Staphylococcus aureus (SA) bacteremia, including infective endocarditis. This study evaluated the activity of BPR and comparators against recent SA isolates causing bloodstream infections (BSI) in patients hospitalized at medical centers in the United States (US).Ceftobiprole (BPR) is an advanced-generation cephalosporin approved in Europe and many non-European countries for the treatment of community-acquired pneumonia and non–ventilator-associated hospital-acquired pneumonia in adults. A Phase 3 clinical trial (NCT03138733) was recently completed with BPR for the treatment of A total of 1,946 SA isolates from 32 US medical centers (2018–2020) were collected from patients with BSI. 53 isolates from endocarditis patients were included. Isolates were tested for antimicrobial susceptibility using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. MIC interpretations for BPR and comparators utilized European Committee on Antimicrobial Susceptibility Testing (EUCAST) or CLSI criteria, respectively. Multidrug-resistant (MDR) isolates were non-susceptible to ≥ 3 of the following drugs without regard to oxacillin resistance: clindamycin, daptomycin, erthryomycin, gentamicin, levofloxacin, tetracycline, and trimethoprim-sulfamethoxazole. No isolates were resistant to linezolid, tigecycline, or vancomycin.50/90, 0.5/2 mg/L). The MIC50/90 values were stable over all 3 surveillance years and identical to previously reported values from analogous isolates collected in 2016–2017. BPR activity was maintained against the methicillin-resistant SA (MRSA) subset . All isolates from endocarditis patients were susceptible to BPR. 10 MRSA isolates (0.5%) were resistant to BPR with MIC values of 4 mg/L. Of 288 MDR isolates, 96.9% remained susceptible to BPR, while only 78.8% of the same isolate set was susceptible to ceftaroline.BPR inhibited 99.5% of all SA at ≤ 2 mg/L, which is the EUCAST susceptibility breakpoint (MICin vitro results extend previous surveillance data that suggest that BPR represents a potential option for treating BSI and endocarditis caused by SA in US hospitals, including MRSA and MDR isolates.These Leonard R. Duncan, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support 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 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


The Infectious Diseases Society of America (IDSA) developed and disseminated a Core Antimicrobial Stewardship (AS) Curriculum intended to formalize AS training in infectious diseases (ID) fellowship programs in 2018. This study identified individual program approaches to curriculum implementation and intended to use this information to develop an implementation guide tailored to specific program needs.We distributed surveys to all fellowship program directors (PDs) who had previously implemented the Core AS Curriculum. Questions were designed to identify ID program structure, curriculum participants, curriculum sections and materials utilized, and resources and barriers to implementation. Both structured and qualitative responses were captured. The results were summarized descriptively and organized into a framework connecting barriers to proposed solutions.Table 1). Additional learners often included ID faculty and pharmacy trainees, and teachers were mostly AS program leadership. Most PDs reported limited faculty time as a barrier to implementation, whereas dedicated AS curricular time was a resource available to most programs . Approaches to curriculum implementation based on survey responses relating to each fellowship program feature were suggested, some of which applied to multiple program features . Qualitative feedback was generally positive, and most PDs indicated that they intended to continue to implement the curriculum. Additional materials such as a facilitator guide and demonstrations were proposed as other components which could assist with curriculum implementation.PDs from 34 unique programs who had administered the Core Curriculum to an estimated 405 ID fellows responded to the survey, out of the 159 institutions invited (21.4%). Most represented adult programs which had administered the curriculum for at least 2 years (Roadmap with infectious diseases fellowship program features (rounded green boxes) connected to identified potential approaches to curriculum implementation (rectangular blue boxes). Program features are categorized as relating to conference structure, program resources, or program barriers. Suggested approaches with potential application to multiple program features are highlighted in orange.The IDSA Core AS curriculum provides an effective means of formalizing basic AS education into ID fellowship training. Curriculum implementation can be optimized by tailoring to training program resources and unique features. An implementation roadmap may be a useful tool to assist ID fellowship PDs with this task.Payal K. Patel, MD MPH, qiagen: Honoraria Julie Ann Justo, PharmD, MS, FIDSA, BCPS, Gilead Sciences: Advisor/Consultant|Shionogi: Advisor/Consultant|Vaxart: Stocks/Bonds Erica J. Stohs, MD, MPH, bioMerieux: Grant/Research Support|Merck: Grant/Research Support Zachary Willis, MD, MPH, Merck Sharp & Dohme Corp: Grant/Research Support|Pfizer Inc: Grant/Research Support 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 Amy Y. Kang, Pharm.D., BCIDP, Paratek: Grant/Research Support Kartik Cherabuddi, MD, FACP, FIDSA, Contrafect Corporation: Grant/Research Support|Labcorp Drug Development: Grant/Research Support|Merck Sharp & Dohme: Grant/Research Support Gary Fong, PharmD, Critical Innovations, LLC: Advisor/Consultant Molly L. Paras, MD, Angiodynamics: Honoraria David Gaston, MD PhD, American Association of Clinical Chemistry: Honoraria|BioMerieux, Inc: Advisor/Consultant|IDbyDNA, Inc.: Grant/Research Support|Illumina, Inc.: Grant/Research Support


Influenza poses a significant burden that can be effectively mitigated with antivirals. Baloxavir marboxil is an oral, single dose first-in-class endonuclease inhibitor that improves influenza symptoms and rapidly reduces virus shedding, shortening the infectious period and potentially reducing viral transmission. This study used real-world data to inform a cost-effectiveness (CE) model of antiviral treatment with baloxavir vs oseltamivir or no treatment.A decision tree CE model was developed for seasonal influenza between 2018 and 2020. Patients aged 12 and older could receive baloxavir, oseltamivir or no treatment . Outcomes included complications, recovery and death. Patient profile and characteristics, complications and costs were derived from the Merative™ MarketScan® Research Databases, including US commercial claims, Medicare and Medicaid Supplemental databases. Healthcare resource use included outpatient visits, hospitalizations and intensive care unit admissions.Clinical inputs, recovery rates and utilities were derived from the literature. The base case model used a lifetime time horizon with 3.0% discounting for costs and 2.7% for quality-adjusted life-years (QALYs), assuming no transmission reduction. A subgroup analysis was conducted for otherwise healthy (OwH) and high-risk groups; scenario analyses explored the impact of reduced viral transmission with baloxavir.In the base case analysis, baloxavir resulted in an incremental CE ratio (ICER) of $7788/QALY vs oseltamivir and $311/QALY vs no treatment; subgroup analyses showed even greater CE in the high-risk population (Table 1). Scenario analyses showed increasing net monetary benefit (NMB) with incremental reductions in viral transmission with baloxavir, where a 5% reduction in transmission yielded a NMB for baloxavir of $4153 vs oseltamivir and $13,098 vs no treatment .This real-world evidence-driven model showed that baloxavir is cost-effective vs oseltamivir or no treatment from a US payer perspective. Transmission reductions with baloxavir can have a substantial health economic benefit, and baloxavir may play an important role in management of seasonal influenza and pandemic preparedness.Svenn Hansen, n/a, F. Hoffman La Roche: Employee|F. Hoffman La Roche: Stocks/Bonds Shih-Chen Cheng, M.S., P.h.D, Genentech/F. Hoffman La Roche: Genentech Employee|Genentech/F. Hoffman La Roche: Stocks/Bonds Andy Surinach, MPH, Genentech/Roche: employee of Genesis Research which receives funding from Genentech/Roche for consulting services Vince Yau, PhD, Genentech/F. Hoffman La Roche: Genentech Employee|Genentech/F. Hoffman La Roche: Stocks/Bonds Jennie H. Best, PhD, Genentech: Stocks/Bonds Hassan Zaraket, PhD, F. Hoffman La Roche: Employee|F. Hoffman La Roche: Stocks/Bonds Hao Zhou, PhD, Genentech/F. Hoffman La Roche: Genentech Employee|Genentech/F. Hoffman La Roche: Stocks/Bonds Marie-Helene Blanchet Zumofen, PhD MBA, F. Hoffman La Roche: Employee|F. Hoffman La Roche: Stocks/Bonds


Acinetobacter baumannii-calcoaceticus complex (ABC) infections, including multidrug resistant strains. Both arms were dosed on a background of imipenem/cilastatin (IMI) to treat co-infecting Gram-negative pathogens. 33% of infections in the primary efficacy population were polymicrobial.Recently, a global, active-controlled Phase 3 trial evaluated the efficacy and safety of SUL-DUR vs. COL for patients with The minimal inhibitory concentrations (MICs) of SUL-DUR, colistin and imipenem against baseline isolates were determined by broth microdilution using CLSI guidelines. The primary efficacy endpoint was 28-day all-cause mortality (ACM) in patients with carbapenem-resistant ABC at baseline (CRABC m-MITT). Clinical and microbiological outcomes were evaluated at Test of Cure (TOC).28D ACM, clinical and microbiological outcomes were similar for patients in the SUL-DUR arm with either monomicrobial or polymicrobial ABC infections while patients in the COL arm with monomicrobial ABC infections had higher mortality rates with worse clinical and microbiological outcomes compared to those with polymicrobial infections (Table 1). Of the 12 patients in the SUL-DUR arm who did not survive to 28 days, 4 (33.3%) were attributed to the index infection . Of the 20 patients in the COL arm who did not survive to 28 days, 10 (50%) were attributed to the index infection  (Table 2).SUL-DUR was equally efficacious in patients with monomicrobial vs. polymicrobial ABC baseline infections and an equal percentage of deaths (33%) were attributable to the index infection in each sub-group. Although fewer patients in the COL arm died with polymicrobial ABC infections  than monomicrobial ABC infections , 60% of the former (3 of 5) were attributable to polymicrobial ABC infections while 46.7% of the latter (7 of 15) were attributable to monomicrobial ABC infections. These results suggest that, if approved, the use of SUL-DUR plus a carbapenem could be an effective approach to treat polymicrobial infections that include ABC.Alita Miller, PhD, Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds Sarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds|Innoviva Specialty Therapeutics: Stocks/Bonds Adam B. Shapiro, Ph.D, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Full Time Employee


Enzyme replacement therapy (ERT) with cerliponase alfa (Brineura) has been shown to slow progression of milestone deterioration in Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), an inherited neurodegenerative lysosomal storage disorder. Brineura must be administered intraventricularly every 2 weeks, necessitating the placement of ventricular reservoirs and requiring frequent access. Traditionally, positive cerebrospinal fluid (CSF) cultures are managed with device replacement and antibiotic treatment. We sought to establish which circumstances might allow for careful observation without device removal. In this study, we report our single-institution experience with clinical outcomes of positive CSF cultures in 16 CLN2 patients over 6 years.We retrospectively reviewed a cohort of 16 patients with CLN2 disease who had ventricular reservoirs placed for ERT administration. At each ERT infusion, CSF was collected by sterile technique and cultured by both thioglycolate broth and agar plate. Epidemiologic and microbiologic data, symptomatology, total antibiotic days, removal and replacement of ventricular reservoir, hospital length of stay, and mortality were analyzed for each patient.Cutibacterium acnes, which typically grew in only broth culture (82%), suggesting low bacterial burden . The other 7 patients with positive cultures remained asymptomatic with no intervention required.In our cohort, 11 of 16 patients (69%) had at least one positive CSF culture . Of the 11 with positive cultures, only 3 had their device removed and replaced for a positive culture with concurrent antibiotic treatment at our center, and 2 patients subsequently have been treated with prophylactic antibiotics at infusions . Out of 1401 total CSF cultures, 64 (4.56%) were positive. The most common organism grown was At our institution, we have found that in asymptomatic patients with frequently accessed ventricular reservoirs, positive CSF culture with low virulence skin flora was common, and rarely required intervention. This strategy reduced the risks of invasive surgery, prolonged antibiotic courses, and missed infusions. In the future, routine screening cultures in asymptomatic patients can be avoided.Raymond Wang, MD, Biomarin Pharmaceutical: Advisor/Consultant|Biomarin Pharmaceutical: Grant/Research Support|Biomarin Pharmaceutical: equity interest 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


Carbapenem-resistant bacteria in patients with cancer are concerning due to the high risk of infection and mortality rates; however, the characteristics and prognoses of carbapenem-resistant infections in this population are currently unknown in Japan. We hence investigated the features and outcomes of carbapenem-resistant bacterial infections (CRBI) in patients with cancer in Japan.From April 1, 2019, to March 31, 2022, patients with CRBI who either had cancer or no cancer were prospectively enrolled at eight centers as part of the Multi-Drug Resistant Organisms Clinical Research Network (MDRnet). The primary outcome was the 30-day all-cause mortality rates in patients with and without cancer. Two secondary outcomes were evaluated: 1) composite outcomes including mortality, worsening of clinical course after culture collection, intensive care unit stay, intubation, new dialysis from the date of culture collection to the end of antimicrobial therapy, and readmission within 90 days after discharge; and 2) the length of hospital stay after CRBI excluding death.We included a total of 167 patients, with 66 (39.5%) in the cancer group and 101 (60.5%) in the non-cancer group. The 30-day mortality rates in the cancer and non-cancer groups were 18.2% (12/66) and 14.0% (14/101), respectively (p = 0.45), while the composite outcomes in the cancer and non-cancer groups were 56.1% (37/66) and 43.6% (44/101), respectively (p = 0.12). Average duration of hospitalization was not significantly different between the two groups . Propensity score analysis using inverse probability weighting also showed no significant difference in 30-day mortality and average duration of hospitalization ; however, the composite outcome was significantly higher in the cancer group than in non-cancer controls .There was no difference in 30-day mortality rates between the cancer and non-cancer patient groups; however, we found a significant difference in the composite outcome. Patients with cancer who had CRBI experienced a worse clinical course that non-cancer patients.Masahiro Suzuki, PhD, KANTO Chemical co., inc.: Grant/Research Support Yasufumi Matsumara, MD, PhD, Beckman Coulter: Grant/Research Support|Presicion System Science: Grant/Research Support|Toyobo: Grant/Research Support David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant Yohei Doi, MD, PhD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Sho Saito, MD, PhD, Shionogi & Company, Limited: Grant/Research Support


Candida species directly from a whole blood specimen within 3-5 hours . The objective of this study is to identify predictors of 30-day mortality in patients with candidemia identified by T2Candida Panel.Candidemia is associated with mortality rates exceeding 40%. However, prior studies indicate mortality may be reduced when antifungal therapy is initiated within 12 hours. The T2Candida Panel is a diagnostic assay that detects This is a retrospective, multicenter study of critically ill patients with candidemia identified by T2Candida Panel from January 2016 - December 2022. Critically ill patients were defined as those who developed candidemia during an intensive care unit (ICU) stay or within 72 hours of ICU admission or discharge. T2Candida sites were chosen across the United States based on T2Candida utilization. Exclusion criteria were patients < 18 years of age, those with prophylactic indications for antifungal therapy, prisoners and pregnant patients. Multivariate logistic regression was conducted to identify factors associated with 30-day mortality measured from the T2Candida draw time.There were 171 ICU patients from seven institutions with candidemia identified by T2Candida panel. The mean (standard deviation [SD]) age was 59.7 (14.8) years and 52.1% were male. Mean (SD) APACHE II and Charlson Comorbidity Index scores were 20.6 (7.1) and 4.9 (2.8), respectively. Empiric antifungal therapy was administered to 36.8% of patients and the majority received infectious diseases (ID) consult (92.4%). Echinocandins were the most common agents used for empiric (72.7%) and definitive therapy (62.6%). Overall, 30-day mortality occurred in 36.0% and was not associated with antifungal de-escalation. Administration of empiric therapy  and ID consult  were associated with reduced odds of 30-day mortality.Empiric antifungal administration and ID consult were independently associated with reduced odds of 30-day mortality in patients with candidemia identified by T2Candida Panel. Future studies are needed to evaluate the impact of the T2Candida panel on antifungal stewardship.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 Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant


A 20-valent pneumococcal conjugate vaccine (PCV20) was recently licensed for use in children by the United States (US) Food and Drug Administration. PCV20 includes 5 and 7 more serotypes than the 15- (PCV15) and 13-valent (PCV13) vaccines, respectively. This study assessed healthcare providers’ (HCPs) preferences for possible changes in pediatric pneumococcal vaccination recommendations, including transitioning from lower-valent vaccines to PCV20 among children partially vaccinated with PCV13/15, administering a supplemental dose of PCV20 among children < 5 years vaccinated with PCV13/15, and using PCV20 alone instead of in sequence with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in children with underlying medical conditions. HCP preferences for the use of PCV15 or PCV20 for children aged ≤ 18 years were also elicited.Pediatricians (N = 268), family medicine physicians/general practitioners (N = 184), physician assistants (N = 77), and nurse practitioners (N = 74) who prescribed, recommended, or administered a pneumococcal vaccine to a child ≤ 18 years in the past 3 months completed an online survey. HCPs responded to direct elicitation questions to assess preferences for each of the potential pneumococcal vaccination recommendations considered above. Practice characteristics, knowledge and awareness of current pediatric pneumococcal vaccination recommendations, and rationale for choices in the preference questions were also assessed.HCPs preferred recommendations that provided protection against more serotypes; 76% of HCPs in this study favored transitioning children who started vaccination with PCV13/15 to PCV20 , and most (≥ 60%) favored a supplemental dose of PCV20 for all children < 5 years fully vaccinated with PCV13/15 . 93% of surveyed HCPs preferred PCV20 over PCV15 for children ≤ 18 years . Among those who preferred PCV20, more than 80% based their decision mainly on serotype coverage.HCPs indicated preference for pediatric pneumococcal vaccination recommendations that provide greater serotype coverage. These results and other data on stakeholder preferences will help inform the updated pediatric pneumococcal vaccination recommendations.Jeffrey T. Vietri, PhD, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds Liping Huang, MD, MA, MS, Pfizer Inc.: Stocks/Bonds Vincenza Snow, MD, Pfizer Vaccines: employee|Pfizer Vaccines: Stocks/Bonds Brett Hauber, PhD, Pfizer: Brett Hauber is an employee of Pfizer. this study was funded by Pfizer, Inc.|Pfizer: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Emplyee|Pfizer: Stocks/Bonds Alejandro D. Cane, MD, PhD, Pfizer: Stocks/Bonds Maria J Tort, PhD, Pfizer Inc: Stocks/Bonds Anna Pierce, BBA, Pfizer, Inc.: Grant/Research Support


Lipid metabolism disorders (LMD) can cause a series of metabolic diseases, including hyperlipidemia, obesity, non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS). Its development is caused by more pathogenic factors, among which intestinal flora dysbiosis is considered to be an important pathogenic mechanism of LMD. In recent years, the research on intestinal flora has made great progress, opening up new perspectives on the occurrence and therapeutic effects of diseases. With its complex composition and wide range of targets, traditional Chinese medicine (TCM) is widely used to prevent and treat LMD. This review takes intestinal flora as a target, elaborates on the scientific connotation of TCM in the treatment of LMD, updates the therapeutic thinking of LMD, and provides a reference for clinical diagnosis and treatment. With the development of society and the improvement of living conditions, the incidence of lipid metabolism disorders (LMDs) is increasing year by year and showing a trend of rejuvenation, which seriously threatens human health. Abnormal lipid metabolism is a pathological process of elevated blood lipid levels and ectopic lipid deposition caused by genetic or acquired factors, and is an important risk factor for many metabolic diseases. Lipid metabolism is central to this process, and when lipid biosynthesis and degradation are abnormal, or when lipoprotein synthesis, metabolism, and transport are impaired, this can lead to disorders of lipid metabolism, contributing to hyperlipoproteinemia , obesityBacteroidetes, and an increase in Firmicutes, Proteobacteria, and Verrucomicrobia  Wolf  water insoluble polysaccharide (WIP) improved markedly glucose and lipid metabolism in ob/ob mice, and the underlying mechanism may be associated with increased numbers of butyrate-producing bacteria Lachnospiracea and Clostridium, elevated butyrate levels in the intestine, improved intestinal barrier function, and activated the intestinal peroxisome proliferator-activated receptor γ (PPAR-γ) pathway (Akkermansia muciniphila and down-regulating the production of pro-inflammatory proteins (Blautia greatly reduced the cholesterol-lowering efficacy of berberine (BBR), revealing that intestinal flora plays a crucial part in BBR’s hypolipidemic impact  , which hydrolyzes conjugated BAs and regulates BAs-mediated lipid metabolism  ratio represents a healthier gut microbial environment, and the risk of obesity and LMD may be increased by an elevated F/B ratio  . In additabolism . Therefo/B ratio . Firmicureatment . Akkermaammation . Bifidobeostasis . Long-teiate LMD . In anotmic rats . Bacterodiseases . LMD infdiseases . Therefovia the cellular bypass pathway, resulting in metabolic endotoxemia, inflammation and metabolic disorders , and a small proportion is processed by CYP27A1 and CYP7B1 in extrahepatic sites . Primary BAs, which including cholic acid (CA) and chenodeoxycholic acid (CDCA), can bind to glycine or taurine to form conjugated BAs like glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), taurocholic acid (TCA) and taurochenodeoxycholic acid (TCDCA). The bile salt export pump (BSEP) or ATP-binding cassette subfamily G member 5 (ABCG5)/ABCG8 subsequently actively transfers these conjugated BAs into the bile, where they contribute to lipid emulsification when the food enters the intestine . The apiactivity . BAs canactivity . In summTrimethylamine oxide (TMAO) is an intestinal flora-dependent metabolite formed by the oxidation of trimethylamine (TMA) in the liver by flavin-containing monooxygenase (FMO), especially FMO3 . StudiesObesity, NAFLD and AS are frequently associated with LMD. Therefore, for the efficient implementation of atherosclerotic cardiovascular disease (ASCVD) preventive and treatment methods, early diagnosis of dyslipidemia and monitoring changes in its levels are key foundations.F/B ratio, while patients with LMD tend to have high F/B ratio  as routine lipid testing items. In addition, the clinical testing items of oxLDL, FFA and non-HDL-C are also receiving increasing attention. In recent years, assays for intestinal flora and its metabolites have also been increasingly used to assist in monitoring lipid levels. Usually healthy people have low /B ratio . The mai/B ratio . SCFA is/B ratio . BA is p/B ratio . Serum T/B ratio . TherefoDesulfovibrio was considerably decreased following ezetimibe treatment and had a negative correlation with TG and HDL-C levels  StatC levels . PCSK9 iC levels . FurtherC levels . In contC levels . Thus, iTCM is widely utilized to treat metabolic diseases in China. The effective components of TCM can directly interact with the intestinal flora once they enter the intestinal system by oral administration and produce therapeutic effects. Studies have shown that TCM  can effectively modify the host intestinal flora structure and its metabolite levels, repair the intestinal mucosal barrier, reduce inflammatory infiltration, as well as regulate lipid metabolism-related pathways and genes expression to correct LMD . TherefoGanoderma lucidum polysaccharide (GLP) (G. lucidum polysaccharide and chitosan (PC)    resistant starch (PYRS)   , G. lucisan (PC) , Puerarisan (PC) , Luteolisan (PC) , Naringisan (PC) , Inulin san (PC) , Epigallsan (PC) , RSV (Chsan (PC)  greatly s (MXYG) , Tian Hus (MXYG) , Tea sees (MXYG) , Kaempfes (MXYG) , Green Bs (MXYG)  were abls (YPHZ) , Qinggans (YPHZ) , Jiangzhs (YPHZ) , Modfieds (YPHZ) , Purple h (PYRS)  and PLS h (PYRS)  also incwhile PC  and Porpwhile PC  were abls (IPTS)  treatmen extract , Jabotic extract  were ablk inulin  and Yinck inulin  can upreeic acid  treatmenF/B ratio in animals with a HFD has been experimentally confirmed. It was found that some natural medicine extracts, proprietary Chinese medicines and Chinese herbal formulas reduce F/B ratio by decreasing Firmicutes abundance and increasing Bacteroidetes abundance, such as Guizhi Tang (GZT) (Laminaria japonica polysaccharide (LJP) (Eleutherococcus senticosus (Rupr. & Maxim.) Maxim.  (Lonicera caerulea L. berry polyphenols (LCBP) (Firmicutes and Bacteroidetes were not mentioned after applying interventions such as Jieyu Qutan Huazhuo Prescription (JYQTHZ) (Gynostemma pentaphyllum (Thunb.) Makino  (GP)  , Naoxintng (GZT) , Huangling (GZT) , Quyu Hung (GZT) , Dangguing (GZT) , Laminarde (LJP) , Porphyrde (LJP) , Ethyl A caulis]  and Lonis (LCBP) . In cont(JYQTHZ) , Shenerj(JYQTHZ) , Jian Pi(JYQTHZ) , Shanmei(JYQTHZ) , Tongxin(JYQTHZ) , Hugan Q(JYQTHZ) , Compoun(JYQTHZ) , Jiangan(JYQTHZ) , Jiangzh(JYQTHZ) , Procyan(JYQTHZ) , Resista(JYQTHZ) , Tea pol(JYQTHZ)  and Gynoba] (GP) , and onlSenna tora (L.) Roxb.  (ST) (Lycium barbarum polysaccharide (LBPs)     , Biejia en] (ST) , Astragaen] (ST) , Lycium e (LBPs) , Inulin e (LBPs) , EGCG (Ze (LBPs) , Usnea dta] (UD)  and Momoae] (MC)  also sigae] (MC) , Gegen Qae] (MC) , Diammonae] (MC)  and GLP ae] (MC)  significae] (MC)  and JZG ae] (MC)  elevatedae] (MC) . Akkermaion. RSV , BBR (Zhion. RSV  and Rosae (RTFP)  were ablDesulfovibrio, a producer of LPS, was positively correlated with inflammation and LMD. Danlou Tablet (DLT) (Rhizoma Coptidis (RC) alkaloids  (The abundance of et (DLT) , DZSM (Get (DLT) , GQD (Liet (DLT) , SLBZ (Zet (DLT) , DG (Li et (DLT) , Chitoolet (DLT) , Rhizomalkaloids , Baicalilkaloids , Quercetlkaloids  and BBR lkaloids  might ambly, DLT , Gastrodbly, DLT  could dobly, DLT , Citrus bly, DLT , HGQZ  , Honokios (RLPs) , Fucoidas (RLPs)  and ST (s (RLPs)  were fous (RLPs) , Chaihu s (RLPs) , RSV (Chs (RLPs) , ST (Luos (RLPs) , Zhibitas (RLPs) , Xiaoyaos (RLPs) , JGJZ (Zs (RLPs) , Qinghuas (RLPs) , RTFP (Zs (RLPs) , LBPs (Gs (RLPs) , Noni frs (RLPs) , Inulin s (RLPs) , Quercets (RLPs) , BBR (Wus (RLPs) , GP (Shes (RLPs) , CPP (Hus (RLPs) , Paeonols (RLPs)  and Blacs (RLPs)  had effeLuffa cylindrica (L.) Roem  (LC)   and Berber] (LC)  resultedZanthoxylum bungeanum Maxim.  (ZB)       , Ginkgo um] (ZB) , Inulin um] (ZB) , NFP (Yaum] (ZB) , TP (Wanum] (ZB) , Bilberrum] (ZB)  and COSMum] (ZB)  significum] (ZB)  and JZG um] (ZB)  intervene (QXJY)  and watee (QXJY)  intervenca (MLJ) , Quercetca (MLJ) , Myricetca (MLJ) , MC (Baica (MLJ)  and GLP ca (MLJ)  administon (ECD)  and EGCGon (ECD)  administia; HGQZ  and DG  , Black tt (GXNT)  and RLPst (GXNT)  treatmenns (GPS)  administnic acid . BTP trenic acid . WIP trenic acid . Dingxinnic acid . The mecnic acid .Radix scutellariae water extract (Penthorum chinense Pursh. (PCP) extract  , Eucommi extract , HYQT  can provide new perspectives for understanding LMD, and promote the development of research and treatment methods of metabolism disorders.Akkermansia to repair intestinal barrier function  against liver fatty lesions in rats (Akkermansia abundance, it also enhanced intestinal tight junction protein expression and colonic mucus layer thickness, reduced HFD-induced metabolic endotoxemia and decreased expression of pro-inflammatory factors and chemokines (Desulfovibrio was reduced in NAFLD rats, and LPS production as well as the secretion of inflammatory factors were inhibited, resulting in improvement of LMD (Prevotella, promoted the production of SCFAs such as Propionic acid and butyric acid, and reduced lipid levels in NAFLD mice (In this review, we systematically analyzed the previous related literature and found that intestinal flora and its metabolites may be major targets of TCM for treating LMD . The comfunction ; upregulesponses ; promotixcretion . At the l health . Notably in rats , while Bemokines . After St of LMD . NXT redt of LMD . RLPs inFLD mice . In addiFLD mice . Given iFLD mice . MyricetFLD mice . After tFLD mice . QGE proFLD mice . RSV regFLD mice . HYQT maFLD mice . It can The study of the interaction between TCM and intestinal microorganisms has an important prospect, and the in-depth study of the interaction between TCM and intestinal flora is conducive to the elucidation of the potential mechanisms of TCM in preventing and treating LMD, as well as to the enrichment of TCM theory. In recent years, a few reviews have been reported on the regulation of intestinal flora by TCM to improve metabolic diseases, but there are shortcomings such as few included studies and few diseases involved . Based oIn summary, intestinal microecology plays a significant part in the development of LMD, and the regulation of intestinal flora and its metabolites is a potential new therapeutic target for LMD. TCM has obtained some achievements in improving lipid metabolism disorder diseases, probably by regulating intestinal flora and its metabolites, but in order to clarify the precise mechanism of action, more extensive research will still be required in the future.


Candida auris (CAU) epidemiology is evolving rapidly. Manogepix is the active moiety of the novel prodrug antifungal fosmanogepix (FMGX), and has broad-spectrum activity against yeasts and moulds, including CAU. Fluconazole (FLC) resistance (R) is common in CAU and R to amphotericin B (AMB) and echinocandins (ECHs) is documented. Global trends on CAU frequency and susceptibility (S) rates to MGX and comparators were evaluated through the MGX Surveillance Program.n=22; 6 centers), Europe , Asia-Pacific , and Latin America  were identified by MALDI-TOF MS and tested by CLSI broth microdilution. CDC tentative breakpoints (BP) were applied.A total of 77 CAU collected (1/patient) in 2017–2022 from 12 medical centers in North America  and 65 in 2020–2022 . CAU incidence spiked between these two time periods in NA (6 to 16), EU (0 to 32), and LA (6 to 16). MGX showed potent activity against CAU overall , inhibiting all isolates at ≤ 0.06 mg/L. MGX was 8-fold more active than ECHs , which inhibited all but 1 isolate at their respective BPs (98.7%S). FLC-R rates rose from 66.7% in 2017–2019 to 89.2% in 2020–2022, but varied among regions from 100.0% in EU to 90.9% in NA and 59.1% in LA. Only 1 AP isolate was recovered in 2022. This isolate exhibited an MGX MIC of 0.015 mg/L and was S to ECH and AMB but R to FLC. A decrease in AMB S rates was noted overall (from 91.7% to 84.6%). The lower AMB S rate was observed in NA isolates (63.6%S) rather than EU (93.8%S) and LA (95.5%S) isolates. The FLC-R and AMB-R phenotypes were noted in 11 isolates . MGX  and ECH (100%S) remained active against those highly R isolates.CAU were mainly recovered from bloodstream infections (68.8%). Twelve CAU isolates were recovered in 2017–2019 , bioMerieux: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Beth Hatch, BS, MT(ASCP), Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


CAR-T therapy has revolutionized the treatment of relapsed/refractory B-cell malignancies. Patients who are receiving such therapy are susceptible to an increased incidence of infections due to post-treatment immunosuppression. The need for antifungal prophylaxis during the period of neutropenia remains to be determined. The clinical outcome of a 55-year-old patient with relapsed/refractory DLBCL who received axicabtagene ciloleucel is described here. The patient developed CRS grade II and ICANS grade IV requiring tocilizumab, prolonged use of steroids and anakinra. An invasive pulmonary aspergillosis arose after 1 month from CAR-T reinfusion, resolved with tracheal sleeve pneumonectomy. The patient is now in Complete Remission. This case suggests that antifungal prophylaxis should be considered. We have now included micafungin as a standard prophylaxis in our institution. Therapy with chimeric antigen receptor T cells directed against the CD19 antigen (CD19 CAR-T) has substantially changed the outcomes of the patients with relapsed/refractory B-cell lymphoma . CAR T-r6 CD3+ T cells . CAR-HAMATOTOX (HT) score was 3 (high risk) (9/L > 7 days), until neutrophil recovery (day +10). On day +1, the patient developed fever with unstable cardiopulmonary function and concomitant IL-6 arising   with multiple involvement of the right lung, had persistent disease after three prior lines of treatments, including anti-CD20 antibody, alkylating agents, anthracycline and antimetabolites. She had no other relevant past medical history, with an ECOG (Eastern Cooperative Oncology Group) Performance Status score of 1 and no organ dysfunctions including normal left-ventricular ejection fraction. She was not candidate for an autologous stem cell transplant because of refractory disease and she was referred for treatment with CD19 CAR-T cell therapy using axicabtagene ciloleucel (gh risk) . Anti-vi arising Figure 2ery day +. On day 9/L > 7 days) severe hypogammaglobulinaemia and disease localization in the right lung are present in our case. With several recommendations in place for CAR T-cell treatments, the appropriate management of infectious consequences remains a clinical challenge  for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.EP: Investigation, Writing – original draft, Writing – review & editing, Data curation, Formal Analysis, Funding acquisition. PS: Data curation, Investigation, Writing – review & editing, Supervision. LC: Data curation, Investigation, Methodology, Writing – review & editing. FR: Data curation, Investigation, Methodology, Writing – review & editing. AD: Data curation, Investigation, Methodology, Writing – review & editing. GD: Data curation, Investigation, Writing – review & editing. RG: Formal Analysis, Methodology, Writing – review & editing. FG: Formal Analysis, Data curation, Writing – review & editing. GC: Methodology, Validation, Writing – review & editing. BF: Methodology, Formal Analysis, Writing – review & editing. SB: Formal Analysis, Methodology, Data curation, Writing – review & editing. MD: Formal Analysis, Conceptualization, Funding acquisition, Investigation, Writing – original draft, Writing – review & editing.


Race/ethnicity (R/E) may be an independent risk factor for developing long COVID or post-acute sequelae SARS-CoV-2 infection (PASC). Evaluation of real-world data will likely reveal PASC-related sociodemographic  disparities.A retrospective claims cohort analysis of Medicare, Medicaid, and Commercial fully-insured members  between October 2021 to December 2022 was conducted to identify members with PASC . Overall differences in PASC estimated incidence and symptomatology and its duration were explored with post-hoc analyses to examine the influence of R/E and insurance type.P = 1.0) had lower incidence . Post-hoc analyses by R/E and insurance type indicated this trend persisted for Asian or Unknown members across all insurance types . Furthermore, compared to White members, lower PASC incidence (P < .001) was observed for a) Black Medicaid and Medicare; b) Hispanic Medicaid; and c) AI/AN Medicare members. The most frequent PASC symptoms identified by claims were pulmonary (36%), neurologic (17%), and cardiac (15%). Compared to White members , Black members had more cardiac symptoms in Medicaid and Medicare groups and more pulmonary symptoms in Commercially insured; and Hispanic or Unknown members had fewer pulmonary, neurologic, and cardiac symptoms among all insured. There were no differences in PASC symptom duration by R/E within insurance type .Overall PASC estimated incidence  was 0.61% and was highest among American Indian/Alaskan Native  members, followed by White (0.78%), Black or Hispanic (0.49%), Pacific Islander , and Asian or Unknown (0.34%) R/E groups. Compared to White members, all other R/E groups except AI/AN (Hispanic and Unknown members had fewer claims for PASC than White members, which may indicate a lower disease burden or disparities in care access. Despite having overall less PASC estimated incidence than White members, Black members had more cardiac and pulmonary symptoms. Pulmonary symptoms were most frequently identified in all R/E groups. There was no association of PASC symptom duration between R/E within insurance type.KJ Craig, PhD, cvs Health Inc: employment|cvs Health Inc: Stocks/Bonds Amanda Zaleski, PhD, CVS: Employee|CVS: Stocks/Bonds Michael Wiggins, MPH, CVS: Employee|CVS: Stocks/Bonds Leah Altieri-Alger, MPH, CVS: Employee|CVS: Stocks/Bonds Dorothea Verbrugge, MD, CVS: Employee|CVS: Stocks/Bonds Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC, bioMerieux: Advisor/Consultant|CVS: Employee|CVS: Stocks/Bonds


Severe COVID-19 predicts increased risk of Post-COVID conditions (PCC). However, the impact of mild COVID-19 in non-hospitalized patients on development of PCC is less clear.We recruited individuals with mild SARS-CoV-2 (SCV2) infection from 7 US sites into a household transmission study, Sep. 2021–Dec. 2022. Index cases and their household contacts (HHC) were enrolled ≤6 days after the index case tested positive for SCV2. At baseline, participants provided sociodemographic, clinical and vaccine history, and dried blood spot for antibody detection. Participants completed daily symptom and medication diaries and collected nasal swabs for quantitative PCR (qPCR) for 10 days as well as a 90-day survey including the PROMIS® Global Health measure of physical, mental, and social health. We defined PCC as presence of ≥1 symptom (Table 1) most or almost all of the time 90 days post enrollment . We calculated the proportion of PCC among adults with SCV2 infection and evaluated factors associated with PCC using Chi-squared, Student’s t-test, or binary logistic regression, as applicableAt 90-days after enrollment, participants were asked how often they experience a list of 17 symptoms with response options of never, sometimes, most of the time, almost all the time. Those who responded most or almost all the time to at least one of the listed symptoms and tested positive for SARS-CoV-2 during enrollment or daily swabbing were defined as having PCC. Constitutional symptoms include fever, fatigue, and dizziness/lightheadedness; Neuropsychiatric symptoms include brain fog, change in mood, problems sleeping, tingling/numbness, and dizziness/lightheadedness; Respiratory symptoms include cough and dyspnea; Cardiovascular symptoms include chest pain and dizziness/lightheadedness; Gastrointestinal symptoms include change in taste/smell, vomiting, constipation, and diarrhea.Among 532 adults with SCV2 who completed a 90-day survey, 326 (61.3%) were female, mean age was 47.4 years (SD 16.8), and 89 (17%) met PCC definition. Among people with PCC, the most common symptoms were neuropsychiatric (60%), fatigue (35%), respiratory (34%), and sleep problems ; 41% reported ≥ 2 symptoms and 23% reported ≥ 3. HHC had lower odds of PCC compared to index cases , college graduates had higher odds of PCC compared to non-graduates  and participants with comorbidities had twice the odds of PCC compared to those without . There were no significant associations between viral load, antibodies, or treatment during acute illness and PCC (Table 3). PCC was associated with higher odds of reporting poor/fair quality of life , physical health , mental health , and social satisfaction .In this household transmission study, 17% of ambulatory adults with COVID-19 reported PCC symptoms 90 days after acute infection. Index cases, people with comorbidities, and college graduates had higher odds of PCC.Michelle Floris-Moore, MD, MS, Viiv Healthcare: Advisor/Consultant 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 Lisa Saiman, MD MPH, Merck & Co., Inc,: Grant/Research Support|Merck & Co., Inc,: Member, DSMB|Pfizer, Inc: Member, DSMB Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support


The presence of pathogenic bacteria in the anterior nares has gained substantial attention due to its association with an increased risk for surgical site infections. Nasal decolonization has been shown to reduce the risk for SSIs. Recent studies have suggested that the profile of the nose microbiome is a determining factor for the susceptibility to develop SSIs. Therefore, this prospective clinical trial was set up to study the profile of nasal microbiome and test the effect of a specific nasal decolonization solution on the microbiome.We conducted a prospective study on 50 individuals who were randomly assigned to receive a nasal antiseptic solution (n=25) or a control PBS solution (n=25). The antiseptic solution (containing povidone-iodine [PVP-I] as the main ingredient) or PBS was administered with a cotton swab and a rotatory movement for 15 s in the anterior part of both nares. Nasal swabs were obtained before application (baseline) and at 3 different timepoints after application . Nasal swabs were subjected next generation sequencing (NGS) analyses and cultured in trypticase soy agar plates.Study designFifty volunteers were recruited for this randomized clinical trial. Block randomization was performed to determine group allocation, thus, PVP-I (n=25) or PBS (n=25) application in the anterior nares. We assessed bioburden at baseline, 5 minutes, 2 hours, and 24 hours post-application, meanwhile microbial diversity and mucociliary clearance was assessed at baseline and 24 hours post-application. Bacterial associations were assessed at baseline and non-desired events were examined at every follow-up visit.10 3.538 ± 0.918 at 5 min; log10 2.961 ± 1.466 at 2 hours; and log10 0.849 ± 1.092 at 24 hours; p< 0.01), compared to PBS. At baseline, there were substantial associations between anaerobic species, Corynebacterium spp, Staphylococcus spp, and Dolosigranulum spp. The top species affected by the treatment were C. acnes, Staphylococcus, and Corynebacterium species, among others. None of the subjects in the study experienced any adverse effects associated with this study, nor increases in MCC time.A high bioburden reduction was observed after the application of PVP-I (logBioburden reduction (A) and mucociliary clearance assessment (B)A) Data is expressed as mean ± SEM CFU log10 reduction, from baseline bioburden. B) Sweetness detection, in minutes, at baseline and 24 hours post-application.Bacterial composition.A) Relative abundance of the most prevalent bacterial species and B) heatmap illustrating the mean relative abundance of bacteria detected to be differentially abundant by ANCOMBC procedure. A cell colored in black can be considered “true” zero, whereas there were no detections of a particular bacteria for that given cell.Network plot shows associations among bacterial species with p<0.10.Each node represents a species and is linked by species associations.There was a considerable difference in the profile of nasal microbiome organisms between individuals. Intranasal application of the PVP-I antiseptic led to a substantial reduction of the nasal flora for up to 24 hours after application. Restoration of the microbial population was observed with slight variations to the baseline profiles. Antiseptic solutions applied to the anterior nares can transiently and markedly reduce the bioburden of the nose.Javad Parvizi, MD, FRCS, 3M: Grant/Research Support|Acumed, LLC: Stocks/Bonds|Aesculap: Grant/Research Support|Alphaeon: Stocks/Bonds|AO Spine: Stocks/Bonds|Becton Dickenson: Advisor/Consultant|Biomet: Grant/Research Support|Cardinal Health: Advisor/Consultant|Cempra: Grant/Research Support|CeramTec: Grant/Research Support|Ceribell: Stocks/Bonds|Coracoid: Stocks/Bonds|Corentec: Advisor/Consultant|Datatrace: Grant/Research Support|DePuy: Grant/Research Support|Elsevier: Grant/Research Support|Elute: Stocks/Bonds|Ethicon: Advisor/Consultant|Hip Innovation Technology: Stocks/Bonds|Illuminus: Stocks/Bonds|Integra: Grant/Research Support|Intellijoint: Stocks/Bonds|Jaypee Publishers: Grant/Research Support|KCI / 3M (Acelity): Advisor/Consultant|Lima: Grant/Research Support|MicroGenDx: Advisor/Consultant|Molecular Surface Technologies: Stocks/Bonds|Myoscience: Grant/Research Support|Nanooxygenic: Stocks/Bonds|National Institutes of Health (NIAMS & NICHD): Grant/Research Support|NDRI: Grant/Research Support|Novartis: Grant/Research Support|OREF: Grant/Research Support|Orthospace: Grant/Research Support|Osteal: Stocks/Bonds|Parvizi Surgical Innovations and Subsidiaries: Stocks/Bonds|Peptilogic: Stocks/Bonds|Peptilogics: Advisor/Consultant|Pfizer: Grant/Research Support|PRN-Veterinary: Grant/Research Support|Rotation Medical: Grant/Research Support|Simplify Medical: Grant/Research Support|SLACK Incorporated: Grant/Research Support|Smith & Nephew: Grant/Research Support|Sonata: Stocks/Bonds|Stelkast: Grant/Research Support|Stryker: Grant/Research Support|Synthes: Grant/Research Support|Tenor: Advisor/Consultant|TissueGene: Grant/Research Support|Tornier: Grant/Research Support|Wolters Kluwer Health - Lippincott Williams & Wilkins: Grant/Research Support|Zimmer Biomet: Advisor/Consultant|Zimmer Biomet: Grant/Research Support


Hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections are increasing; recently, the Centers for Disease Control and Prevention (CDC) reported a 35% increase during the COVID-19 pandemic. We evaluated the impact of HO CRE blood stream infections (BSI) on outcomes compared to community-onset (CO) CRE BSI.Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between April 30, 2016 to November 30, 2019 with a qualifying CRE bloodstream culture were eligible. Infections were defined per CDC guidelines as CO when the culture was obtained immediately prior to admission or through the first three days of hospitalization, and HO when the culture was obtained on or after the fourth day of admission. Categorical variables were tested using a chi-square test; continuous variable distributions were compared using Wilcoxon rank sum and Kruskal Wallis tests, as appropriate. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% confidence intervals (CI).Figure 1. The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI is 60.6% (95% CI: 56.8-64.3%). Mortality at 30-days was 11.6% higher in HO BSI than CO BSI . A Kaplan-Meier curve of all-cause 30-day mortality is in Figure 2Among 891 patients with CRE BSI (Table 1), 65% of BSIs were hospital-onset (582/891). Compared to those with CO CRE, patients with HO CRE were younger , had lower Charlson comorbidity score , and more often had Pitt bacteremia sore ≥4, indicative of critical illness, . ICU admission prior to first culture was associated with HO BSI . Distribution of DOOR outcome at 30 days is shown in Desirability of outcome ranking at 30-days. Events evaluated included 1) deleterious effects, including absence of clinical response, prolonged hospitalization (>30 days following first positive culture), or readmission within 30 days; 2) any adverse events including renal failure or C. difficile infection; and 3) mortality at 30 days. Two subjects  missing 30-day DOOR due to missing disposition information are not included in the figure.Two subjects  are excluded from the figure due to missing mortality outcome information. One subject in the hospital onset group died on day 30 and is still considered at risk in the figure.HO CRE BSIs are associated with worse outcomes than CO CRE BSIs; this unique population warrants special attention. As CRE often contain mobile genetic elements that facilitate horizontal transfer, close monitoring of HO CRE rates and optimizing hospital infection prevention methods are critical to prevent added morbidity and mortality.Yohei Doi, MD, PHD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|SNIPRBiome: Grant/Research Support Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant


Immunocompromised (IC) patients are at risk of adverse COVID-19 outcomes. The risk of treatment emergent resistance may be high in this population. This study investigated clinical and virological outcomes in sotrovimab-treated IC patients in Great Britain while the Omicron variant was predominant.IC, non-hospitalized patients aged ≥ 18 years who were infected with SARS-CoV-2 and received early treatment with sotrovimab 500 mg IV for COVID-19 as per standard of care were included in this multicenter, single arm, observational prospective cohort study. Nasal/oropharyngeal samples were collected at baseline, Day (D) 7, 14, and 28 (+/-2 days) for viral load and sequencing analyses. Clinical  and safety outcomes were assessed through D28. This interim analysis included patients enrolled from 1 July 2022–31 January 2023.10 copies/mL at baseline to 0.55 log10 copies/mL at D28 (Table 1). Of 189 patients with spike consensus sequencing data, all harbored the Omicron variant, with 32 sublineages identified. Omicron BA.4, BQ.1, BE.9, BA.5.1.18, and BN.1 were most common in this data cut. We also plan to present interim data on treatment emergent substitutions. No patients were hospitalized due to COVID-19. Six (1.3%) patients had all-cause hospitalizations; none were admitted to ICU. One patient  with progressive neuromuscular disease needed high flow oxygen/non-invasive mechanical intervention and died on D18 (death deemed not COVID-19 related by investigator) (Table 2). Three mild sotrovimab-related adverse events were reported.Among 195 patients (median age: 58 years), 56% were female, 86% were white, and 98.5% had ≥ 1 COVID-19 vaccine dose prior to enrollment. All patients received sotrovimab within 8 (median: 2) days of diagnosis. Absolute median viral load declined from 7.46 logSotrovimab-treated patients had reduced viral load by D7 which further decreased through D28, despite being IC and infected with Omicron subvariants . Few severe clinical outcomes were reported .Judith Breuer, MD, GSK: Funding to conduct study|MRC/UKRI: Grant/Research Support|National Institutes of Health: Grant/Research Support|NIHR: Senior investigator|UKNIHR: Grant/Research Support|Vir Biotechnology, Inc: Funding to conduct study|Wellcome Trust: Grant/Research Support Myriam Drysdale, PhD, GSK: Employee|GSK: Stocks/Bonds Jill Walker, PhD, GSK: Employee|GSK: Stocks/Bonds Jennifer Han, MD, GSK: Employment|GSK: Stocks/Bonds Magdalena Gorczycka, MSc, GSK: Employee|GSK: Stocks/Bonds Alicia Aylott, MSc, GSK: Employee|GSK: Stocks/Bonds Melissa K. Van Dyke, PhD, GSK: Employee|GSK: Stocks/Bonds Helen Birch, PhD, GSK: Employee|GSK: Stocks/Bonds Elizabeth McKie, PhD, GSK: Employee|GSK: Stocks/Bonds David M. Lowe, FRCP, PhD, Biotest: Speaker fees|Blood Cancer UK: Grant/Research Support|Bristol Myers Squibb: Grant/Research Support|British Society of Antimicrobial Chemotherapy: Grant/Research Support|Gilead: Speaker fees |GSK: Funding to conduct study|Langland: Speaker fees|LifeArc: Grant/Research Support|Merck: Personal fees for a round-table discussion|National Institute of Health Research: Grant/Research Support|Octapharma: Travel, accommodation and conference fees|UK Medical Research Council: Grant/Research Support|Vir Biotechnology, Inc: Funding to conduct study


Clostridioides difficile infection (CDI) and recurrence. Fecal microbiota, live-jslm  is the first FDA-approved, microbiota-based live biotherapeutic for the prevention of recurrent CDI (rCDI) in adults following antibiotic treatment for rCDI. An ad hoc subgroup analysis of PUNCH CD3-OLS (NCT03931941), an ongoing, open-label, phase 3 trial evaluating the efficacy and safety of RBL, assessed outcomes in participants with renal comorbidity.Patients with renal comorbidity are at risk of severe PUNCH CD3-OLS participants were ≥ 18 years old with medically documented rCDI, including first recurrence determined by the treating physician, and assessed with standard-of-care (SOC) diagnostic methods. After SOC antibiotics, participants received a single dose of rectally administered RBL. Treatment success was defined as remaining recurrence free for 8 weeks after treatment. Treatment-emergent adverse events (TEAEs) through 6 months of treatment were reported. Participants with renal comorbidity were identified from the medical history dictionary-derived terms in the modified intent-to-treat (mITT) population.Within the mITT population, 98 of 402 participants with adjudicated outcomes had renal comorbidity, including chronic kidney disease (n=29) and end-stage renal failure (n=5). Of participants with renal comorbidity, 50% had Charlson Comorbidity Index scores of ≥ 5, versus 18% of participants without renal comorbidity. Treatment success was achieved by 66% (65/98) and 77% (235/304) of participants with and without renal comorbidity, respectively. TEAEs occurred in 71% (n=70) of participants with renal comorbidity and 64% (n=194) of participants without renal comorbidity. In both groups, most TEAEs were moderate in severity and related to preexisting conditions. Serious TEAEs were reported by 16% (n=16) and 8% (n=24) of participants with and without renal comorbidity, respectively. The most commonly reported serious TEAE was CDI recurrence, occurring in 3.1% (n=3) and 1.6% (n=5) of participants with and without renal comorbidity, respectively.RBL treatment success and TEAE incidence were numerically comparable for those with and without renal comorbidity.Monika Fischer, MD, Ferring Pharmaceuticals Inc.: Advisor/Consultant|Rebiotix Inc., a Ferring Company: Board Member|Seres Pharmaceuticals: Advisor/Consultant Joan Thul, BA, Ferring Pharmaceuticals Inc.: Employee Beth Guthmueller, AS, Rebiotix Inc., a Ferring Company: Employee Christian Sandrock, MD, Allergan: Advisor/Consultant|National Institutes of Health: Grant/Research Support|Shionogi: Advisor/Consultant|The Health Resources & Services Administration: Grant/Research Support Nicholas Van Hise, PharmD, Ferring Pharmaceuticals Inc.: Advisor/Consultant|Ferring Pharmaceuticals Inc.: investigator Glenn S. Tillotson, PhD, Dynavax: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Peggy Lillis Foundation: Honoraria|Spero Therapeutics: Advisor/Consultant


MEIA urine diagnostic was developed as an enzyme immunoassay, by Johns Hopkins (JH) and Pearl Diagnostics. In a retrospective study of 310 people, the assay was 90.5% (95% CI 70-99) sensitive and 89.2% (95% CI 82-94) specific. We report results of a prospective study performed at JH Hospital (JHH).The MycoMEIA results in subjects with possible IA, mixed infections, or other infections (non-IA) were evaluated descriptively.People with suspected invasive aspergillosis (IA) were identified by screening of diagnostic tests sent by clinicians at JHH. Urines from consented subjects were tested in the clinical mycology lab within 8 hours of collection. Results were not used to inform care. Established diagnoses were adjudicated by clinicians blinded to lab results, using consensus criteria. Performance was analyzed in evaluable subjects who had CTs within 2 weeks of suspected IA. Findings supporting proven or probable IA, or no infection defined cases and controls, respectively. MycoMEIA urine tests.107 urines were tested from 72 subjects with suspected IA. 15 subjects had >1 samples tested. Subjects were mostly male , with median age of 51 (range 7 – 87 years). IA was suspected during treatment for heme malignancies , solid organ transplant (9), cancer (5), and rheumatologic disease (1). Of 72 subjects enrolled, 30 had possible IA (42%), 30 no infection (42%), 4 probable IA (6%), 4 mixed infections (6%) and 4 other infections, including bacterial abscess (1), fusariosis (1), fungal sinusitis (1) and otitis externa (1). The assay was 100% sensitive (95% CI 76–98) and 93% specific (95% CI 79–99) for IA, with likelihood ratio of 15. Five of 30 (16.7%) people with possible IA and 1 with fusariosis had positive MycoMEIA – Aspergillus test appears consistent with retrospective findings and favorable compared to current blood assays. The proportion of lab confirmed diagnoses using current commercial assays was low; high negative predictive value with urine testing may support restriction of empirical antifungals. Cross reactivity amongst pathogenic Ascomycetes is biologically anticipated and requires further study. The study remains ongoing.In prospective testing by the clinical lab, performance of the urine MycoNitipong 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 Kieren Marr, MD, Cidara Therapeutics: Advisor/Consultant|Merck: Advisor/Consultant|Pearl Diagnostics: salary|Pearl Diagnostics: Ownership Interest|Sfunga Therapeutics: salary|Sfunga Therapeutics: Ownership Interest Irina Baburina, PhD, Pearl Diagnostics: salary Dana Neitzey, BS, Pearl Diagnostics: salary Patricia X. Marques, PhD, Pearl Diagnostics: salary Sean Zhang, MD, PhD, Applied BioCode: Grant/Research Support|IMMY Diagnostics: Grant/Research Support|KARIUS: Advisor/Consultant|Pearl Diagnostics: Grant/Research Support|Scanogen: Grant/Research Support|T2 biosystems: Advisor/Consultant|Vela Diagnostics: Grant/Research Support


Invasive meningococcal disease (IMD) is associated with a high case fatality rate and serious long-term sequelae (LTS). The current US vaccination platform targets serogroups ACWY with a routine recommendation in adolescents  and serogroup B (16-23 years) based on shared clinical decision making. A novel pentavalent meningococcal vaccine (MenABCWY) may improve protection against all five serogroups and simplify vaccination schedule. The study objective was to assess the cost-effectiveness of MenABCWY from a societal perspective in the US.A steady-state model was developed to estimate the impact of various vaccination strategies on IMD cases, LTS, and deaths. Cohorts of 11- and 16-year-olds were simulated over a lifetime (up to 100 years of age) after vaccination. The same vaccine uptake rate was applied to all strategies. Costs included vaccination acquisition and administration, and IMD direct and indirect costs. Disutilities of IMD and LTS were applied to estimate losses of quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated as the difference in costs over QALY gained comparing a strategy of implementing the MenABCWY vaccine with the current standard of care (SoC). Extensive scenario analyses were conducted.In the base case, compared with the SoC , introducing two doses of the MenABCWY vaccine at 11 years followed by a booster at 16 years (2+1 schedule) would prevent 63 IMD cases, 17 IMD cases with LTS, and 6 IMD-related deaths while providing savings (dominant ICERs). Results on ICERs, IMD cases, and IMD-related deaths were robust in scenario analyses when inputs most likely to influence the public health impact  were modified over plausible ranges.The MenABCWY vaccine fits the current vaccination platform. Results of the cost-effectiveness analysis demonstrate that the 2+1 schedule could offer the most public health benefits by providing the full protection against all five serogroups at an early age, while being a dominant economic strategy.Katharina Schley, Dr., Pfizer Pharma GmbH: Employee|Pfizer Pharma GmbH: Employee|Pfizer Pharma GmbH: Stocks/Bonds|Pfizer Pharma GmbH: Stocks/Bonds Jessica V. Presa, MD, Pfizer Inc.: Stocks/Bonds|Pfizer Inc.: Stocks/Bonds Vincenza Snow, MD, Pfizer Vaccines: employee|Pfizer Vaccines: Stocks/Bonds Alejandro D. Cane, MD, PhD, Pfizer: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds Ray Farkouh, PhD, Pfizer: Stocks/Bonds Shannon M. Sullivan, PhD, Evidera: I am an employee of Evidera that is a consultancy to multiple pharma companies|Pfizer: Advisor/Consultant Hossein Zivaripiran, PhD, Pfizer: Advisor/Consultant|Pfizer: I am an employee of Evidera that is a consultancy to multiple pharma companies Diana Teloian, MA, Merck & Co., Inc: Grant/Research Support Jörgen Möller, MSc, Evidera: I am an employee of Evidera that is a consultancy to multiple pharma companies|Pfizer: Advisor/Consultant J. Jaime Caro, MDCM, FRCPC, FACP, Evidera: I am an employee of Evidera, a consultancy serving the pharmaceutical industry.|Pfizer: Advisor/Consultant


Scientific Reportshttps://doi.org/10.1038/s41598-022-17806-8, published online 16 August 2022Correction to: The original version of this Article contained errors in the Author Information section.“These authors contributed equally: Yoojoong Kim, Jong-Ho Kim, Hyung Joon Joo and Sanghoun Song.”now reads:“These authors contributed equally: Yoojoong Kim and Jong-Ho Kim.These authors jointly supervised this work: Hyung Joon Joo and Sanghoun Song.”Additionally, Hyung Joon Joo was omitted as a corresponding author. Correspondence and requests for materials should also be addressed to drjoohj@korea.ac.kr.The original Article has been corrected.


Post-transplant lymphoproliferative disorder (PTLD), which is often driven by Epstein-Barr virus (EBV), causes significant morbidity and mortality in lung transplant recipients (LTRs). EBV viremia surveillance with reduction of immunosuppression at certain viral load thresholds is a common strategy used to prevent PTLD or mitigate progression of PTLD in pre-clinical stages, but the utility of EBV surveillance in adult seropositive LTRs is poorly understood.In a retrospective cohort study of EBV seropositive adults who underwent lung transplant at a single academic center between 1/1/2019-12/31/2020, we compared peak whole blood EBV viral load (VL) among samples collected from 1) LTRs who developed PTLD, before PTLD symptom onset, 2) LTRs who developed PTLD, after PTLD symptom onset and 3) LTRs who did not develop PTLD. LTRs without any recorded EBV VLs were excluded. Patients were followed through 1/31/2023 (maximum 49 months post-transplant). Center protocol recommended quantitative EBV PCRs every 3 months between 3-18 months post-transplant, and as clinically indicated thereafter. Reduction of immunosuppression and evaluation for PTLD was at the discretion of clinicians.Table 1). Six (2.6%) LTRs developed biopsy-proven PTLD 8-35 months post-transplant (median 17 months); 5/6 PTLDs were EBV+. Clinical symptoms, rather than an asymptomatic high EBV VL, triggered evaluation for PTLD in all 6 cases. Only one of six LTRs with PTLD had an EBV VL above the assay’s lower limit of quantification before PTLD symptom onset ; among the other 5 LTRs, median time between most recent negative EBV PCR and PTLD symptom onset was 125 days (range 35-216). Peak EBV VL in LTRs with PTLD was significantly higher after PTLD symptom onset than in the asymptomatic period (p=0.016), but peak EBV VL was similar between asymptomatic LTRs who later developed PTLD and LTRs who did not develop PTLD .Two-hundred twenty-nine LTRs with a total of 1095 EBV PCRs were included (40% female, median age 65 years at transplant, In EBV seropositive adult LTRs , EBV surveillance rarely facilitated PTLD diagnosis and may not be an effective strategy for identifying asymptomatic individuals at high risk for future PTLD.Arthur W. Baker, MD, MPH, Insmed: Grant/Research Support|Medincell: Advisor/Consultant Eileen K. Maziarz, MD, Karius, Inc: Advisor/Consultant Barbara D. Alexander, MD, F2G Pharmaceuticals: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Leadiaint: Grant/Research Support|Merck: Advisor/Consultant|Scynexis: Grant/Research Support|Thermofisher: Advisor/Consultant


Cabotegravir+Rilpivirine (CAB+RPV) is the first FDA-approved complete long-acting (LA) injectable antiretroviral therapy (ART) for treatment of HIV-1 infection among ART-experienced, virologically suppressed (VL < 50 c/mL) people with HIV (PWH). We assessed utilization and effectiveness among PWH with VL ≥ 50 c/mL at initiation in real world clinical setting.Adult PWH who received ≥ 1 CAB+RPV injections through March 2023 with VL ≥ 50 c/mL at initiation were identified using electronic medical records from Trio Health HIV Network. Results were stratified by VL ≥ 50 c/mL and ≥ 200 c/mL at initiation. Genotypic resistance data prior to initiation of CAB+RPV LA was available for a subset of individuals, with resistance interpretation described using Stanford HIVdb algorithm.Among 329 PWH with ≥ 1 CAB+RPV injections, 29 (9%) had VL ≥ 50 c/mL at initiation. All were treatment-experienced and 12 (41%) had VL ≥ 200 c/mL, median log VL 3.1  at initiation; 21% were women, 48% were Black, median age was 43 , and 41% had a BMI ≥ 30.At the time of analysis, all individuals remained on CAB+RPV LA with median follow-up of 4.0 months  with median 3 injections ; 20 individuals had ≥ 2 injections and 16 had ≥ 3, with 80/86 (93%) follow-up injections administered within target window. Median time from first to second injection was 32 days , and median time from second to third injection was 59 days . Among the 16 individuals with ≥ 3 injections, 12 were on every-2-month dosing schedule.Sixteen (55%) individuals had a follow-up VL. Of them, the last VL was < 50 c/mL in 12 individuals (75%), < 200 c/mL in 15 (94%), and 1 with VL 1202 c/mL (pre-index VL 2138 c/mL).Historical HIV genotype results were available for 15 individuals (52%). One individual had low-level resistance to CAB based on Y143R mutation and this individual had a follow-up VL < 50 c/mL. Five individuals had NNRTI mutations, one with low-level resistance to RPV and a follow-up VL < 200 c/mL.This real-world data of individuals who received ≥ 1 CAB+RPV LA injections with VL ≥ 50 c/mL at initiation demonstrated high rates of virologic suppression. Future analysis with longer follow-up will allow for evaluation of long-term outcomes.Rick A. Elion, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Proteus: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Andrew Frick, MS, Trio Health Inc.: Employee Janna Radtchenko, MBA, Trio Health: Employee Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Full Time Employee Supriya Sarkar, PhD, MPH, ViiV Healthcare: Employee Joseph J. Eron, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Karam Mounzer, MD, Clinical Care Options: Speakers Bureau|Epividian: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Speakers Bureau|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Speakers Bureau|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Speakers Bureau|Prime: Speakers Bureau|Simply Speaking: Speakers Bureau|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Speakers Bureau Jean A. van Wyk, MBChB, MFPM, ViiV Healthcare Ltd: Stocks/Bonds Vani Vannappagari, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee


Cutaneous invasive fungal infections CIFIs (primary or secondary to hematogenous seeding) are frequent and often fatal in immunocompromised cancer patients (pts). There is a paucity of studies on the prognostic significance and concordance of histopathologic features with cultures.We reviewed all pts with histologically diagnosed CIFIs at MD Anderson Cancer Center (06/2016-06/2020). Demographic, clinical, histopathologic , culture, and outcome  data were recorded.Fusarium  or Mucorales . Angiotropism was most frequently associated with Fusarium , and neurotropism with Mucorales . Eighty-four-day all-cause mortality rate was 62% . Fungal angiotropism  and neurotropism  were associated with significantly increased mortality, while lymphocytic inflammation, seen only in 20%, was associated with reduced mortality .We identified 61 pts ; 37 (61%) were male. Most had hematologic malignancy , especially acute leukemia . CIFI was primary in 53 pts (87%), with acute onset (≤ 1 week) in 66% of pts; 37 pts (61%) had multiple skin lesions. Fungal organisms were seen on H&E-stained sections in 47 cases (77%), whereas ancillary studies (GMS/PAS) were required in 14 cases (23%). Of the 59 concurrent microbiology cultures, only 43 (73%) were positive. In 16 cases, fungal order/genus was identified by both histopathology and culture; 13/16 (81%) were concordant . The causative fungal order/genus was determined in 55 pts (90%), most commonly Figure 1(A) Concordance of histopathologically determined and cultured fungal order/genus. Fleiss’ kappa 0.67 , p < 0.001. (B) Distribution of causative fungal pathogens.Figure 2Histopathological features significantly associated with 84-day all-cause mortality in CIFI patients. Error bands denote 95% confidence interval. Mantel-Cox log-rank test.Table 1Association between type of organism and histopathological characteristics. Six patients with no identified organism were excluded. Fisher’s exact test. Abbreviation: PEH = pseudoepitheliomatous hyperplasia.CIFIs have poor prognosis, especially when caused by molds and if fungal angio-/neurotropism is identified. Inflammation may be associated with better prognosis. Since cultures might be false negative (27%) or discordant (19%), more efforts are needed for culture-independent molecular detection of fungi. Incorporation of histopathologic features might inform prognostic risk stratification.Dimitrios P. Kontoyiannis, MD, MS, ScD, PhD, AbbVie: Board Member|Astellas: Grant/Research Support|Cidara: Board Member|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Scynexis/MSGERC: Board Member


Broad-range bacterial PCR sequencing (BRBPS) has emerged as a novel tool to detect fastidious organisms. While its utility has been characterized in different specimen types, its role in culture-negative blood specimens remains poorly understood.We reviewed all clinical specimens sent for culture-negative blood BRBPS  to the Laboratoire de santé publique du Québec, the reference laboratory for a large Canadian province, from May 2018 to November 2022. Sanger sequencing of the amplified 16s rRNA gene was performed in all PCR-positive specimens. Data were extracted from the laboratory information system, and the analysis was restricted to the first specimen per patient. Microbiological outcomes were categorized as interpretable sequence, uninterpretable sequence, or negative PCR result. Interpretable sequences were identified and then classified based on the National Healthcare Safety Network database  and microbiological characteristics.A total of 1199 blood specimens were analyzed using BRBPS from 852 unique patients. Of these, there was no PCR amplification in 152, amplification with uninterpretable sequences in 445 and an interpretable sequence in 255 specimens . Blood specimens received at room temperature, in blood culture bottles, or with positive gram stain were more likely to yield interpretable sequences (Table 2). We identified 174 patients with BRBPS results suggestive of organisms associated with mucosal barrier injury (n=89) or possible pathogens (n=85), summarized in Figure 2. In contrast, 75 patients had results suggestive of contamination from common commensal organisms (n=44) or taxa not in the NSHN database (n=31).Classification of interpretable sequences using the National Healthcare Safety Network database classification of microorganisms.Mucosal barrier injury (A) and possible pathogens (B) are categorized based on the National Healthcare Safety Network database. Microorganisms are colour classified based on microbiological characteristics.Our findings demonstrate the potential utility of BRBPS in blood specimens from culture-negative patients, particularly infectious syndromes caused by fastidious gram-negative bacteria associated with animal or arthropod exposures or anaerobic bacteria. However, the frequent recovery of commensal and environmental organisms argues for careful and judicious use. Additional technical optimization is likely required to improve diagnostic yield, particularly with mixed sequences.Matthew Cheng, MD, Amplyx Pharmaceuticals: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|GEn1E lifesciences: Advisor/Consultant|GEn1E lifesciences: Stocks/Bonds|Kanvas Biosciences, Inc.: Board Member|Kanvas Biosciences, Inc.: Pending patents|Kanvas Biosciences, Inc.: Ownership Interest|Merck: Honoraria|nomic bio: Advisor/Consultant|nomic bio: Stocks/Bonds|Pfizer: Honoraria|Scynexis Inc.: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria


TM) platform. Quality of prescribing was assessed based on local guidelines and clinical justification using published definitions . The objective of the study was to evaluate the impact of PAF+NAPS interventions on antibiotic use (AU) in acute leukemia patients at an academic cancer center, compared to PAF-only.Prospective audit-and-feedback (PAF) for hospitalized leukemia patients is resource-intensive, while data on stadardized assessment of the quality, i.e. appropriateness, of antimicrobial prescribing are scarce. We implemented a multifaceted program combining patient-level PAF with unit-level appropriateness reports generated by serial point-prevalence surveys using the web-based Canadian National Antimicrobial Prescribing Survey , the AMS team led 30-minute PAF rounds with prescribers 2x/week. After implementating PAF+NAPS (Jun 1 2019-Mar 31 2020), we met 2x/month for 30 minutes. At each meeting we presented an automated NAPS dashboard report  of aggregate appropriateness adjudication of antibiotic prescriptions, followed by targeted PAF on select patients with complex antimicrobial needs. We analyzed the impact of the two-step approach on the primary outcome of AU (defined daily dose [DDD]/100 patient-days [PD]) using interrupted time series models. Secondary outcomes were appropriateness of AU during PAF+NAPS, lenght of stay and in-hospital mortality. Target appropriatenesss was at least 90%. Categorical variables were compared using chi-square test and continuous variable using Mann Whitney U test.Patient characteristics and outcomes were presented in Table 1. AU data were presented in Table 2. AU of piperacillin-tazobactam and vancomycin decreased significantly after implementation of 2x/month PAF+NAPS, compared to 2x/week PAF-only interventions . Overall appropriateness was 91.4% (1757/1921 prescriptions).Despite reducing frequency of interventions from 2x/week to 2x/month, PAF+NAPS was an efficient and sustainable AMS model that promoted appropriate and judicious antimicrobial use in hematology-oncology patients , allowing the AMS team to expand to other specialized areas.Shahid Husain, MD, Astellas: Grant/Research Support|Avir: Grant/Research Support|F2G: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Pulmocide: Grant/Research Support|Synexis: Grant/Research Support|Takeda: Honoraria


Delusional memories or retrospective delusions have been extensively reported in subjects during or after intensive care stays. In major psychoses, authors have classically observed delusional memories impacting the prognosis and mental well-being.Our aim was to review the phenomenology, psychological/biological factors contributing to delusional memories in delusional disorder (DD), and potential treatment strategies.Systematic review using PubMed, Scopus, SciELO and Web of Science electronic databases (inception-September 2022). Search terms:  AND  [MeSH]. Studies were included if they reported psychopathology, clinical characteristics or treatment strategies of “delusional memories” in DD. Team members: AGR, JAM, MS, MB, MF, ACP, FD, MVS.A total of 786 records were retrieved, including six studies. Psychogenesis:A novel cognitive neuropsychological research model (based on hypnosis) in erotomania delusions suggest a potential recall and reinterpretation of delusions beliefs in highly hypnotizable subjects. Biological basis: Frontal lobe (or executive) dysfunction does not seem to contribute to delusional memories in De Clérambault syndrome (erotomania). Phenomenology: 1)General knowledge was essentially intact, while the perceptual characteristics of delusional memories were stronger than real memories. 2)Correlations were found between delusional ideation, positive dimension of schizotypy (r=0.18), and false memories (r=0.27). 3)Jumping-to-conclusions and liberal acceptance bias influence delusional memories. Treatment:Efficacy of 1)Cognitive Behavioural Therapy (CBT) (significant reduction delusions), and 2)Metacognitive control over false memories.This is the first review exploring the genesis and management of delusional memories in DD. Memory deficits/executive dysfunctions do not seem to be the only cause of this phenomenon.None Declared


Clostridioides difficile infection (CDI) is increasing. However, CDI testing practices and incidence among patients seeking care for diarrhea in the outpatient setting have not been well described. Further, little is known about healthcare utilization and outcomes of patients with medically-attended CDI who are not subsequently hospitalized.Population-based surveillance by the Centers for Disease Control and Prevention (CDC) indicates that the incidence of community-associated C. difficile testing and outpatient CDI (oCDI), defined as a positive CDI test without hospitalization in the following 0-7 days. We described the demographic and clinical characteristics of patients with MAD and oCDI and calculated incidence rates (IR) of oCDI. We also described the occurrence of oCDI-associated healthcare visits, CDI testing, and oCDI treatment in the 12 months following oCDI diagnosis.We conducted a retrospective cohort study of Kaiser Permanente Southern California (KPSC) and Northwest (KPNW) adult (≥ 18 years of age) members from January 1, 2016 to December 31, 2021. We identified medically-attended diarrhea (MAD) in the outpatient setting through ICD-10 diagnosis codes. Among those with MAD, we identified We identified 777,533 outpatient MAD episodes of which 93,964  were tested for CDI. Among tested episodes, 10,110 ), involving 9,517 patients, had a positive CDI laboratory test. IR of outpatient oCDI decreased from 58.2 (95%CI: 55.7-60.7) per 100,000 person-years (PY) in 2016 to 45.7 (43.7-47.8) per 100,000 PY in 2021. Among 9,517 oCDI patients, 84.1%  CDI were ‘community-associated’  and only 44.1%  received an antibiotic in the previous 30 days. Only 6.7% (n=526) of oCDI patients had a CDI-associated hospitalization in the 12 months after diagnosis.There was a high incidence of MAD and CDI in among outpatients. The majority of our outpatient CDI population had no recent hospitalization and no recent antibiotic exposure. Further studies are needed to understand the factors associated with CDI diagnosed and managed in the outpatient setting.Sara Y. Tartof, PhD MPH, Genentech: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Grant/Research Support|SPERO: Grant/Research Support Mark A. Schmidt, PhD, MPH, Intercept Pharmaceuticals: Grant/Research Support|Pfizer: Grant/Research Support|Vir Biotechnology: Grant/Research Support Fredrick J. Angulo, DVM, PhD, Pfizer Vaccines: Employee|Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds|Pfizer Vaccines: Stocks/Bonds Ana Florea, PhD MPH, Gilead: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Joann M. Zamparo, MPH, Pfizer Inc.: Full Time Employee|Pfizer Inc.: Stocks/Bonds Deborah S. Ling Grant, PhD, MPH, MBA, Pfizer: Grant/Research Support Elisa Gonzalez, MPH, Pfizer: Stocks/Bonds Jennifer L. Kuntz, MS, PhD, Pfizer: Grant/Research Support


Acinetobacter baumannii-calcoaceticus complex (ABC), including multidrug-resistant and carbapenem-resistant isolates. SUL-DUR is predominantly renally eliminated, with altered exposures in patients with renal impairment (RI) or with augmented renal clearance (ARC). Using population pharmacokinetic (PPK) approaches with Phase 1-3 clinical data, alternate dosing regimens to those used in the Phase 3 trial were assessed across renal function categories.Sulbactam-durlobactam (SUL-DUR) is a β-lactam/β-lactamase inhibitor combination in development for the treatment of infections caused by CR), on the variability in SUL-DUR PK. The population mean clearance of both drugs increased with increasing CLCR. Using this model, simulations were conducted to evaluate appropriate dosing regimens (as 3-hour intravenous infusions) for patients with RI and ARC based on PK exposure and probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA).A PPK model was previously constructed using data from 373 subjects, of which 110 were infected Phase 3 patients, and included the impact of statistically significant covariates, such as creatinine clearance (CLCR < 45 mL/min had higher exposures of SUL-DUR compared to patients with CLCR ≥ 60 mL/min (Table 1), suggesting that further dose adjustments may be needed in these subgroups. To streamline the dosing regimens across renal function categories, a dosing regimen of 1 g/1 g SUL-DUR q4h instead of 1.5 g/1.5 g SUL-DUR q6h was also evaluated for patients with ARC. Alternate dosing regimens (Table 2) yielded Day 3 plasma exposures that were generally contained within the 5th and 95th percentiles of the exposure distribution of simulated patients with normal renal function . Based on PK/PD targets associated with a 1-log10 CFU reduction from baseline on Day 1, a PTA > 90% for MIC values ≤ 4 mg/L across CLCR categories was achieved in both plasma and epithelial lining fluid.Patients with CLCR < 45 mL/min and ≥ 130 mL/min resulted in exposures that were comparable to those in patients with normal renal function with a high PTA, indicating that these doses are expected to be safe and efficacious.Alternate SUL-DUR dosing regimens in simulated patients with CLKajal Larson, PhD, Entasis Therapeutics, a wholly-owned subsidiary of Innoviva: Employee|Entasis Therapeutics, a wholly-owned subsidiary of Innoviva: Stocks/Bonds 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 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 John O'Donnell, B.S, Entasis Therapeutics, a wholly-owned subsidiary of Innoviva: Employee|Entasis Therapeutics, a wholly-owned subsidiary of Innoviva: 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