preset similarity thresholds available with EPISEQ CS provide ease-of-use for cluster assessment. Additional features, such as resistome and virulome analysis, are available by both pipelines. Predictive WGS-AST is an additional asset available with AREScloud.Karen C. Carroll, MD, Abbott Diagnostics: Board Member|Co-Diagnostics, Inc.: Board Member|Great Basin: Grant/Research Support|Meridian Diagnostics: Grant/Research Support|Pattern Diagnostics: Advisor/Consultant|Pattern Diagnostics: Stocks/Bonds|Qiagen, Inc.: Grant/Research Support|Scanogen: Advisor/Consultant|Scanogen: Grant/Research Support Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support


Bacillus cereus can cause serious nosocomial infections, including neuroinvasive infections in immunocompromised patients. Three patients with AML developed hospital-onset neuroinvasive B. cereus infections in close temporal proximity at our institution in 2022, triggering an extensive epidemiological investigation.Bacillus species >48 hours after admission, and neurological symptoms with radiologic findings admitted between January 2018 and October 2022 . Infection control practices were observed, environmental samples obtained, and a dietary case-control study was performed. Bacillus isolates were sequenced, including 2 case isolates, 61 environmental specimens, and 19 samples of a protein supplement common to most AML patients.We identified all patients with AML, positive microbiologic assays for B. cereus neuroinvasive disease were identified. Four were identified via blood culture and one via metagenomic sequencing of plasma cell-free DNA. All patients were hospitalized for induction chemotherapy and were neutropenic . Central nervous system findings included intraparenchymal and subarachnoid hemorrhage, and rim-enhancing lesions. All patients were treated with ciprofloxacin and survived without neurologic sequelae. B. cereus was positively identified in 7/61 environmental and 1/19 protein samples. There was no single exposure common to all patients per the dietary case-control study, hospital construction records, or environmental samples. Sequencing confirmed all isolates were unrelated. Ciprofloxacin was added to the empiric antimicrobial regimen for AML patients with neutropenic prolonged or recurrent fevers in September 2022; no new cases have since been identified through April 2023 .Five AML patients with B. cereus is ubiquitous in the hospital environment, sometimes leading to pseudoclusters with unrelated isolates. Fastidious infection control practices addressing a broad range of potential exposures are warranted to prevent nosocomial infections. Including B. cereus coverage in empiric regimens for AML patients with prolonged or recurrent neutropenic fever may prevent serious infections from this pathogen.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 Chanu Rhee, MD, MPH, Cytovale: Advisor/Consultant|Pfizer: Advisor/Consultant|UpToDate, Inc.: Honoraria Michael Klompas, MD, MPH, UpToDate, Inc.: Royalties for chapters on pneumonia


Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data. Thorax 2021;76:860-866.Shah SA, Quint JK, Nwaru BI, Author acknowledgements have been updated in the online HTML and PDF.


We sought to compare B/F/TAF and DTG/3TC in virologically suppressed, treatment-experienced people with HIV in the OPERAAll treatment-experienced adults with HIV switching to B/F/TAF or DTG/3TC (01Aug2020-30Jun2022) with a viral load (VL) < 200 copies/mL at switch and ≥1 follow-up VL were included. Confirmed virologic failure (VF) was defined as 2 consecutive VL ≥200 copies/mL or regimen discontinuation following a VL ≥200 copies/mL; VL ≥50 copies/mL was used in a sensitivity analysis. Discontinuation was defined as any regimen modification or a treatment gap >45 days. Incidence rates (Poisson regression) and hazard ratios  were estimated with inverse probability of treatment weights (IPTW) to adjust for race, payer, CD4 count and eGFR at baseline. Covariate balance was assessed with standardized mean differences; values ≤0.10 indicated adequate balance.≥200 incidence rates per 100 person years were low ; risk with B/F/TAF was not statistically different than with DTG/3TC . VF≥50 incidence rates were higher, but risk did not differ between groups . All-cause regimen discontinuation was less likely with B/F/TAF than DTG/3TC . Treatment-related discontinuation  was identified in 6% of B/F/TAF and 9% of DTG/3TC discontinuers.On B/F/TAF, 3713 individuals were followed for a median of 16 months . On DTG/3TC, 2327 individuals were followed for a median of 15 months . The distribution of key characteristics differed between groups; balance was achieved with IPTW (Table 1). VFIn this real-world US cohort, virologically suppressed individuals switching to B/F/TAF were less likely to discontinue their regimen than those switching to DTG/3TC. VF was infrequent and no statistical difference was observed in the risk of VF between regimens over the study duration.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 Michael Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Megan Dunbar, PhD, Gilead: Employment Joshua Gruber, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Douglas Dieterich, MD, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria Gregory P. Fusco, MD, MPH, Epividian, Inc.: Board Member|Epividian, Inc.: Ownership Interest|Epividian, Inc.: Stocks/Bonds


Histological presence of fungal organisms associated with tissue damage is the hallmark for invasive fungal diseases. Rapid and accurate identification (ID) of these fungal pathogens present is critical for initiating appropriate treatment without delay. We investigated an automated sample-to-answer targeted NGS workflow for the ID of fungi directly from FFPE tissues.170 FFPE tissues (93 cases) from 2002 to 2022 at Johns Hopkins Hospital were selected based on histologic findings of the presence of fungal pathogens. Samples were run by PathoKey SQ Flex assay, (Vela Diagnostics) which includes automated extraction, library preparation and emulsion PCR followed by NGS on a Sentosa SQ301 and analyzed using Vela’s curated database. Two negative controls (NCs) were included on each run. To compare NGS results, 51 samples were extracted using the MagMAX™ FFPE DNA/RNA Ultra Kit (Applied Biosystems) followed by pan-fungal PCR (ITS1/ITS2/D1D2) and Sanger sequencing (SS) and analyzed through NCBI nucleotide blast for ID.116/170 (68%) samples had culture results: 69/116 (59%) were concordant with Vela NGS (VS) ID to the genus/species level; 18/28 (64%) samples were concordant with SS ID to the genus/species level. Among 54 samples with no/negative culture results: 26/54 (48%) were presumptive Mucorales, of which 23/26 (88.5%) were supported by VS ID and 5/12 (42%) supported by SS ID; 12/54 (22%) were presumptive aspergillus-like hyphae fungi, of which 10/12 (83%) were supported by VS ID and 4/9 (44%) supported by SS ID. 15/170 (8.8%) samples had no VS ID due to QC failures, and 15/26 (58%) with no VS ID had no organism seen or scant amount of fungal load in the histology slide.VS detected fungal organisms in 76% (129/170) of FFPE tissues, of which it correctly ID-ed pathogens down to the genus/species level in 94% (102/129) of samples. VS is more sensitive to pathogen ID than SS. Samples with discordant or no results by VS were mostly due to small tissue input or low fungal loads present in histology. Environmental or human skin flora contamination reads overshadowing possible pathogens were observed in few cases; therefore, it is critical to include NCs in each run to distinguish them from clinically significant fungal pathogens.Marissa C. Totten, MA, Vela Diagnostics: Grant/Research Support Pramila Ariyaratne, n/a, Vela Diagnostics: Employee Tony Zhang, n/a, Vela Diagnostics: Employee Sean Zhang, MD, PhD, Applied BioCode: Grant/Research Support|IMMY Diagnostics: Grant/Research Support|KARIUS: Advisor/Consultant|Pearl Diagnostics: Grant/Research Support|Scanogen: Grant/Research Support|T2 biosystems: Advisor/Consultant|Vela Diagnostics: Grant/Research Support Charlie Lee, Ph.D, Vela Diagnostics: Employee


Clinical outcomes associated with bacterial bloodstream infections (BSI) are influenced by multiple factors, including the infecting bacterial species and choice of antibiotic therapy. However, the mechanisms by which differences in such factors influence patient outcomes are poorly understood. We hypothesized that variations in bacterial etiology and antibiotic therapy may alter clinical outcomes in part through differential host gene expression signatures. Therefore, we aimed to identify bacterial- and antibiotic-specific host transcriptional signatures in patients with bacterial BSI.Escherichia coli (n=30) or Klebsiella pneumoniae (n=28) vs. methicillin-susceptible Staphylococcus aureus [MSSA] (n=24) or methicillin-resistant S. aureus (MRSA) (n=58). Patients were matched by age, gender, and race. Differential gene expression and gene co-expression analyses were performed .RNA-Seq was performed on whole blood samples in patients infected with BSI due to prototypic Gram-negative vs. Gram-positive bacterial pathogens: Figure 1Overview of study design.E. coli versus K. pneumoniae BSI, so these groups were considered together as gram-negative BSI. Relative to S. aureus BSI, patients with gram-negative BSI had increased activation of the classical complement system . However, the most significant signal was a reduction in host transcriptional signatures involving mitochondrial energy transduction and oxidative burst in MRSA vs. MSSA . This attenuated host transcriptional signature in MRSA BSI remained after controlling for antibiotic therapy.Clinical characteristics of patients with BSI in this study are shown in Table 1. No significant differences were detected in overall host transcriptomes in patients with Table 1Demographics and outcomes of patients with bacterial bloodstream infections (BSI) included in this study.Figure 2Whole blood gene transcript level changes in patients with gram-negative bloodstream infection (BSI) relative to gram-positive  BSI. (A) Volcano plot showing gene transcript level differences in patients with gram-negative versus S. aureus BSI. Genes that had log2-transformed fold change (Log2FC) greater than 1 or less than -1 and had a false discovery rate (FDR) less than 0.1 are shown in red. Genes meeting only the Log2FC or FDR criteria are shown in green and blue, respectively. Genes meeting neither criteria (NS) are shown in gray. (B) g:Profiler biological processes associated with the gene transcript differences in patients with gram-negative versus S. aureus BSI. For each biological process, the number of genes associated with the process (count) and p-value associated with the process are shown. In (C), the genes associated with the process shown in (B) are listed.Figure 3Whole blood gene transcript level changes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI) relative to methicillin-resistant S. aureus (MRSA) BSI. (A) Volcano plot showing gene transcript level differences in patients with MSSA versus MRSA BSI. Genes that had log2-transformed fold change (Log2FC) greater than 1 or less than -1 and had a false discovery rate (FDR) less than 0.1 are shown in red. Genes meeting only the Log2FC or FDR criteria are shown in green and blue, respectively. Genes meeting neither criteria (NS) are shown in gray. Circled in red is a group of genes that are particularly different between the two groups and further described in (B). In (B), the log2-transformed fold changes (Log2FC) (C) g:Profiler biological processes analysis of gene transcript level differences in patients with MSSA versus MRSA BSI. For each pathway, the number of genes associated with the pathway (count) and p-value associated with the pathway are shown.S. aureus. Given the importance of respiratory functions and reactive oxygen species in eliminating intracellular S. aureus, this finding may offer new insights into persistence of MRSA BSI relative to other bacteria.We uncovered an MRSA-specific host transcriptional signature that was driven in large part by suppressed mitochondrial responses necessary for essential immune functions in oxidative killing of Joshua T. Thaden, MD, PhD, Resonantia Diagnostics, Inc: 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


Borrelia burgdorferi, is the most common vector-borne disease in the United States. It drives a multisystem disorder, of which Lyme arthritis is the most common feature of late disseminated disease, seen in approximately 60% of untreated individuals. While most Lyme arthritis resolves with oral or IV antibiotics, termed “antibiotic-responsive” arthritis, a small percentage of individuals develop progressive synovitis despite both oral and IV antibiotic therapy, called “antibiotic refractory” Lyme arthritis (LA), requiring treatment with immunosuppressive, disease modifying antirheumatic drugs (DMARDs). The primary drivers behind antibiotic refractory disease are likely multifactorial and remain incompletely understood. More specifically, it remains unclear whether antibodies, specific for Borrelia or autoantibodies, may act as biomarkers or play a mechanistic role in driving pathogenesis in the joint.Lyme disease, caused by the spirochete Borrelia burgdorferi -specific antibodies to B67 lysate, CRASP1, CRASP2, DbpA, DbpB, Arp37, Flagellin, OspA, OspB, OspC, OspE, p27, p35, p39, VlsE, and autoantigen Apolipoprotein B100.We performed a matched, cross-compartmental comparison of antibody profiles from blood and joint fluid of individuals with antibiotic responsive (n = 11) or antibiotic refractory arthritis (n= 31). We used a multiplexed luminex assay to perform biophysical profiling of B.burgdorferi-specific antibodies in the joint fluid was able to discriminate antibiotic responsive from refractory LA patients. Cross compartmental comparison of antibody glycosylation, IgA1, and antibody-dependent complement deposition (ADCD) revealed differences across compartments, with more poorly coordinated Lyme-specific humoral responses and increased antibody-dependent complement deposition in antibiotic-refractory arthritis.While serum antibody profiles poorly discriminated responsive from refractory LA patients, a discrete profile of B.burgdorferi-specific serological markers that may support the early stratification and clinical management of LA, but also point to immune complex driven complement activation as a key mechanism underlying persistent Lyme arthritis.These data demonstrate Christine Wiggins, B.S., Takeda Pharmaceutical Company: Stocks/Bonds Elizabeth Deriso, PhD, Takeda: Employee Klemen Strle, PhD, Takeda: I am an employee of Takeda. My work at Takeda does not overlap with my academic efforts in Lyme disease. John A. Branda, M.D, Analog Devices Inc.: Grant/Research Support|DiaSorin: Grant/Research Support|Gold Standard Diagnostics: Grant/Research Support|Pfizer Inc: Grant/Research Support|Zeus Scientific: Grant/Research Support Douglas A. Lauffenburger, PhD, Sanofi: Board Member|Sanofi: Honoraria|Sanofi: Honoraria Galit Alter, PhD, Leyden Labs: Ownership Interest|Moderna Therapeutics: Employee|Seromyx Systems: Ownership Interest


Vaccination is recommended for prevention of infectious diseases. For individuals with a history of corneal transplantation, however, there are concerns that vaccination may trigger allograft rejection through elevated immune activity. The association between vaccination and graft rejection remains unclear.We conducted a nested case-control study to evaluate the association between graft rejection and vaccination in corneal transplant recipients at Kaiser Permanente Southern California (KPSC) between January 2008 and August 2022. We identified all KPSC members who received a corneal transplant during the study period, with no history of prior transplant or rejection. Cases were those who experienced a graft rejection during the study period and eligible controls were those who had not experienced a rejection at the time of a given case. Controls were randomly selected via risk-set sampling and matched in a 3:1 ratio to cases on age, sex, and transplant date (±12 weeks). Index date was the date of rejection for cases. For controls, index date was determined by adding the number of days between transplant and rejection of the matched case to the control’s transplant date. We performed multivariable conditional logistic regression to compare the odds of vaccination  in the 12 weeks prior to the index date in cases and controls, while adjusting for potential confounders.Table 1). A total of 136 (23%) cases and 373 (21%) controls received vaccination within 12 weeks of the index date  (Table 2).Our study included 601 corneal transplant recipients with rejection (cases), and 1,803 matched controls. The overall cohort was 48% female and 47% white, with a mean age of 66 years (s.d. 17) (We did not find evidence of an elevated risk of graft rejection associated with vaccination given in the 12 weeks prior to the index date. Although our study is the largest study examining the association between corneal transplant rejection and vaccination to our knowledge, this study may be underpowered to detect a minimal increase in risk. Our findings provide support for completion of recommended vaccinations for patients who are planning or have received a corneal transplant.Jennifer H. Ku, PhD MPH, GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support Julia Tubert, MPH, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Yi Luo, PhD, GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Kevin L. Winthrop, MD, MPH, AN2: Advisor/Consultant|AN2: Grant/Research Support|Insmed: Advisor/Consultant|Insmed: Grant/Research Support|Insmed: This study was funded by Insmed Inc.|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Red Hill Biopharma: Advisor/Consultant|Red Hill Biopharma: Board Member|Red Hill Biopharma: Grant/Research Support|Renovion: Advisor/Consultant|Renovion: Grant/Research Support|Spero: Advisor/Consultant|Spero: Grant/Research Support Divya Srikumaran, MD, Alcon: Advisor/Consultant|Claris Biotherpeautics: Grant/Research Support Ana Florea, PhD MPH, Gilead: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Hung Fu Tseng, PhD MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support


Long-acting (LA) cabotegravir/rilpivirine (CAB/RPV) may simplify antiretroviral therapy (ART), improve adherence, and reduce pill stigma for people with HIV (PWH). However, real-world implementation is challenged by various barriers. We describe an integrated LA CAB/RPV workflow and the clinical characteristics and outcomes of PWH referred for and initiated on CAB/RPV in a Ryan White HIV/AIDS Program-funded clinic in South Florida (serving more than 1600 PWH).The clinic engaged an interdisciplinary team  to develop and maintain an infrastructure required to transition virologically suppressed (HIV RNA < 50 copies/mL) PWH from oral ART to LA CAB/RPV . MD/APRN referred pre-screened and interested PWH to PharmDs for eligibility evaluation, medication counseling, and drug acquisition. RNs administered injections, scheduled and tracked clinic appointments to ensure on-time injections, and ordered appropriate labs. PWH followed up with MD/APRN every 4 months to ensure efficacy and safety.Between January 2022 and March 2023, 83 PWH were referred to PharmDs for initiation of LA CAB/RPV and 30 (36%) initiated LA CAB/RPV. Those not initiated on LA CAB/RPV included those who declined to start  (n=23), clinician adherence concerns (n=9), insurance denial (n=7), and baseline resistance (n=7). Payor source for LA CAB/RPV included 40% RWHAP, 36% private, and 24% Medicare/Medicaid. For those initiated on LA CAB/RPV (Table 1), we observed a mean turnaround time of 23 days from PharmD eligibility evaluation to the first injections. Three PWH discontinued LA CAB/RPV: 2 due to side effects and 1 due to pregnancy. Five PWH experienced low-level viremia (HIV RNA < 200 copies/mL) following the switch, all others maintained viral suppression.A large number of eligible and interested PWH referred for LA CAB/RPV did not initiate the drug. Those who initiated CAB/RPV tolerated the drug well and maintained viral suppression. Implementation of LA CAB/RPV is enhanced by an interdisciplinary team to provide services, optimize workflows, and maintain infrastructure needed for a successful program.All Authors: No reported disclosures


Pseudomonas aeruginosa; however, comparative data are lacking. The purpose of this study was to compare rates of tx-emergent resistance among patients (pts) with bacteremia or pneumonia at a single center.CZA and CT are front-line agents for treatment (tx) of MDR Adult pts treated for >48 hours with CZA or CT were included. Pts with cystic fibrosis or colonization were excluded. Isolates were tested by broth microdilution (BMD) in triplicate and underwent whole-genome sequencing.Table 1). CT-treated pts were less likely to receive prolonged infusions and monotherapy, but more likely to have empyema/endovascular infections. Baseline median (range) MICs were 4 (2–8mg/L) and 2 (0.25–8mg/L) for CZA and CT, respectively. Within 90-days from tx onset, rates of resistance defined as either ≥4-fold MIC increase or MIC >8mg/L were higher among CZA-treated pts (Table 1). Corresponding median MICs of resistant isolates were 16 (16–128mg/L) and 64 (32–512mg/L), respectively. Across 107 baseline isolates, 59 different sequence types (ST) were represented. The most common P. aeruginosa cephalosporinase (PDC) variants were PDC-3, PDC-5, and PDC-8, present in 10%, 21%, and 10% of isolates, respectively. Resistance evolved across varying STs. A subgroup of contemporary pts was well-balanced and supported overall findings (Table 2). From this subgroup, rates of tx-emergent resistance among pts receiving CZA or CT monotherapy were 50% (6/12) and 6% (1/17), respectively (P=0.01). Rates of CT-resistance were lower among pts who received prolonged  versus standard  infusions. Paired baseline and resistant isolates showing ≥4-fold MIC increase were compared (Table 3). CZA resistance was associated with sequence changes in ampD and/or efflux genes in 5 pts; 2 additional pairs showed mutations in ftsI (PBP3). CT resistance was associated with new ampC mutations in 83% of pairs.113 pts were included. Demographics, severity of illness, and durations of tx were similar for pts tx’d with CZA or CT : Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support


Cisgender women (CGW) account for 48% of new HIV infections globally and 18% of new HIV infections in the United States (US) but comprise only 8% of daily oral PrEP users in the US. Social-structural factors including stigma, gender norms, and medical provider bias have been linked to daily oral PrEP inequities among CGW. These factors influencing PrEP utilization merit further attention as additional options emerge, including long-acting (LA) injectable PrEP.Table 1). CGW in the DR were female sex workers (FSW), while those in DC were seeking reproductive health services. Thematic content analysis was employed.PrEP preferences, barriers, and facilitators to uptake were explored through 60 in-depth interviews with CGW with indications for PrEP (n=40), and HIV and reproductive healthcare providers (HCPs) (n=20) in Washington, DC, US and Santo Domingo, Dominican Republic (DR) in 2021 and 2022  and HCP training on CGW’s PrEP needs.Tailored CGW-centered awareness campaigns and sensitivity training for HCPs related to PrEP options for CGW are needed. Access to LA PrEP for FSW is critical given the disproportionate impact of HIV on this community and their work-related PrEP preferences. Interventions must address social-structural factors among CGW to support equitable PrEP uptake.Aimee A. Metzner, PharmD, AAHIVP, ViiV Healthcare: Full-time employee |ViiV Healthcare: Stocks/Bonds Alan Oglesby, MPH, GlaxoSmithKline: Employment|GlaxoSmithKline: Stocks/Bonds Cindy Garris, MS, GSK: Stocks/Bonds|ViiV Healthcare: Employee Rachel Scott, MD,MPH,FACOG, Gilead Science: Grant/Research Support|ViiV/GSK: Grant/Research Support