A variant-adapted bivalent BNT162b2 mRNA vaccine  comprising original SARS-CoV-2 and Omicron BA.4/BA.5 spike proteins is authorized by the US FDA from 6 months of age as a primary series or as booster doses. We studied whether bivalent BNT162b2 booster generates improved immune responses against Omicron BA.4/BA.5 and ancestral strains and had a comparable safety profile to original BNT162b2 in 5–11-year-olds.This substudy is part of a phase 1/2/3 master study (NCT05543616) examining safety and immunogenicity of bivalent BNT162b2 in healthy children. The substudy group reported here is open label and evaluates a fourth dose with bivalent BNT162b2 10 μg  in 5–11-year-olds who previously received 3 original BNT162b2 10 μg doses. Reactogenicity (7 day), and 1 month safety and immunogenicity were assessed. SARS-CoV-2 Omicron BA.4/BA.5 and ancestral strain neutralization titers post dose 4 were descriptive immunogenicity endpoints. The comparator group for immunogenicity assessments included 113 participants from the initial pediatric study (NCT04816643) who received 3 original BNT162b2 10 μg doses and who were matched by age and SARS-CoV-2 infection status.Figure). No serious adverse events were reported. The safety and tolerability profile was generally consistent with that of original BNT162b2. Bivalent BNT162b2 elicited higher neutralizing titers against Omicron BA.4/BA.5 and similar titers against the ancestral strain 1 month post dose 4 compared with original BNT162b2 at 1 month post dose 3 overall and in those who were SARS-CoV-2 positive (Table).Of the 113 children who received bivalent BNT162b2, 50% were female, 58% White, and 58% SARS-CoV-2 positive at baseline. Median (range) time from dose 3 of original BNT162b2 to bivalent BNT162b2 was 5.5 (2.6−8.6) months. Bivalent BNT162b2 was well tolerated with mostly mild to moderate reactogenicity; no grade 4 events were observed  of bivalent BNT162b2 10 µg had a similar safety profile to original BNT162b2 10 µg and induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers. These data support booster dosing with variant-adapted bivalent BNT162b2 in 5–11-year-olds.Grant C. Paulsen, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lawrence Sher, MD, Pfizer Inc: Clinical Investigator Charu Sabharwal, MD, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Nicholas Kitchin, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Sungeen Hill, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Emily Wasserman, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Xia Xu, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB 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 Emmanuel Walter, MD, Clinetic: Clinical Investigator|Iliad Biotechnologies: Advisor/Consultant|Moderna: Clinical Investigator|Najit Technologies: Clinical Investigator|Pfizer Inc: Clinical Investigator|Sequiris: Clinical Investigator|Vaxcyte: 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 Eric Simoes, MD DCH, Abbott Diagnostics: Advisor/Consultant|Abbvie Inc: Advisor/Consultant|Abbvie Inc: DSMB study section|AstraZeneca: Grant/Research Support|AstraZeneca: travel|Bill and Melinda Gates Foundation: Advisor/Consultant|Bill and Melinda Gates Foundation: Grant/Research Support|Bill and Melinda Gates Foundation: travel, DSMB study section|CDC: Advisor/Consultant|CDC: travel|GSK plc: Advisor/Consultant|GSK plc: DSMB study section|Johnson & Johnson: Advisor/Consultant|Johnson & Johnson: Grant/Research Support|Merck & Co Inc: Grant/Research Support|National Institutes of Health: Grant/Research Support|National Institutes of Health: travel, DSMB study section|Novavax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: travel|Regeneron: Grant/Research Support|Roche: Grant/Research Support|Roche: travel|USAID: Advisor/Consultant|USAID: Grant/Research Support|USAID: travel|WHO: Advisor/Consultant|WHO: travel Kawsar R. Talaat, MD, Intralytix: Advisor/Consultant|Merck: Advisor/Consultant|NIAID: DSMB|Pfizer: Grant/Research Support|Pfizer: Pfizer contract with institution|Sanofi: Grant/Research Support|Takeda: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Lisa Moyer, BS, Pfizer: Employee|Pfizer: Stocks/Bonds Vrunda Parikh, PharmD, Pfizer: Employee|Pfizer: Stocks/Bonds Hua Ma, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Xingbin Wang, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kenneth Koury, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kena A. Swanson, Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds Alejandra C. Gurtman, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds


COVID-19 highlighted health inequities and the differential impact that vaccination can have on health, with respect to social advantage. While many national immunisation programmes (NIP) consider health equity as a key recommendation criterion, most lack robust frameworks and methods to quantify the impact of healthcare interventions on health equity. Equity strata can be defined by socioeconomic status, race/ethnicity, geographic location, etc…The inclusion of equity in guidelines for vaccination recommendation was assessed. Vaccination policy experts and health economists were consulted on how to best capture the equity-related public health impact (PHI) of NIP. The framework of distributional cost-effectiveness analysis (DCEA) was selected to be further explored. A stepwise approach was applied to account for equity in PHI analysis i.e., the impact on health outcome distribution by equity strata, by estimating the distributional impact (step 1) and HE impact (step 2) of vaccination. A practical application of the method was illustrated through a case study on the meningococcal B (MenB) disease vaccination program in England.Impact of vaccination in health equity is formally captured in policy decision making in the US ACIP Evidence to Recommendation framework and the Canadian EEFA  Framework. In UK, France, Australia, Spain and Germany it is qualitatively included as part of the deliberative process, while it is not captured in the Netherlands. The DCEA framework was applied for health equity benefits of MenB infant vaccination in UK, with impact assessed across population subgroups categorised using a deprivation index. Nearly 80% of prevented cases were among the three most deprived groups. Additionally, MenB vaccination decreased inequity in the population, with positive net equity impact.PHI of vaccination on health equity can be quantified and usefully considered in decision making. The case study demonstrates how the proposed framework could be applied to fully incorporate impact on equity in cost-effectiveness analysis. The health equity impact of vaccination can be captured in health economic evaluation although there is a need to improve the evidence base and its implementationEliana Biundo, PhD, GSK: employee|GSK: Stocks/Bonds Mariia Dronova, PhD, GSK: Grant/Research Support Annie Chicoye, PhD, GSK: Board Member|GSK: Grant/Research Support|GSK: Honoraria Richard Cookson, PhD, Genetech: Advisor/Consultant Nancy Devlin, PhD, GSK: Honoraria T. Mark Doherty, PhD, GSK: employee|GSK: Stocks/Bonds Antonio J Garcia-Ruiz, PhD, CHIESI: Advisor/Consultant|CHIESI: Grant/Research Support|CHIESI: Honoraria|Consumers and Users Organisations (CEACCU): Advisor/Consultant|Consumers and Users Organisations (CEACCU): Grant/Research Support|Consumers and Users Organisations (CEACCU): Honoraria|Foundation for Progress and Health : Advisor/Consultant|Foundation for Progress and Health : Grant/Research Support|Foundation for Progress and Health : Honoraria|GSK: Honoraria|Ministry of Science and Innovation of Spain: Advisor/Consultant|Ministry of Science and Innovation of Spain: Grant/Research Support|Ministry of Science and Innovation of Spain: Honoraria|Official College of Physicians: Advisor/Consultant|Official College of Physicians: Grant/Research Support|Official College of Physicians: Honoraria|Royal Academy of Medicine and Surgery of Eastern Andalusia: Advisor/Consultant|Royal Academy of Medicine and Surgery of Eastern Andalusia: Grant/Research Support|Royal Academy of Medicine and Surgery of Eastern Andalusia: Honoraria|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Honoraria|Sociedade Galega de Neuroloxía: Advisor/Consultant|Sociedade Galega de Neuroloxía: Grant/Research Support|Sociedade Galega de Neuroloxía: Honoraria|UCB: Advisor/Consultant|UCB: Grant/Research Support|UCB: Honoraria Louis P Garrison, PhD, GSK: Honoraria Terry Nolan, MD, PhD, Clover: Board Member|CSL Seqirus: Advisor/Consultant|CSL Seqirus: Grant/Research Support|Dynavax: Grant/Research Support|GSK: Advisor/Consultant|GSK: Board Member|GSK: Grant/Research Support|Iliad: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|Novavax: Board Member|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|SK Bio: Board Member Maarten Postma, Dr., Consumers and Users Organisations (CEACCU): Advisor/Consultant|Consumers and Users Organisations (CEACCU): Honoraria|Foundation for Progress and Health : Advisor/Consultant|Foundation for Progress and Health : Honoraria|GSK: Honoraria|Royal Academy of Medicine and Surgery of Eastern Andalusia: Advisor/Consultant|Royal Academy of Medicine and Surgery of Eastern Andalusia: Honoraria David M. Salisbury, CB FMedSci FRCP FRCPCH FFPH, Clover Pharmaceuticals: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Novavax Inc: Honoraria|Sanofi: Advisor/Consultant Hiral Shah, PhD, GSK: employee|GSK: Stocks/Bonds Jurgen Wasem, PhD, AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Clover: Advisor/Consultant|Clover: Board Member|GSK: Board Member|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Honoraria|Seqirus: Advisor/Consultant|Seqirus: Honoraria|Serum Institute of India: Advisor/Consultant|Serum Institute of India: Board Member|Zeria: Advisor/Consultant|Zeria: Board Member Ekkehard Beck, PhD, GSK: employee|GSK: Stocks/Bonds


Fusarium solani species complex fungal DNA was identified in cerebral spinal fluid (CSF) by polymerase chain reaction and next-generation metagenomic sequencing; a highly resistant strain was isolated from a single tissue culture. We describe epidemiology, demographics, and clinical features to inform prevention messaging, guidance, and future responses.US public health officials are responding to a multinational, multistate fungal meningitis outbreak involving travelers who had primarily cosmetic procedures  under epidural anesthesia at 2 Matamoros, Mexico clinics (closed 5/13/2023 by Mexican authorities). Public health officials collected data on confirmed and probable cases (1/1/23–7/25/2023) using a standardized case report form; data were analyzed in Microsoft Excel.In total, 10 probable (1 death) and 10 confirmed (8 deaths) US fungal meningitis cases were identified; all involved epidural anesthesia from the same anesthesiologist at both clinics. Most cases (80%) occurred in Texas residents. Median patient age was 31 years (range: 23–52); 19 patients were women; 13 were Hispanic/Latino. None had underlying conditions reported. At least 4 patients were uninsured, with several reporting associated care-seeking delays. Common symptoms were headache (n=18), nausea (n=13), fever (n=12), and stiff neck (n=12). Median (IQR) initial CSF results were white blood cell count (498/µL [343–825]), glucose (31 mg/dL [26–40]), and protein (99 mg/dL [52–2140]). In 8 patients, CSF -β-D-Glucan was ≥ 500 pg/ml. From procedure date, average days (range) to symptom onset was 19 (0–58), to hospitalization was 52 (14–106).In the US, the fungal meningitis outbreak has primarily affected young, healthy Hispanic/Latino women travelling to Matamoros, Mexico, for procedures and resulted in a high mortality rate (40%). CDC advises US residents against having elective procedures in Matamoros involving epidural anesthetic injection. Insurance barriers may have led to medical tourism to Mexico and subsequent delayed treatment for fungal meningitis, highlighting the need for preparation to address healthcare access disparities in future outbreaks.Luis Ostrosky-Zeichner, MD, FACP, FIDSA, FSHEA, FECMM, CMQ, Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Astellas: Honoraria|F2G: Advisor/Consultant|F2G: Grant/Research Support|F2G: Honoraria|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Melinta: Honoraria|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Expert Testimony|Pfizer: Honoraria|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support|Pulmocide: Honoraria|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Scynexis: Honoraria|T2 biosystems: Advisor/Consultant|T2 biosystems: Grant/Research Support|T2 biosystems: Honoraria|Viracor: Advisor/Consultant|Viracor: Grant/Research Support|Viracor: Honoraria


Pseudomonas aeruginosa is complex and multifaceted. While the novel β-lactamase inhibitors (BLI), avibactam, relebactam, and vaborbactam inhibit serine-based β-lactamases, the comparative potency of the novel β-lactam (BL) /BLI combinations against serine-carbapenemase producing P. aeruginosa is unknown. The present study sought to compare the in vitro activity of ceftazidime/avibactam, ceftazidime, imipenem/relebactam, imipenem, meropenem/vaborbactam, and meropenem against serine-β-lactamase producing P. aeruginosa.Antimicrobial resistance in P. aeruginosa were collated through the Enhancing Rational Antimicrobials against Carbapenem-resistant P. aeruginosa (ERACE-PA) Global Surveillance. Isolates positive for serine-based carbapenemases were assessed. Minimum inhibitory concentrations (MICs) were determined by broth microdilution to each novel-BL/BLI and BL alone. In vitro potency was assessed by MIC50/90 and percent of isolates susceptible per CLSI guidance.Carbapenem-resistant 50/MIC90 values of 4/8 mg/L and 91% of isolates were susceptible. Conversely, ceftazidime alone was active against only 3% of isolates. The MIC50/MIC90 of imipenem/relebactam were 16/ >16 mg/L and 13% of all isolates were defined as susceptibility. Against the KPC-producing isolates, 38% were susceptible to imipenem/relebactam compared with 0% for imipenem. The meropenem/vaborbactam MIC50/MIC90 were >16/ >16 mg/L, and 6% of isolates were susceptible which was similar to meropenem alone  suggesting the addition of vaborbactam cannot overcome co-expressed, non-enzymatic resistance mechanisms.GES was the most common carbapenemase identified (n=59) followed by KPC (n=8). Ceftazidime/avibactam had MICin vitro activity and thus is a rational treatment option for serine-carbapenemase harboring P. aeruginosa. While imipenem/relebactam displayed some activity particularly against isolates with KPCbla, meropenem/vaborbactam exhibited poor activity with MICs similar to meropenem alone. These data can be integrated with rapid molecular diagnostics to guide empiric therapy.Among the novel BL/BLIs, ceftazidime/avibactam displayed better Christian M. Gill, PharmD, Cepheid: Grant/Research Support|Entasis therapeutics: Grant/Research Support|Everest Medicines: Grant/Research Support|Shionogi: Grant/Research Support David P. Nicolau, PharmD, Allergan: Advisor/Consultant|Allergan: Grant/Research Support|Cepheid: Advisor/Consultant|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Tetraphase: Advisor/Consultant|Tetraphase: Grant/Research Support|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support|Wockhardt: Advisor/Consultant|Wockhardt: Grant/Research Support


To the Editor: Despite widespread use of photography, data on patient attitudes towards photography is scarce,https://doi.org/10.1016/j.jdin.2023.05.010).After Institutional Review Board exemption from approval, English-speaking patients over the age of 18 undergoing in-room clinical photography (IRCP) or 3D-total body photography (3D-TBP) using Vectra WB360 system in the Memorial Sloan Kettering dermatology clinic from December 2019-September 2020 were eligible for enrollment. Participants were interviewed using a semi-structured guide, consisting of a loosely predetermined framework allowing for open-ended discussion, based on a framework by Kallio et al  and IRCP (n = 9) , alopecia , and rash .Thirty-nine patients were approached, and 18 were recruited (49%) in 2 groups: 3D-TBP ( (n = 9) . Median https://doi.org/10.1016/j.jdin.2023.05.010). Other responses included physician recommendation  and diagnosis . No patients expressed concern about the consent process. Most participants were willing to allow nonclinical use of their photography: research/publication , teaching/education , and training artificial intelligence  but only if certain conditions were met: deidentification , removal of sensitive areas , or if separate consent was obtained . Almost all  considered face identifiable, but some also noted tattoos/piercings , scars , birthmarks , and jewelry  were identifiable.When asked about the reasons for photography, most participants  responded it was a routine part of care (Supplementary Table, available via Mendeley at Our study provides insight into patient perspectives on various aspects of photography. Although the experience was positive for most, some expressed concerns with sharing photographs with other providers and for nonclinical use of photographs. Patients preferred image access, particularly images containing identifiable or sensitive features, is limited to clinically necessary scenarios. For nonclinical use of photography, patients expressed need for separate consent. The wide variability in patient perspectives on “identifiability” highlights the need for consensus definition. Generalizability of the results is limited due to single-institution study design at a tertiary cancer center and low diversity in participants’ background. The findings of this exploratory study lay important groundwork for qualitative and quantitative studies, including ongoing quantitative studies evaluating patient and population-wide perspectives on clinical photography.Yuna Oh: Dennis Gross Skincare Foundation Grant; Mary Sun: None; Lilly Gu: None; Trina Salvador: None; Liliane Sar-Graycar: None; Dr Hay: None; Dr Quigley: None; Dr Marchetti: None; Dr Halpern: Receiving personal fees from Canfield Scientific, SciBase, and Lloyd Charitable Trust and having an equity position with HCW Health and Skip Derm; Dr Rotemberg: Expert advising for Inhabit Brands, Inc.


EBONI is a phase 4 effectiveness-implementation hybrid study focused on evaluating implementation of CAB LA delivery to Black cisgender and transgender women in US Ending the HIV Epidemic (EHE) jurisdictions. Results from the baseline survey of Staff Study Participants (SSPs) are presented here.Black women comprise 55% and 46% of new HIV diagnoses among cisgender and transgender women in the United States, respectively.1 CDC, 2021; CDC, 2019SSPs (N=65) from 14 clinics completed surveys with questions pertaining to their clinic characteristics, perceptions of populations appropriate for CAB LA, and their perceived appropriateness of CAB LA for Black women as measured by the Intervention Appropriateness Measure (IAM). The IAM uses a 5-point rating scale (1=completely disagree to 5=completely agree). One designated SSP for each clinic completed a questionnaire to assess use of PrEP at the clinic level.SSP and clinic-level characteristics are described in Tables 1 and 2. Most clinics were in the South (71.4%) and were private practice (36.4%), FQHCs (18.2%), or community-based organizations (18.2%). A total of 225 Black women across all clinics used any kind of PrEP and 69 received at least one injection of CAB LA at baseline. Most SSPs (86.2%) reported patients asked about CAB LA in their clinic.Overall, SSPs perceived Black women in their clinic as appropriate for CAB LA (IAM Mean Score=4.6). Sixty-six percent of SSPs reported there were individuals with specific demographics more appropriate for CAB LA. Of these, lesbian women, people older than 50 years of age, and heterosexual men were rated relatively lower than other demographics as appropriate by SSPs (Table 3). Having a partner living with HIV, condomless sex, and having multiple sexual partners were rated as behaviors most appropriate for CAB LA.Healthcare staff reported high levels of appropriateness of CAB LA for Black women and ranked populations and behaviors traditionally associated with PrEP as most appropriate for CAB LA. Better tools are needed to support SSPs in identifying individuals who could benefit from CAB LA.Michael Dunn, MD, Gilead: Speaker Rimgaile Urbaityte, MSc, GSK: Employment|GSK: Stocks/Bonds Kenneth Sutton, MA, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Denise Sutherland-Phillips, MD, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Alftan Dyson, PharmD, GSK: Stocks/Bonds|ViiV Healthcare: Employment Deanna Merrill, PharmD, MBA, AAHIVP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Amber Haley, PhD, ViiV Healthcare: Former Employment Kimberley Brown, PharmD, J&J: Stocks/Bonds|ViiV Healthcare: Empoyment Tammeka Evans, MoP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds


Streptococcus pneumoniae (iSpneumo) and Streptococcus pyogenes (iGABHS) have substantial morbidity and mortality. Decrease in culture (Cx) proven iSpneumo during COVID has been reported. We used PCR in empyema fluid for enhanced SBI microbiologic diagnosis. Here, we evaluate Cx/PCR diagnosed community acquired SBI (CA-SBI) in children and relationship with Flu burden and social distancing.Association of serious bacterial infections (SBI) and preceding respiratory viral illness (RVI) has been described. Social distancing, (masking and lockdowns), in response to pandemic resulted in > 95% decrease in RVI, specifically influenza (Flu). Invasive Data from surveillance of bacteremia and CA-empyema (Cx and PCR) at our institution was used to identify CA-SBI cases in children 3 months – < 18 years. Spinal fluid Cxs were reviewed to identify meningitis cases. We used data from the Orange County Health Care Agency for detection of countywide Flu trends. We normalized yearly CA-SBI cases per 10,000 discharges, grouped them into before COVID (BC) (7/1/2017 – 12/31/19) and after covid (AC) (1/1/2020 – 6/30/2022), and compared to countywide Flu cases 7/1/2017 – 6/30/2022.S aureus  and E coli  were most common overall  and per cohort  respectively ; 35.7% and 12.9% of iSpneumo and iGABHS respectively were identified by PCR only. Both decreased during COVID . iSpneumo and iGABHS mortality was 3.6% and 12.9% respectively. There were no iSpneumo (5/2020 – 10/2021) or iGABHS 12/2020 – 11/2021) cases or deaths when Flu was not circulating.We identified 361 CA-SBIs. iSpneumo and iGABHS cases decreased during social distancing, which included mandatory masking. No cases or deaths occurred when Flu was not circulating supporting association with Flu. Decrease in iSpneumo by routine pediatric vaccination has limitations due to differential protection by serotype and serotype replacement. Seasonal masking should be evaluated to decrease CA-SBI associated pediatric morbidity and mortality due to iSpneumo and iGABHS, further Flu vaccine development is needed.Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support Delma Nieves, MD, Merck: Grant/Research Support|Summit Therapeutics: Grant/Research Support Negar Ashouri, MD, Merck: Grant/Research Support


Enterobacterales resistant to commonly used antibiotics, rapid diagnostic tests, such as BioFire’s Blood Culture Identification 2 (BCID2) multiplex PCR panel, can be utilized to detect potential antimicrobial resistance more rapidly and help direct more appropriate empiric therapy. We describe the epidemiology of Enterobacterales bloodstream infection (BSI), associated antimicrobial resistance genes using BCID2, and subsequent susceptibility patterns at an academic medical center to develop a genotypic antibiogram.With the increasing incidence of infections from Enterobacterales BSI were included. Patient demographics, antimicrobial resistance markers, BCID2, culture, and susceptibility results were assessed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of blaCTX-M marker were compared to ceftriaxone susceptibility patterns.We reviewed all positive BCID2 results at Nebraska Medical Center from 8/1/2021–11/1/2022. Only monomicrobial Enterobacterales isolates, of which 236 were from male patients (52%), 189 (41%) immunocompromised patients, and 342 (75%) community onset. The most common species identified were Escherichia coli (55%) and Klebsiella pneumoniae (17%). blaCTX-M was detected in 49 (11%) isolates, with 41 (84%) E. coli and 6 (12%) K. pneumoniae. blaKPC was detected in 2 isolates (1 K. oxytoca and 1 K. variicola), but no other carbapenemase genes were detected. blaCTX-M sensitivity and specificity for detection of ceftriaxone resistance was 83% and 100%, respectively. blaCTX-M PPV for ceftriaxone resistance was 100%, while the NPV of absent blaCTX-M for ceftriaxone susceptibility was 97%.We reviewed 456 unique E. coli and Klebsiella BSIs harbor blaCTX-M, while carbapenemases are rare. Utilization of rapid diagnostics can optimize antimicrobial therapy for Enterobacterales by creation of a genotypic antibiogram.Locally, the majority of ceftriaxone-resistant Scott J. Bergman, PharmD, bioMerieux, Inc.: Honoraria Trevor C. Van Schooneveld, MD, FSHEA, FACP, AN2 Therapeutics: Grant/Research Support|Biomeriuex: Advisor/Consultant|Biomeriuex: Grant/Research Support|Insmed: Grant/Research Support|Thermo-Fischer: Honoraria


Correction: BMC Complement Med Ther 23, 404 (2023)10.1186/s12906-023-04225-zFollowing publication of the original article , the autStacked bar graphs representing association with chiropractic degree program of graduation and ideologies, beliefs, and practice patternsEach bar graph represents the sum of all response by the labeled subgroup on the x-axis and the color, matched to each graphs respective key, is the proportion of respondents within the subgroup who selected each answer and only identified a single correct answer. Respondents who answered for more than once choice were not represented in the bar graphs.Palmer: Palmer College of Chiropractic Main Campus, Davenport, IA; CCC-KC: Cleveland University Overland Park, KS; CCC-LA: Cleveland Chiropractic College Los Angles; Life: Life University, GA; Life West: Life Chiropractic College West Hayward, CA; Logan: Logan University, Chesterfield, MO; National: National University of Health Sciences, Lombard IL and Seminole, FL; Northwestern: Northwestern Health Sciences University, Bloomington, MN; NYCC: Northeast College of Health Sciences (formerly New York Chiropractic College), Seneca Falls, NY; Palmer-FL; Palmer College Of Chiropractic Florida Campus, Port Orange, FL; Palmer-West: Palmer College of Chiropractic West Campus, San Jose, CA; Parker: Parker University, Dallas, TX; SCUHS: Southern California University of Health Sciences, Whittier, CA; Sherman: Sherman College of Chiropractic, Spartanburg, SC; TCC: Texas Chiropractic College, Pasadena, TX; Bridgeport: University of Bridgeport, Bridgeport, CT; Western States: University of Western States, Portland, ORSurvey Question #1 labels: DDx: Differential Diagnosis only; DDx > SA: Focus on differential diagnosis, sometimes includes spinal analysis; DDx + SA: Equal focus on spinal analysis to detect subluxation and differential diagnosis; SA > DDx: Focus on Spinal analysis, sometimes includes differential diagnosis; SA: Spinal analysis to detect subluxation onlySurvey Question #2 labels: nMSK: Neuromusculoskeletal Conditions; MSKgen: General and Biomechanical Conditions; MSKsub: Vertebral Subluxation as a Musculoskeletal Condition; Somatovisc: Biomechanical and Organic/Visceral Conditions; Broad: Broad Spectrum of Health Concerns Including Lifestyle and Wellness Issues; VS: Vertebral Subluxation as an Encumbrance to HealthSurvey Question #3 labels: NMSK: spine and neuromusculoskeletal focused subgroup; Primary Care: General primary care focused subgroup; Subluxation: Subluxation detection and removal subgroupSurvey Question #4 labels: None: No Role; QoL: Improving Pain/Quality of Life; ImmuneFx: Improving Nervous System/Immune System Function; Innate: Removing Interference to Innate IntelligenceSurvey Question #5 labels: SA + A: Strongly Agree and Agree responses; SD + D: Disagree and Strongly Disagree responsesSurvey Question #6 labels: SD + D: Strongly Disagree and Disagree responses; A + SA: Agree and Strongly Agree responsesThe original article has been corrected.


Pseudomonas aeruginosa expressing serine and metallo-β-lactamases. CERTAIN-1 (Cefepime Rescue with Taniborbactam in cUTI) demonstrated that FTB was superior to meropenem (MEM) for the treatment of cUTI. Subgroup analyses were performed to determine the consistency of response, including for subgroups potentially more challenging to treat .Cefepime-taniborbactam (FTB) is an investigational β-lactam/β-lactamase inhibitor combination that is active against carbapenem-resistant Enterobacterales and multidrug resistant CERTAIN-1 was a randomized, double blind, double dummy, Phase 3 study comparing FTB to MEM in adults hospitalized with cUTI or Acute Pyelonephritis (AP). The primary endpoint was the composite  response at the test of cure (TOC) visit in the microITT population. A pre-specified test for superiority for the primary endpoint was performed following confirmation of non-inferiority. Patient demographic and baseline characteristics were analyzed for composite success. Treatment difference in success rate and corresponding 95% CI were calculated.661 patients were randomized and 436 patients (66.0%) were included in the microITT population; 38.1% of patients were ≥ 65 years of age and 13.1% had baseline bacteremia. Composite success rates were 70.6% and 58.0% for FTB and MEM groups, respectively for the primary endpoint at the TOC visit and FTB was superior to MEM . Composite success rates were consistent with the primary analysis for subgroups, including BMI and renal impairment, in patients with potentially more serious infections , and in at-risk patient subgroups  (Table). No subgroup appears to have driven the overall result of superiority of FTB compared to MEM for the composite success rate.FTB was superior to MEM for the primary endpoint at TOC and composite response rates were numerically higher in all subgroups, consistent with the primary efficacy response.Mary Beth Dorr, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Merck and Co.: Shareholder|Pfizer: Shareholder|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder Leanne Gasink, MD, MSCE, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|CSL Behring: Advisor/Consultant|CSL Behring: Consulting fees|Everest Medicines: Grant/Research Support|Evopint Biosciences: Advisor/Consultant|Evopint Biosciences: Consulting fees|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|LBG Consulting, LLC: Principal|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Consulting fees|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Consulting fees|Vera Therapeutics: Advisor/Consultant|Vera Therapeutics: Consulting fees Tim Henkel, MD, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Employee, consulting fees, shareholder Greg Moeck, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder Hongzi Chen, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee|Venatorx Pharmaceuticals, Inc.: Stocks/Bonds Scott A. McConnell, PharmD, Venatorx: employee|Venatorx: Stocks/Bonds Paul McGovern, MD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Paratek Pharmaceuticals: Shareholder|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder


Candida auris (C. auris) is a highly pathogenic, often multidrug resistant organism, that spreads in healthcare facilities. CDC recommends UWRC when a case is found in a unit. Currently, no recommendation exists for C. auris SOAC. We investigated if UWRC can be avoided, and clinical cases be prevented by SOAC in high-risk patients being admitted to an ICU.C. auris colonization  were screened for skin colonization with fungal axillary and groin swab cultures. These patients were placed on contact precautions pending test results. If C. auris was recovered, the patient would be upgraded to “Contact plus” precautions. If cultures were negative, precautions were downgraded to standard. No UWRC would be required if patients were identified and isolated upfront. We tracked the number of SOAC and clinical cases and compared them to the number of UWRC and clinical cases in the pre-study period.We conducted a pilot QI study in which high-risk patients for C. auris UWRCs were performed per month in reaction to 18 clinical cases, with 8 positive surveillance cultures over those 3 months (0.98% positive rate). In April 2023, our pilot study month, a total of 13 admission screening cultures were collected, of which none were positive. No UWRC were performed, and no clinical cases were detected.Between January 2023 and March 2023, an average of 273 Although limited by the pre- and post-nature, the abbreviated time, and the sample size of this pilot QI study, we found that risk based SOAC is a strategy that warrants further study as an alternative to UWRC, which are costly and labor intensive.Luis Ostrosky-Zeichner, MD, FACP, FIDSA, FSHEA, FECMM, CMQ, Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Advisor/Consultant|F2G: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Pulmocide: Grant/Research Support|Scynexis: Grant/Research Support|T2 Biosystems: Grant/Research Support|Viracor: Advisor/Consultant


Pythium insidiosum, is a neglected, life-threatening condition which carried a 100% mortality rate, within 3 months, among patients with residual disease after surgery, regardless of antifungal treatment. Recently, Thai P. insidiosum isolates were found to susceptible to doxycycline and azithromycin, with evidence of synergy. We report results of a clinical trial from 15 centers in Thailand .Vascular pythiosis, caused by P. insidiosum-specific antibodies, positive cultures, or positive histopathology. All received surgery, itraconazole, doxycycline, and azithromycin. Patients were followed up until 6 months after diagnosis. Subsequent follow-ups after 6 months were at the clinician’s discretion if there were any concerns for residual diseases or unresectable arterial lesions.This study enrolled patients with vascular pythiosis who had 2 of the 4 diagnostic criteria: consistent clinical presentation, positive serum Klebsiella pneumoniae bacteremia). Among patients with residual disease, 1 (7.1%) died and 13 are still alive. Median follow-up time (IQR) among patients with residual disease was 385 (209-622) days. There were no statistical differences in time from onset to surgery and time from onset to first antimicrobial between patients with and without residual disease after surgery (Table). One patient had to stop doxycycline prematurely due to photosensitivity.40 patients were enrolled, with a median age (interquartile range [IQR]) of 51 (45-56) years. 38 (95%) had major thalassemia, 1 (2.5%) had liver cirrhosis, and 1 (2.5%) had myeloproliferative syndrome. None had known immunocompromised conditions. After surgery, 14 (35%) still had residual diseases. At 6 months after diagnosis, 3 (7.5%) patients died (disseminated pythiosis, sepsis with multi-organ failure, and ESBL Patient characteristicsIQR: interquartile range; N: numberThe new treatment combination with surgery, itraconazole, azithromycin, and doxycycline improved survival among patients with vascular pythiosis who had residual disease.Nitipong Permpalung, MD, MPH, Alcimed: Advisor/Consultant|CareDx: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|Clarion: Advisor/Consultant|ClearView: Advisor/Consultant|IMMY Diagnostics: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support


The 11,805 Enterobacterales from the USA were tested for susceptibility (%S) using CLSI broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) or iron-depleted CAMHB for CFDC. Comparator agents included β-lactam/β-lactamase inhibitor (BL/BLI) combinations ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (I-R) meropenem-vaborbactam (MVB), piperacillin-tazobactam (P/T) as well as meropenem (MEM), cefepime (FEP) and ceftazidime (CAZ). Susceptibility was interpreted according to 2022 CLSI & FDA breakpoints. Carbapenem resistant Enterobacterales (CRE) was defined as resistant to imipenem (IPM) and MEM. Multidrug-resistant (MDR) Enterobacterales was defined as nonsusceptible to at least 1 drug from ≥ 3 classes and extensively drug resistant (XDR) as susceptible to ≤ 2 classes per 2022 CLSI criteria.The most common infection type from which isolates were collected was urinary tract infection , followed by bloodstream infection , pneumonia , intra-abdominal infections , and skin-soft tissue infections . Among CRE and MDR isolates, CFDC was the most active agent ( > 98%S) for isolates from BSI, PNA, and UTI. Among XDR isolates from BSI and PNA, %S to CFDC ( > 97%) was highest amongst all agents tested. Of the Bl/BLIs, C/T and P/T demonstrated the lowest %S against CRE and MDR isolates from BSI, PNA, UTI and among XDR isolates from BSI and PNA.in vitro activity against Enterobacterales regardless of infection type. Susceptibility for comparator agents was generally lower against isolates with CRE, MDR, and XDR phenotypes. CFDC represents a potential early treatment option for infections caused by Enterobacterales with presumed or defined CRE, MDR, XDR phenotypes, regardless of infection type.CFDC demonstrated high Jason J. Bryowsky, PharmD, MS, Shionogi Inc.: Employee Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee Joshua Maher, PhD, AbbVie: Grant/Research Support|Affinity Biosensors: Grant/Research Support|AimMax Therapeutics, Inc: Grant/Research Support|Alterity Therapeutics: Grant/Research Support|Amicrobe, Inc: Grant/Research Support|Arietis Pharma: Grant/Research Support|Armata Pharmaceuticals, Inc: Grant/Research Support|Astrellas Pharma, Inc.: Grant/Research Support|Basilea Pharmaceutica AG: Grant/Research Support|Becton Dickinson And Company: Grant/Research Support|bioMerieux, Inc: Grant/Research Support|Boost Biomes: Grant/Research Support|Diamond V: Grant/Research Support|Fedora Pharmaceuticals, Inc: Grant/Research Support|Iterum Therapeutics plc: Grant/Research Support|Johnson & Johnson: Grant/Research Support|Kaleido Biosciences, Inc.: Grant/Research Support|Meiji Seika Pharma Co. Ltd.: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer Inc.: Grant/Research Support|Roche Holding AG: Grant/Research Support|Shionogi Inc.: Grant/Research Support|Summmit Therapeutics, Inc.: Grant/Research Support|Zoetis Inc: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Miki Takemura, n/a, Shionogi & Co., Ltd.: Stocks/Bonds Yoshinori Yamano, PhD, Shionogi HQ: Employee


Ceftobiprole medocaril is currently being developed for the treatment of patients with SAB, including infective endocarditis. PK-PD target attainment analyses were performed in order to provide support for ceftobiprole dosing regimens for the treatment of patients with SAB.Ceftobiprole medocaril is an intravenously (IV) administered cephalosporin that is rapidly converted to the active moiety ceftobiprole in vitro surveillance data for S. aureus, percent probabilities of PK-PD target attainment were evaluated for ceftobiprole dosing regimens among simulated patients with SAB. Simulated patients by creatinine clearance group (CLcr) and resembling the clinical trial population of the ERADICATE Phase 3 study  were generated using replication of these clinical trial data. Dosing regimens by CLcr group that matched drug exposures to ceftobiprole 500 mg IV every 6 hours on Days 1 to 8 and every 8 hours on Day 9 and onwards among simulated patients with normal renal function were identified and then assessed among simulated patients. Randomly assigned ceftobiprole free-drug plasma %T > MIC targets associated with net bacterial stasis and a 1-log10 CFU reduction from baseline for S. aureus based on data from a neutropenic murine-thigh infection model were assessed.Using a previously developed population PK model for ceftobiprole, %T > MIC targets for efficacy, and Table 1. Table 2 shows the percent probabilities of PK-PD target attainment by MIC value and overall on Days 1 and 10. The highest MIC values at which percent probabilities of PK-PD target attainment were ≥ 90% based on free-drug plasma %T > MIC targets associated with net bacterial stasis and a 1-log10 CFU reduction from baseline for S. aureus were ≥ 4 µg/mL  among simulated patient groups. Overall percent probabilities of PK-PD target attainment were > 99.9%.Selected ceftobiprole dosing regimens for patients with SAB by CLcr group are shown in Results of PK-PD target attainment analyses provided support for ceftobiprole dosing regimens for patients with SAB with 500 mg IV every 6 hours on Days 1 to 8 and every 8 hours from Day 9. Dosing regimens were adjusted for renal function.Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Jeffrey P. Hammel, MS, Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Employee|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Anthony J. Rinaldo, B.S., Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Employee|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Karine Litherland, Ph.D., Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Full time employee|Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Leonard R. Duncan, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mark E. Jones, PhD, Astellas Pharma Global Development, Inc: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Marc Engelhardt, MD, Astellas Pharma Global Development, Inc.: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Paul G. Ambrose, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Christopher M. Rubino, PharmD, Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support


Acinetobacter baumannii calcoaceticus species complex (ACB) isolates, including multidrug-resistant (MDR) and carbapenem-resistant strains. SUL-DUR is a combination of sulbactam, a β-lactam antibacterial with activity against ACB and durlobactam, a β-lactamase inhibitor with activity against Class A, C and D β-lactamases. In this study, we evaluated the in vitro activity of SUL-DUR, as well as double and triple combinations of SUL, DUR and cefiderocol or imipenem against a set of 66 ACB isolates.Sulbactam-durlobactam (SUL-DUR) is in clinical development for the treatment of Activity of sulbactam-durlobactam (fixed 4 mg/L), antibacterial combinations, and comparators against a set of 66 A. baumannii-calcoaceticus species complex isolatesBacterial isolates consisted of 41 ACB isolates from the Centers for Disease Control and Prevention Antimicrobial Resistance Bank and 25 molecularly characterized cefiderocol-resistant ACB clinical isolates from the SENTRY Antimicrobial Surveillance Program. ACB identifications were confirmed by MALDI-TOF. Susceptibility testing of SUL-DUR and comparators was conducted according to CLSI M07 (2018) and M100 (2023) guidelines. Susceptibility testing of cefiderocol and cefiderocol combinations was conducted in Chelex-treated Mueller-Hinton broth. Cefiderocol and imipenem results were interpreted using CLSI breakpoint criteria50/90, 2/4 mg/L; 98.5% inhibited at ≤4 mg/L), cefiderocol-sulbactam-durlobactam , and imipenem-sulbactam-durlobactam  were the most active combinations tested against the set of 66 A. baumannii isolates (Table). Against these isolates, cefiderocol and imipenem susceptibilities were 37.9% (CLSI) and 9.1% (CLSI), respectively.SUL-DUR  was active against the ACB isolates tested regardless of cefiderocol susceptibility, including MDR and carbapenem-resistant isolates. The addition of imipenem or cefiderocol to SUL-DUR did not greatly improve SUL-DUR activity  when compared to SUL-DUR tested alone. The potent activity of SUL-DUR against this set of ACB isolates, including cefiderocol-resistant strains, supports the continued development of this combination.Overall, SUL-DUR (MICMichael D. Huband, BS, BARDA: This study has been funded in part by BARDA under Contract No. 75A50120C00001.|Entasis: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Gina M. Morgan, MS, Entasis: Grant/Research Support Holly Huynh, BS, Entasis: 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


Mpox virus was declared a public health emergency of international concern by the World Health Organization in July 2022. The full range of clinical manifestations of this emerging infectious disease continues to be elucidated.We present a case series and literature review of patients with mpox myocarditis and pericarditis, including demographics, clinical symptoms, diagnostic and management strategies, and outcomes.We identified 13 patients aged 21-51 (median 32) years with polymerase chain reaction-confirmed mpox and myopericarditis (n=3), pericarditis (n=1), or myocarditis (n=9), from 6 countries on 3 continents. All but one were men. One was HIV-positive  and 4 were on HIV pre-exposure prophylaxis. None had prior cardiac disease and 3 used tobacco. Most acquired mpox via sexual contact; one heterosexual patient reported non-sexual close contact. Cutaneous/mucosal lesions occurred in 11/13 patients, and fever in 11/13. Where reported, cardiac symptom onset was 2-8 (median 5.5) days after mpox illness onset. C-reactive protein ranged from 9.3-154.5 (median 52.6) mg/L. Diagnosis of myocarditis/myopericarditis was based on symptoms , elevated troponin , supportive electrocardiogram (ECG) findings , and/or cardiac imaging findings . In the pericarditis case, ECG showed widespread ST elevation and echocardiogram showed hyperdynamic LV. Treatments included ASA or non-steroidal anti-inflammatory drugs (n=7), tecovirimat (n=5), colchicine (n=4), ACE-inhibitors (n=3) and bisoprolol (n=3). All were hospitalized, with lengths of stay of 4-10 days, and at least 3 patients required intensive care. Cardiac symptom recovery occurred within 1-3 days of admission; in at least 1 patient symptoms continued beyond 1 month.Mpox is rarely associated with myocarditis and/or pericarditis, with cardiac symptoms beginning on day 2-8 after illness onset. Long-term outcomes require further study.Cécile Tremblay, MD, Association canadienne de protection médicale: Expert Testimony|Astra-Zeneca: Advisor/Consultant|Astra-Zeneca: Honoraria|Canadian Institutes of Health Research: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Honoraria|Medicago: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|National Institute of Health: Grant/Research Support|Sanofi: Advisor/Consultant Darrell H. S. Tan, MD PhD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Glaxo Smith Kline: Grant/Research Support


Mucormycosis is a life-threatening invasive fungal infection associated with high mortality. Amphotericin B is first-line therapy; however, the benefit of high doses remains uncertain. The purpose of this study is to describe outcomes in patients treated with high dose versus standard dose liposomal amphotericin B (L-AMB) for mucormycosis.This was a retrospective cohort study of adults ≥ 18 years treated with L-AMB for proven or probable invasive mucormycosis at Massachusetts General Hospital and Brigham & Women’s Hospital from 2016-2022. L-AMB dosing was based on clinician preference. Patients were excluded if L-AMB began > 7 days prior to admission. Patients were categorized per L-AMB dose: standard dose  and high dose (≥ 6 mg/kg for at least one dose). The primary outcome was 6- and 12-week mortality.67 patients were treated with L-AMB for proven or probable mucormycosis during the study period: 57 with standard dose and 10 with at least 1 high dose of L-AMB. Baseline characteristics are shown in Table-1. More patients in the standard dose group had underlying hematologic malignancy. About one third of patients had underlying diabetes and this was evenly distributed between groups. Table-2 shows infection- and treatment-related details. Proven invasive mucormycosis was diagnosed in 51/57 (89%) and 6/10 (60%) patients in the standard and high dose groups, respectively. The most common site of infection in both groups was skin/bone. Approximately 35/57 (61%) and 8/10 (80%) patients in the standard and high dose groups, respectively, had surgical debridement. Mortality at 6- and 12- weeks and renal toxicity outcomes are shown in Table-3. In the entire cohort at 6- and 12 weeks death occurred in 25/67 (37%) and 33/67 (49%) patients, respectively; no difference in mortality was seen between the standard and high dose groups. There appeared to be no difference in renal outcomes, though more patients in the standard dose group required renal replacement therapy within 6-weeks of diagnosis.We observed no difference in 6- and 12-week mortality among patients treated with L-AMB at standard and high doses for invasive mucormycosis. Mortality at 6- and 12-weeks of mucormycosis diagnosis remains high.Ramy H. Elshaboury, PharmD, DayZero Diagnostics: Advisor/Consultant|Gilead, Inc: Grant/Research Support|Thermofisher: Grant/Research Support Sophia Koo, MD, SM, Aerium Therapeutics: Advisor/Consultant|GSK: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant


E. coli caused uUTI using predictive modeling and evaluated its clinical validity.Empiric antibiotic (ABX) treatment for uncomplicated urinary tract infections (uUTIs) can be ineffective due to antimicrobial resistance (AMR). Understanding the risk of AMR using data-driven approaches can inform appropriate ABX selection. We developed an AMR pathogen risk categorization framework in E. coli urine culture treated with nitrofurantoin (NTF), trimethoprim/sulfamethoxazole (SXT), fluoroquinolones (FQs), or beta-lactams (BLs) were identified from the Optum de-identified electronic health record data set (Oct 2015–Feb 2020). We developed predictive models using machine learning to quantify AMR probability for each ABX class. A framework with 3 risk categories  was constructed using the predicted probability (PP) of non-susceptibility (NS) (Table 1). Six patient profiles from differing risk categorizations were reviewed for clinical validity by 5 clinicians .Eligible females with uUTI confirmed by positive Figure 1). After review of the patient profiles (Table 2), clinical experts confirmed the consistency of modeled risk classification for all 6 patients with their own assessment of AMR risk across all drug classes. Patient 1 was aged 20 yrs, White, West residence, no UTI or ABX history 1 year prior to her uUTI; PP of NS was low  and was classified as low risk for all ABX classes. In contrast, patient 6 was post-menopausal, Black, Midwest residence, and had UTI episodes, prior AMR, and multiple healthcare visits 1 year prior to uUTI. She had high PP of NS  and was categorized as high risk for all ABX classes.Of 87,487 eligible patients, approximately half were classified as low or high risk (44.0–49.1% across ABX classes). The proportion of patients with infections due to NS organisms was 5–12-fold higher among patients classified as high or moderate vs low risk (AMR risk varied greatly between patients. Our prediction model contextualizes patients’ AMR PP to 4 commonly prescribed ABX classes in the setting of uUTIs. Clinical application of this framework could inform appropriate empiric ABX selection for patients with uUTI.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 Wendy Y. Cheng, MPH, PhD, ORCID: 0000-0002-8281-2496, Analysis Group, Inc.: Wendy Y. Cheng is an employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Kalé Kponee-Shovein, ScD, Analysis Group, Inc: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Fernando Kuwer, MSc, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Chi Gao, ScD, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Ashish V. Joshi, PhD, GSK: Employee|GSK: Stocks/Bonds Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds Patrick Schwab, PhD, GSK: Employment|GSK: Stocks/Bonds Diogo Ferrinho, PharmD, GSK: Employee|GSK: Stocks/Bonds Malena Mahendran, MS, Analysis Group, Inc.: Malena Mahendran is an employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Daniel Indacochea, PhD, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Lisa Pinheiro, MFin, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Jimmy Royer, PhD, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds Jennifer Han, MD, GSK: Employment|GSK: Stocks/Bonds Richard Colgan, MD, GSK: Advisor/Consultant


Patient Prefer Adherence 2012; 6 369–88). Esketamine nasal spray (NS), in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI), increases remission and response rates in patients with TRD compared with placebo plus SSRI/SNRI . ESCAPE-TRD (NCT04338321) is the first randomised clinical trial to compare esketamine NS to quetiapine extended-release (XR), an antipsychotic augmentation therapy for patients with TRD.Treatment resistant depression (TRD) is estimated to affect 10–30% of patients with major depressive disorder (Al‑Harbi To explore the efficacy and safety of esketamine NS compared with quetiapine XR in TRD over 32 weeks (wks).In the ESCAPE-TRD phase IIIb open-label, rater-blinded trial, patients were randomised 1:1 to esketamine NS  or quetiapine XR (150–300 mg daily) both in combination with an ongoing SSRI/SNRI. Remission  and response  rates were analysed over time using last observation carried forward. MADRS change from baseline was analysed using Mixed Models for Repeated Measures (MMRM). The most common adverse events (AEs) leading to discontinuation are reported for patients who received ≥1 dose of study medication.Figure). The most common AEs leading to treatment discontinuation for esketamine NS were dizziness , dissociation  and vomiting , and for quetiapine XR were sedation , weight increased  and somnolence .At baseline, 336 patients were randomised to esketamine NS and 340 to quetiapine XR. A significantly higher percentage of patients in the esketamine NS group achieved remission (at each visit from Wk6 [p=0.008] onward) and response (at each visit from Day 15 [p<0.001] onward) versus patients treated with quetiapine XR. Esketamine NS significantly improved MADRS score compared to quetiapine XR at each visit from Day 8 onwards, with an average difference over time in the least squares means total MADRS score change from baseline of -2.4  on major depression, bipolar disorder, ADHD and suicidal behaviour (aided in developing guidelines); board member of DGBS, DGPPN, ECNP and German Depression Foundation, Speakers bureau of: (and participated in advisory boards over the last 3 years) for Cyclerion, Janssen, Medice, SAGE/Biogen and Shire/Takeda; received speaker’s honoraria from Das Fortbildungskolleg; , A. E. Anıl Yağcıoğlu Grant / Research support from: Participated as an investigator for Janssen, Speakers bureau of: (and participated in advisory boards over the last 3 years) for Janssen and Abdi İbrahim Otsuka, A. Luts Speakers bureau of: (or participated in advisory boards for or participated as an investigator) for Janssen-Cilag, Asarina Pharma, Bristol Meyer Squibb, Dr August Wolff GmbH & Co, Eli Lilly, Lundbeck, Pfizer, Allergan, Sunovion and Regeneron., T. Messer Consultant of: National Care Guidelines  on major depression (aided in developing guidelines), Speakers bureau of: (and participated in advisory boards) for Janssen-Cilag and Otsuka/Lundbeck, R. Nielsen Consultant of: Board member of DSAL and IGSLi, Speakers bureau of:  for Boehringer Ingelheim, Compass Pharmaceuticals, Janssen-Cilag, Lundbeck, Otsuka, Sage and Teva Pharmaceuticals, J. Buyze Employee of: Janssen, T. Ito Employee of: Janssen, Y. Kambarov Employee of: Janssen, S. Mulhern Haughey Employee of: Janssen, B. Rive Employee of: Janssen, I. Usankova Employee of: Janssen, C. von Holt Employee of: Janssen, Y. Godinov Employee of: Janssen


Correction: Journal of Orthopaedic Surgery and Research (2023) 18:778 https://doi.org/10.1186/s13018-023-04211-81, Chuchard Punsawad1, Rapheeporn Khwanchuea1, Naparat Sukkriang1, Pirada Yincharoen1 and Chaiwat Rerkswattavorn1* have been added to the author group and are presented correctly in this correction article.Following publication of the original article , the autFirst author: Wandee ChanprasertpinyoSecond author: Chuchard PunsawadThird author: Rapheeporn KhwanchueaFourth author: Naparat SukkriangFifth author: Pirada YincharoenCorresponding author: Chaiwat RerkswattavornThe affiliation of all authors is School of Medicine, Walailak University, 222, Thai Buri, Tha Sala, Nakhon Si Thammarat, 80160, Thailand.The original article  has been


Acinetobacter spp., including multidrug resistant strains. ATTACK was a global, active-controlled Phase 3 trial conducted to evaluate the efficacy and safety of SUL-DUR vs. colistin for patients with Acinetobacter infections. Both arms were dosed on a background of imipenem/cilastatin to treat co-infecting Gram-negative pathogens. Here, the in vitro activity of carbapenems with or without SUL-DUR added against P. aeruginosa (PA) or Enterobacterales is presented.Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination in development for the treatment of infections caused by Broth minimal inhibitory concentrations (MICs) for single, double, and triple combinations of sulbactam, durlobactam and imipenem or meropenem were determined following CLSI methodologies. Two different sets of isolates were tested: 104 molecularly characterized clinical isolates and 69 co-infecting baseline pathogens from the ATTACK trial.Enterobacterales isolates, the MIC90s of imipenem and meropenem were reduced from 32 and >32 μg/ml to 2 μg/ml in the presence of durlobactam. Against 49 carbapenem-resistant P. aeruginosa, addition of durlobactam reduced the imipenem MIC90 8-fold from 32 to 4 μg/ml and the meropenem MIC90 from 64 to 16 μg/ml. Of the 39 co-infecting pathogens from ATTACK, 30 (43%) were carbapenem non-susceptible . Addition of durlobactam restored imipenem susceptibility to 83% (N = 25) and meropenem susceptibility to 70% (N = 21) of these isolates. No antagonism was observed for any durlobactam combination tested. The addition of sulbactam had no effect on the antibacterial activity of either carbapenem -/+ durlobactam added for any of the isolates in this study.Against 55 in vitro antibacterial activity of imipenem and meropenem against a majority of carbapenem-resistant Enterobacterales and P. aeruginosa clinical isolates, while the addition of sulbactam had no effect on any combination tested. These results indicate that durlobactam has the potential to restore carbapenem activity against these organisms when present in Acinetobacter polymicrobial infections.The addition of durlobactam restored the Sarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds|Innoviva Specialty Therapeutics: Stocks/Bonds Nicole Carter, MS, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds Samir Moussa, PhD, Innoviva: Stocks/Bonds|Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds Alita Miller, PhD, Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds


Respiratory syncytial virus (RSV) is ubiquitous and infects almost all children during the first two years of life; infants (<1 year) and children with high-risk conditions  are at an increased risk for severe infection and hospitalization. Most patients are managed at home, yet data are sparse on the natural history of RSV infection in non-hospitalized populations. To address this gap, the natural history of RSV infection in children (< 2 years) initially managed in the outpatient setting was examined in two US data sources, by COVID-19 era.In Optum and Truveta, both US-based, electronic health record databases, infection episodes among children (< 2 years) with a positive RSV laboratory test  in the ambulatory setting were identified prior to , or during  the COVID-19 pandemic. Episodes were excluded if immediately hospitalized (within 24 hours of index), and multiple infections per patient were allowed if >28 days apart. First occurrence of all-cause hospitalization was assessed 14 and 28 days after index.During the pre-COVID-19 era, mean age ranged from 8.6-8.7 months, while during the COVID-19 era, mean age was slightly higher at 9.7-9.8 months (Table 1). Infants < 1 month were most commonly hospitalized after an initial outpatient visit, compared to older infants (Table 2). In 28 days of follow-up, the hospitalization proportion among children < 2 years ranged from 4.8-5.6% pre-COVID-19 and 3.6-5.4% during the COVID-19 pandemic (Table 2), similar to values using 14 days of follow-up. Risk was higher in Truveta than Optum; hospitalization in neonates (< 1 month) increased in the COVID-19 era compared to pre-COVID-19, while the opposite was true for children < 2 years.Most RSV outcomes occurred within 14 days of a positive test. Despite healthcare disruptions of the COVID-19 pandemic, an appreciable proportion of children were hospitalized after RSV infection diagnosed in the outpatient setting, especially among infants < 1 year. Future work will investigate sources of heterogeneity in results across data sources.Diana Garofalo, PhD MPH, Pfizer: Stocks/Bonds Sima Toussi, MD, Pfizer: Stocks/Bonds Joshua T. Swan, PharmD, MPH, BCPS, FCCM, CareDx: Grant/Research Support|Genentech: Grant/Research Support|Grifols Share Services North America: Grant/Research Support|Heron Therapeutics: Grant/Research Support|Kedrion Biopharma: Advisor/Consultant|Kedrion Biopharma: Grant/Research Support|Pacira Pharmaceuticals: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Employee|Pfizer: Stocks/Bonds|VigiLanz Corporation: Grant/Research Support Maria Kudela, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Padmalatha Reddy, Ph.D., Pfizer: Stocks/Bonds Stephen E. Schachterle, Pfizer Inc., Pfizer Inc.: Full time employee|Pfizer Inc.: Ownership Interest|Pfizer Inc.: Stocks/Bonds Suzanne Landi, PhD, Pfizer, Inc: Employment|Pfizer, Inc: Stocks/Bonds Anindita Banerjee, Phd, Pfizer: Employee and stockholder Margaret Tawadrous, MD, MS, Pfizer: Full time employee|Pfizer: Full-time employee|Pfizer: Full-time employee|Pfizer: Full -time employee|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Niki Alami, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Scott P. Kelly, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds


While the number of immunocompromised (IC) individuals continues to rise, the existing literature on influenza vaccine effectiveness (VE) in IC populations is limited. IC individuals have a higher risk of severe influenza and influenza-related hospitalizations, and understanding the VE of the seasonal influenza vaccines in IC populations remains paramount.>18 years.Using 2017-2018 US Flu VE Network (US Flu VE) data, we examined the VE of the 2017-2018 seasonal influenza vaccine against symptomatic influenza in outpatient settings among IC adults. Patients were enrolled from outpatient sites in five states. IC status was determined by ICD-10 codes. We used logistic regression and adjusted for enrollment site, race, self-reported general health status, age, and onset date of symptoms. Separate models were used to calculate and compare the VE for non-IC and IC among outpatient adults 5671 participants were included in the adult analytic dataset, and 455 (8%) were IC. The VE among non-IC was 31%  and among IC participants was -4 % . P-value for interaction by IC status was 0.100.We observed lower VE against symptomatic influenza among non-hospitalized patients with immunocompromising conditions though the difference was not statistically significant. This study demonstrates the capacity to study a large IC population using an existing influenza VE network and contributes to the literature to support large, multicenter VE studies for IC populations.Richard K. Zimmerman, MA; MD; MPH; MS, Sanofi Pasteur: Grant/Research Support MaryPatricia Nowalk, PhD, RDN, Merck & Co.: Grant/Research Support|Merck & Co.: Honoraria|Sanofi: Grant/Research Support Fernanda P. Silveira, MD, Ansun: Grant/Research Support|Eurofins Viracor: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Grant/Research Support|Regeneron: Grant/Research Support|Takeda: Advisor/Consultant Emily T. Martin, PhD, MPH, Merck: Grant/Research Support


Pseudomonas aeruginosa with difficult-to-treat resistance are likely to receive meropenem (MEM) as an empiric therapy before escalation to broader agent such as ceftolozane/tazobactam (C/T) after antimicrobial susceptibility data are available. We assessed if pre-exposure to MEM impacted the development of C/T-resistance upon C/T exposure.Patients infected with P. aeruginosa isolates were assessed. Isolates were exposed to 16 mg/L MEM concentration for 72h, interrupted by wash step every 24h to avoid drug degradation and antibiotic carryover. Then, isolates were serially passaged in the presence of C/T as two groups: MEM-exposed group inoculated with MEM pre-exposed isolates and non-MEM control group. Three consecutive passages took place at a C/T concentration of 10 mg/L for 72h. After 24 h intervals, samples were serially diluted, plated onto Mueller Hinton agar, and incubated to quantify bacterial densities (log10 cfu/mL). Samples were plated on drug free and drug containing agar (C/T concentration 16 mg/L) where growth on C/T agar indicated resistance development. Resistant population was calculated by dividing the cfu/mL on C/T containing plates by the cfu/mL on drug free agar . Percentage of C/T-resistant population was compared between MEM-exposed and MEM non-exposed passages of each isolate.Six clinical Table 1). In three isolates, MEM exposure significantly increases the prevalence of resistance development against C/T; the percentage of resistance population for the three isolates were 100%, 31%, and 3% for the MEM-exposed versus 0%, 0.35%, and ≤0.0003% in the unexposed groups. One isolate had similar percent resistant population at 72 h between groups (≤0.003 and ≤0.005%). The remaining isolates showed no development of resistance in either group.At 72 h, resistant populations were detected in 4/6 isolates (in vivo and clinical data are needed to further assess the clinical implications of these findings.Previous MEM exposure may pre-dispose to C/T resistance development upon exposure limiting therapeutic utility. Resistance may be a result of the stress exposure or molecular level mutations conferring cross-resistance. Further Samantha Nicolau, PhD, Sanofi Pasteur: full time research scientist 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 David P. Nicolau, PharmD, Allergan: Advisor/Consultant|Allergan: Grant/Research Support|Cepheid: Advisor/Consultant|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Tetraphase: Advisor/Consultant|Tetraphase: Grant/Research Support|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support|Wockhardt: Advisor/Consultant|Wockhardt: Grant/Research Support Christian M. Gill, PharmD, Cepheid: Grant/Research Support|Entasis therapeutics: Grant/Research Support|Everest Medicines: Grant/Research Support|Shionogi: Grant/Research Support


While Rhinovirus/Enterovirus (RV/EV) infections are common, the clinical characteristics of infections in hospitalized adults are not fully understood.Adults ≥ 50 years of age hospitalized for Acute Respiratory Infections (ARI) or exacerbations of CHF or COPD in two hospitals in Atlanta, GA during the 2018-2019 and 2019-2020 respiratory seasons were offered enrollment. Following informed consent, participants were tested via BioFire® FilmArray® respiratory panels of nasopharyngeal and oropharyngeal swabs (combined), and standard-of-care molecular testing results were also recorded. Subjects were considered positive for RV/EV if any method of testing resulted positive. Baseline characteristics and clinical features were gathered via subject interviews and medical record abstractions. Variables were compared between subjects with RV/EV and two control groups: those negative for all pathogens and those negative for only RV/EV. Participants with RV/EV who had co-infections were excluded from the analysis. Descriptive statistics were performed using SAS v9.4.Of 1429 enrolled participants, 123 (8.6%) were positive for RV/EV, of whom 111 had RV/EV alone. When compared to those negative for all tested pathogens (n=1034), participants with RV/EV more commonly had underlying COPD  and less commonly had CHF  or experienced acute myocardial dysfunction . Participants with RV/EV also more commonly experienced fever , cough , sore throat , chest pain , and dyspnea/respiratory distress  than those negative for all pathogens. Differences between RV/EV positive and negative groups were similar to the all pathogen negative group, with the exception of no significant differences in acute myocardial dysfunction, fever, and COPD in the RV/EV negative group.Among older adults hospitalized with ARIs, CHF, and/or COPD exacerbations, RV/EV was associated with symptoms of both upper and lower respiratory tract infection and was more frequent identified among those with COPD.Elizabeth Begier, M.D., M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Bradford J. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support


Mangrove wetlands are coastal ecosystems with important ecological features and provide habitats for diverse microorganisms with key roles in nutrient and biogeochemical cycling. However, the overall metabolic potentials and ecological roles of microbial community in mangrove sediment are remained unanswered. In current study, the microbial and metabolic profiles of prokaryotic and fungal communities in mangrove sediments were investigated using metagenomic analysis based on PacBio single-molecule real time (SMRT) and Illumina sequencing techniques.Candidatus Cosmopoliota with a ubiquitous distribution is proposed. Genomic analysis revealed that this new phylum is capable of utilizing various types of organic substrates, anaerobic fermentation, and carbon fixation with the Wood-Ljungdahl (WL) pathway and the reverse tricarboxylic acid (rTCA) cycle.Comparing to Illumina short reads, the incorporation of PacBio long reads significantly contributed to more contiguous assemblies, yielded more than doubled high-quality metagenome-assembled genomes (MAGs), and improved the novelty of the MAGs. Further metabolic reconstruction for recovered MAGs showed that prokaryotes potentially played an essential role in carbon cycling in mangrove sediment, displaying versatile metabolic potential for degrading organic carbons, fermentation, autotrophy, and carbon fixation. Mangrove fungi also functioned as a player in carbon cycling, potentially involved in the degradation of various carbohydrate and peptide substrates. Notably, a new candidate bacterial phylum named as The study not only highlights the advantages of HiSeq-PacBio Hybrid assembly for a more complete profiling of environmental microbiomes but also expands our understanding of the microbial diversity and potential roles of distinct microbial groups in biogeochemical cycling in mangrove sediment.Video AbstractThe online version contains supplementary material available at 10.1186/s40168-023-01630-x. With the development of high-throughput sequencing techniques, metagenomic sequencing has becoming a paradigm shift for the study and exploration on microbial community , 2. ContIllumina sequencing platform has become the most widely used method for metagenomic studies because of its high accuracy (0.1–1% error rates) and throughput . HoweverRepresented by Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT), the recently emerged third-generation sequencing platforms offer a possible solution to partly resolve ambiguous repetitive regions and to improve genome contiguity , 13. AltMangrove wetlands represent an important coastal ecotype widely distributed in tropical and subtropical regions , 23. BecHere, we conducted a metagenomic survey based on separate assembly of Illumina short reads, PacBio long reads, and a combination of these two (Hybrid assembly) to investigate the microbial community and metabolic potentials in the mangrove sediment Fig. . Our res4+), nitrate nitrogen (N/NO3−), total phosphorus (TP), and total sulfur (TS), were determined following the description of Zhang et al. -Hydrogenases, [FeFe]-Hydrogenases, Carbohydrate-Active Enzymes (CAZymes), and dissimilatory sulfite reductase (dsr) genes. Fig. S8. Read count of microbial community and specific genes in different sediment depth. Read counts are standardized to CPM (count (read) per million reads). (a) Read count of Prokaryotes, Eukaryotes, Archaea, Bacteria, and Fungi based on 16S rRNA and ITS genes against SILVA database and UNITE database for all eukaryotes, respectively. (b) Read count of Hydrogenases, [NiFe]-Hydrogenases, [FeFe]-Hydrogenases, Carbohydrate-Active Enzymes (CAZymes), and dissimilatory sulfite reductase (dsr) genes. Fig. S9. Read count of metagenomic reads for specific genes in different sediment depth. Read counts are standardized to CPM (count (read) per million reads). Abbreviation: NiFe/FeFe, [NiFe]-/[FeFe]-hydrogenases; atpA, ATP synthase; coxA, cytochrome c oxidase; cyoA, cytochrome o ubiquinol oxidase; ccoN, cytochrome c oxidase; HCO, haem-copper oxidase genes ; cydA, cytochrome bd oxidase; acsB, acetyl-CoA synthase; mcrA, methyl-CoM reductase; dsr, dissimilatory sulfite reductase; sor, sulfur oxygenase/reductase; narG, dissimilatory nitrate reductase; napA, periplasmic nitrate reductase; nir, dissimilatory nitrite reductase; nrf, ammonifying nitrite reductase; nif, nitrogenase; nifH, nitrogenase iron protein; rbcL, ribulose 1,5-bisphosphate carboxylase; pfor, pyruvate-ferredoxin oxidoreductase. Fig. S10. Glycoside hydrolases (GH) identified by CAZy searches of the MAGs. GH families that contain enzymes that are not specifically involved in degradation were specifically identified by Pfam or EC numbers in the annotations, based on Wrighton et al. 2014. Fig. S11. Pathway completeness of all refined MAGs calculated by KEGGDecoder. The pathway completeness is defined as the percentage of core genes of specific pathways identified in each MAG. Complete lists of metabolic genes or pathways can be found in Dataset Shttps://github.com/bjtully/BioData/blob/master/KEGGDecoder/KOALA_definitions.txt. The up row of heatmap shows the MAG completeness, and the bottom raw represent the phylogenetic information of each MAG at phylum level (Archaea in purple and Bacteria in blue). Fig. S12. The phylogenetic tree of Candidatus Cosmopoliota and the adjacent phyla based on 16S rRNA genes. The genomes of Ca. Cosmopoliota are labeled in orange color and bold font. Fig. S13. The average amino acid identity (AAI) values between each genome in Candidatus Cosmopoliota and the adjacent phyla. The genomes of Ca. Cosmopoliota are labeled in orange color and bold font. Fig. S14. The average nucleotide identity (ANI) values between the 16S rRNA genes of Ca. Cosmopoliota and the adjacent phyla. The genomes of Ca. Cosmopoliota are labeled in orange color and bold font.Additional file 2: Dataset S1. Sheet1: Sample information; Sheet2: Stats of raw data; Sheet3: Microbial community estimated based on 16S rRNA (for Prokaryotes) and ITS (for Eukaryotes) by graftM search on SILVA database and blastn search on UNITE database, respectively; Sheet4: Specific genes of prokaryotic community.Additional file 3: Dataset S2. Sheet1: Assembly details of different sequencing methods; Sheet2: Stats of MAGs derived from different sequencing methods and refined MAGs; Sheet3: Draft MAGs used to compare the effects of different assemble methods; Sheet4: Classification, quality, details, coverage depth, and gene number of refined MAGs; Sheet5: Pathway completeness of all refined MAGs calculated by KEGGDecoder; Sheet6: Gene numbers of each pathway annotated by METABOLIC software; Sheet7: Glycoside hydrolases (GH) identified by CAZy searches of the MAGs. GH families that contain enzymes that are not specifically involved in degradation were specifically identified by Pfam or EC numbers in the annotations; Sheet8: Peptidase genes identified against MEROPS database by METABOLIC software; Sheet9: Anaerobic hydrocarbon degradation genes annotated by METABOLIC software.Additional file 4: Dataset S3. Sheet1: The metabolic characteristics of the major fungal groups annotated against KEGG; Sheet2: Detail information of the carbohydrate-active enzyme family (CAZymes) detected in major fungal groups; Abbreviations: GH, glycosidases or glycosyl hydrolases; PL, polysaccharide lyases; CE, carbohydrate esterases; GT, glycosyltransferases; AA, auxiliary activities; CBM, carbohydrate binding modules; Sheet3: Detail information of the peptidase family genes detected in major fungal groups; Abbreviations: Aspartic (A), Cysteine (C), Metallo (M), Mixed (P), Serine (S) and Threonine (T).Additional file 5: Dataset S4. Sheet1: Detail information for MAGs belong to Candidatus Cosmopoliota; Sheet2: The metabolic characteristics of Ca. Cosmopoliota, annotated against KEGG database; Sheet3: Detail information of CAZymes encoded in Ca. Cosmopoliota; Abbreviations: GH, glycosidases or glycosyl hydrolases; PL, polysaccharide lyases; CE, carbohydrate esterases; GT, glycosyltransferases; AA, auxiliary activities; CBM, carbohydrate binding modules; Sheet4: Detail information of peptidase encoded in Ca. Cosmopoliota; Abbreviations: Aspartic (A), Cysteine (C), Metallo (M), Mixed (P), Serine (S) and Threonine (T); Sheet5: Gene functions of each MAG annotated by metabolic software; Sheet6: Information of sequences belonging to Ca. Cosmopoliota (identity > 83%) retrieved from GenBank; Sheet7: SRA samples with sequences belonging to Ca. Cosmopoliota (identity > 83%) retrieved from Microbe Atlas Project by MAPseq.


Bacillus anthracis administered in conjunction with recommended antibacterial regimen. A drug-vaccine interaction study (NCT04067011) was conducted to examine whether co-administration of AV7909 with ciprofloxacin (CIP) or doxycycline (DOX) affects antibiotic pharmacokinetics (PK) or AV7909 immunogenicity in healthy adults.AV7909  vaccine was developed for post-exposure prophylaxis (PEP) of disease following suspected or confirmed exposure to 50) values generated by a toxin neutralizing antibody (TNA) assay. Steady-state maximum concentration, Cmax and area under the curve from 0 to 12 hours, AUC0-12hrs for CIP and DOX were calculated. Safety was evaluated by collection of solicited reactogenicity and reports of adverse events (AEs).A Phase 2, randomized, open-label study was conducted to assess the effects of AV7909 (intramuscularly (IM) at 0, 2 weeks) on PK profiles of orally administered CIP and DOX in healthy adults between 18 and 45 years of age. Participants (n=210) were randomized to receive AV7909+CIP, AV7909+DOX or AV7909 alone. Serum concentrations of CIP and DOX were determined using liquid chromatography with tandem mass spectrometry, while AV7909 immunogenicity was evaluated using 50% neutralizing factor  of 90% CI for AUC0-12h  was within the equivalence criteria, but LB of 90% CI for Cmax (0.79) was below the equivalence criteria . This result for steady-state DOX Cmax is likely limited given that its efficacy is mainly AUC-driven. The immunogenicity endpoint was met, wherein LB of two-sided 95% CI of the geometric mean ratio of TNA NF50 was >0.5 . The majority of solicited reactogenicities and AEs were Grade 1 or 2 in severity.Primary PK endpoint for CIP was met, wherein 90% confidence intervals (CIs) of mean ratios for steady-state AUCCo-administration of CIP or DOX with AV7909 did not alter the relevant PK parameters of antibacterials or immunogenicity of AV7909 and was well tolerated in healthy adults.Gideon Akintunde, Director Clinical Development, Emergent Biosolutions: Employee Bojan Drobic, Director Clinical Development, Emergent Biosolutions: Employee Lisa Bedell, Director Biostatistic, Emergent Biosolutions: Employee Lu Gan, Director Biostatistic, Emergent Biosolutions: Employee Julia Kim, Scientist Clinical Development, Emergent Biosolutions: Employee Marinda Beah, Manager Clinical Trials Development, Emergent Biosolutions: Employee Isaac Ghinai, Medical Director, Emergent Biosolutions: Employee Santiago Barona Collado, Medical Director, Emergent Biosolutions: Employee