In a study initiated in 2020, we recruited nursing home (NH) residents and collected blood samples serially after SARS-CoV-2 vaccinations. While sex differences in vaccine-induced immune response have been previously observed, similar vaccine efficacy across sex groups was reported for Moderna and Pfizer mRNA vaccines. Sex differences in immune response may diminish in very late life, so we sought to compare immune response to mRNA primary series and monovalent and bivalent boosters in NH residents, a frail elderly population.We analyzed anti-Spike antibodies and neutralizing titers to Wuhan strain for sex differences in immune response following primary series and subsequent booster doses. We summarized demographics and infection history of NH subjects with available sample data at each vaccine dose. Omicron BA.5 assays were compared for the second monovalent and bivalent boosters. Comparisons were stratified by prior infection at the time of sample. Samples collected about breakthrough infections were excluded. Geometric mean titers were calculated for each post-vaccine time and compared across sex groups using t-tests on log-transformed titers.Despite new enrollment and loss to follow up, our cohort retained a sex balance ranging from 39% women, 61% men to an even split across four post-vaccine timepoints. Men and women had similarly advanced age and rates of prior COVID-19 over time (Table). Following the primary series, women with prior infection had significantly higher anti-Spike antibodies and higher neutralizing titers than men with prior infection . Following both monovalent booster doses and a bivalent booster dose, no sex differences were detected in these endpoints among those with prior infection. Neither were differences observed in infection naive subjects nor in titers for the Omicron BA.5 strain .Post-vaccine Wuhan anti-Spike antibodies and neutralizing titers by vaccine dose and sex, with bars showing geometric mean titers and 95% confidence intervals. Significant differences in GMT indicated with * at p < 0.05.Post-vaccine Omicron BA.5 anti-Spike antibodies and neutralizing titers by vaccine dose and sex, with bars showing geometric mean titers and 95% confidence intervals. No sex differences detected.Sex differences observed among NH residents with prior infection following primary series mRNA vaccination diminished with additional vaccine doses. Within NH residents, this may be a result of sex differences in attrition among the lowest responders. Further study is required to assess sex differences in the durability of immune response between doses and in T-cell response.Stefan Gravenstein, MD, MPH, CDC: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|GSK: Honoraria|Janssen: Advisor/Consultant|Janssen: Honoraria|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Grant/Research Support|Seqirus: Honoraria David Canaday, MD, Pfizer: Grant/Research Support


Trichomonas vaginalis (TV) and Chlamydia trachomatis (CT) from single dose to a 7-day course. Social Determinants of Health (SDOH) are non-medical factors that influence a person’s life; little is known regarding the association between SDOH and TV and CT treatment. The study objective was to evaluate treatment of TV and CT infections after the guideline update and determine if health inequities exist with use of preferred therapy.The 2021 CDC Sexually Transmitted Infections (STI) Treatment Guideline modified preferred therapy for IRB approved, retrospective cohort of patients ≥ 15 years with confirmed diagnosis of uncomplicated TV or CT in outpatient settings. Excluded: pregnant/nursing, allergy to preferred therapy, unable to take oral. Primary outcome: proportion who received guideline preferred vs non-preferred  antibiotic therapy. Logistic regression was used to identify variables associated with preferred treatment; SDOH were exposures of interest. Secondary outcomes: test of cure (≤ 3 months), any repeat positive test (recurrence/reinfection), any retreatment, expedited partner therapy (EPT) offered. A sample of 712 patients was needed to detect a 10% difference between two exposures .Table 1. Patients < 25 years had more asymptomatic disease compared to older patients . Patients who received Emergency Department (ED) care were more likely to receive preferred therapy compared to outpatient clinics . Black race, lower median income, and public insurance covaried with ED care. After adjusting for female sex, receipt of ED care was independently associated with preferred therapy (Table 2). 181 (25%) patients had 3-month test of cure performed; repeat positive test/retreatment was more frequent in patients who received non-preferred therapy . EPT was offered in 35 (7%) and 8 (3%) patients in the preferred and non-preferred groups (P=0.03).473 (66%) patients received preferred therapy; patient characteristics are in Preferred therapy was more frequent in patients who received ED care. EDs represent an important safety net and provide high-level care for patients with SDOH barriers.Erin Eriksson, PharmD, BCPS, BCIDP, Stryker Corp: Stocks/Bonds Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Michael Veve, PharmD, MPH, National Institutes of Health: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support


Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. Uncomplicated UTI, or acute uncomplicated cystitis (AUC), is an area of interest for antimicrobial stewardship in Japan due to high prevalence of community antibiotic use. This analysis estimated the annual prevalence of AUC in Japan from 2016 to 2021.This cross-sectional observational study used Japanese Medical Data Center (JMDC) data from January 1, 2016 to November 30, 2021 to examine the epidemiology of AUC in Japan. Female patients aged ≥18 to < 75 years with an AUC diagnosis claim  in the outpatient setting, including emergency room, were included. The annual prevalence for each year of interest was calculated as the number of patients with ≥1 AUC diagnosis claim in the outpatient setting divided by the number of female patients in the JMDC claims database who were ≥18 years old; values were multiplied by 100,000 to obtain prevalence per 100,000 females. Prevalence was calculated for subgroups of patients aged ≥18–49 years and ≥50–74 years (age ranges chosen as a proxy for menopause status). The annual prevalence of AUC in the Japanese female population (≥18 years old) was projected for the years 2016–2021 using population data taken from the annual Japan census.The mean annual prevalence of AUC among women in Japan 2016–2021 was 7421 cases per 100,000 females (Table 1). The prevalence of AUC was higher for women aged ≥50 years at index compared with those aged < 50 years, with annual rates of 8716 vs 6273 cases per 100,000, respectively (Table 1). Annual prevalence projections of AUC in Japan (2016–2021) ranged from 2.6–3.9 million women, with 6.0–8.6% of the female population affected each year . Among patients who experienced recurrent AUC (≥2 AUC episodes in 12 months), the mean number of episodes per year was 3.45 .Our study shows that the burden of AUC among female patients in Japan is moderate, with annual prevalence between 6.0 and 8.6%, and higher prevalence among women over the age of 50. Patients with AUC recurrence averaged 3.45 episodes per year.Meg Franklin, PharmaD, PhD, Franklin Pharmaceutical Consulting: Owner and President|Franklin Pharmaceutical Consulting: Ownership Interest|GSK: Grant/Research Support|PRECISIONheor: Contractor Maia R. Emden, BA, GSK: Grant/Research Support|PRECISIONheor: Employee Elise Bauer, MS, GSK: Grant/Research Support|PRECISIONheor: Employee Naomi Sacks, PhD, GSK: Grant/Research Support|PRECISIONheor: Employee Shinya Kawamatsu, PhD, GSK: Employee|GSK: Stocks/Bonds Yoshiaki Kawano, MD, PhD, GSK: Employee|GSK: Stocks/Bonds Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds Ashish V. Joshi, PhD, GSK: Employee|GSK: Stocks/Bonds Shinyoung Ju, MS, GSK: Employee|GSK: Stocks/Bonds Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds


Correction: BMC Infect Dis 23, 250 (2023)10.1186/s12879-023-08204-0The original publication of this article  containeIncorrect title:Research article network analysis of polymicrobial chronic wound infections in Masanga, Sierra LeoneCorrect title:Network analysis of polymicrobial chronic wound infections in Masanga, Sierra Leone.The original article  has been


Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic, inflammatory disease with systemic manifestations affecting multiple aspects of patients’ lives. It can require lifelong management, as recurrence is common, however current microbiologic outcomes are often difficult to obtain and insufficient to reflect the impact on patients. We aim to identify the core outcome domains essential to evaluate in future clinical research studies of outcomes in MAC-PD, using an international consensus process, and we describe the Round 1 preliminary results.We invited relevant stakeholders in MAC-PD research including patients, caregivers/family members, clinicians, researchers, nonprofit and patient education organizations, and federal research funding organizations to participate in the Delphi consensus process. We used respondent driven sampling to expand our cohort. Participants were asked to rate preliminary domain importance, without regard to availability, feasibility, or validity of measurement instruments, using the Grading of Recommendations Assessment, Development and Evaluation scale (score 1-9). We administered surveys via email through DelphiManager software. We used SAS version 9.4 to describe our participants and the Round 1 core outcome domain scores.Critical (score >7) by more than 70% and had fewer than 15% identifying the domain as Not Important (score <3).We had a total of 48 participants, including 30 (62.5%) clinicians, 10 (20.8%) researchers, 6 (12.5%) patients, and 2 (4.2%) from organizations that fund MAC-PD research. A majority were women , ages 60-69  who identified as White  and were from North America . Most had 10 years or more experience  in their MAC-PD stakeholder role. Symptoms, Microbiology, Treatment Side effects, Chest imaging, Physical function, Treatment burden, and Vitality/Energy domains were rated as We report the initial evaluation of core outcome domains for MAC-PD through an international consensus process. Identification and dissemination of these domains will help guide research priorities on future outcome measures.Alexandra L. Quittner, PhD, AN2: Advisor/Consultant|Insmed Pharmaceutical Corp: Advisor/Consultant Kevin L. Winthrop, MD, MPH, AN2: Advisor/Consultant|AN2: Grant/Research Support|Insmed: Advisor/Consultant|Insmed: Grant/Research Support|Insmed: This study was funded by Insmed Inc.|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Red Hill Biopharma: Advisor/Consultant|Red Hill Biopharma: Board Member|Red Hill Biopharma: Grant/Research Support|Renovion: Advisor/Consultant|Renovion: Grant/Research Support|Spero: Advisor/Consultant|Spero: Grant/Research Support


NHs are high-risk settings for MDRO spread.C. auris), and from bilateral nares . We assessed overall MDRO prevalence, as well as MDRO co-carriage patterns across organisms and MDRO body site carriage for each pathogen.We evaluated NH MDRO prevalence and co-carriage patterns in 22 NHs in Orange County, CA from Fall 2022-Spring 2023. 25 MDRO sweeps each involved 50 randomly-sampled occupied beds. Residents had swabs collected from bilateral axilla/groin and peri-rectal areas , CRAB (2.1%), and CRE (1.0%). Of the 719 MDRO carriers, 62.2% (447) carried 1 MDRO and 37.8% (272) carried ≥2 MDROs. Carriers of one MDRO were likely to carry another (Table 1). For example, MRSA carriers had 48.1% likelihood of carrying another MDRO. Conversely, carriers of any other MDRO had a 45.9% (range: 44.9%-69.2%) likelihood of carrying MRSA. Notably, all CRE carriers and 92.3% of CRAB carriers carried another MDRO. Table 2 shows common body sites for carriage of each MDRO. Nares was the most common site of MRSA carriage; axilla/groin, for CRE and C. auris; peri-rectal areas, for VRE and ESBL; and axilla/groin and peri-rectal carriage, for CRAB.Of 1250 residents, 57.5% (719) had MDRO carriage at any body site. Prevalence was highest for MRSA (36.7%), followed by ESBL (24.9%), VRE (14.2%), This table represents patterns of multidrug-resistant organism (MDRO) co-carriage among nursing home (NH) residents, for MDROs including Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE), Extended Spectrum beta-lactamase (ESBL) producers, Carbapenem-resistant Enterobacterales (CRE), Carbapenem-resistant Acinetobacter baumannii (CRAB), and Candida auris. Each row shows the prevalence of MDRO co-carriage for a specific pathogen. For example, the first row shows MDRO co-carriage patterns among 459 MRSA carriers. MRSA carriers had 48.1% likelihood of carrying any other MDRO. Conversely, the last row shows that carriers of any MDRO other than MRSA had a 45.9% likelihood of carrying MRSA whereas carriers of any MDRO other than C. auris had a 9.2% likelihood of carrying C. auris.This table shows body site carriage of multidrug-resistant organisms (MDROs) among nursing home residents, for MDROs including Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE), Extended Spectrum beta-lactamase (ESBL) producers, Carbapenem-resistant Enterobacterales (CRE), Carbapenem-resistant Acinetobacter baumannii (CRAB), and Candida auris. For each pathogen, the number and percent of carriers are shown per body site . The dominant site of carriage for each MDRO is as follows: nares for MRSA (76.0%), peri-rectal for VRE (88.1%) and ESBL (84.6%), axilla/groin for CRE (76.9%) and C. auris (88.8%). Axilla/groin and peri-rectal sites had equal carriage for CRAB (63.2% each). By necessity, all dominant sites were the most common body site for solo carriage. For example, among nursing home residents with MRSA nares carriage, (42.1%) had MRSA only in the nares and 57.9% had MRSA at another body site.Multi-MDRO carriage is common among NH residents with MDROs harbored at multiple body sites. Co-carriage was especially high among those harboring a carbapenem-resistant organism, likely reflecting accrued MDROs from extensive and repeated antibiotic exposure. Understanding MDRO co-carriage patterns can identify strategies that may be effective across MDROs. For example, nearly half of residents colonized with a non-MRSA MDRO also carried MRSA, suggesting that nasal decolonization of any MDRO carrier may benefit outcomes for MRSA, the most common MDRO in NHs.Gabrielle Gussin, MS, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product|Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Raveena D. Singh, MA, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product|Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Raheeb Saavedra, AS, Medline Industries, Inc: Conducted studies where participating hospitals/nursing homes received cleaning & antiseptic product|Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Connie Nguyen, n/a, Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Alice Lee, n/a, Xttrium Laboratories: Conducted studies where participating hospitals & nursing homes received antiseptic bathing product Susan S. Huang, MD, MPH, Medline: Conducted studies in which participating nursing homes received contributed antiseptic bathing and cleaning products|Xttrium: Conducted studies in which participating nursing homes and hospital patients received contributed antiseptic soap


The causative role of RSV on CAAP has been strongly suggested from multiple epidemiological studies. Although pneumococcal-RSV coinfections in pneumonia were suggested by a pre-licensee PCV9 study, no solid real-life data were generated to substantiate the potential effect of PCVs on RSV-associated CAAP (RSV-CAAP). The current prospective study evaluates the impact of PCV7/PCV13 implementation in Israel on all-cause CAAP and RSV-CAAP incidence dynamics in young children during RSV seasons.The important role of PCV7/PCV13 were implemented in Israel in July 2009/November 2010. A prospective population-based surveillance on CAAP rates in children < 5 years in southern Israel has been ongoing since 2002 . Nasal samples of RSV (by PCR) were tested in most episodes and were extrapolated for total CAAP episodes. RSV season was defined as all months with >5 positive RSV tests in southern Israel. The impact was determined by incidence rate ratio (IRR) comparing each RSV season (and the four years 2015-19 combined) to the five pre-PCV implementation years, 2004-09, combined).Table, Figure). Generally, yearly seasonal IRRs for all-cause CAAP and RSV-CAAP were similar.From Jul-2004 to Jun-2019, 7,654 CAAP episodes were recorded; 3,661 (47.8%) were tested for RSV, of which 1,662 (45.4%) were positive. The seasonal proportions of RSV-CAAP of all episodes ranged from 37.4% to 67.2%. Compared to 2004-09 (combined), IRR (95% CI) for 2015-19 were 0.68 (0.56-0.84) for RSV CAAP and 0.70 (0.61 – 0.80) for all-cause CAAP  together with the real-life impact of PCVs on RSV-CAAP confirm the mutual role of RSV and S. pneumoniae in CAAP.The abrupt, steep , and seasonal reduction of hospitalization of young children for both all-cause CAAP and RSV-CAAP strongly support the important role of RSV-Ron Dagan, Professor MD, GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Expert Testimony|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria David Greenberg, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Shalom Ben-Shimol, Dr. MD, GSK: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria


Lipohypertrophy  accumulation) is a common and significant problem in people with HIV (PWH). Pathogenesis remains elusive; yet, AT abnormalities are key drivers of cardiometabolic co-morbidities in HIV. We aimed to assess effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on AT in PWH with lipohypertrophy.2, increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after ART initiation. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly subcutaneous injection) or matching placebo. Computed tomography and whole-body dual-energy X-ray absorptiometry were used to measure area/density in abdominal AT  and body composition , resp. Semaglutide effects were estimated using generalized estimating equations or simultaneous quantile regressions on outcome variables.We conducted a randomized, double-blinded, placebo-controlled trial of virologically-suppressed, non-diabetic PWH ≥ 18 years of age on stable antiretroviral therapy (ART) with body mass index (BMI) ≥ 25 kg/mth), TAT, and SAT with trends (P < 0.1) for limb fat and VAT . Semaglutide effects remained significant for BMI, HOMA-IR, trunk fat, TAT, and VAT after adjusting for age, sex, CD4, and ART duration (Table 2); caloric intake was also significant at ≤ 50th quantile. No differences were seen in LBM, AT density, or VAT/TAT ratio. Semaglutide was well-tolerated; serious adverse events were rare.108 participants were enrolled . Groups were well-matched at baseline. In unadjusted models, semaglutide group had greater reductions (P < 0.05) in BMI, homeostatic model of insulin resistance (HOMA-IR), trunk fat, TBF (at quantile ≥ 75Semaglutide significantly decreased central fat in PWH with lipohypertrophy, primarily driven by reductions in VAT. Semaglutide may offer an effective treatment to decrease visceral adiposity and reduce co-morbidity risk. Further investigation is needed to determine mechanisms by which reductions in visceral adiposity occur.Grace A. McComsey, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support


Nirsevimab is an extended half-life monoclonal antibody that binds the prefusion conformation of RSV fusion (F) protein and has been approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants in the EU, Great Britain, and Canada. Global surveillance studies found that the nirsevimab binding site was highly conserved across RSV variants between 1956–2021. While RSV B F protein binding site substitutions I206M and Q209R have dominated since the 2017/2018 RSV season, both remain fully susceptible to nirsevimab. OUTSMART-RSV is a multi-year (from 2015) prospective molecular surveillance study to monitor the prevalence and distribution of RSV variants in the USA and track the emergence and susceptibility of RSV F variants to nirsevimab.in vitro microneutralization assays.Nasal swabs were collected from infants and adults seeking medical attention for respiratory infection (inpatient or outpatient); RSV-positive isolates underwent next generation sequencing. Subtyping comprised analysis of the hypervariable region of the G protein. F protein polymorphisms were identified by comparing with RSV A and B reference sequences; variants with increasing prevalence were phenotypically evaluated using reverse genetics rescue and 50 fold change = 1.24 vs reference). Also, no new nirsevimab binding site substitutions were seen in the 2021/2022 RSV season vs previous seasons.RSV A and B subtypes circulated with alternate frequency during OUTSMART-RSV , with RSV B dominant in the 2021/2022 RSV season . From 2020, several additional RSV B F protein substitutions have increased in prevalence, including the S211N binding site substitution. Importantly, S211N retains full susceptibility to nirsevimab (ICWhile I206M and Q209R substitutions in RSV B F protein continue to dominate, the S211N nirsevimab binding site substitution has increased in prevalence since the 2020-2021 season. However, similar to I206M and Q209R, S211N variants remain fully susceptible to nirsevimab. Among recent circulating RSV strains, the frequency of emergent nirsevimab escape variants continue to be rare and not persistent.Christopher A. Morehouse, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Bahar Ahani, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Anastasia A. Aksyuk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tyler Brady, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kevin M. Tuffy, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Hong Ji, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Elizabeth J. Kelly, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds


Chronic liver disease (CLD) is a major cause of morbidity and mortality, with high risk of infection as CLD progresses. Gut microbiome disruption, which worsens with CLD severity, causes loss of colonization resistance and impaired gastrointestinal (GI) barrier function, enabling pathogen translocation across the GI tract. We evaluated shotgun metagenomic data from 3 studies and 288 patients with CLD to evaluate the role of the microbiome in the progression of disease, and enable the rational design of SER-147, a cultivated consortium of human commensal bacteria, to restore colonization resistance against key pathogens and promote GI homeostasis in CLD patients.SER-147 design relied on both (1) microbiome targets identified from a bioinformatic analysis of public observational datasets in CLD patients and (2) past Seres clinical trial pharmacology data. We ingested genomic and matching clinical data from 3 studies and 288 patients (Table 1), processing all primary read data through Seres genomic databases to enable comparison with internal healthy comparator cohorts. Functional characterization of the Seres strain library (SSL) facilitated SER-147 design to include traits important to colonization resistance and GI barrier integrity .The design framework for preclinical drug candidates integrates a combination of public observational datasets in CLD patients, Seres interventional clinical trials, and proprietary bioinformatic algorithms to inform disease target identification. These data are subsequently fed into a rational design framework that utilizes (1) trial engraftment, (2) disease-informed preclinical microbiome modeling, and (3) functional learnings from SSL to identify taxa with the desired pharmacological properties.Bioinformatic analyses support evidence of progressive microbiome disruption and diversity loss as CLD worsens, as key Firmicutes are reduced while Proteobacteria are enriched. Rational design yielded candidate consortia with taxa that can (1) generate barrier-restorative metabolites , (2) reduce inflammatory cytokine production, (3) tolerate oxidative and acid stress, and (4) decolonize intestinal pathogens in preclinical models .Nineteen candidate bacterial strains were selected for inclusion in SER-147 candidate consortia based on numerous genotypic and phenotypic traits. Evidence of engraftment of strains in Seres clinical trials was a minimum inclusion criterion to help ensure pharmacokinetic capability of SER-147. Genomic and in silico design features included: depletion during CLD progression, predicted lantibiotic production, presence of KEGG-Orthologs for oxygen tolerance, and predicted contribution to decolonization phenotypes based on preclinical modeling. Phenotypic design features were selected based on extensive in vitro and in vivo characterization of strains and include the generation of barrier-restorative metabolites like short-chain fatty acids (SCFA), secondary bile acid conversion, and tryptophan metabolism. SER-147 candidate strains were additionally assessed in vitro for their capacity to tolerate low pH, grow in hypoxic culture conditions, suppress IL-8 activity, and utilize lactulose as a sole carbon source as it is a commonly prescribed medication in the CLD patient populationPatients with CLD are at increased risk of mortality from infections seeded from the GI tract due to microbiome disruption and GI barrier compromise. Microbiome therapeutics such as SER-147 represent a potentially powerful and novel approach to reducing the risk of infection in CLD by directly targeting key risk factors of GI-seeded infections.Jenna Wurster, PhD, Seres Therapeutics: Paid Employee|Seres Therapeutics: Stocks/Bonds Tim Straub, MS, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Edward J. O'Brien, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Nathaniel J. Ennis, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Melissa Mayol, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Jessica Brown, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Marin Vulić, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Nicholas Beauchemin, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Elizabeth Halvorsen, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Christopher Ford, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Matthew Henn, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds


Clostridioides difficile (CD) colonization is common among hospitalized patients. Screening for toxigenic CD (TCD) colonization with rectal swab nucleic acid amplification tests (NAAT) may identify people at risk for CDI and help prevent onward TCD transmission, especially in immunocompromised patients with long hospitalizations. The study objective was to test whether rectal swab NAAT could detect TCD colonized patients and whether NAAT results identify patients that contribute to environmental contamination.tcdA or tcdB by whole genome sequencing (WGS).This was a prospective cohort study on two BMT/Leukemia units. Stool specimens, rectal swabs, and environmental swabs  were collected from patients at admission and weekly and cultured semi-quantitatively for TCD. NAAT (Cepheid) was performed on rectal swabs . The relationship between stool TCD concentration, NAAT Ct, and a positive environmental culture was evaluated using univariate logistic regression. Bleach was used for daily and terminal discharge cleaning of all rooms. Toxigenicity was determined by detection of From January 2019 - July 2019, 659 stool specimens and 495 rectal swabs were collected from 384 patients. Specimens from 554 patient-days were cultured and 126 (23%) were positive. Of those, 88 (70%) were TCD. 21 of 987 (2%) environmental swabs were TCD positive; 18 (86%) were from bedrails. Among 61 unique patient calendar days with paired rectal swab NAAT and stool culture results (paired samples), overall sensitivity of rectal swab NAAT to detect toxigenic CD colonization compared to culture was 44%, with 4/16 (25%) of people colonized with > 0 - < 10,000 CFU/g of TCD and 7/9 (78%) with ≥ 10,000 CFU/g TCD . There was no relationship between stool culture or rectal swab NAAT result and risk of a positive environmental swab .Rectal swab NAAT may not be sufficiently sensitive to screen for TCD colonization that contributes to environmental contamination.Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support


Nirmatrelvir/ritonavir (N/R) protects against severe outcomes after SARS-CoV-2 (SCV2) infection, but patients and studies have described symptom and viral rebound after treatment. Our aim was to compare symptom and viral trajectories during acute illness among individuals with COVID-19 treated with N/R compared to similar individuals who did not receive any COVID-19 treatment.10(IU/mL) over a minimum of 5 log10(IU/mL). We used Wilcoxon Test to compare mean daily symptoms and viral loads and logistic regression to calculate odds of rebound.This analysis included participants enrolled ≤ 6 days of index symptom onset in a US household transmission study who tested SCV2-positive, Mar. 2022–Mar. 2023. We followed participants for 10 days after enrollment, obtaining demographics, clinical history, daily symptoms (list of 15), medications, and specimens for SCV2 quantitative PCR. Symptomatic participants eligible for N/R were included . We used propensity score matching to select untreated participants who were similar to N/R treated participants (Table 1). We assessed symptoms and viral load  from N/R completion (N/R treated) or after seven days since symptom onset (untreated) to the end of follow up. We defined symptom rebound as an increase of ≥ 2 symptoms and viral load rebound as an increase of ≥ 0.5 logCase-ascertained household transmission study participants were included in this analysis if they were enrolled in March 2022 (first report of nirmatrelvir/ritonavir) or after and tested positive for SARS-CoV-2 (n=2075). We included symptomatic N/R eligible participants who had non-missing data for propensity score model variables and daily specimens and symptoms (n=1224) and then excluded N/R treated participants who did not complete N/R in 5-6 days according to EUA (n=108). Propensity score matching was performed by calculating propensity score of nirmatrelvir/ritonavir use based on age, sex, race/ethnicity, prior COVID-19, recruitment method, participant type, medical care access, COVID-19 vaccination history, comorbidities, and predominant variant at the time of index onset. The best covariate balance was achieved using nearest propensity score matching method with a ratio of 2:1 no treatment to N/R treated. Those that did not match to a treated participant were excluded (n=768). The two recruitment sources collected different specimen types  and used different viral load quantification standards. Because of this, viral load analysis was limited to only those that collected nasal swabs and had at least two viral load results after nirmatrelvir/ritonavir completion or, for the no treatment participants, after day 7 since symptom onset. N/R=nirmatrelvir/ritonavir; SCV2=SARS-CoV-2; EUA=Emergency Use AgreementN/R treated (n=116) and untreated (n=232) participants had similar baseline characteristics (Table 1). Median days from symptom onset to N/R initiation was 2 days (IQR=1-3). Symptom rebound occurred among 32% of N/R treated and 19% of untreated participants . Mean daily symptoms were lower among N/R treated  and significantly lower among N/R treated when rebound did not occur . Viral load rebound occurred among 25% of N/R treated and 13% of untreated participants  and mean daily viral load was significantly lower among N/R treated overall (1.5 vs 2.7), without rebound (1.1 vs 2.5), and with rebound .The following symptoms were elicited daily from participants: fever/feverish/chills, cough, sore throat, runny nose, nasal congestion, fatigue/feeling run down, wheezing, trouble breathing/shortness of breath, chest tightness/chest pain, loss of smell/loss of taste, headache, abdominal pain, diarrhea, vomiting, and muscle or body aches. Symptom rebound was defined as an increase of at least two symptoms after the completion of nirmatrelvir/ritonavir or, when no treatment was reported, after seven days since symptom onset. Daily symptoms after end of treatment were averaged from the day after the last day of nirmatrelvir/ritonavir or, if no treatment, day eight since symptom onset to the last available symptom diary follow up. N/R=nirmatrelvir/ritonavirNasal swabs were tested for SARS-CoV-2 by PCR using the Panther Fusion Hologic system. Viral load as logIU/mL was determined using WHO standard. Negative results were set to zero and below limit of quantification (3 logIU/mL) results were set to 1.5 logIU/mL. Viral load rebound was defined as an increase of at least 0.5 logIU/mL (with a threshold of 5 logIU/mL) after the completion of nirmatrelvir/ritonavir or, if no treatment was reported, after seven days since symptom onset. Daily viral load after end of treatment was averaged from the day after the last day of nirmatrelvir/ritonavir or, if no treatment, day eight since symptom onset to the last available viral load result. N/R=nirmatrelvir/ritonavir; IU=international unitsIn outpatient settings, N/R treated individuals had fewer symptoms and lower viral loads, but greater odds of symptom and viral rebound compared to similar untreated individuals.Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edward Belongia, MD, Seqirus: Grant/Research Support Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support


Sotrovimab is a dual-action Fc-engineered human monoclonal antibody (mAb), developed for early treatment of mild-to-moderate COVID-19. We evaluated the safety and tolerability of sotrovimab 500 mg administered intramuscularly (IM) at dorsogluteal (DG), anterolateral (AL) thigh and deltoid injection sites.This Phase 1 open-label, parallel group, randomized, healthy volunteer study comprised three parts. Part A investigated the relative bioavailability, safety and tolerability of 2 sotrovimab concentrations administered IM at different injection sites. 216 participants were randomized (2:2:1:1) to 4 treatment arms: 62.5 mg/mL DG administered as two 4 mL injections; 100 mg/mL DG administered as one 5 mL injection; 100 mg/mL AL thigh administered as one 5 mL injection; 100 mg/mL deltoid administered as one 2.5 mL injection into each muscle. Incidence of adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESI) through Day (D) 29 were assessed. Patient-reported outcomes included Perception of Injection (PINS) v3 and Pain-Numeric Rating Scale (NRS).2). Overall, 46% (n=99/215) of participants reported AEs; most common ( > 5%) were injection-site pain  and COVID-19 . There were no SAEs; all AESIs were Grade 1 or 2 (Table 1). Mean Pain-NRS values were < 1 and similar across injection sites; values were highest on D1 at 15 mins post-dosing and then decreased through 60 mins post-dosing , with 8 participants reporting pain after D2. D1 PINS results showed the majority felt injection site reactions were “not at all” bothersome, and local reactions and pain were “totally or very acceptable”. No or little impact on sleep and movement were reported (Table 2).215 participants were exposed to study intervention (mean [range] age: 39 [19–65] years; 57% female; mean [standard deviation] body mass index: 25.4 [2.87] kg/mSotrovimab 500 mg IM injection had a favorable safety profile and was generally well tolerated at all injection sites, and at volumes of up to 5 mL at DG and AL thigh sites, and one 2.5 mL injection into each deltoid muscle. To our knowledge, these are the first data to show that a 2.5 mL mAb injection into each deltoid muscle was well tolerated.Jennifer Moore, MD, GSK: Employee|GSK: Stocks/Bonds Wen-Hung Chen, PhD, GSK: Employee|GSK: Stocks/Bonds Jerzy Daniluk, MD, PhD, GSK: Employee|GSK: Stocks/Bonds Sergio Parra, MD, Vir Biotechnology, Inc: Employee|Vir Biotechnology, Inc: Stocks/Bonds Megan Turner, BA, GSK: Employee|GSK: Stocks/Bonds Yasmin Sanchez-Pearson, PhD, GSK: Employee|GSK: Stocks/Bonds Prosenjit Sakar, MSc, GSK: Employee|GSK: Stocks/Bonds Ian A. Hawes, BSP, ACPR, GSK: Employee|GSK: Stocks/Bonds Alicia Aylott, MSc, GSK: Employee|GSK: Stocks/Bonds


Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. In these patients, there is an unmet need for effective antimicrobial therapy. This study enrolled participants mainly from China to support the regional use of imipenem/cilastatin/relebactam (IMI/REL). The aim of the study was to assess the efficacy and safety of IMI/REL compared with piperacillin/tazobactam (PIP/TAZ) for the treatment of HABP/VABP.This study was a Phase 3, randomized trial conducted in 8 countries (NCT03583333). Participants 18–90 years of age with HABP/VABP requiring intravenous (IV) antibiotic treatment were randomized 1:1 to receive either IV IMI/REL (500 mg IMI/250 mg REL) or PIP/TAZ (4000 mg/500 mg) administered every 6 h for 7–14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (excluding patients with only gram-positive cocci at baseline). Secondary endpoints included clinical response rate, microbiological response rate and adverse events (AEs).In total, 270 patients  were included in the MITT population, with 201 patients from mainland China . Demographics and baseline characteristics were generally comparable for both treatment groups in the MITT population, with the exception of preexisting cerebrovascular conditions which were higher in IMI/REL vs PIP/TAZ group. The median age (range) was 60.0 (19–87) years and 73.3% were male (Table 1). In the MITT population, IMI/REL was non-inferior to PIP/TAZ for day 28 all-cause mortality . Results for key secondary endpoints were comparable between treatment groups (Table 2). Overall, the incidence of AEs was comparable between IMI/REL vs PIP/TAZ (Table 3).In a patient population mainly from China, IMI/REL was non-inferior to PIP/TAZ for the treatment of HABP/VABP assessed by the endpoint of day 28 all-cause mortality and was associated with favorable outcomes regarding clinical and microbiological response.IMI/REL was well tolerated and had a safety profile comparable to PIP/TAZ.Maria C. Losada, BA, Merck & Co., Inc., Rahway, New Jersey, USA: Employee|Merck & Co., Inc., Rahway, New Jersey, USA: Stocks/Bonds|Merck & Co., Inc., Rahway, New Jersey, USA: Stocks/Bonds Zlatka Iamboliyska, MD, MSD China: Employee|MSD China: Stocks/Bonds Mingfen Zhu, MD, MSD China: Employee|MSD China: Stocks/Bonds Xiaodan Guo, MD, MSD China: Employee|MSD China: Stocks/Bonds Xiaoling Du, n/a, MSD China: Employee|MSD China: Stocks/Bonds Chang Chen, MD, MSD China: Employee|MSD China: Stocks/Bonds Luke Francis Chen, MD, Merck & Co., Inc., Rahway, New Jersey, USA: Employee|Merck & Co., Inc., Rahway, New Jersey, USA: Stocks/Bonds


In July 2022, an outbreak of MPox was reported in the United States as part of a world-wide health emergency. Healthcare settings in the US started to see possible cases, and the public health and clinical diagnostics infrastructure was quickly overwhelmed. As the concept of diagnostic stewardship is becoming increasingly more important, we sought to identify clinical information obtainable at presentation that would predict a positive MPox PCR in order to streamline testing and optimize resource utilization.Table 1RR and diagnostic performance for single and combined clinical factors resulting in a positive MPox PCRThe charts of 146 patients presenting for MPox testing in a large healthcare system in Texas in July and August 2022 were reviewed to identify clinical factors upon presentation that would correlate with a positive lesion PCR.49.3% of patients tested positive. The mean (SD) age of patients was 31.9 (8.41) years. The mean (SD) time of symptoms was 5.47 (5.08) days. The mean (SD) time from last sexual encounter was 17.6 (11.01) days. Table 1 shows the RR and diagnostic performance for each clinical factor resulting in a positive MPox PCR as well as the RR for those with 2, 3, and 4 combined high risk clinical factors.Male gender, non-heterosexual sexual orientation, recent sexual encounter, painful lesions, contact with a known MPox case, systemic symptoms, and shorter symptom duration less than or equal to 6 days increased the risk of a positive Mpox PCR result and may be used to prioritize testing in a resource constrained environment. Patients presenting with a combination of 2, 3, and 4 risk factors further increased the likelihood of a positive test. Risk factors can be used for diagnostic stewardship in MPox testing. Further research will focus on creation and prospective validation of clinical prediction rules.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


A population pharmacokinetic (PK) model was constructed from nine Phase 1 studies and three Phase 3 studies in patients with acute bacterial skin and skin structure infections (ABSSSI) or hospital- or community-acquired bacterial pneumonia (HABP or CABP) and refined using Phase 3 data from patients with Staphylococcus aureus bacteremia (SAB).Ceftobiprole medocaril is an intravenously administered cephalosporin prodrug that is rapidly converted Structural PK models for systemic compartments and linear vs. non-linear elimination were considered. Covariate analyses were carried out. Model evaluation involved goodness-of-fit and prediction-corrected visual predictive check plots and a sampling-importance-resampling procedure. The model was externally qualified and refined using Phase 3 SAB PK data.Figure 1). Model-based simulations to predict exposure in subgroups  showed that renal function is the most clinically relevant covariate, consistent with the predominance of renal elimination for ceftobiprole . While model-based simulations showed that predicted exposure in subjects with extreme body weight (120 kg) fall below the bioequivalence reference range of healthy subjects weighing 75 kg, these weight-based differences are unlikely to be clinically significant. Neither sex nor infection type are expected to have a clinically relevant impact.The initial dataset included 4890 plasma concentrations from 773 healthy subjects or patients with ABSSSI, HABP, or CABP. This dataset was expanded to include 1134 plasma concentrations from 180 patients with SAB. External qualification showed that the model predicted data from patients with SAB well but the model was refined to best capture data from these patients. The refined model (three-compartment model with linear elimination) provided a robust fit to the pooled data (A population PK model that described the plasma PK of ceftobiprole well in healthy and infected patients was developed. The derived measures of plasma exposure are expected to be both accurate and precise.Anthony P. Cammarata, M.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 Karine Litherland, Ph.D., Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Full time employee|Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds M. Courtney Safir, 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|Genetech: 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 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 Mikael Saulay, MSc, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Full time employee|Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds 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 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


Streptococcal species.Rapid diagnostic testing (RDT) allows antimicrobial stewardship programs (ASP) to intervene early in the setting of sepsis and septic shock leading to lower rates of death. Combining RDT with ASP results in faster antibiotic de-escalation compared to RDT alone; however, the utility of this approach for Streptococcal bacteremia is unproven. The objective of this study was to evaluate the impact of RDT with real-time ASP intervention on blood cultures growing Streptococcus spp. bacteremia over two 6-month periods. During the pre-RDT period, patients were prospectively followed by ASP who provided recommendations based on gram-stain and organism identification results. During the post-RDT period, blood cultures were tested by GenMark ePlex BCID-GP that identifies S. agalactiae, S. anginosis group, S. pneumoniae, S. pyogenes and Streptococcus spp. within 90 minutes which were reported directly to ASP for recommendations on antibiotic discontinuation, de-escalation, and additional diagnostic testing.Retrospective, observational study comparing patients with Table 1). The median ages were 58 and 56, 62% and 68% were men, and a total of 12% and 16% were immunocompromised. The mean qSOFA scores were 1.9 and 2. The most common Streptococcus spp. was S. mitis (figure 1). Prior to RDT, the median time to antibiotic de-escalation was 88 hours. Following implementation of RDT, median time to de-escalation was 42 hours (P=0.002). De-escalation to targeted therapy improved from 50% to 86% in post-RDT (P< 0.01). Transition to oral antibiotics increased from 14% to 30% (P=0.08). There were no differences in hospital re-admission or acute kidney injury. A trend toward decreased 30-day mortality was identified in the post-RDT period (P=0.06).94 patients were included in the analysis, 50 pre- and 44 post-RDT. Across cohorts, patient demographics, clinical characteristics, and severity of illness were comparable (Streptococcal bacteremia. We noted significant reductions in broad-spectrum antibiotic use and a trend towards lower mortality. Larger studies are needed to demonstrate the full potential of this approach.Our study highlights the impact of RDT with ASP intervention on clinical outcomes for patients with 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


Coronavirus is one of the major pathogens that primarily targets the human respiratory system. In COVID-19 patient’s, bloodstream infections (BSI) have not been extensively studied in Latin-America. Given the impact of COVID-19 pandemic in Colombia and the high rate of hospitalizations, information about risk factors and ways to prevent BSI among COVID-19 patients is urgently needed. This investigation aimed to identify risk factors in BSI in hospitalized patients with COVID-19.A case-control design was used; cases were patients with a PCR confirmed COVID-19 infection and BSI. Controls were patients with a PCR confirmed COVID-19 who did not have a BSI during their hospitalization. Information about demographic, clinical characteristics, comorbidities and exposures that could be related to BSI were reviewed. Descriptive statistics were calculated, odds ratios (ORs) and 95% confidence intervals were estimated using multivariable conditional logistic regression models. In accordance with Colombian regulations -Resolution 8430 of the Ministry of Health of 1993- this project was classified as risk-free.306 patients (153 cases and 153 controls) from four participating hospitals were included. Cases and controls had similar average age (62-63 years), median length of stay (19-25 days), comorbidities and similar Newscore scale regarding severity on admission to the hospital; all cases and 89% of controls required at least one invasive device. Cases were more likely to have required an orotracheal tube , central venous catheter , or urinary catheter  compared with controls. Cases had higher previous antimicrobials use , pronation  and chlorhexidine bath  than controls. However,no statistically significant differences in mortality between cases and controls was found. In the multivariate analysis, urinary catheter used  was a risk factor and chlorhexidine bath  was a protective factor for BSI.CASE AND CONTROL CHARACTERISTICSBIVARIATE AND MULTIVARIATE ANALYSISCOVID-19 patients are more propense to BSI, but bathing with chlorhexidine and care and monitoring of invasive devices are modifiable factors to minimize the risk of infections.Christian Pallares, MD, MSc, 3M: Advisor/Consultant|3M: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Westquímica: Advisor/Consultant|Westquímica: Grant/Research Support|Westquímica: Honoraria María Virginia Villegas, n/a, MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Westquímica: Advisor/Consultant|Westquímica: Grant/Research Support|Westquímica: Honoraria Karen Melissa Ordoñez, n/a, Pfizer: Advisor/Consultant|Pfizer: Honoraria


Carbapenem-resistant Enterobacterales (CRE) represent an urgent threat. Mortality rates associated with this pathogen approach 80%. Timely treatment of serious infections, even with highly resistant organisms, among hospitalized patients improves the chances of survival. We explored whether meropenem/vaborbactam (MEV) conforms to this observation.We conducted a multicenter retrospective cohort study in ∼300 hospitals reporting microbiology data within the Premier Healthcare Database, 2019-2021, to explore the effect of timely (MEV-T) vs. delayed (MEV-D) CRE treatment. We included all adult hospitalized patients who either upon admission or during hospitalization had sepsis, a UTI, a cIAI, or pneumonia, and had at least one corresponding culture positive for CRE. Treatment was MEV-T if instituted within 2 days of obtaining the index culture. All other was considered MEV-D.C. difficile infection (CDI) and acute kidney injury (AKI) were lower with MEV-T (Table). Mean post-infection hospital length of stay  and hospital costs  were lower with timely MEV therapy.Among 1,513 patients with CRE, 87 (5.8%) received MEV. Among those treated with MEV, 29 (33.3%) were treated in a timely manner. At baseline, MEV-T patients were directionally sicker than those in the MEV-D group, as evidenced by a higher prevalence of DNR on admission and a higher mean Charlson Comorbidity score (Table). Similarly, MEV-T patients were slightly more likely to require admission to an intensive care unit and mechanical ventilation. Although not statistically different, hospital mortality trended lower with MEV-T relative to MEV-D. Rates of incident TableDespite being more severely ill, the group treated with timely initiation of MEV for CRE resulted in a significantly lower incidence of CDI and AKI. The post-infection LOS and hospital costs were also lower in the MEV-T group. Hospital mortality trended lower in the MEV-T group. Despite the small sample size, these differences suggest that timely administration of MEV may improve select significant clinical outcomes.Marya D. Zilberberg, MD, MPH, Melinta Therapeutics: Grant/Research Support|Merck: Grant/Research Support|scPharmaceuticals: Advisor/Consultant|scPharmaceuticals: Grant/Research Support Brian H. Nathanson, Ph.D., Merck & Co., Inc: Advisor/Consultant Mark Redell, PharmD, Melinta Therapeutics: Full-time employee|Melinta Therapeutics: Full-time employee|Melinta Therapeutics: Stocks/Bonds|Melinta Therapeutics: Stocks/Bonds Kate Sulham, MPH, Melinta Therapeutics: Advisor/Consultant


The mechanism study of inhibition effect of prepared Radix Rehmanniainon combined with Radix Astragali osteoporosis through PI3K-AKT signaling pathway, which DOI is: https://doi.org/10.1590/acb371101, published in the journal Acta Cirúrgica Brasileira, 2022;37(11)e371101, page 5, in the axis Y of Figure 2(b):In the manuscript Instead of: lumbar vertebra boneShould be: left tibia bone