Cerebral Cortex, 2021, bhab447, https://doi.org/10.1093/cercor/bhab447.This is a correction to: Gunnar Norrman, Emanuel Bylund, Guillaume Thierry, Irreversible Specialization for Speech Perception in Early International Adoptees, In the originally published version of this manuscript, the following funding statement was omitted from the Funding section:“GT is supported by the Polish National Agency for Academic Exchange (NAWA) under the NAWA Chair Programme (PPN/PRO/2020/1/00006)”This error has been corrected.


Polymerase chain reaction (PCR)-based diagnostic testing for BSIs, such as the BioFire FilmArray® Blood Culture Identification (BCID) Panel, has the potential to shorten time to appropriate therapy and duration of overly broad-spectrum antibiotics. The clinical benefit of PCR-based diagnostic technologies for BSIs has been demonstrated but data supporting their utility in larger multi-center settings are limited. This study sought to evaluate outcomes associated with the implementation of the BioFire BCID in the US Veterans Affairs (VA) system.A retrospective multi-center pre-post quasi-experimental study was performed among patients admitted to any VA hospital that adopted BioFire BCID Panel for ≥ 1 year. Patients with ≥ 1 BSI due to bacteria on the BioFire BCID Panel  were included. Exclusion criteria were polymicrobial BSI or death within 48 hours of BSI. Patients were categorized into two groups: i) BSI in the 1-year prior to implementation (pre-BCID) and ii) 1-year post implementation (post-BCID). Post-BCID period commenced 2 months after first BCID-BSI. Outcomes included early de-escalation, defined as a reduction in antimicrobial spectrum score within 48 hours of index BSI, time to appropriate therapy, 30-day mortality, and 90-day CDI incidence.n=2088 pre-BCID; n=2011 post- BCID). Groups were similar at baseline (Table). BioFire BCID implementation was associated with an improvement in early de-escalation  and reduction in median (IQR) time to appropriate therapy . There was no significant difference in 30-day mortality  or CDI  between BCID groups.A total of 4099 patients across 33 VA facilities met study criteria (In this large VA cohort study, implementation of the BioFire BCID panel was associated with a significant improvement in early antimicrobial de-escalation and time to appropriate therapy. These data suggest this rapid diagnostic technology aids in optimization of antimicrobial use in hospitalized VA patients with BSIs.Nicholas Britt, PharmD, MS, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Shionogi: Grant/Research Support Karim Khader, PhD, BioFire Diagnostics: Grant/Research Support Tristan T. Timbrook, PharmD, bioMerieux: Employee of bioMerieux Thomas Lodise, Jr., Pharm.D., PhD, BioFire Diagnostics: Grant/Research Support|cidara: Advisor/Consultant|cidara: Honoraria|Entasis: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Paratek: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant|Venatrox: Advisor/Consultant.


Public health surveillance indicates that there is a high population-based incidence of laboratory-confirmed hospitalized CDI cases in the United States. Although reported CDI cases are identified via standard-of-care (SOC) specimen collection and CDI testing practices, the impact of SOC misdiagnosis on the reported CDI incidence is uncertain.>50 years = 276 456). Study stool specimens from inpatients with diarrhea were screened by rapid GDH/toxin membrane enzyme immunoassay and the positive samples tested by PCR and cell cytotoxicity neutralization assay (CCNA). A study CDI case was a patient with PCR positive/CCNA positive stool or PCR positive stool with pseudomembranous colitis (PMC). Incidence (non-recurrent CDI cases/100 000 persons aged >50 years per year [PY]) was adjusted for the hospitalization share of participating hospitals and, in a sensitivity analysis, for patients with diarrhea without a CDI test result. SOC stool specimen CDI testing occurred independent of the study.Active surveillance from Oct 14, 2019, to Apr 11, 2020, identified inpatients aged ≥50 years with diarrhea (≥3 stools with Bristol score ≥5 in 24 hours) at all wards at 8 of the 9 adult hospitals in Louisville, Kentucky  had PMC, 36 (33.0%) were admitted to intensive care, and 21 (19.3%) died during the 90-day follow-up. Study hospitalized CDI incidence was 154/100 000 PY . SOC hospitalized CDI incidence was 121/100 000 PY. Of the 109 study CDI cases, 44 (40%) were not SOC-diagnosed (SOC under-diagnosis). Of the 75 SOC CDI cases that also had study testing, 12 (16%) were not study CDI cases (SOC over-diagnosis). SOC-undiagnosed and SOC-diagnosed CDI cases had similar demographics, medical histories, and clinical outcomes. Study testing identified 24% more CDI cases than SOC testing.>50 years . Of the hospitalized CDI cases, one-third were admitted to ICU and one-fifth died. Public health surveillance estimates of the incidence of laboratory-confirmed hospitalized CDI cases, which are based on SOC testing, may be under-estimated by 24%.There was a high incidence of hospitalized CDI in persons aged Frederick Angulo, DVM PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Joann M. Zamparo, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Elisa Gonzalez, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Pingping Zhang, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Michael W. Pride, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Sharon Gray, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Catia Matos Ferreira, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Forest W. Arnold, DO, MSc, Gilead Sciences, Inc.: Grant/Research Support Raul E. Isturiz, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Nadia Minarovic, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Jennifer Moisi, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Luis Jodar, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds.


Scientific Reports 10.1038/s41598-022-15172-z, published online 29 June 2022Correction to: The original version of this Article contained errors in Table 1, where values in column “Control”, under the subheading “Clinical/biochemical data” were omitted for TC (mmol/l), TG (mmol/l), HDL-c (mmol/l) and LDL-c (mmol/l). The complete and incomplete tables appear below.Incomplete:Complete:The original Article has been corrected.


SAB is common, serious, and potentially lethal. Antibiotic options are limited, especially for MRSA. Ceftobiprole is an advanced-generation cephalosporin with bactericidal activity against Gram-positive (including MRSA) and Gram-negative pathogens, with efficacy and safety demonstrated in previous Phase 3 studies in acute bacterial skin infections and pneumonia. The present study evaluated ceftobiprole in patients with complicated SAB.ERADICATE was a randomized (1:1), double-blind, multicenter, Phase 3, non-inferiority trial comparing ceftobiprole (BPR) vs daptomycin (DAP) ± optional aztreonam, for up to 42 days of treatment, in patients with complicated SAB (NCT03138733). The primary efficacy endpoint was overall clinical success 70 days post-randomization, adjudicated by a blinded independent Data Review Committee. Success required survival, no new SAB complications, symptom improvement, SAB clearance, and no receipt of other potentially effective antibiotics. The non-inferiority margin for the difference in success rates was -15% . Safety was assessed through adverse events (AE) and laboratory data.S. aureus (94 MRSA). Median treatment duration was 21 days for both groups. Key baseline characteristics were balanced . In the BPR group 69.8% experienced success, compared to 68.7% for DAP . There were no significant differences in mortality, microbiological eradication, or in key subgroup analyses . The proportion of patients experiencing ≥1 AE was 63% for BPR and 59% for DAP. Treatment-related severe or serious AEs were infrequent. Gastrointestinal AEs, mostly mild nausea, were more frequent with BPR, consistent with data from previous Phase 3 studies.Of 390 patients randomized, 387  were in the modified intent-to-treat (mITT) population who received study medication and had a positive baseline blood culture for Ceftobiprole is non-inferior to daptomycin for overall success in patients with complicated SAB. All-cause mortality, microbiological eradication rates and new SAB complications were similar between treatment groups. Both treatments were well tolerated.Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Sara E. Cosgrove, MD, Basilea: Advisor/Consultant|Debiopharma: Advisor/Consultant Sarah B. Doernberg, MD, MAS, Basilea: Advisor/Consultant|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Johnson and Johnson: Advisor/Consultant|NIH: Grant/Research Support|Regeneron: Grant/Research Support Maziar Assadi Gehr, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Marc Engelhardt, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Kamal Hamed, MD, Basilea Pharmaceutica: previous full time employee of Basilea Pharmaceutica International Ltd|Lysovant: full time employee of Lysovant Daniel Ionescu, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Mark Jones, PhD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Mikael Sauley, MSc, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Jennifer Smart, PhD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Harald Seifert, MD, Basilea Pharmaceutica: Advisor/Consultant|Debiopharm: Advisor/Consultant|Eumedica: Advisor/Consultant|Gilead: Advisor/Consultant|MSD: Advisor/Consultant|Shionogi: Advisor/Consultant Timothy C. Jenkins, MD, Basilea: Clinical outcomes adjudication committee Vance G. Fowler, Jr, MD, MHS, Armata Valanbio Akagera Aridis Roche: Advisor/Consultant|BASILEA: Grant/Research Support|Basilea Novartis Debiopharm Genentech: Advisor/Consultant|MedImmune Bayer Janssen Contrafect Regeneron Destiny Amphliphi Integrated Bioth: Advisor/Consultant|NIH MedImmune Allergan Theravance Novartis Merck Contrafect Karius Genentech Regeneron Janssen: Grant/Research Support.


There is a continued need for therapeutics for the treatment of COVID-19, including intramuscular (IM) agents, which will enable broader use across a variety of healthcare delivery settings.D1-8) in nasopharyngeal swabs and predefined 90% confidence interval (CI) limits of 0.5-2.0 indicating equivalence.COMET-PEAK (NCT04779879) is a 3-part study evaluating the safety, tolerability, pharmacokinetics (Part A), and viral pharmacodynamics (PD) of sotrovimab as treatment in adults ≥ 18 years with early mild/moderate COVID-19. In Parts B and C, the safety, tolerability and viral PD of sotrovimab administered as a 500 mg intravenous (IV) infusion or as a 500 mg or 250 mg IM injection, respectively, was evaluated. The primary objective for Parts B and C was to compare the virologic response of sotrovimab IM to IV, with an endpoint of mean area under the curve (AUC) of SARS-CoV-2 viral load as measured by qRT-PCR from Day 1 to Day 8  of sotrovimab IM vs IV was 1.04  and 1.02 , for Part B and C, respectively.The viral load at baseline and through Day 29 of follow-up for each arm is shown in Table 1 and Figure 1. The primary objective was met for both study parts: the ratio of the least square geometric mean viral load AUCThrough Day 29 of follow-up, the most common adverse event was injection site reactions (ISRs) in the IM arms. A total of 10 (12%) participants in the 500 mg IM group and 4 (5%) participants in the 250 mg IM group experienced an ISR, all Grade 1. Serious adverse events were uncommon, and related to COVID-19 progression, including one death in the 250 mg IM arm (Table 2). ISRs aside, there were few treatment-related AEs  in Part B, none serious.IM administration of sotrovimab 500 mg and 250 mg each demonstrated equivalence to 500 mg sotrovimab IV in viral load assessments. Overall, there were no treatment-related serious AEs and sotrovimab was well tolerated. An 500 mg IM formulation will allow for expanded treatment potential with sotrovimab.Vir/GSK (NCT04779879).Anil K. Gupta, MD, Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support|Vir Biotechnology: Speaker Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Grant/Research Support|Gilead Sciences Inc.: Advisor/Consultant|Gilead Sciences Inc.: Grant/Research Support|Gilead Sciences Inc.: Honoraria|Gilead Sciences Inc.: Stocks/Bonds|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|GlaxoSmithKline: Stocks/Bonds|Janssen Research & Development LLC: Advisor/Consultant|Janssen Research & Development LLC: Grant/Research Support|Janssen Research & Development LLC: Honoraria|Janssen Research & Development LLC: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Merck: Stocks/Bonds|Shionogi: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support Jennifer Han, MD, GlaxoSmithKline: Employee Jennifer Moore, MD, GlaxoSmithKline: Employee Rudrani Banerjee, PhD, GSK: Employee|GSK: Stocks/Bonds Phillip Yates, PhD, GSK: Employee during conduct of this research|GSK: Stocks/Bonds Jill Walker, PhD, GlaxoSmithKline: Employee Gretja Schnell, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Mary Beth Connolly, PharmD, GSK: Employee|GSK: Stocks/Bonds Andrea L. Cathcart, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Varsha Imber, MSc, GSK: Employee|GSK: Stocks/Bonds Rabia Anselm, n/a, GSK: Employee|GSK: Stocks/Bonds Lindsay Winograd, MSc, GSK: Employee|GSK: Stocks/Bonds Nancy Haeusser, n/a, GSK: Employee|GSK: Stocks/Bonds Scott Segal, MD, GSK: Employee|GSK: Stocks/Bonds Andrew Skingsley, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Melissa Aldinger, PharmD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Amanda Peppercorn, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds.


Cytomegalovirus (CMV) disease is associated with increased morbidity and mortality following solid organ and hematopoietic cell transplantation. Currently, standard of care CMV treatments often have significant myelosuppressive or renal toxicities. Given letermovir’s favorable safety profile when used prophylactically, it may be a safe and efficacious alternative agent for CMV treatment.A proof-of-concept, open-label trial was conducted in patients who lacked effective therapeutic options or presented with baseline organ dysfunction. Participants were eligible for enrollment if they were ≥12 years old and had documented CMV infection refractory to treatment defined as failure to achieve >1 log reduction in CMV viral load (VL) (when VL > 500 IU/mL) or lack of clinical improvement for CMV end-organ disease after ≥14 days of standard CMV treatment. Alternatively, patients with severe myelosuppression and renal dysfunction at baseline or genotypic antiviral resistance were also eligible. Participants were excluded if their current CMV infection developed while receiving letermovir for CMV prophylaxis. Letermovir was administered daily (480 mg PO/IV) for up to 12 weeks, with optional additional 12 weeks of treatment for secondary prophylaxis if clinically indicated.Ten patients met eligibility criteria and were enrolled. Reasons for enrollment included ganciclovir resistance (1/10), refractory CMV infection (6/10), renal dysfunction (7/10), and myelosuppression (7/10). The median baseline CMV VL was 1272 IU/ml . Six patients completed the study, three died due to complications of primary disease, and one discontinued due to diarrhea. Five patients (50%) had documented CMV viremia clearance, with a median time to first unquantifiable/undetectable CMV VL of 13 days  and a median treatment duration of 53 days . Infections and GI disorders were the most common adverse events (AE), none considered related to study drug. No unexpected AE were observed during letermovir treatment.Letermovir may be a safe and tolerable alternative for patients with treatment refractory CMV infection or for patients with severe baseline myelosuppression and renal dysfunction.Matthew Cheng, MD, AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|Scynexis Inc.: Grant/Research Support Sandra Burchett, MD, MSc, merck: Grant/Research Support Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|pfizer: Advisor/Consultant|Scynexis: Grant/Research Support Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Merck: Grant/Research Support Francisco M. Marty, MD, SM, AlloVir: Advisor/Consultant|Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Ansun: Grant/Research Support|Avir: Advisor/Consultant|Chimerix: Grant/Research Support|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Kyorin: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Regeneron: Advisor/Consultant|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Scynexis: Grant/Research Support|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|United Medical: Advisor/Consultant|WHISCO: Grant/Research Support.


Cefiderocol is a parenteral siderophore cephalosporin with potent activity against aerobic Gram-negative pathogens, including carbapenem-resistant strains. We evaluated the A total of 11434 clinical isolates of Gram-negative bacilli were systematically collected from 16 EU countries, Israel and Turkey in 2020 and 2021. Minimum inhibitory concentrations (MICs) were determined by broth microdilution for a panel of twenty-two antibiotics according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller-Hinton broth (CAMHB) except for cefiderocol, for which iron-depleted CAMHB was used. Susceptibility was determined according to CLSI breakpoints, and DTR pathogens were defined as being resistant to cefepime, ceftazidime ceftriaxone, imipenem, meropenem, ciprofloxacin and levofloxacin according to CLSI breakpoints.st line therapy including cephalosporins, carbapenems and fluoroquinolone and could be defined as DTR. DTR was most frequently observed in Acinetobacter spp. , Enterobacterales  and Pseudomonas aeruginosa . Ampicillin/sulbactam was active in less than 1% of the DTR-Acinetobacter spp isolates. None of the drugs recommended by the IDSA for the treatment of resistant Gram-negative infections were as potent as cefiderocol (Table 1).Among 11434 Gram-negative isolates collected in 2020 and 2021, 792 (7.0%) were resistant to all 1Cefiderocol was the only treatment option with demonstrated in vitro activity against more than 95% of all the tested DTR Gram-negative pathogens with limited treatment options.Anne Laurence Santerre Henriksen, PhD, Shionogi: Contractor|UTILITY therapeutics Ltd: Advisor/Consultant Christopher M. Longshaw, PhD, Shionogi: Employee Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Miki Takemura, n/a, Shionogi: Employee Yoshinori Yamano, PhD, Shionogi: Employee.


Here, we report near-complete genome sequences of three foot-and-mouth disease viruses isolated in 2016 from bovine and porcine epithelial tissue samples collected in Nonthaburi, Songkhla, and Ratchaburi provinces, Thailand. These viruses were classified as serotype O, topotype ME-SA, and sublineage Ind-2001e. Aphthovirus, Picornaviridae) causes FMD, which is the most contagious disease of cloven-hoofed mammals, characterized by vesicles on the feet and in oral cavities (Foot-and-mouth disease (FMD) virus  (LC438822) (http://blast.ncbi.nlm.nih.gov/Blast.cgi). These genomes were classified as O/ME-SA/Ind-2001e by phylogenetic analysis together with sequences obtained from the GenBank database  under BioProject accession number PRJDB14377 and DRA Run accession number DRR408791 (O/TAI/269-2/2016), BioProject accession number PRJDB14378 and DRA Run accession number DRR408792 (O/TAI/315/2016), and BioProject accession number PRJDB14379 and DRA Run accession number DRR408793 (O/TAI/317-3/2016).The nucleotide sequences of the three FMDVs reported here were deposited in GenBank under accession numbers


Pontonidessibogae was collected from a dendrophylliid coral by trimix SCUBA diving at a depth of 75 m during fieldwork around Jejudo Island, Korea in 2020. The morphology of the specimen corresponds closely to the main diagnostic characters of the holotype, especially in the presence of a distinct tubercle on the eyestalk, as well as the second pereiopod with fusiform setae along the dorsal border of the ischium.A single specimen of Pontonides had previously not been reported from Korean waters. Herein, colour photographs are provided, as well as an illustrated description including previously unreported characteristics.The genus  Pontonides Borradaile, 1917 currently comprises seven hexacoral-associated species from tropical to temperate waters on the Indo-West Pacific: Pontonidesmaldivensis  (type species); P.unciger Calman, 1939; P.asperulatus Bruce, 2005; P.loloata Bruce, 2005; P.sibogae Bruce, 2005; P.ankeri Marin, 2007; and P.tatianae Marin, 2007 , based on the specimen assigned by P.unciger, using the presence of the tubercle on the eyestalk as a diagnostic character. The material described by Pontonidescf.sibogae on their host coral, Dendrophyllia sp., from an unspecified location in Japan. No further records of the species are known to date.P.sibogae was collected on a scleractinian dendrophylliid coral by trimix SCUBA diving at a depth from 75 m. In the present study, we recorded this species and indeed, the genus as a whole, as a new addition to the Korean fauna, including colour photographs, illustrations and a detailed description.During fieldwork in the waters surrounding Jejudo Island, Korea in January 2020, a single specimen of Pontonidessibogae was collected from the scleractinian dendrophylliid coral Dendrophyllia sp. with the aid of trimix diving at a depth of 75 m in Munseom Islet. Habitats were recorded using a digital camcorder  in an underwater housing . Photographs of the specimen were taken using a digital camera  with a high-definition lens . Field collection number (fcn) was recorded and the sample preserved in 80% ethanol for morphological and molecular examinations. Morphological characteristics were observed using a stereomicroscope . Images for digital drawings were taken and postorbital carapace length  was measured from the postorbital margin to the posterior dorsal margin of the carapace using a microscope-mounted digital camera  and Leica software . Digital line drawings were made using Helicon focus software  and a drawing tablet  with Adobe Illustrator software  following the method described by Faunal surveys around Jejudo Island, Korea were organised in 2020 jointly by Seoul National University (SNU), the Marine Biodiversity Institute of Korea (MABIK) and the National Institute of Biological Resources (NIBR). A single specimen of Bruce, 2005B2660DC5-4BFD-58A7-87AA-1BADFC75BC9Ahttps://www.marinespecies.org/aphia.php?p=taxdetails&id=389607Pontonidessibogae Bruce, 2005 - Pontonidesunciger - Pontonidescf.sibogae - Type status:Other material. Occurrence: recordNumber: JH1109; recordedBy: Jin-Ho Park; Damin Lee; Sang-Hui Lee; individualCount: 1; sex: female; lifeStage: adult (pocl 2.4 mm); reproductiveCondition: ovigerous; preparations: whole animal; dissected  (ETOH); Taxon: scientificNameID: urn:lsid:marinespecies.org:taxname:389607; scientificName: Pontonidessibogae Bruce, 2005; kingdom: Animalia; phylum: Arthropoda; class: Malacostraca; order: Decapoda; family: Palaemonidae; genus: Pontonides; specificEpithet: sibogae; taxonRank: species; nomenclaturalCode: ICZN; Location: higherGeography: East Asia; Korea; Jejudo Island; Munseom Islet; waterBody: West Pacific Ocean; island: Jejudo Island; country: Korea; countryCode: Korea/KR; locality: SW Munseom Islet, 33.225092° 126.563375°, 75 m in depth (fcn JH1109); verbatimDepth: 75 m; decimalLatitude: 33.225092; decimalLongitude: 126.563375; Identification: identifiedBy: Jin-Ho Park; Event: samplingProtocol: Trimix SCUBA diving; eventDate: 2020-01-15; fieldNotes: Dendrophyllia sp. (leg. DM Lee)from a colonial dendrophylliid coral ; Record Level: language: kr & en; institutionID: NIBRIV0000896187; collectionID: fcn JH1109; institutionCode: National Institute of Biological Resources (NIBR)Small-sized palaemonid shrimp, body flattened dorsoventrally.Carapace Fig. A and B sAbdominal pleura of first to fifth somite rounded Fig. C. Sixth Telson Fig. D and E aEye Fig. A and B wAntennule Fig. A and B wAntenna Fig. A and B wMandible Fig. A withoutMaxillula Fig. B with biMaxilla Fig. C with taFirst maxilliped Fig. D with diSecond maxilliped Fig. E with coThird maxilliped Fig. F with coFirst pereiopod Fig. A coxa anSecond pereiopods similar in shape, unequal in size. Major second pereiopod Fig. C coxa anMinor second pereiopod Fig. F coxa anAmbulatory pereiopods subequal in shape; left fourth pereiopod slightly shorter and more slender than right third and fifth; right ambulatory pereiopods subequal in length. Third pereiopod Fig. A coxa anFourth pereiopod Fig. C coxa anFifth pereiopod Fig. E coxa anUropods Fig. D extendiThe single collected specimen exhibits cryptic colouration in relation to the host species Fig. . Body anThe species is currently reported in tropical to temperate waters in the West Pacific Ocean, as follows: Indonesia , Japan (Amakusa Island), and Korea (Jejudo Island)   Fig. C. The hoPontonidessibogae examined herein corresponds closely to the main diagnostic characters and the illustrations of the holotype .The present specimen was found in association with the scleractinian coral


Despite the recognized value of life-course vaccination, adult vaccine uptake remains low. State-level vaccination coverage disparities may be associate with state-level variables . The objective of this study was to identify state-level variables associated with increased adult vaccination coverage rates (VCR) in the US for influenza, tetanus, herpes zoster (HZ), and pneumococcal vaccines over time.Retrospective, exploratory database analysis of 2011-2019 Behavioral Risk Factor Surveillance System (BRFSS) data was used to calculate state-level VCRs for adults 18-64 years old. Using publicly available data, state-level variables associated with increases in VCRs were identified via a systematic variable selection. The multivariable regression models included variables meeting the criteria: correlations > 0.4 or < -0.4 (continuous) or Kruskal-Wallis Test p-value < 0.2 .Final multivariable regression models included 5 variables: Medicaid expansion status, accountable care organizations in place, health homes program, percentage of adults who report not seeing a doctor in past 12 months because of cost, and percentage of adults who report participating in any physical activity.Influenza: percentage of adults who report participating in any physical activity (p = .01)Pneumococcal: percentage of adults who report not seeing a doctor in the past 12 months because of cost (p = .02)HZ: health homes (p = .04); percentage of adults who report participating in any physical activity or exercise (p = .01); percentage of adults who report not seeing a doctor in past 12 months because of cost Tetanus: noneIn the multivariable models, the following state-level variables were significantly associated with changes in VCR:Few state-level variables demonstrated an association with changes in VCR but some significant findings were observed in final models. Associated variables may not have a direct relationship but may be associated with public health infrastructure supporting vaccination ecosystems. Further research is underway to better understand the factors affecting adult vaccination.Amanda Eiden, PhD, MBA, MPH, Merck & Co., Inc.: Stocks/Bonds Mark A. Price, MA, MEd, Merck: Advisor/Consultant|Merck: I am an employee of RTI Health Solutions. Merck has contracted with my company to conduct the study described in the abstract. Alexandra Bhatti, JD, MPH, Merck & Co. Inc.: Grant/Research Support|Merck & Co. Inc.: Stocks/Bonds.


Numerous predictive clinical scores with varying discriminatory performance have been developed in the context of the current coronavirus disease 2019 (COVID-19) pandemic. To support clinical application, we test the transferability of the frequently applied 4C mortality score (4C score) to the German prospective Cross-Sectoral Platform (SUEP) of the National Pandemic Cohort Network (NAPKON) compared to the non COVID-19 specific quick sequential organ failure assessment score (qSOFA). Our project aims to externally validate these two scores, stratified for the most prevalent variants of concerns (VOCs) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in Germany.A total of 685 adults with polymerase chain reaction (PCR)-detected SARS-CoV-2 infection were included from NAPKON-SUEP. Patients were recruited from 11/2020 to 03/2022 at 34 university and non-university hospitals across Germany. Missing values were complemented using multiple imputation. Predictive performance for in-hospital mortality at day of baseline visit was determined by area under the curve (AUC) with 95%-confidence interval (CI) stratified by VOCs of SARS-CoV-2  .2-test: p=0.001) and the qSOFA does not seem to be a suitable tool in this context.Preliminary results suggest a high predictive performance of the 4C score for in-hospital mortality (Table 1). This applies for the overall cohort (AUC 0.813 (95%CI 0.738-0.888)) as well as the VOC-strata ; delta: AUC 0.769 (95%CI 0.657-0.882); omicron: AUC 0.866 (95%CI 0.724-1.000)). The overall mortality rates across the defined 4C score risk groups are 0.3% (low), 3.2% (intermediate), 11.6% (high), and 49.5% (very high). The 4C score performs significantly better than the qSOFA : Grant/Research Support|German Centre for Infection Research (DZIF): Grant/Research Support|German Centre for Infection Research (DZIF): Honoraria|German Federal Ministry of Education and Research (BMBF): Grant/Research Support|German Society for Infectious Diseases (DGI): Honoraria|German Society for Internal Medicine (DGIM): Honoraria|GILEAD: Advisor/Consultant|GILEAD: Grant/Research Support|GILEAD: Honoraria|Janssen: Honoraria|Merck / MSD: Grant/Research Support|Merck / MSD: Honoraria|Molecular Health: Honoraria|Netzwerk Universitätsmedizin: Honoraria|NordForsk: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Rigshospitalet Copenhagen: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria|University Hospital Aachen: Honoraria|University Hospital Freiburg/ Congress and Communication: Honoraria|University of Bristol: Grant/Research Support.


In phase 3 randomized controlled trials (RCTs), dolutegravir/lamivudine (DTG/3TC) demonstrated durable efficacy in treatment-naive (GEMINI-1/-2) and virologically suppressed switch  participants. Eligibility criteria for these RCTs included no history of treatment failure or any major nucleoside reverse transcriptase inhibitor or integrase inhibitor–associated mutations, no hepatitis B virus (HBV) or need for hepatitis C virus (HCV) therapy, and viral load (VL) < 500,000 c/mL at screening (GEMINI) or < 50 c/mL for > 6 months . We analyzed real-world evidence (RWE) for DTG + 3TC use in people with HIV (PWH) with baseline characteristics not consistent with these inclusion criteria.®, Embase®, PubMed, Cochrane library, and relevant international conference proceedings from January 2013 to February 2022.We conducted a systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. RWE studies that reported on DTG + 3TC use in PWH were retrieved from Ovid MEDLINEThis review includes 122 publications from 103 RWE studies of 44 unique cohorts . In the 1 study that described outcomes in PWH with previous virologic failure , probability of VF at 1 year was low . In cohorts with > 10 PWH with baseline resistance that reported outcomes , VF was low (ranging from 0%-5.4% at ∼1 year), and the difference in VF between those with or without M184V/I was not significant in 3 of 4 cohorts. A treatment-emergent resistance mutation  was observed in 1 PWH with evidence of baseline resistance. None of the 35 PWH with HBV experienced VF, and 89% (16/18) of treatment-naive PWH with baseline VL > 500,000 c/mL achieved virologic suppression at Week 24. There were no studies describing effectiveness outcomes in PWH with HCV who were receiving DTG/3TC.DTG + 3TC has been used in PWH with various baseline characteristics, including RCT exclusion criteria. Outcomes from published RWE in these subgroups further support the clinical data demonstrating the high effectiveness and barrier to resistance of DTG + 3TC.Jihad Slim, MD, FACP, abbvie- speaker bureau: Honoraria|Gilead Speaker Bureau: Honoraria|Janssen Speaker Bureau: Honoraria|Merck Speaker Bureau: Honoraria Douglas Ward, MD, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Stefan Schneider, MD, GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Madhusudan Kabra, BPharm, MSc, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Gustavo Verdier, BSc, BPharm, MBA, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare ULC: Salary Clifford B. Jones, BSc MSc MB ChB, GSK: Stocks/Bonds|viiv healthcare: Employee Emilio Letang, MD, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee.


Pseudomonas aeruginosa (PA) infections, and 2) examine whether antimicrobial resistance in PA infections is associated with worsening functional status and higher health care resource utilization (HCRU).The aims of the study were to 1) evaluate the prevalence of multidrug resistant (MDR) /Extensively drug resistant (XDR) strains among hospitalized adults with PA as confirmed by local evaluation of microbiological results. MDR PA was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. XDR PA was defined as acquired non-susceptibility to at least one agent in all but two or fewer antimicrobial categories. HCRU metrics evaluated included hospital length of stay (LOS) and intensive care unit (ICU) LOS.This multicenter prospective study was conducted in 9 large Italian teaching hospitals between June 2018-February 2020. We included patients aged ≥18 years with a diagnosis of nosocomial pneumonia (NP), complicated urinary tract infections (cUTI) or complicated intra-abdominal infections (cIAI) due to PA were enrolled. The main baseline characteristics of overall patients were reported in Table 1. Almost one-third of patients (28.4%) reported either MDR or XDR PA infection, with more patients experiencing MDR (Table 1). Health care resource use stratified by patients with and without MDR/XDR status are reported in Table 2. Overall, in our study population, median hospital LOS and ICU LOS were 42.0 (IQR=39.0) and 15.5 (IQR=37.0) days, respectively. There was a statistically significant longer median hospital LOS for patients with MDR/XDR infections compared to non MDR/XDR PA infections . ICU LOS also trended towards being longer for patients with MDR/XDR infections compared to those with non-MDR/XDR infections .A total of 95 patients with a nosocomial infection due to PA, particularly in those with cIAI. Overall, the present study may suggest a positive correlation between having MDR-XDR PA nosocomial infections  and increased HCRU that require further attention from a disease management perspective.MDR/XDR isolates were prevalent among patients with nosocomial infections due to Matteo Bassetti, PhD, Angelini: Advisor/Consultant|Astellas: Grant/Research Support|Bayer: Advisor/Consultant|Bayer: Honoraria|BioMe ´ rieux: Advisor/Consultant|BioMe ´ rieux: Honoraria|Cidara: Advisor/Consultant|Cidara: Honoraria|Cipla: Advisor/Consultant|Cipla: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Menarini: Advisor/Consultant|Menarini: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Tetraphase: Advisor/Consultant Francesco Menichetti, n/a, Aneglini: Advisor/Consultant|Aneglini: Board Member|Aneglini: Grant/Research Support|Aneglini: Honoraria|Astellas: Advisor/Consultant|Astellas: Honoraria|Becton: Advisor/Consultant|Becton: Honoraria|bioMérieux: Advisor/Consultant|bioMérieux: Honoraria|Biotest: Advisor/Consultant|Biotest: Board Member|Biotest: Honoraria|Bristol-Myers Squibb: Advisor/Consultant|Bristol-Myers Squibb: Honoraria|Correvio: Advisor/Consultant|Correvio: Speaker honoraria|Dickinson: Advisor/Consultant|Dickinson: Honoraria|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Honoraria|MSD: Advisor/Consultant|MSD: Speaker honoraria|Nordic pharma: Board Member|Nordic pharma: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|ViiV: Advisor/Consultant|ViiV: Honoraria Nicola Petrosillo, n/a, Becton & Dickinson,: Honoraria|MSD: Honoraria|ohnson & Johnson: Honoraria|Pfizer: Honoraria|Shionogi: Honoraria.


The manogepix prodrug fosmanogepix is in Phase 2 development for the treatment of invasive mold infections caused by Aspergillus and rare molds (NCT04240886) and has completed Phase 2 studies for candidemia (NCT03604705) and C. auris (NCT04148287) infections. We evaluated the in vitro activity of manogepix and comparators against 2,810 geographically diverse fungal isolates collected in the SENTRY Surveillance Program during 2020-2021 and stratified them by infection type.Manogepix is a new antifungal with a novel mechanism of action and potent Antifungal susceptibility testing of manogepix and comparator agents was conducted according to CLSI M27 (2017) and M38 (2017) guidelines. Fungal surveillance isolates were collected from medical centers located in North America , Europe , Asia-Pacific , and Latin America . Infection sites included bloodstream infections , pneumonia in hospitalized patients , skin and skin structure infections , urinary tract infections , intra-abdominal infections , and other infection types (19.3%).in vitro activity against Candida spp. isolates  regardless of infection type (Table). Similarly, manogepix was highly active against 534 Aspergillus spp. isolates . Manogepix was active against 53 Cryptococcus neoformans var. grubii , 19 Fusarium spp. , 12 Lomentospora prolificans , and 17 Scedosporium spp. isolates .Manogepix demonstrated potent in vitro activity against Candida spp., Aspergillus spp., C. neoformans var. grubii, and rare molds, including Fusarium spp., L. prolificans, and Scedosporium spp. isolates. Notable activity was also demonstrated by manogepix against C. auris isolates. Further clinical development of fosmanogepix in difficult-to-treat, resistant fungal infections is warranted.Manogepix showed potent Michael D. Huband, BS, AbbVie: Grant/Research Support|Melinta: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.


Correction: BMC Health Serv Res 23, 10 (2023)https://doi.org/10.1186/s12913-022-09021-yFollowing publication of the original article , the autThe incorrect author names are: Withanarachchie Vinuli, Rychert Marta and Wilkins ChrisThe correct author names are: Vinuli Withanarachchie, Marta Rychert and Chris WilkinsThe author group has been updated above and the original article  has been


Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa (PSA). S. aureus (SA) and PSA are common pathogens causing pneumonia in cystic fibrosis (CF) patients. In this study, the in vitro susceptibilities of DLX and comparator quinolones were determined for clinical isolates from US CF patients collected during 2019-2021.Delafloxacin (DLX) is a broad-spectrum fluoroquinolone antibacterial approved in the US for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections. DLX is indicated to treat CABP caused by multiple pathogens, including methicillin-susceptible Isolates from CF patients hospitalized with pneumonia were consecutively collected at 17 US medical centers participating in the SENTRY Surveillance Program. Sites submitted 1 isolate per patient per infection episode. Isolate identification was determined at each site and confirmed using MALDI-TOF at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology. FDA interpretive criteria were used for DLX, and CLSI (2022) criteria were applied to comparators.A total of 115 SA, including 72 MSSA and 67 PSA, were submitted. Susceptibilities (%S) to DLX, levofloxacin (LEV), and moxifloxacin (MOX) for MSSA are shown in the table. As MOX does not have breakpoints for PSA, ciprofloxacin (CIP) was tested. Against all SA, %S was 73.9%, 67.0%, and 67.0% for DLX, LEV, and MOX, respectively. DLX had the highest %S against MSSA (94.4%). The %S to LEV and MOX was 87.5% and 87.5%. DLX was also more active than comparators against PSA, with DLX 68.7%S, while LEV was 43.3%S and CIP was 50.7%S.in vitro data suggest that DLX could be a useful therapy when coverage of both MSSA and PSA is needed.DLX had good activity against recent CF isolates from US hospitals, and had the highest percent susceptibility of the quinolones tested against MSSA and PSA. These Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Michael D. Huband, BS, AbbVie: Grant/Research Support|Melinta: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.


VGCV is approved for prophylaxis in adult KTRs at high risk for CMV disease (donor CMV-seropositive/recipient CMV-seronegative [D+/R-]); however, its use is limited by myelosuppression. LET is non-myelotoxic, does not require dose modification in renal impairment, and is approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. This randomized, double-blind, Phase 3 non-inferiority study  evaluated CMV prophylaxis with LET vs. VGCV in adult CMV D+/R- KTRs.Adult CMV D+/R- KTRs were randomized 1:1 within 7 days post-kidney transplant (KT) to receive either LET 480 mg QD (PO/IV) with acyclovir , or VGCV , through Week 28 post-KT and followed up through Week 52 post-KT. Randomization was stratified by use of lymphocyte-depleting induction immunosuppression. The primary endpoint was the proportion of participants (pts) with CMV disease adjudicated by blinded committee through Week 52 post-KT .Table 1). Drug-related adverse events (AEs) were reported in 19.9% of pts with LET and 35.0% of pts with VGCV through Week 28 post-KT. The rate of discontinuations due to an AE was 4.1% in the LET arm and 13.5% in the VGCV arm (Table 2). The incidence of neutropenia (absolute neutrophil count < 1000/µL) during the treatment phase was lower with LET than with VGCV .A total of 601 pts were randomized; 589 received ≥ 1 dose of study medication , of whom two had detectable CMV viral DNA on Day 1 and one was CMV R+ . The proportion of pts with CMV disease through Week 52 post-KT was 10.4% with LET vs. 11.8% with VGCV  KTRs through Week 52 post-KT, and led to a lower rate of myelotoxicity than VGCV.Ajit P. Limaye, MD, AiCuris: Advisor/Consultant|MedPace: Data Safety Monitoring Boards|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Novartis: Data Safety Monitoring Boards|Sana: Advisor/Consultant Klemens Budde, MD, Abbvie: Grant/Research Support|Abbvie: Honoraria|Alexion: Grant/Research Support|Alexion: Honoraria|Astellas: Grant/Research Support|Astellas: Honoraria|Bristol Myers Squibb: Grant/Research Support|Bristol Myers Squibb: Honoraria|Chiesi: Grant/Research Support|Chiesi: Honoraria|CSL Behring: Grant/Research Support|CSL Behring: Honoraria|Fresenius: Grant/Research Support|Fresenius: Honoraria|Hansa: Grant/Research Support|Hansa: Honoraria|Hexal: Grant/Research Support|Hexal: Honoraria|Hookipa Biotech: Grant/Research Support|Hookipa Biotech: Honoraria|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|Novartis: Grant/Research Support|Novartis: Honoraria|Otsuka: Grant/Research Support|Otsuka: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Grant/Research Support|Roche: Honoraria|Sandoz: Grant/Research Support|Sandoz: Honoraria|Shire: Grant/Research Support|Shire: Honoraria|Siemens: Grant/Research Support|Siemens: Honoraria|Takeda: Grant/Research Support|Takeda: Honoraria|Veloxis: Grant/Research Support|Veloxis: Honoraria|Vitaeris: Grant/Research Support|Vitaeris: Honoraria Atul Humar, MD, MSc, FRCPC, Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support|Takeda: Advisor/Consultant Julia Garcia-Diaz, MD, Astellas Pharma US, Inc.: Advisor/Consultant|Astellas Pharma US, Inc.: Speaker's Bureau Robert P. Carroll, BM BCh (Oxon), FRACP, DM (Oxon), Bristol Myers Squibb: Grant/Research Support|HANSA Biopharma: Advisor/Consultant Yoshihiko Murata, MD, PhD, Former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Valerie L. Teal, MS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Current Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Christopher L. Gilbert, n/a, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Barbara A. Haber, MD, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co.,: Stocks/Bonds.


Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp  is ongoing for the treatment of patients intolerant of, or with fungal disease refractory to, standard antifungal therapy. We present an interim analysis of patient outcomes from the FURI study by fungal disease type.There are limited oral treatment options for patients with fungal infections who fail currently available antifungals or have an infection caused by resistant organisms. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor with activity against FURI patients are eligible for enrollment if they have proven or probable: severe mucocutaneous candidiasis, invasive candidiasis, chronic or invasive aspergillosis, with documented evidence of failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment; or patients who cannot receive approved oral antifungal options , and continued IV antifungal therapy is clinically undesirable or unfeasible.An independent Data Review Committee (DRC) provided an assessment of treatment response for 113 enrolled patients in the FURI study from 27 centers in US, UK and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016–2021. Fifty-six patients (49.5%) had invasive candidiasis/candidemia, 32 (28.3%) had mucocutaneous candidiasis, 14 (12.4%) had vulvovaginal candidiasis (VVC), and 11 (9.7%) patients had aspergillosis.Upon DRC review, the percent of patients with complete or partial response, or for VVC, clinical improvement  was 58.4%; stable disease was 23.9%; and 11.5% had disease progression . There was 1 death due to underlying causes, and 6 outcomes were indeterminate. The table presents outcomes by disease type.Analysis of 113 patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options.George R. Thompson, III, MD, Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Merck: Grant/Research Support|Pfizer: DSMB|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support Thomas King, MS MPH, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds Nkechi Azie, MD MBA FIDSA, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds David A. Angulo, MD, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds.


Sotrovimab (VIR-7831) is an engineered human monoclonal antibody targeting a conserved region of the SARS-CoV-2 spike protein; it has been shown to have a favorable safety profile and be effective for early treatment of high-risk COVID-19 patients. The COMET-TAIL phase 3 study evaluated sotrovimab administered intravenously (IV) or intramuscularly (IM) for the treatment of participants with mild to moderate COVID-19 who are at high risk of disease progression.Between June to August 2021, 973 participants were randomized and received sotrovimab by 500 mg IV infusion or by 500 or 250 mg IM injection. Deep sequencing of the spike gene was performed on nasopharyngeal samples. Baseline , post-BL (Day 5 or later), treatment-emergent (TE) substitutions at sotrovimab epitope positions, and presence of variants of concern/interest (VOC/VOI), were evaluated at a ≥5% allelic frequency. Phenotypic analyses were conducted using a pseudotyped virus assay.in vitro.Sequences were available from 764 participants . Consistent with VOC circulation during enrollment, the Delta variant was detected in 88.2% (674/764) of participants. Alpha and Mu variants were also seen at >2% prevalence. Of the 764 participants, 26 met the primary endpoint for clinical progression to hospitalization >24 hours or death due to any cause through day 29 and were infected with Delta , Alpha (500 mg IM: 1), or Mu (500 mg IV: 1) variants. Substitutions at sotrovimab epitope positions were similar across arms and were detected in 82/764 (10.7%) participants at any visit . Of these, 2 participants experienced clinical progression: 1 participant infected with the Mu variant (500 mg IV) carried the characteristic R346K substitution at BL; 1 participant infected with the Delta variant (500 mg IM) had P337L and E340K substitutions detected at Day 3 and P337L was enriched at Day 8. The predominant TE epitope substitutions included P337L and E340A/K/V, which confer reduced susceptibility to sotrovimab Overall, TE epitope substitutions were not associated with clinical progression.Vir & GSK (NCT04913675)Maria L. Agostini, PhD, Vir Biotechnology, Inc: Employee|Vir Biotechnology, Inc: Stocks/Bonds Gretja Schnell, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Julia di Iulio, PharmD, PhD, MBA, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Anita Kohli, MD, GlaxoSmithKline: Third party funding to Vir|Vir Biotechnology Inc: Support as a trial site paid to my institution and non-financial support for medical writing support Adrienne E. Shapiro, MD, PhD, Vir Biotechnology: Support as a trial site paid to my institution and non-financial support for medical writing GlaxoSmithKline third party funding to Vir support Elias H. Sarkis, MD, Abbvie: Grant/Research Support|Abbvie: Speakers Bureau|Eisai: Grant/Research Support|GlaxoSmithKline: Third party funding to Vir|Ironshore: Grant/Research Support|Janssen: Speakers Bureau|Lilly: Grant/Research Support|Otsuka: Grant/Research Support|Teva: Speakers Bureau|Vir Biotechnology Inc: Support as a trial site paid to my institution and non-financial support for medical writing support Dave Inman, MSc, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Amanda Peppercorn, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Andrew Skingsley, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Leah A. Gaffney, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Melissa Aldinger, PharmD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Christy M. Hebner, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Andrea L. Cathcart, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds.


Appropriate diagnostic testing can be used to inform infection control measures and reduce SARS-CoV-2 transmission, yet the test kinetics, infectivity, and immunological responses during acute, non-severe SARS-CoV-2 infection need clarity.We conducted a prospective cohort study between Nov 2020-July 2021 in Seattle, Washington of 95 unvaccinated, immunocompetent adults with no prior SARS-CoV-2 infection. Nasal swabs  and blood serum samples were serially collected at six visits over two months. Viral RNA, N and S antigen concentrations, and viral growth/infectivity were measured from nasal samples. Anti-S total antibody and IgG assays were performed on serum. We fit loess curves to quantitative data corresponding to each testing modality by days since symptom onset (DSSO) and compared qualitative test results across time points to demonstrate time-dependent agreement of PCR, N antigen, and culture results. Generalized estimating equations were used to approximate relative risk of culture positivity (a proxy for infectiousness) for positive vs. negative test results (antigen and PCR), stratified by presence/absence of symptoms and DSSO.Sampling SchemaNasal swabs and venous blood were collected at visits 1-4; venous blood only at visits 5-6. All participants were enrolled within 14 days of symptom onset (median: 6) and 7 days of a positive test (median: 4).Infections in this cohort (median age: 29y) were mild . Median (IQR) time to negative result was 11 (4), 13 (6), and 20 (7) DSSO for culture growth, N antigen, and PCR tests, respectively. Viral RNA quantities declined more slowly than antigen and culturable virus; antibody titers rose rapidly 5-15 DSSO and plateaued 20-30 DSSO. All culture-positive samples collected 0-5 DSSO were positive by PCR, but relative risk of culture positivity (infectiousness) for positive vs. negative PCR results declined 6-10 DSSO. Relative risk of culture positivity for positive vs. negative antigen results was consistently high 0-10 DSSO, with similar results when stratified by presence of symptoms.Diagnostic test kinetics and immunological responsesDiagnostic test kinetics and immunological responses measured in adults with non-severe, symptomatic SARS-CoV-2 infection: loess trendlines and 95% confidence intervals are given for SARS-CoV-2 viral load , TCID50 from viral culture, mean concentrations of nucleocapsid and spike antigen proteins, and anti-S total and IgG antibody concentrations.The results reinforce the importance of molecular PCR testing as a highly sensitive diagnostic tool but with limited utility as an indicator of viral culturability and likely infectiousness. N antigen testing may be a preferable diagnostic test within two weeks of symptom onset, especially 6-10 DSSO, because it more closely correlates with culture growth over the course of infection.Daphne Hamilton, BA, Roche (spouse is employed by Roche): Employee Alexander L. Greninger, MD, PhD, Abbott: Contract Testing|Cepheid: Contract Testing|Gilead: Grant/Research Support|Gilead: Contract Testing|Hologic: Contract Testing|Merck: Grant/Research Support|Novavax: Contract Testing|Pfizer: Contract Testing Geoffrey S. Gottlieb, MD, PhD, Abbott Molecular Diagnostics: Grant/Research Support|Alere Technologies: Grant/Research Support|BMGF: Grant/Research Support|BMS: Grant/Research Support|Cerus Corp.: Grant/Research Support|Gilead Sciences: Grant/Research Support|Janssen Pharmaceutica: Grant/Research Support|Merck & Co: Grant/Research Support|Roche Molecular Systems: Grant/Research Support|THERA Technologies/TaiMed Biologics: Grant/Research Support|ViiV Healthcare: Grant/Research Support.


Coagulase-negative staphylococci (CoNS) are commonly isolated from blood cultures (BCx). Most do not require treatment (tx), yet antibiotics are frequently initiated. Workup of CoNS BSI consumes significant resources. We aimed to demonstrate the safety and efficacy of an early algorithm-based rapid diagnostic testing (RDT) plus antimicrobial stewardship (ASP) intervention.S. epidermidis and other non-aureus/lugdunensis Staphylococcal species. Results were called to ASP in both RDT-only and RDT+ASP periods. In the latter, a prospective algorithm was implemented to standardize ASP recommendations  for cases classified as simple, uncomplicated, and complicated BSI. The primary outcome was receipt of < 24h of antibiotic tx. Safety outcomes included rates of recurrent BSI and hospital readmission.BCx with CoNS were captured in 3 time periods to represent pre-RDT, RDT-only, and RDT+ASP. GenMark ePlex RDT was implemented for all Gram-positive BCx, identifying Fig 2). The median age was 62, 54% were male, and the median Charlson comorbidity index was 5. 41% had a central venous catheter at time of BSI. Overall, 67%, 19%, and 12% of cases were classified as simple, uncomplicated, or complicated BSI, respectively . BSI class and patient demographics did not vary between periods. During pre- and post-RDT periods, median days of antibiotic tx did not vary significantly for patients with simple BSI (1.1 vs 1.2). In contrast, median days of tx were reduced to 0 (P=0.005) for simple BSI in the RDT+ASP period. Overall, 54% of patients with CoNS BSI received < 24h of tx in RDT+ASP time period compared to 34% (P=0.009) in the combined pre-RDT and RDT-only periods. Tx was entirely avoided in 28% of CoNS BSI cases in the RDT+ASP period compared to 16.5% of cases in other periods (P=0.07). 7 cases classified as simple were reclassified as uncomplicated or complicated after further work up. Rates of recurrent BSI and 30-day readmission were comparable across time periods.184 patients were included (Our algorithm-based ASP + RDT intervention reduced antibiotic tx for CoNS BSI, an effect not realized with RDT alone. These data attest to the safety and efficacy of early ASP intervention for patients with CoNS BSI identified by RDTs at the time of positive BCx.J Ryan Bariola, MD, Infectious Disease Connect: Salary support|Merck: Grant/Research Support Tina Khadem, PharmD, Infectious Disease Connect: Salary support|Merck: Grant/Research Support Brian Potoski, PharmD, BCPS-AQ ID, Merck Group: Grant/Research Support Ryan K. Shields, PharmD, MS, Infectious Disease Connect: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support.


Toxoplasma gondii: a rapid method for the isolation of pure tachyzoites: preliminary characterization of its genome”, DOI number: 10.1590/s0074-02761990000400007, published in Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 85(4), 1990, on page 429:In the article “Where it reads:Viviana PzsennyIt should read:Viviana Pszenny


This study evaluated the performance of an Investigational Use Only (IUO) version of the BioFire R/ST Panel in the near patient setting.Limited availability of multiplex molecular tests in the near-patient setting can impact the rapid diagnosis and treatment of patients experiencing symptoms of respiratory tract infections, including pharyngitis. The BioFireStreptococcus from throat swabs).NPS and TS specimens were prospectively enrolled from symptomatic consented/assented volunteers of all ages, or obtained as residual leftover specimens. Enrollment was conducted between December 2020 and September 2021 at five study sites in the US and UK (adult and pediatric emergency departments or urgent care clinics) with testing performed by personnel representative of the intended users . Several analytes that were not circulating during the COVID-19 pandemic were supplemented with archived specimens of known analyte composition. Performance was determined for both sample types by comparison to FDA cleared multiplex PCR tests or culture and PCR followed by sequencing of isolates  overall positive percent agreement (PPA) was 98.7% and negative percent agreement (NPA) was 99.1%, and for TS specimens (prospective and archived) overall PPA was 95.9% and NPA was 99.2%.The BioFire R/ST Panel is a sensitive, specific, and robust test for rapid detection of a wide range of organisms in NPS and TS specimens in the near-patient setting. This test is expected to aid in the timely diagnosis and appropriate management of pharyngitis and other respiratory infections.Data presented are from assays that have not been cleared or approved for diagnostic use.Jeffrey Bastar, PhD, MSCI, bioMerieux: Employee|bioMerieux: Stocks/Bonds Ashley Ky, MLS(ASCP), bioMérieux: Employee|bioMérieux: Stocks/Bonds Kristen Holmberg, n/a, bioMerieux: Employee Hana Bay, BS, Biomerieux: Employee|Biomerieux: Stocks/Bonds Daria Drobysheva, PhD, bioMerieux: Employee Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Virve Enne, BSc PhD, Biomerieux: Advisor/Consultant Cynthia Andjelic, PhD, bioMerieux: Employee.


Acinetobacter baumannii-calcoaceticus species complex (ACB) and Stenotrophomonas maltophilia (SM) are opportunistic, non-fermentative organisms that can cause serious hospital-acquired infections in immunocompromised patients. These pathogens are inherently resistant to several common drug classes and often acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the susceptibility of contemporary ACB and SM isolates to minocycline (MIN), levofloxacin (LEV), meropenem (MER) for ACB, and trimethoprim-sulfamethoxazole (T/S) for SM. Isolates were collected as a part of the SENTRY Antimicrobial Surveillance Program from 2014-2021.Susceptibilities of SM and ACB to MIN and comparators, 2014-2021Isolates were collected from hospitalized patients in 35 US medical centers. Hospitals submitted 1 isolate per patient per infection episode that met local criteria for being the likely causative pathogen. Identification was performed by the submitting laboratory and confirmed by JMI Laboratories with matrix-assisted laser desorption ionization-time of flight mass spectrometry or other standard methods as required. Isolates were tested for susceptibility (S) to MIN and comparators using the CLSI broth microdilution method. All infection types were included in the analysis. CLSI (2022) breakpoints were applied.A total of 1,029 ACB and 1,520 SM were tested. Pneumonia in hospitalized patients was the most common infection from which ACB (57.0%) and SM (73.9%) were isolated. The %S of the agents tested against the organisms in this study are shown in the table. MIN had the highest %S for ACB (86.2%S) and SM (99.5%S). The %S of ACB and SM to all 3 agents varied over the period studied. MIN %S to ACB decreased in 2020 (80.6%) but rebounded in 2021 (86.2%). LEV and MER showed an overall trend of increasing S for ACB, with slightly lower %S in 2020-2021. SM had stable %S to MIN and T/S . LEV varied from 84.3%S (2015) to 69.2%S (2018).in vitro data suggest that MIN is a useful treatment option for infections caused by ACB or SM.%S to MIN remained stable and higher than other agents tested for both ACB and SM, pathogens which have limited therapeutic alternatives. ACB showed < 6% decrease in %S to all 3 agents in 2020-2021. These Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.


Epetraborole (EBO), an orally available bacterial leucyl transfer RNA synthetase inhibitor with potent activity against nontuberculous mycobacteria, is under clinical development for treatment of MAC lung disease. A population pharmacokinetic (PK) model describing the disposition of EBO after oral (PO) and intravenous (IV) administration was developed to support EBO PK-PD analyses and dose selection for patients with MAC lung disease.Table 1).Model development was conducted using NONMEM (v.7.4.3). Models were attempted for oral absorption, systemic compartments, and linear vs. non-linear elimination. Model evaluation involved goodness-of-fit plots and prediction-corrected visual predictive plots, which describe the ability of model-based simulations to capture the observed data. Included were data from 5 Phase 1 (3 IV and 2 PO) and 2 Phase 2 studies (IV only) (Table 2). The impact of body weight on PK was included using an allometric scaling approach to accommodate observed lower body weight in MAC lung disease patients. PO dosing was modeled using an absolute bioavailability term (F) and transit compartments with separate absorption rates for fed and fasted administration. Interindividual variability (IIV) in systemic clearance was low (7.9%), but IIV in F (32.7%) contributed to slightly higher variability in PK for PO vs. IV administration. Moderate shrinkage was observed for the IIV in the model parameters. This was considered acceptable given inclusion of patients with limited PK data in the model and the objective to facilitate simulations designed to inform dose selection. The prediction-corrected visual predictive check plots for the data obtained from a recently completed Phase 1b study evaluating 28-day oral dosing regimens (NCT04892641) are provided in Figure 1.The pooled dataset included 2637 EBO PK samples from 138 subjects/patients. A robust fit to observed data across studies was obtained using a three-compartment model with linear elimination (This model is useful for describing expected PK in MAC lung disease patients and was used to conduct simulations for the advancement of the oral EBO 500 mg q24h dosing regimen into clinical studies in patients with MAC lung disease.Harish Ganesan, MS, Adagio Therapeutics, Inc.: 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|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: 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|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: 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|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co.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|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support M. Courtney Safir, PharmD, Adagio Therapeutics, Inc: 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|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: 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|Evopoint Biosciences Co: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: 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|Lassen Therapeutics: 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|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc: 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|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: 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|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|Insmed Inc: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: 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|Novartis Pharmaceuticals Corp: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc: 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|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: 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|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|Insmed Inc: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: 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|Novartis Pharmaceuticals Corp: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc: 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|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: 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|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|Insmed Inc: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: 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|Novartis Pharmaceuticals Corp: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Kevin M. Krause, MBA, AN2 Therapeutics: Employee|AN2 Therapeutics: Stocks/Bonds Christopher M. Rubino, PharmD, Adagio Therapeutics: 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|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: 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|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: 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|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics,: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support.


The clinical presentation and management of acute hematogenous osteomyelitis (AHO) in children can vary significantly. Scores to predict acute complications utilize prolonged fever after antibiotics, bone abscess, suppurative arthritis, disseminated infection and delayed source control. By contrast, elevated CRP after 48-96 hours of therapy, disseminated disease and bone debridement are predictive of chronic complications. Such scoring systems have undergone limited validation. We examined factors associated with acute and chronic AHO complications at our center to identify other variables that may enhance published scores.< 14 days at Texas Children’s Hospital from January 2012 through December 2020. An acute complicated course was defined as treatment failure within 6 weeks of starting antibiotics, > 2 bone debridements, prolonged admission ( >14 days) and acute avascular necrosis. Chronic complications included growth arrest or limb leg discrepancy, pathologic fracture, avascular necrosis, chronic osteomyelitis or frozen joint. Statistical analysis was completed using STATA 17.A retrospective chart review was conducted of all children 6 mo-18 years with AHO and with acute symptoms of S. aureus/MRSA, presence of multifocal or disseminated infection, DVT, fever > 48 hours of antibiotic therapy, admission laboratory values including higher absolute neutrophil count (ANC) and higher CRP, ICU admission, associated suppurative arthritis, bacteremia, bone abscess, surgical debridement and delayed source control.418 patients met the inclusion criteria. 106 (25.4%) had an acute complicated course. 51 (13.5%) of 377 followed had a chronic complication. Clinical factors associated with acute and chronic complications were very similar. Factors associated with either an acute complicated course  or chronic orthopedic complications  included: older age, tibia involvement, infection due to In children with AHO, risk factors for acute and chronic complications are highly similar. Older age, tibia involvement, MRSA, higher ANC and bacteremia were linked to complications in our population and will be assessed in current clinical scoring systems which may help guide management.Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality: Grant/Research Support|Allergan: Provided reagents for unrelated research|Nabriva: Site investigator for multicenter clinical trial Kristina G. Hulten, PhD, Me-med: Grant/Research Support|Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support.


Angarotipula is a small genus of Tipulidae with only fourteen described species in the world and seven known species in China.Angarotipulalaetipennis  is presented and the morphologies of all stages are described.Here, one new species is added to the fauna of Sichuan. The life history of  Angarotipula is a small genus of Tipulidae with only fourteen described species in the world  are offered and the life history of this species is reported. The feeding habits of genus Angarotipula are reported for first time.In this paper, one species, Rearing of larvaeCeratophyllumdemersum) and fed algae feed (Chlorellavulgaris). Sand and gravel were used to make slopes for pupariation of mature larvae. All larvae were reared in Luxi County under natural conditions .Male and female adults were collected from Luxi County, Yunnan Province and placed in a plastic water bottle to mate. The eggs were laid in shallow water. After hatching, the larvae were transferred to a foam box with attachments like wooden sticks and coontail (2H5OH), to observe pruinescence after drying. Genitalic preparations of males and head shell of last instar larvae were made using Lactic acid solution (C3H6O3 > 85%) heated in a water-bath to 95-97°C for 4-6 minutes and cooled down to room temperature. After examination, it was transferred to fresh glycerine (C3H8O3) and stored in a microvial tied to the specimen.The spiracular disc of the 1st instar larva is drawn under an OLYMPUS BX43 microscope. All other specimens were studied and illustrated with OLYMPUS SZ61 stereomicroscope. Details of colouration were checked in specimens immersed in 75% ethyl alcohol , Beijing. The distribution map was obtained from Arcmap and modified with Adobe Photoshop CS6. All pictures were adjusted and assembled into plates with Adobe Photoshop CS6.The morphological terminology of the male hypopygium mostly follows that of Yang, 2022sp. n.439DD83D-E56E-53E0-AEC9-235492F5330AC268B3B5-96EA-4CB7-971B-95EC8A86662EType status:Holotype. Occurrence: recordedBy: Cai Xiao-Dong; sex: male; Taxon: higherClassification: Animalia; Arthropoda; Insecta; Diptera; Nematocera; Tipulomorpha; Tipuloidea; Tipulidae; Tipulinae; Angarotipula; kingdom: Animalia; phylum: Arthropoda; class: Insecta; order: Diptera; family: Tipulidae; genus: Angarotipula; specificEpithet: tristis; Location: continent: Asia; country: China; countryCode: CN; stateProvince: Sichuan; county: Ganzi Tibetan Autonomous Prefecture; municipality: Daocheng; locality: Yading Hongcaodi (亚丁 红草地); verbatimLocality: Hongcaodi (红草地); verbatimElevation: 3751 m; verbatimLatitude: 29°06'11"N; verbatimLongitude: 100°13'59.6"E; Identification: identifiedBy: Yang Qi-Cheng; Event: year: 2019; month: 7; day: 9; verbatimEventDate: 9-VII-2019; habitat: intermittent wetlands; fieldNotes: PolygonaceaePlant dominant species: ; Record Level: type: PhysicalObject; language: en; institutionCode: CAUType status:Paratype. Occurrence: recordedBy: Cai Xiao-Dong; sex: 2 males; Taxon: higherClassification: Animalia; Arthropoda; Insecta; Diptera; Nematocera; Tipulomorpha; Tipuloidea; Tipulidae; Tipulinae; Angarotipula; kingdom: Animalia; phylum: Arthropoda; class: Insecta; order: Diptera; family: Tipulidae; genus: Angarotipula; specificEpithet: tristis; Location: continent: Asia; country: China; countryCode: CN; stateProvince: Sichuan; county: Ganzi Tibetan Autonomous Prefecture; municipality: Daocheng; locality: Yading Hongcaodi (亚丁 红草地); verbatimLocality: Hongcaodi (红草地); verbatimElevation: 3751 m; verbatimLatitude: 29°06'11"N; verbatimLongitude: 100°13'59.6"E; Identification: identifiedBy: Yang Qi-Cheng; Event: year: 2019; month: 7; day: 9; verbatimEventDate: 9-VII-2019; habitat: intermittent wetlands; fieldNotes: PolygonaceaePlant dominant species: ; Record Level: type: PhysicalObject; language: en; institutionCode: CAUMales (n = 3): body length 11.3–11.5 mm, wing length 13.4–13.6 mm, antenna length 2.9–3.0 mm.Head Fig. A, B. Mai1 cell approximately triangular, petiole of m1 cell long, as long as m1 cell. Halter with stem brownish-yellow, knob grey .A.frommeri , based on the shape of hypopygium. However, in A.frommeri, the body is greyish-yellow; Rs arises at an acute angle from R.; the outer gonostylus has the lateral projections; and tergite IX has no projection E956E59B-0519-5349-95EA-CBB26BE283E6Type status:Other material. Occurrence: recordedBy: Yang Qi-Cheng and Yang Hao-Cheng; lifeStage: egg; larva; pupa; adult; Taxon: kingdom: Animalia; phylum: Arthropoda; class: Insecta; order: Diptera; family: Tipulidae; genus: Angarotipula; specificEpithet: laetipennis; scientificNameAuthorship: ; taxonomicStatus: accepted; Location: continent: Asia; country: China; countryCode: CN; stateProvince: Yunnan; county: Honghe Hani and Yi Autonomous Prefecture; municipality: Luxi; verbatimElevation: 1710 m; verbatimLatitude: 24°33'N; verbatimLongitude: 103°45'E; Identification: identifiedBy: Yang Qi-Cheng; Event: startDayOfYear: 12; endDayOfYear: 145; year: 2020; month: 5; day: 1; habitat: Rice field; lotus pond; eventRemarks: Angarotipulalaetipennis were reared at the outbreak of the COVID-19 epidemic in China, 2020.; Record Level: type: PhysicalObjectType status:Other material. Occurrence: recordedBy: Yang Qi-Cheng; lifeStage: egg; larva; pupa; adult; Taxon: kingdom: Animalia; phylum: Arthropoda; class: Insecta; order: Diptera; family: Tipulidae; genus: Angarotipula; specificEpithet: laetipennis; scientificNameAuthorship: ; taxonomicStatus: accepted; Location: continent: Asia; country: China; countryCode: CN; stateProvince: Yunnan; county: Honghe Hani and Yi Autonomous Prefecture; municipality: Luxi; locality: Xiaoxilong (小习龙), Wujiepu town.; verbatimElevation: 1700 m; verbatimLatitude: 24°32'N; verbatimLongitude: 103°34'E; Identification: identifiedBy: Yang Qi-Cheng; Event: startDayOfYear: 119; endDayOfYear: 145; year: 2020; month: 4; day: 29; habitat: Rice field ; lotus pond ; eventRemarks: Angarotipulalaetipennis were reared at the outbreak of the COVID-19 epidemic in China, 2020.; Record Level: type: PhysicalObjectEggs : length 0.7–0.75 mm, middle width 0.2 mm. Black, cylindrical; apical side with a round micropyle, ventral surface with slightly longitudinal indentations. Basal side with a long terminal filament, which is more than 6 times the length of egg . Length 2.0–2.2 mm, width 0.35–0.4 mm, spiracular disc width 0.5–0.55 mm. Body cream coloured and partially translucent, body surface with pale brown corrugated pubescence, dorsal pubescence darker than those on ventral surface. Head capsule brown, posterior margin black. Spiracular disc white, with eight fusiform structures, the end structures are smaller, each of which bear moderately bifurcated long bristles; innermost pair of fusiform structures with three to five  bristles; laterally from it, the pair with three to five  bristles; outermost pair on outside of spiracles with three bristles; locations of bifurcations of these structures not fixed and the number of bifurcations not absolutely symmetrical. Spiracle small, with pale brown margin, distance beween spiracles 4 times as long as width of spiracle. Lateral lobe below spiracle, surface sclerotised, roughly sickle-shaped, tip rounded, bearing twelve to thirteen long bristles; ventral lobe finger-like with three long stiff bristles, a short stiff bristle and two tiny bristles, close together. Ventral surface of anal segment with two pairs of long anal papillae and anal papillae white, translucent : length 3.0–4.0 mm, width 0.4–0.5 mm, spiracular disc width 0.65 mm. Morphological characteristics are similar to 1st instar, but head capsule darker than 1st instar; inside pair of ventral anal papillae longer than those of 1st instar and tips of outside pair of ventral anal papillae blunt and black : length 15.0–24.0 mm, width 2.0–3.0 mm, spiracular disc width 2.2–3.0 mm. Female last instar (n = 4): length 22.0–28.0 mm, width 2.5–3.8 mm, spiracular disc width 2.8–4.0 mm. Body brown and partially translucent, body surface with brown corrugated pubescence. Head capsule length 2.4 mm, width 1.2 mm, black, strongly sclerotised medially. Incision extending to 1/4 length of head, ends of internolateralia with a pair of long spiny processes and a pair of small triangular processes; internolateralia longer than externolateralia. Both labrum and clypeus with two pairs of brush-like setae, the smaller one on inside and the larger one on outside. Antenna cylindrical :Male .Angarotipulalaetipennis can be observed in late April. In Luxi County, adults are more common in rice fields and artificial ponds. Adults have strong positive phototaxis. Females are able to lay eggs on the same day after mating. Under natural conditions, the eggs are attached to other things, such as water plants to form egg masses. Females can eject the eggs quickly without choice when it is pinched by the body. Eggs mostly hatch in 2–4 days above 22°C. Larvae move after evening and feed on brown algae and chlorella. Old instar larvae gnawed the foam box and hornwort, but they did not seem to feed on live hornwort directly. The moulting time of larvae varies according to the temperature and food. Generation overlap is found. The last instar larvae pupate on any attachments near the water surface generally. Around 29°C, the pupae usually emerge at night, but a few of the pupae emerge during the day after 4–5 days. Adults mate immediately after eclosion, male adults customarily force the incompletely ossified females. Both males and females can mate for multiple times. Adults survive for only three days without water, but they could live for more than a week in the state of feeding water.In Luxi County, Yunnan Province, the adults of Females can mate for multiple times in the artificial environment (possibly forced) and they laid eggs on the same day. The eggs were laid out of water or on a paper towel soaked in water. The terminal filament has strong elasticity, but can be pulled apart by hand, the filaments of all eggs were anchored together and tightly attached to other things. As shown in Fig. The last instar larvae prefered to pupate near the sandy soil by water, but they did not bury their bodies in the soil. Conversely, they slightly attached to the sand and stone where they can breathe the air. Sometimes, they also pupated on the water plants close to the water. The bodies of newly-pupated pupae were white and translucent Fig. E.The last instar larvae preferred to pupate near the sandy soil by water, but they did not bury their bodies in the soil. Conversely, they slightly attached to the sand and stone where they can breathe the air. Sometimes they also pupated on the water plants closed to the water. The bodies of newly pupated pupae were white and translucent Fig. E.Angarotipula seem to be similar, they all live near freshwater ponds or swamps. The A.laetipennis we collected lived in paddy fields or lotus ponds (Fig. A.tristis, sp. n. lived in intermittent swamps (Fig. Angarotipula is widely distributed in the southwest of China (Fig. A.laetipennis for the first time and they can complete their entire life cycle by feeding on algae and have a high survival rate, which may mean that they have unique ecological niches in freshwater ponds or swamps, and we expect more studies support this view.The habits of nds Fig. , while Amps Fig. A. Angaroina Fig. B, which


Scientific Reportshttps://doi.org/10.1038/s41598-021-87977-3, published online 21 April 2021Correction to: The original version of this Article contained an error in Affiliation 2, which was incorrectly given as ‘Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou, China’. The correct affiliation is listed below:Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, ChinaThe original Article has been corrected.