CAB+RPV LA is the only complete long-acting regimen for treatment of virologically suppressed people with HIV (PWH). Administered monthly or every 2 months by a healthcare provider (HCP), CAB+RPV LA may alleviate challenges associated with daily oral antiretroviral therapy (ART). Perspectives of PWH receiving CAB+RPV LA in real-world US healthcare settings are needed.This 2-year prospective, observational study enrolled treatment experienced PWH following the decision to switch to CAB+RPV LA (monthly or every 2 months) across 30 participating US sites. Participants completed baseline (BL) surveys prior to first injection and follow-up surveys at Month 6 (M6). Surveys assessed challenges with daily oral ART, reasons for initiating CAB+RPV LA, HIV treatment satisfaction using the HIV Treatment Satisfaction Questionnaire (HIVTSQ), preference for daily oral vs. injectable, and benefits of more frequent clinic visits.A total of 308 PWH were enrolled and completed BL surveys (Table 1); 217 PWH had reached the M6 timepoint and completed M6 surveys as of data cut-off (Jan 2023); of the 217 PWH, 8 reported they had discontinued CAB+RPV LA. At BL, 49% respondents reported sometimes, often, or always hiding their prior oral ART for fear of disclosing HIV status. The common primary reasons PWH chose to start CAB+RPV LA were: tired of taking daily oral ART, wanted a more convenient treatment option, and worried about missing a dose (Table 2). At M6, PWH receiving CAB + RPV LA reported a decrease from BL in fear of disclosure, anxiety around adherence, and daily reminder of HIV. At M6, 88% of PWH reported CAB+RPV LA was rarely or never an unwelcome reminder of their HIV status vs. 50% at BL with prior oral ART. Most participants preferred CAB+RPV LA (95%), 2% preferred daily oral ART, and 2% had no preference at M6. Treatment satisfaction increased from BL to M6; most reported multiple additional benefits with more frequent clinic visits (Table 3).Switching to CAB + RPV LA demonstrated improvements in fear of disclosure, anxiety around adherence, and daily reminder of HIV status at M6 . PWH reported a strong preference for CAB+RPV LA, increased treatment satisfaction, and more opportunities to engage with their HIV care.Dima Dandachi, MD, MPH, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Douglas Cunningham, DO, ViiV Healthcare: Advisor/Consultant William M. Valenti, MD, FIDSA, Gilead: Grant/Research Support|ViiV Healthcare: Grant/Research Support John Phoenix, MSN, APRN, FNP-C, Gilead: Grant/Research Support|Gilead: Speaker Bureau|Huntridge Family Clinic: Ownership Interest|Napo Pharmaceuticals: Speaker Bureau|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Speaker Bureau Paula Teichner, PharmD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employment Maria Reynolds, MStat, RTI Health Solutions: Employment|ViiV Healthcare: Grant/Research Support Cindy Garris, MS, GSK: Stocks/Bonds|ViiV Healthcare: Employee


Lenacapavir (LEN) is a highly potent, long-acting, first-in-class inhibitor of HIV-1 capsid protein approved for the treatment of HIV-1 infection in adults with multidrug resistance in combination with other antiretrovirals. CALIBRATE is an ongoing phase 2 study in people with HIV-1 (PWH) who are newly initiating treatment. At Week 80 (W80), subcutaneous (SC) and oral LEN, in combination with other antiretrovirals, maintained high rates of virologic suppression. In PWH initiating treatment, weight increases associated with a return to health effect have been observed. This analysis examined weight and metabolic changes to the W80 timepoint.Participants were randomized (2:2:2:1) to 1 of 4 treatment groups (TG). TG1 and TG2 both received SC LEN (927 mg) every 6 months + oral once daily (QD) emtricitabine/tenofovir alafenamide (F/TAF) for 28 weeks, after which virologically suppressed participants continued a 2-drug maintenance regimen: SC LEN (927 mg) with oral QD TAF (TG1) or oral QD bictegravir (BIC) (TG2). TG3 received oral QD LEN + F/TAF, and TG4 received oral QD BIC/F/TAF throughout. The metabolic profile of LEN was assessed from baseline to W28 and after initiating the 2-drug maintenance regimen to W80. Due to the small sample size, no statistical testing was performed.2, respectively. Weight, BMI, and fasting lipid profiles for each treatment group through W80 are presented (Table).182 participants  were randomized and dosed . Baseline median age was 29 years; 15% had baseline viral load >100,000 c/mL. Baseline median weight and body mass index (BMI) were 78.2 kg and 25.8 kg/mIn this phase 2 study of treatment-naïve PWH, treatment regimens that included SC or oral LEN in combination with other antiretroviral agents led to expected weight gain and increase in BMI, consistent with the return to health phenomenon, and were not associated with clinically relevant increases in lipids.Princy N Kumar, MD, Gilead Sciences, Inc: Grant/Research Support|Gilead Sciences, Inc: Stocks/Bonds|Johnson & Johnson: Advisor/Consultant|Johnson & Johnson: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Stocks/Bonds|Pfizer: Stocks/Bonds|Theratechnologies: Advisor/Consultant|Theratechnologies: Grant/Research Support|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Stocks/Bonds Aditya H Gaur, MD, Gilead Sciences, Inc (Grant support/CTA with St. Jude): Grant/Research Support|Janssen (Grant support/CTA with St. Jude): Grant/Research Support|Viiv (Grant support/CTA with St. Jude and Serve on Pediatric Advisory Board): Board Member|Viiv (Grant support/CTA with St. Jude and Serve on Pediatric Advisory Board): Grant/Research Support Anson K Wurapa, MD, Gilead Sciences, Inc: Clinical Trial Investigator Ann M. Khalsa, MD, Gilead Sciences, Inc: Advisor/Consultant|Gilead Sciences, Inc: Grant/Research Support|Gilead Sciences, Inc: Honoraria|Glaxo Smith Kline: Advisor/Consultant|Viiv: Advisor/Consultant Cheryl L Newman, MD, Gilead Sciences, Inc: Grant/Research Support|GSK Viiv: Grant/Research Support|GSK Viiv: Honoraria|Janssen: Grant/Research Support|Merck: Grant/Research Support Gary Saunders, BSc, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Shan-Yu Liu, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Hadas Dvory-Sobol, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Martin Rhee, MD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Samir K. Gupta, MD, Gilead Sciences: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support


Influenza point of care (POC) testing can support rapid influenza detection and outbreak management in nursing homes (NHs). We hypothesize cost-free on-site access to influenza POC tests increases POC test use and influenza detection. A current study positions us to evaluate this hypothesis.A prospective cohort of U.S. NHs enrolled in a comparative effectiveness trial of baloxavir versus oseltamivir for outbreak management through 2 influenza seasons, 2020-2022 (NCT05012189). We compared study NHs provided with influenza POC tests for use when clinically indicated to non-study facilities participating in weekly National Healthcare Safety Network (NHSN) reporting for occurrence of influenza outbreaks. For study facilities, we received reports upon influenza detection and directly surveyed them for POC use and influenza incidence. We compared study NHs and other NHSN NHs for reported influenza case rates.We recruited 586 facilities with an average of 89 long-stay residents and 120 Medicare certified beds which reported 185 new influenza activity in 159 facilities. Study test use frequency was reported (N=250), mean use was 28 tests per facility whether or not influenza was detected. Upon influenza detection, 52% of NHs initiated antiviral treatment or chemoprophylaxis on 1 or more residents. Study NHs reported 201 cases with a cumulative incidence of 3.7 cases per 1000 resident days versus 2,124 cases (1.7 per 1000) in non-participating NHs in the same period. Non-participating U.S. NHs had fewer beds (76 long-stay residents), 106 Medicare certified beds and less than half the rate of outbreak detection from study facilities.NHs that participated in our prospective study reported influenza disproportionately more than other NHs reporting to NHSN. We interpret that the availability of easy-to-use and freely accessible rapid POC influenza tests positions NHs to detect better and manage influenza outbreaks. The ease of access to POC on-site tests may play a significant role and become a best practice approach in this positive outcome to improve influenza detection and support early intervention.Yasin Abdul, MD, Genentech: Grant/Research Support Ed Davidson, PharmD, MPH, Genentech: Grant/Research Support Kevin McConeghy, PharmD, Genentech: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Kaley Hayes, PharmD, PhD, Sanofi Aventis: Grant/Research Support Lisa Han, MPH, Genentech: Grant/Research Support Melissa LaMantia, MA, Genentech: Grant/Research Support Elie Saade, MD, Envision Pharma: Speaker, Presenter|Johnson and Johnson: Speaker, Travel, Lodging|Protein Sciences Corp: Grant/Research Support|Sanofi Pasteur: Speaker, Travel, Lodging David Canaday, MD, Pfizer: Grant/Research Support Stefan Gravenstein, MD, MPH, CDC: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|GSK: Honoraria|Janssen: Advisor/Consultant|Janssen: Honoraria|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Grant/Research Support|Seqirus: Honoraria


Nontuberculous mycobacterial pulmonary disease (NTMPD) is a chronic lung infection that is challenging to treat, especially refractory NTMPD. Data are limited on the natural history, risk profile, and burden of refractory NTMPD. The objective of this study was to evaluate the burden of illness (BOI) among patients with NTMPD who later develop refractory NTMPD vs those who do not.This was a retrospective analysis using BRR data. Patients treated for NTMPD were included and stratified as refractory  or nonrefractory. Modified bronchiectasis severity index (mBSI) at baseline visit and BOI including comorbid conditions and surgeries at the treatment visit were compared by cross-sectional analysis between the two groups. Longitudinal analysis of BOI focused on exacerbations and hospitalizations in the refractory group at their pre-refractory visit and refractory visit (first visit meeting the refractory definition).A total of 1,064 patients treated for NTMPD were included: 462 (43.4%) refractory and 602 (56.6%) nonrefractory. During the baseline period, the refractory group had more severe bronchiectasis . At the time of treatment, bronchiectasis was more common in the refractory than nonrefractory (96.2% vs 89.7%) group, as were hemoptysis (26.6% vs 16.3%) and GERD (50.5% vs 39.9%). Except BMI, there were no statistically significant differences between the pre-refractory and nonrefractory treatment visits (Table 2). In the refractory group, exacerbations and hospitalizations remained high from the pre-refractory to refractory visit . Oxygen and bronchial hygiene use increased from the pre-refractory to the refractory visit  consistent with increased management of respiratory conditions when not responding to treatment (Table 2).Refractory NTMPD imposes a high disease burden on patients in the BRR. This high burden was present at pre-refractory visits and through the development of refractory status.Timothy R. Aksamit, MD, AstraZeneca: Advisor/Consultant|Baxter International, Hill-Rom: Advisor/Consultant|Insmed Incorporated: Advisor/Consultant|Johnson & Johnson: Advisor/Consultant|Redhill Biopharma: Advisor/Consultant|RespirTech: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Zambon: Advisor/Consultant David M. Mannino, MD, AstraZeneca: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Up to Date: Advisor/Consultant Ping Wang, PhD, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds Mariam Hassan, PhD, B. Pharm, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds


Social vulnerability impacts the transmission of SARS-CoV-2 (SCV2) among household contacts. Understanding these correlates can inform interventions to prevent infection among close contacts. We examined whether the social vulnerability index (SVI), a composite measure of socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation, is associated with the risk of SCV2 infection among household contacts.Overall Social Vulnerability Index DiagramWe used data from a multi-site, prospective, case-ascertained household transmission study with daily nasal swabs for 10 days and RT-PCR testing to detect SCV2 infections in household contacts. Age and gender were self-reported and vaccination status was self-reported and verified. We mapped households to 2020 census tracts and the 2020 SVI . We examined the association between census tract-level SVI (in quartiles) and the risk of infection among household contacts using Poisson regression with generalized estimating equations, accounting for household clustering.Inclusion criteria for analysis in this study.Inclusion criteria for analysis in this study.Among 1,171 household contacts from 719 households, 67.4% developed SCV2 infection. After adjusting for the age of the contact and study site, contacts living in the most vulnerable SVI quartiles, Q3  and Q4 , had higher rates of infection compared to those living in the least vulnerable quartile (Q1) at the census tract level. To describe the effect of SVI accounting for vaccination, we performed a second regression adjusting for vaccine receipt among participants. We found that Q3  still had higher rates of infection compared to those living in the least vulnerable quartile (Q1). Q4 was directionally consistent but confidence bounds crossed 1 .Household contacts from census tracts with greater social vulnerability at the census tract level had a greater risk of SCV2 infection. These risks held even after accounting for vaccine receipt among participants. Future public health interventions should focus on reducing infection and transmission among individuals living in areas with higher social vulnerability beyond vaccination coverage.Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member


Provisional US data indicated that enterovirus D68 (EV-D68) circulated during summer 2022. However, in contrast to 2018 (a previous high circulation year), EV-D68 circulation in 2022 was associated with unusual increases in asthma-specific healthcare visits and a lack of concomitant increases in acute flaccid myelitis (AFM). To explore these distinctions by year, we characterized respiratory EV-D68 circulation in 2022 and compared patient characteristics in 2022 to 2018.We enrolled children aged < 18 years with acute respiratory illness (ARI) seeking care in an emergency department (ED) or as an inpatient (IP) across 7 US medical centers in the New Vaccine Surveillance Network (NVSN). Data sources included parent interview, medical chart review, and collection of a respiratory swab for molecular virus testing. Swabs were tested for EV-D68 from Jul–Nov 2017–2020, and year-round from Jul 2021. A convenience sample of EV-D68-positive swabs was sequenced. We assessed monthly EV-D68 percent positivity among children with ARI. We examined demographics, underlying conditions, and severity markers among children with EV-D68 in 2018 and 2022, by care setting (ED vs IP) and used 0.05 as a threshold of statistical significance.Figure). All viruses sequenced in 2018 and 2022 were lineage B3. Compared to 2018, IPs with EV-D68 in 2022 less frequently reported any underlying medical condition or a history of asthma, yet more frequently required supplemental oxygen or intubation (Table). Supplemental oxygen use was also more common among ED patients in 2022 than 2018 . Asthma exacerbation was a common primary discharge diagnosis among IPs but was less common in 2022 than 2018 .Between 2017–2022, there were 994 ED and IP EV-D68 detections at NVSN sites, with distinct peaks during the Jul-Nov testing periods in 2018 and 2022 , FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support Geoffrey A. Weinberg, MD, Merck & Co: Honoraria Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant


Leishmania infantum is endemic in Afghanistan, although its distribution is poorly characterized. The spectrum of VL ranges from asymptomatic to active VL with symptoms of fever, weight loss, organomegaly, and pancytopenia. Most symptomatic patients die without treatment; asymptomatic patients remain at risk lifelong for symptomatic reactivation—especially if immunosuppressed. Travelers returning from VL endemic areas may harbor latent infection years after their return. We aimed to determine the prevalence of asymptomatic VL (AVL) in US military personnel previously deployed to Afghanistan.Visceral leishmaniasis (VL) is a chronic protozoal disease caused from the bite of an infected sand fly. VL due to LeishmaniaHealthy adult US military personnel who deployed to Afghanistan over summer months were recruited from the Washington DC area. 90 volunteers completed a risk factor survey, blood draw, and had completed results. Diagnostic testing utilized ELISA, interferon gamma release assay (IGRA), and quantitative PCR (qPCR). Statistical analyses included Fisher exact test, Pearson χ2 test, Welch Two Sample t-test, and Mann-Whitney U test. IRB approval was obtained.The prevalence of AVL  in the volunteers was 9/90 (10%). Two (2.2%) PCR, 7 (7.8%) ELISA, and no (0%) IGRA samples were positive. AVL+ participants were a median of 10.6 years (range 8 - 18.6) post Afghanistan deployment, and compared to AVL- volunteers, were older  and more likely to self-identify as African-American (n = 5 (56%) vs 16 (20%), p = 0.029). No risk factors for AVL were identified in exploratory analysis of the volunteers’ military roles, types of outdoor exposure, or deployment location within Afghanistan.In this preliminary cross-sectional analysis of US military personnel who returned from Afghanistan, the prevalence of AVL was 10%–comparable to other published studies on the prevalence of AVL in endemic areas and of concern when one considers the several million US military personnel previously deployed to Iraq and Afghanistan. Due to the persistence of this intracellular infection, clinicians should be alerted for reactivation potential in previously deployed Servicemembers.Naomi E. Aronson, MD, british medical journal: Honoraria|British Medical Journal: honoraria for writing chapter for Best Evidence|Elsevier: royallties serve as textbook editor|Elsevier: Royalties as text editor|UpTo Date: royalties for writing chapters|UpToDate: royalties for writing chapters|Wellcome Foundation: Honoraria|Wellcome Foundation: program advisory board|Wellcome Trust: Honoraria|Wellcome Trust: program advisory board Naomi E. Aronson, MD, british medical journal: Honoraria|British Medical Journal: honoraria for writing chapter for Best Evidence|Elsevier: royallties serve as textbook editor|Elsevier: Royalties as text editor|UpTo Date: royalties for writing chapters|UpToDate: royalties for writing chapters|Wellcome Foundation: Honoraria|Wellcome Foundation: program advisory board|Wellcome Trust: Honoraria|Wellcome Trust: program advisory board


Escherichia coli is a common Gram-negative bacterium that can infect normally sterile body sites and cause invasive E. coli disease (IED) including bacteremia, sepsis and septic shock. E. coli surface O-antigens are important virulence factors that contribute to pathogenicity, making them promising targets for the development of multivalent conjugate vaccines to protect against IED. Here, we describe the prevalence of O-serotypes and O-genotypes of clinical E. coli isolates across a multinational cohort of patients with IED.E. coli presence in cultures from any normally sterile body site or urine in patients exhibiting clinical criteria of invasive disease  and no other identifiable site of infection. O-serotyping (agglutination) and O-genotyping (whole genome sequencing [WGS]) were conducted. Subgroup analyses were performed in isolates from patients with bacteremic vs nonbacteremic IED and in patients ≥60 years old.This was a retrospective, multicenter, noninterventional study across 17 tertiary care hospitals in Europe, North America and Asia. Patients with an IED diagnosis in the 12 months prior to data collection were included. IED was defined as Table 1). Collectively, these 6 most prevalent serotypes accounted for 55.0% of total isolates. A similar pattern of O-serotypes was observed in the subgroup of patients ≥60 years old (Table 2), with serotypes O25, O2 and O6 most common in both bacteremic and nonbacteremic IED isolates.902 patients with IED were identified . The most common O-serotypes  based on O-genotyping were O25 , O2 , O6 , O1 , O15  and O75  : Grant/Research Support|Bionorica: Honoraria|Bionorica: Meeting/travel support, study participation|Deutsches Zentrum für Infektionsforschung (DZIF): Study participation|Enteris BioPharma: Study participation|Everest Medicines: Grant/Research Support|German S3 guideline Urinary tract infections: Board Member|Glaxo Smith Kline: Advisor/Consultant|Glaxo Smith Kline: Honoraria|Glaxo Smith Kline: Consulting fees, meeting/travel support, advisory board member, principal investigator in a GSK-sponsored study|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Guidelines European Association of Urology: Infections in Urology: Board Member|Helperby Therapeutics: Study participation|Janssen: Honoraria|Janssen: Advisory Board member|Klosterfrau: Honoraria|LeoPharma: Advisory Board member|MerLion: Advisory Board member|MIP Pharma: Honoraria|MSD: Advisory Board member|OM Pharma/Vifor Pharma: Advisory Board member, study participation|OM-Pharma: Honoraria|Pfizer: Honoraria|Pfizer: Advisory Board member|RosenPharma: Advisory Board member|Shionogi: Advisory Board member, study participation|Speaker research group German research foundation (DFG) Bacterial Renal Infections and Defense (FOR 5427): Study participation|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Consulting fees|University Hospital Giessen and Marburg GmbH, and Justus Liebig University, Germany: Employee|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Consulting fees, Advisory Board member Tetsuya Matsumoto, MD; PhD, member of the international study steering committee for the E.mbrace study and reports payment: Board Member Marc Bonten, MD, PhD, chair of the international study steering committee for the E.mbrace study (Janssen Vaccines), with payments made to UMC Utrecht: Board Member Michal Sarnecki, MD, Janssen: Employee|Janssen: Stocks/Bonds Jan Poolman, PhD, Janssen: Employee|Janssen: Stocks/Bonds


Stenotrophomonas maltophilia is a leading cause of carbapenem-resistant, Gram-negative bacterial bloodstream infections (BSI).S. maltophilia BSI between 1/1/2015 through 12/31/2020 with available antimicrobial susceptibility testing (AST) as reported by the local clinical microbiology laboratories were included. Data extracted from the electronic medical record and collected in a central database. Acute critical illness was measured through the Pitt Bacteremia Score, and chronic comorbidities through the Charlson Comorbidity Index. Desirability of outcome ranking (DOOR) outcomes were determined as shown.A retrospective, observational study was conducted at four centers in Italy and the United States. Patients who were treated for Table.DOOR OutcomesMedian age of 143 patients was 54 years (IQR 40-65 years), and 77/143 (54%) were women. The median Charlson Comorbidity Index and Pitt bacteremia score were 3 (IQR 2-5), and 1 (IQR 0-2). At time of culture, 22/143 (15%) patients were in the intensive care unit, and 15/143 (10%) patients were on mechanical ventilation. Of tested isolates, 4/142 (3%), 0/53 (0%), 17/140 (12%) were non-susceptible to trimethoprim/sulfamethoxazole, minocycline, and levofloxacin, respectively. In the first 14 days after culture, 68/143 (48%) received at least 2 different antibiotics either together or sequentially. Levofloxacin , trimethoprim/sulfamethoxazole , and tetracyclines  were most used. Novel treatment approaches were less commonly employed; cefiderocol in 5/143 (3%), and ceftazidime-avibactam & aztreonam in 6/143 (4%) of patients. Overall mortality at 30 days was 29/143 (20%); 30-day mortality was 8/17 (47%) in patients with fluoroquinolone-non-susceptible isolates, vs. 20/123 (16%) in patients with fluoroquinolone-susceptible isolates (p< 0.01). DOOR distribution of outcomes is shown in Figure 1. A randomly selected patient with a fluoroquinolone -susceptible isolate had a 74%  likelihood of a better outcome as compared to a randomly selected patient with a fluoroquinolone-non-susceptible isolate.S. maltophilia BSI is associated with poor outcomes and high mortality, especially in patients with fluoroquinolone-non-susceptible isolates.Giusy Tiseo, MD, Shionogi: Honoraria Robert A. Bonomo, MD, Entasis: Grant/Research Support|Merck: Grant/Research Support|venatorax: Grant/Research Support|Wockhardt: Grant/Research Support Marco Falcone, MD, PhD, Gilead: Board Member|Gilead: Honoraria|Menarini: Board Member|Menarini: Grant/Research Support|Menarini: Honoraria|MSD: Board Member|MSD: Grant/Research Support|MSD: Honoraria|Nordic Pharma: Honoraria|Pfizer: Board Member|Pfizer: Honoraria|Shionogi: Honoraria David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant


Beta-lactam allergy (BLA) is associated with increased broad-spectrum antibiotic (Br-ABX) use, worse clinical outcomes, and higher costs. Our hospital-wide BLA protocol (BLA-P) was launched in 7/2021 with following categories: intolerance, low-risk , and high-risk . Delabeling was done directly based on antibiotic history/interview alone (direct-delabeling), or via graded challenge for low-risk patients. We evaluated the delabeling rate and its impact on Br-ABX usage.Hospitalized patients ≥ 18 years old with listed BLA during 10/2021-12/2022 were eligible. Exclusion criteria were critically ill, surgical, hospice or comfort care, or non-verbal patients. Assessment was counted each time a pharmacist evaluated BLA; multiple assessments could occur in case of prolonged hospital stay or multiple admissions. Interventions were categorized as no further action , updated allergy label, or delabeled. Missed assessments were reported due to logistical issues. Br-ABX usage was compared in the delabeled patients: the empiric antibiotic use 90 days post-intervention versus pre-intervention using McNemar test (SPSS).A total of 700 assessments in 631 unique patients with BLA were identified . 556 assessments in 489 unique patients  met inclusion criteria. In this cohort, the assessments revealed 8% intolerance, 54% low-risk, 17% high-risk and 21% unknown allergy. Interventions resulted in no further action 7%, updated label 72%, and delabeling 21%. 65% of the delabeling was done via direct-delabeling and 35% via graded challenge . Passing rate with graded challenge was 97%. The use of aztreonam and meropenem decreased significantly in delabeled patients compared to pre-delabeling while cefepime and piperacillin-tazobactam usage increased (Table 1).Implementation of BLA-P led to 21% delabeling, which resulted in increased use of preferred Br-ABX and a significant decrease in meropenem and aztreonam use.Sanjeet S. Dadwal, MD, FACP, FIDSA, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope, Inc: Stocks/Bonds|Astellas: Honoraria|Karius: Grant/Research Support|Matinas Biopharma: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer/Amplyx: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria|Viracor: Honoraria Randy Taplitz, MD, Karius: Advisor/Consultant|Merck: Advisor/Consultant|SNIPR biome: Advisor/Consultant


Respiratory syncytial virus (RSV) is a common viral pathogen identified in older adults with acute respiratory infections (ARIs). Data describing the durability of immune responses to RSV are limited but suggest responses may be short-lived. In this study, we assessed longitudinal antibody responses following RSV-associated hospitalization for 3 years.Between September 2018 and March 2020, adults ≥ 50 years of age hospitalized with ARI at two Emory University hospitals who had a positive RSV test via PCR were enrolled. A nasopharyngeal swab, oropharyngeal swab, and 10mL blood were collected at enrollment (V1), 30 days after enrollment (V2), and in the 4 weeks prior to the start of the influenza season(s) for three years after enrollment . Syndrome-positive, RSV-negative controls were also enrolled. Serum samples were analyzed for RSV A/B lysate antigen by enzyme-linked immunosorbent assay (ELISA) and end-point titers were interpolated to a standard curve. Geometric mean titers (GMTs) were calculated, and statistical comparisons of log-transformed titers were performed using a mixed effects model in GraphPad Prism v9.0.Of the 30 enrolled participants who completed follow-up, there were 20 RSV-positive cases and 10 controls (Table 1). Of these, 22 (73%) were female, 22 (73%) Black, and 30 (100%) non-Hispanic ethnicity. Baseline demographics were similar in cases and controls. However, being immunocompromised was more common in cases, and heart disease was more common in controls. Peak antibody titers were observed in cases at V2 , and these declined non-significantly prior to the start of the next RSV season  . Titers then declined significantly 2 years  and 3 years  after infection. RSV IgG GMTs were not significantly different between cases and controls at any time point. Results were similar when immunocompromised participants were excluded from the analysis.RSV antibody responses peaked in early convalescence and persisted for 3 years after RSV-associated hospitalization. Antibody titers were similarly elevated in cases and controls, indicating the durability of RSV antibodies in older adults.Elizabeth Begier, M.D, M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Bradford J. Gessner, M.D, M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support


A new formulation of oritavancin (ORI) was developed and approved by the US FDA to be infused over 1 hour for the treatment of acute bacterial skin and skin structure infection (ABSSSI).Staphylococcus aureus (SA), β-hemolytic streptococci (BHS), and Viridans group Streptococcus (VGS) causing SSSI in US medical centers in 2022 and 2017–2019 was compared.The activity of ORI and comparators against 6,110 SSSI pathogens, including 705/4,550 SA from 2022/2017–2019, 158/613 BHS, and 27/57 VHS isolates, respectively, were collected (1/patient) from 33 US medical centers. Isolates were identified by MALDI-TOF MS and susceptibility (S) tested by CLSI broth microdilution. CLSI clinical breakpoints (BP) were applied.50/90, 0.015/0.03 mg/L) was similar to 2017–2019 . The MRSA rate (36.2%) was slightly lower in 2022 than previous years (41.3%), but the ORI S rate remained 100% in 2022. Vancomycin (VAN), daptomycin (DAP), and linezolid (LZD) also remained active (≥ 99.9% S) against SA and MRSA from both periods. Equivalent activity was observed for ORI against the BHS group between 2022  and 2017–2019 , but variation among species was noted. All S. agalactiae were inhibited by ORI at ≤ 0.25 mg/L in 2022 while 5 isolates showed ORI MIC values ≥ 0.5 mg/L in 2017–2019 (97.2%S). 2 and 10 S. pyogenes displayed ORI MICs ≥ 0.5 mg/L in 2022 (97.3%) and 2017–2019 (97.4%S), respectively. ORI MICs ≥ 0.5 mg/L were noted for 7/19 and 5/47 S. dysgalactiae in 2022 (63.2%S) and 2017–2019 (89.4%), respectively. Penicillin (PEN), VAN, DAP, and LZD inhibited all BHS isolates at their respective BP, regardless of the period or BHS species. All VGS were inhibited by ORI, VAN, DAP, LZD, and PEN in 2022 and 2017–2019, except for 1 Streptococcus salivarius group in 2022 .ORI activity against SA from 2022 (MICS. dysgalactiae showed the largest changes in %S between periods but isolate numbers were low.ORI data from 2022 showed similar activity to 2017–2019 for SA, including MRSA, BHS, and VGS isolates causing SSSI in US medical centers. VAN, DAP, and LZD also exhibited stable activity against these pathogens over time. Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Dee Shortridge, PhD, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


Coccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles necessitating evaluation of additional therapeutic options.Patients with coccidioidomycosis who received Isavuconazole were identified by cross-indexing ICD-9 and ICD-10 codes from patients and data abstracted. Responses to Isavuconazole therapy were measured using a modified Mycoses Study Group Coccidioidomycosis Scoring system as described previously.82 patients met the criteria for inclusion. Over half of the patient exhibited pulmonary involvement 45/82 (55%), although meningitis 32/82 (39%), bone and joint disease 14/82 (17%) and skin/soft tissue infection 7/82 (9%) were also seen. The majority of patients experienced a decrease in their MSG score following initiation of Isavuconazole therapy . Overall improvement was noted in 58/82 (71%) patients, while no change was observed in 19/82 (23%) and 5/82 (6%) who were unresponsive to antifungal changes.Isavuconazole demonstrated efficacy in the majority of patients treated, with failures observed only in a subgroup of patients with coccidioidal meningitis.Rupam Sharma, PGY-1/MD, Astellas: Grant/Research Support George R. Thompson, III, MD, Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mayne: Advisor/Consultant|Mayne: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support


C. glabrata (CGLA). Echinocandins (ECHs) are often used as first-line therapy. R to ECHs has been associated with FKS1 and FKS2 gene alterations. Rezafungin (RZF), a new ECH approved by the US FDA to treat candidemia and invasive candidiasis, was evaluated against a collection of ECH–non-wild type (NWT) CGLA isolates.Fluconazole (FLC) resistance (R) is common in n=459; 20 centers), Europe , Asia-Pacific , and Latin America  were identified by MALDI-TOF and/or sequencing and tested by CLSI broth microdilution. CLSI breakpoints (BP) and epidemiological cut-off values were applied. ECH NWT isolates were submitted to FKS analysis by whole genome sequencing.A total of 1045 CGLA collected (1/patient) in 2014–2021 from 58 medical centers located in North America . RZF was active against >50% of these isolates. RFZ was also active against >90% of ECH-NWT CGLA carrying wildtype FKS genes. Equivalent activity was noted to other ECHs against ECH-NWT isolates. However, ECHs were 4 to 8-fold more active against ECH-NWT CGLA that did not display alterations in FKS genes than those with FKS alterations. FKS2 hot spot(HS)-1 alterations were observed in 22 isolates (12 displayed S663F), while FKS1-HS1 alterations were noted in 9 isolates (7 displayed S629P). FLC-R was observed in 6.9% of CGLA overall and 16.7% of the ECH-NWT isolates.RZF showed similar activity to other ECHs against CGLA (Table), inhibiting 98.5% at ≤0.5 mg/L. Anidulafungin (ANF), caspofungin (CSF), and micafungin (MCF) susceptibility (S) rates were 96.2%, 97.5%, and 97.3%, respectively. ECH-NWT CGLA were detected in 42 isolates : NA showed the highest rate of ECH NWT isolates , followed by EU , AP , and LA . The RZF S rate was 61.9% of ECH-NWT CGLA, while the S rate to ANF, CSF, and MCF was 21.4%, 40.5%, and 33.3%, respectively. Alteration in in vitro activity against CGLA and remained active against most isolates of CGLA displaying an ECH-NWT phenotype with or without FKS alterations.RZF demonstrated potent Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), bioMerieux: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Abby Klauer, BS, Melinta: Grant/Research Support Lalitagauri M. Deshpande, PhD, Melinta: Grant/Research Support|Paratek: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


Aspergillus fumigatus (AFM) is a growing concern, mainly caused by mutations within CYP51 genes. The activity of ISC and other azoles against AFM causing IA worldwide was evaluated by applying the new CLSI ISC clinical breakpoints (BP).Isavuconazole (ISC) was approved by the US FDA and is considered first-line therapy for the treatment of invasive aspergillosis (IA). Azole resistance in n=282; 18 centers), Europe , Asia-Pacific , and Latin America  were identified by MALDI-TOF MS and/or sequencing and tested by CLSI broth microdilution. CLSI BP and epidemiological cut-off values were applied where available. Isolates displaying a non-wildtype (NWT) phenotype to at least 1 azole were submitted to CYP51 analysis by whole genome sequencing.A total of 846 AFM collected (1/patient) in 2017–2021 from 44 medical centers located in North America  showed similar activity to other azoles against AFM (Table), inhibiting 93.4% at ≤ 1 mg/L (CLSI-approved susceptible [S] BP). Voriconazole , itraconazole , and posaconazole  inhibited 91.6%, 92.0%, and 97.2% at their respective S or wildtype criteria. The AZ-NWT phenotype was detected in 88 AFM (10.4%); NA showed the highest frequency of AZ-NWT isolates , followed by EU  and AP . No AZ-NWT AFM was noted in LA. Azole activity varied against AZ-NWT isolates with and without CYP51 alterations. Applying CLSI BPs, 43.9% of the AZ-NWT AFM without CYP51 alteration remained S to ISC and 73.2% were S to VRC. ISC and VRC inhibited 46.7% and 43.3%, respectively, of AZ-NWT AFM isolates displaying CYP51 alterations other than L98H/TR34 at the respective BP. AFM isolates carrying L98H/TR34 (17 occurrences) in the CYP51A sequence displayed elevated MIC ranges for all azoles: ISC, 2– > 8 mg/L; VRC, 1– > 8 mg/L; ITC, 2– > 8 mg/L; and PSC, 0.5–4 mg/L.Overall, ISC , bioMerieux: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Abby L. Klauer, BS, Pfizer: Grant/Research Support Beth Hatch, BA MT(ASCP), Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


COVID-19 vaccines reduce the risk of symptomatic SARS-CoV-2 infection, but it is unclear the extent to which vaccines or prior infection reduce the risk of infection in high transmission settings like households.We screened individuals who tested positive for SARS-CoV-2 (index cases) recruited at 7 sentinel testing sites and through a nationwide effort during Sep 2021–Apr 2023. Index cases and their households (HH) were enrolled ≤6 days after the index case’s illness onset. Household contacts (HHC) had daily self-collected nasal swabs or saliva samples tested by RT-PCR for SARS-CoV-2. We determined COVID-19 vaccination status by plausible self-report (with date) or vaccination records, and prior SARS-CoV-2 infection by self-reported prior positive test (with year) or anti-nucleocapsid antibodies assessed at enrollment. We considered HHC with prior COVID-19 and ≥2 COVID-19 vaccine doses as having “hybrid immunity”, and assessed the effects of ≥2 vaccine doses, prior COVID-19, or hybrid immunity on the risk of PCR-confirmed SARS-CoV-2 infection among HHC by GEE Poisson regression adjusted for age of the HHC, recruitment strategy, household density (ppl/bedroom), and enrollment month.We included 1,324 HHC ; 73% enrolled May–Nov 2022, when Omicron BA.4/5 predominated; 28% were aged < 18 years (Table 1). Most (89%) had some immunity to COVID-19: 54% from vaccination only, 7% from infection only, and 26% from hybrid immunity. Most HHC without immunity to SARS-CoV-2 were children (64%). Of HHCs, 61% became SARS-CoV-2 positive during follow-up. In a model that accounted for all sources of immunity (figure 2), prior vaccination or prior infection alone did not provide significant protection, only HHC with hybrid immunity had significantly reduced risk of infection . The risk of infection was lowest (43%) when the HHC’s last immunizing event (vaccination or infection) occurred ≤6 months before the index case’s illness onset.Eligibility and inclusion of HH contacts in analysis of COVID-19 transmissionFigure 1Table 1Demographic characteristics of HH contacts by COVID-19 vaccination or prior COVID-19Figure 2Adjusted relative risk of infection among HH contacts by COVID-19 vaccination or prior COVID-19The risk of SARS-CoV-2 infection among HHCs continues to be high. While vaccination alone was not effective at preventing SARS-CoV-2 infection, HHCs with hybrid immunity from recent vaccination or prior infection had the lowest risk of infection.Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support


Acinetobacter baumannii-calcoaceticus complex (CRABC) is recognized as an urgent/critical antimicrobial resistant threat by the Centers for Disease Control and Prevention and World Health Organization. The development of new antibiotics targeting CRABC is an urgent unmet medical need that Roche is tackling through development of a novel antimicrobial compound . A significant challenge for the planned pathogen-focused clinical trial is the need to rapidly identify eligible patients with CRABC infections. Here, we describe a prototype assay for the rapid detection of CRABC causing HAP/VAP or bloodstream infections (BSI).Carbapenem-resistant A. baumannii- calcoaceticus complex (ABC) organisms harboring the most prevalent associated carbapenemases genes . This work entailed the assay design and optimization for use on the automated, high-throughput (HTP) cobas® 5800/6800/8800 Systems, including primers/probes, sample processing, and result interpretation for three sample types . The assay utilizes the commercially available cobas omni Utility Channel Kit, a defined oligo pool, controls, and an off-instrument analysis package. Assay inclusivity, exclusivity, limit of detection (LoD), and specificity were evaluated using archived or contrived clinical specimens.This prototype assay was developed for the qualitative detection of in silico and wet lab testing. Using preliminary interpretive cutoffs, high specificity (100%) was observed with negative clinical samples  and LoDs of 5280 (95% CI: 4010-9166), 6180 (95% CI: 4548-11285) and 1250 CFU/mL (95% CI: 1050-1750) were observed for BAL, sputum and positive blood culture, respectively.The CRABC prototype assay had 100% inclusivity for ABC and claimed resistance markers and 100% exclusivity for other bacteria commonly found in respiratory or positive blood culture samples based on cobas® 5800/6800/8800 Systems could be adopted to rapidly identify patients with CRABC-associated HAP/VAP or BSI for enrollment in a pathogen-focused clinical trial.This CRABC prototype assay for use on the automated, HTP Natacha Martins Sorenson, PhD, Roche: Grant/Research Support Hai Nguyen, n/a, Roche: Grant/Research Support Arrash Moghaddasi, n/a, Roche: Grant/Research Support Aishwarya Sathish, n/a, Roche: Grant/Research Support Indira Somanathan, n/a, Roche: Grant/Research Support Letong Jia, n/a, Roche: Grant/Research Support Patrick Lin, n/a, Roche: Grant/Research Support Xun Zhuang, PhD, Roche: Grant/Research Support Colin Lam, n/a, Roche: Grant/Research Support Brian Lee, MD, GE Healthcare: Stocks/Bonds|Invitae: Stocks/Bonds|Merck: Stocks/Bonds|OPKO Health: Stocks/Bonds|Roche Diagnostics: Employment|Roche Diagnostics: Stocks/Bonds|Spero Therapeutics: Stocks/Bonds Kyle C. Cady, PhD, Roche: Grant/Research Support|Roche: Stocks/Bonds


While BPR does not have clinically relevant activity against Enterococcus faecium, BPR is active against E. faecalis, an opportunistic bacterial pathogen of increasing clinical relevance and a significant cause of infective endocarditis. This study evaluated the activity of BPR and comparator agents against E. faecalis isolated from patients hospitalized in US medical centers.Ceftobiprole (BPR) is an advanced-generation cephalosporin that has E. faecalis isolated from 34 US medical centers (2016–2020) were included. Isolates collected were responsible for bloodstream infections (40.8%), urinary tract infections (23.4%), skin and skin structure infections (22.0%), and other infection types (13.9%), including bone and joint infections , diabetic foot infections , and endocarditis . Isolates were tested for susceptibility using the CLSI broth microdilution method and MIC interpretations followed CLSI criteria. For BPR, the PK/PD non–species-related breakpoint of ≤4 mg/L was used.A total of 1,834 E. faecalis at ≤4 mg/L, whereas the comparator agents, ampicillin (AMP), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN), inhibited between 97.0% to 100% of all isolates at their respective breakpoints. A total of 3% of all E. faecalis isolates were VAN resistant. BPR had similar MIC90 results of 2 mg/L and 4 mg/L when tested against VAN-susceptible and -resistant isolates, respectively. AMP, DAP, and LZD were also active against VAN-susceptible and -resistant E. faecalis. All (100%) isolates causing difficult-to-treat infections, such as bone/joint and diabetic foot infections and infective endocarditis, were inhibited by BPR at ≤4 mg/L in addition to AMP, DAP, and LZD at their respective breakpoints.BPR inhibited 99.3% of all E. faecalis in US hospitals, including isolates causing difficult-to-treat infections.These data suggest that BPR represents a potential option for empirical and guided treatment of infections caused by Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Leonard R. Duncan, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Helio S. Sader, MD, PhD, FIDSA, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Mark E. Jones, PhD, Astellas Pharma Global Development, Inc: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


Patients with cancer are at increased risk for severe and lethal COVID-19, compared to the general population. Currently, with no anti-spike monoclonal antibodies available against circulating variants of SARS-CoV-2, the logistic limitations of outpatient remdesivir infusions, and lack of efficacy of molnupiravir in vaccinated patients, nirmatrelvir/ritonavir (Paxlovid™) is the only effective oral therapy for outpatient use against COVID-19. However, its efficacy specifically in immunocompromised patients, including patients with cancer, has not been adequately studied.In this pilot analysis, we retrospectively studied the records of patients with history of or active cancer at Brown University-affiliated hospitals diagnosed with SARS-CoV-2 after Emergency Use Authorization  of Paxlovid™, and until 2022-07-21. Patients not meeting EUA criteria or receiving other outpatient antivirals were excluded . The primary outcome was 90-day COVID-19-attributed mortality, with 90-day all-cause mortality and hospitalization as secondary outcomes. Patients who died within 90 days from other causes were excluded from COVID-19-attributed mortality analyses.Figure 1.Flow diagram illustrating patient selection.33 of 85 eligible patients were excluded . Of the 52 remaining, 26 received Paxlovid™. Baseline demographic and clinical characteristics were well-balanced between the two groups (Table 1). 50% were male, one was Black, five were Hispanic (10%); median age was 68 (interquartile range [IQR] 56-77) years; most patients (61.5%) had received 3 or more vaccine doses prior to infection. Paxlovid™ use was associated with numerically lower all-cause mortality rate (8% vs. 23%), and significantly lower rates of 90-day COVID-19-attributed mortality , and hospitalization .Table 1.Baseline characteristics and clinical outcomes.Figure 2.Kaplan-Meier survival curves.Paxlovid™ use was associated with a strong signal for improved clinical outcomes among patients with cancer and COVID-19, compared to similar contemporary controls, most of whom were fully vaccinated. Larger studies of Paxlovid™ use and efficacy in high-risk patients with cancer and other immunocompromised individuals are needed and ongoing.Panos Arvanitis, MS, NIH: Grant/Research Support|NIH: Brown University Summer Assistantship program and from the Brown Emerging Infectious Disease Scholars (EIDS) (5R25AI140490) Jeremy L. Warner, MD, MS, AACR: Grant/Research Support|Flatiron Health: Grant/Research Support|Melax Tech: Advisor/Consultant|NIH: Grant/Research Support|Roche: Advisor/Consultant|Westat: Advisor/Consultant Dimitrios Farmakiotis, M.D., Astellas: Grant/Research Support|Merck: Grant/Research Support|Viracor: Advisor/Consultant|Viracor: Grant/Research Support


Nirsevimab is an extended half-life monoclonal antibody (mAb) newly authorized for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in infants born during or entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe disease through their second season. Anti-RSV mAbs are currently assessed based on their direct virus neutralization activity in the absence of a well-established correlate of protection. We explored trends in anti-RSV neutralizing antibody (nAb) levels in participants dosed with nirsevimab, or palivizumab, the standard of care during the MEDLEY trial (NCT03959488).. Participants provided blood samples at baseline and during site visits on Day (D) 31, 151, and 361 of their respective seasons. nAb levels were determined using a fluorescent focus-based microneutralization assay. Pharmacokinetic (PK) modeling was used to predict peak and trough palivizumab nAb levels.nAb levels following dosing with nirsevimab or palivizumab were evaluated in infants born preterm (for season [S] 1) or with chronic lung disease or congenital heart disease (CLD/CHD) across two RSV seasons (S1/2) Fig 2. As expected, nAb levels in S1-nirsevimab recipients were highest in samples collected during the first visit, D31, and declined over S1, but were still > 16-fold above baseline at D361 . nAb levels in S1-palivizumab recipients increased incrementally and were highest in samples obtained at the D151 visit. nAb levels at D151 were ∼10-fold higher with S1-nirsevimab compared with S1-palivizumab. S1 D361 (baseline S2) nAb levels among participants who received palivizumab in S1 fell towards the assay’s lower limit of detection . Overall patterns in nAb levels in S2 were similar to those in S1. S1-palivizumab/S2-palivizumab recipients had ∼10-fold lower levels of nAbs over the S2 PK model-predicted time course to D151 compared with participants receiving S2-nirsevimab.The dynamics of nAb levels during the trial are depicted in Nirsevimab is associated with ∼10-fold higher and sustained levels of nAbs through 1 year post dose compared with palivizumab, suggesting nirsevimab may offer protection for a period beyond a typical 150-day RSV season.Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Ulrika Wählby Hamrén, PhD, AstraZeneca: Patent holder re. dosing|AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Yue Chang, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Joseph B. Domachowske, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support Janet A. Englund, MD, AbbVie: Advisor/Consultant|Ark Biopharmaceutical: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Meissa Vaccines: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant William J. Muller, MD, Ansun Biopharma: Grant/Research Support|Astellas Pharma: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|DiaSorin Molecular LLC: Advisor/Consultant|Eli Lilly and Company: Grant/Research Support|Enanta Pharmaceuticals: Grant/Research Support|F. Hoffmann-La Roche: Grant/Research Support|Finley Law Firm, P.C.: Expert Testimony|Gilead Sciences: Grant/Research Support|Invivyd: Advisor/Consultant|Janssen Biotech: Grant/Research Support|Karius, Inc.: Grant/Research Support|Melinta Therapeutics, Inc.: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Nabriva Therapeutics plc: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur LLC: Advisor/Consultant|Tetraphase Pharmaceuticals, Inc.: Grant/Research Support Amanda Leach, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tonya L. Villafana, PhD, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Elizabeth J. Kelly, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds


COVID-19 has been associated with a very high mortality in patients having received CAR T cell treatment for hematological malignancies. The aim of this study was to investigate whether the outcome has improved over time.This is a retrospective analysis of prospective data collected into the EBMT registry regarding risk factors, clinical features, and outcome of patients having received CAR T cell therapy for hematological malignances diagnosed with SARS-CoV-2 infection between March 2020 and December 2022. SARS-CoV-2 was diagnosed by PCR and from January 2021 also antigen tests were accepted. All patients gave informed consent to data collection. The study was approved by the Swedish National Ethical Review Board and by local IRBs as required.182 patients were included in the analysis; 39 diagnosed in 2020, 35 in 2021, and 108 were diagnosed in 2022. 152 patients were treated for B-cell lymphoma, 19 for acute lymphoblastic leukemia, and 11 for plasma-cell disorders. The median age at COVID-19 diagnosis was 58.7 ys (7.2 - 78.4). The median time from CAR T cell infusion to COVID-19 diagnosis was 7.0 months (1.0 - 42.5). 28% of the patients had lower respiratory tract disease at diagnosis. 27 (25.8%) of patients had received three or more vaccine doses and only 2.2% had received pre-exposure tix/cil. 45.1% required hospitalization, 33.4% required oxygen, and 17% was admitted to ICU. COVID-19 attributable mortality over the entire period was 18.1% with significant improvement over time .Survival after COVID-19 diagnosisAlthough the COVID-19 attributable mortality has decreased over time, it remains several times higher than what can be expected in an healthy population of comparable age. Therefore, preventive measures need to be maintained for this vulnerable patient group..Per Ljungman, MD; PhD, AlloVir: Grant/Research Support|Gilead: Honoraria|Moderna: Honoraria|MSD: Honoraria|Takeda: Honoraria Rafael de la Camara, MD, AstraZeneca: Advisor/Consultant|Moderna: Advisor/Consultant|MSD: Advisor/Consultant Marie Jose Kersten, MD, PhD, BMS: Advisor/Consultant|BMS: Honoraria|Celgene: Advisor/Consultant|Celgene: Grant/Research Support|Celgene: Honoraria|Kite/Gilead: Advisor/Consultant|Kite/Gilead: Grant/Research Support|Kite/Gilead: Honoraria|Kite/Gilead: Travel|Miltenyi Biotech: Advisor/Consultant|Miltenyi Biotech: Honoraria|Miltenyi Biotech: Travel|Novartis: Advisor/Consultant|Novartis: Honoraria|Novartis: Travel|Roche: Advisor/Consultant|Roche: Grant/Research Support|Roche: Honoraria|Takeda: Grant/Research Support Stephan Mielke, MD, PhD, BMS: Honoraria|Celgene: Honoraria|Janssen: Honoraria|Kite/Gilead: Honoraria|Mendes: Honoraria|Miltenyi: Honoraria|Pfizer: Honoraria


PILLAR evaluates the feasibility and acceptability of implementation strategies for delivering long-acting Cabotegravir for PrEP (CAB LA) to men who have sex with men and transgender men in low and high-volume PrEP Sites across the United States. We report staff study participants’ (SSPs) baseline perceptions of implementation prior to study sites commencing enrollment and using implementation strategies.86 SSPs from 17 clinics completed surveys on implementation outcomes assessed using the acceptability of intervention measure (AIM) and feasibility of intervention measure (FIM), whose summary scores are averages of four items measured on a 5-point rating scale (1=completely disagree to 5=completely agree). Perceived barriers to CAB LA implementation were assessed via a 5-point rating scale . Results were compared by clinic volume of PrEP seeking individuals where high-volume sites (HVS) were defined as serving greater than 50 persons per month.Table 1 reports SSP demographics. SSPs reported high levels of feasibility and acceptability of implementing CAB LA (mean FIM=4.4 and mean AIM=4.7) and implementation support (mean FIM=4.1 and mean AIM=4.0) (Table 2). SSPs at low volume sites’ (LVS) had higher levels of feasibility and were more extremely positive about implementing CAB LA (71% vs. 34% ) compared to those at HVS.Top perceived barriers to delivering CAB LA, “moderately concerned” to “extremely concerned” SSP ratings included: medication cost (51%), patients’ ability to keep appointments (32%), patients’ willingness to travel for 2-monthly appointments (28%), ability to identify and flag missed injection visits (23%), and staff resourcing (20%) (Table 3). A higher proportion of HVS’ SSPs reported being concerned about these barriers. SSPs were least concerned about the gluteal medial injection, managing oral lead-in, the medication’s efficacy, and patients feeling stigmatized.At baseline, SSPs found CAB LA to be highly acceptable and feasible to implement into standard of care with notable differences by site volume. HVS may be more aware of PrEP introduction complexities than LVS. Support with benefits navigation, scheduling and managing missed injection visits is key for SSPs.Dima Dandachi, MD, MPH, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Bo Li, PhD, GSK: Employment|GSK: Stocks/Bonds Alison Gaudion, PhD, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Deanna Merrill, PharmD, MBA, AAHIVP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds David Andrae, PhD, Evidera: Employment William Lenderking, PhD, Evidera: Employment|Pfizer: Former Employment|Pfizer: Stocks/Bonds Riya Moodley, FCP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Annemiek de Ruiter, MBBS FRCP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Maggie Czarnogorski, MD MPH, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Nanlesta Pilgrim, PhD, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds


Norovirus (NoV) results in potentially severe, relapsing, remitting diarrhea in immunocompromised hosts (ICH). A number of interventions, including nitazoxanide (NTZ), have been tried with unclear success in managing cases of NoV in ICH.We conducted a NIH-sponsored multi-center, prospective, randomized, double-blind study of NTZ for the treatment of Norovirus in adult HSCT and SOT recipients between 2018 and 2021. Subjects with a positive Norovirus test within 14 days of enrollment and active GI symptoms were randomly assigned (1:1) to NTZ 500 mg twice daily or placebo (P) for 56 consecutives doses and were followed for 6 months, including patient reported outcomes (PRO) diary assessments. Primary endpoint was to determine the clinical efficacy, assessed as the time from randomization until symptoms resolution for at least 48 hours. Secondary endpoints included virologic efficacy assessed as the time from randomization to first negative viral load and safety through frequency of adverse events.31 subjects  were enrolled and had balanced demographics (See Table 1). Early withdrawal was documented in 5 subjects from each group. Thirty (30) had received solid organ transplants. Most had chronic ( > 14 days) symptoms (77%). In the mITT population, the median time to initial clinical resolution was 19.0 days  for the Nitazoxanide group and 11.0 days  for the placebo group . The difference between time to first negative viral load for the Norovirus GII genotype was not significant . Patients appear to have clinical improvement based on PRO results while on active therapy. No serious adverse event related to the study treatment was documented. One severe unsolicited adverse event, abdominal pain, was reported on the day of first dose NTZ. Hospitalization and non-serious or laboratory adverse events were not significantly different between the two arms. Analysis of PK and viral genetics is ongoing and will be reported at the meeting.NTZ did not shorten time to clinical resolution or viral shedding duration but may have resulted in transient symptom improvement. Although NTZ appears safe, its role is likely limited in the setting of chronic NoV among ICHs.Daniel Kaul, MD, Medscape: Honoraria|Nobelpharma: Grant/Research Support|Takeda: Grant/Research Support Robin K. Avery, MD, Aicuris: Grant/Research Support|Astellas: Grant/Research Support|Astra-Zeneca: Grant/Research Support|Chimerix: Grant/Research Support|Merck: Grant/Research Support|Oxford Immunotec: Grant/Research Support|Qiagen: Grant/Research Support|Regeneron: Grant/Research Support|Takeda: Grant/Research Support Ajit Limaye, Professor/MD, MedPace: DSMB member|merck: Advisor/Consultant|merck: Grant/Research Support|moderna: Advisor/Consultant|moderna: site investigator|syneos: DSMB member Steven A. Pergam, MD, MPH, Cidara: Investigator in clinical trials|F2G: Investigator in clinical trials|Global Life Technologies: Grant/Research Support|Symbio: Investigator in clinical trials Michael D. Green, MD, MPH, ADMA: Advisor/Consultant|Allovir: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|ITB-MED: Advisor/Consultant Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support Lara A. Danziger-Isakov, MD, MPH, Aicuris: Contracted Clinical Research|Ansun Biopharma: Contracted Clinical Research|Astellas: Contracted Clinical Research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted Clinical Research|Pfizer: Contracted Clinical Research|Roche Diagnostics: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Contracted Clinical Research Michael P. Angarone, DO, Abbvie Pharmeciuticals: Advisor/Consultant|DKBMed Inc: Advisor/Consultant|DKBMed Inc: Honoraria


Infants ≤ 90 days old are at increased risk of severe disease from both viral and bacterial pathogens. Differentiating between these two etiologies has long presented a diagnostic challenge and has resulted in many risk algorithms to determine which infants are infected by bacteria and require antibiotics. The increased availability of rapid molecular diagnostics presents an opportunity to refine these algorithms. While the prevalence of urinary tract infection in the presence of a respiratory virus has been described, large-scale studies with comprehensive viral testing describing the prevalence of invasive bacterial infection (IBI), defined as bacteremia or bacterial meningitis, are lacking.The CDC’s New Vaccine Surveillance Network (NVSN) enrolls children < 18 years old with acute respiratory illness in the emergency department or inpatient setting of 7 hospitals. Upper respiratory specimens are collected and tested for respiratory viruses by real-time PCR. In this analysis respiratory viral positivity is described in febrile and non-febrile infants ≤ 90 days old. We then compared the prevalence of IBI  among febrile infants with and without a respiratory virus detected. IBIs were defined as a positive blood or CSF culture with bacteria unlikely to be a contaminant.n=2,138 febrile, n=1,593 non-febrile) were enrolled. Respiratory viral positivity was 68% for febrile infants and 78% for non-febrile infants. Among febrile infants, 68%  had either a blood or CSF culture obtained; 3% (n=41) had an IBI. Febrile infants in whom a respiratory virus was detected, were significantly less likely to have an IBI (OR: 0.26 [95% CI: 0.13–0.52]) than febrile infants with negative viral testing (Table).From December 2016 to March 2020, 3,731 infants . These findings may help develop future risk algorithms for bacterial infection in febrile infants aged ≤90 days aiming to decrease unnecessary antibiotic use in this population.Erin G. Nicholson, MD, MS, Blue Lake Biotechnology Inc.: Grant/Research Support|Novavax: Advisor/Consultant Pedro A. Piedra, MD, Ark Bioscience: Advisor/Consultant|Ark Bioscience: Grant/Research Support|GSK: Grant/Research Support|Icosavax: Advisor/Consultant|Icosavax: Grant/Research Support|Mapp Biologics: Grant/Research Support|Meissa Vaccines: Grant/Research Support|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Novavax: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Takeda: Advisor/Consultant Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant John V. Williams, MD, Merck: Grant/Research Support|Quidel: Board Member Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support Geoffrey A. Weinberg, MD, Merck & Co: Honoraria Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support


Invasive fungal infections (IFI) in Asia/Pacific are a threat to patients with malignancies, uncontrolled diabetes mellitus or undiagnosed/untreated human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). Adequate and early access to diagnostic tools and antifungals is essential for the IFI clinical management and patient survival.www.clinicalsurveys.net/uc/IFI_management_capacity/. The survey aimed to collect the following dimensions: a) institution profile, b) perceptions on IFI in the respective institution, c) microscopy, d) culture and fungal identification capacity, e) serology, f) antigen detection, g) molecular tests availability, and h) therapeutic drug monitoring.The IFI diagnostic capacity survey was online accessible at As of June 2022, 235 centres from 40 countries/territories in Asia/Pacific answered the questionnaire. More than half of them were from six countries: India (25%), China (17%), Thailand (5%), Indonesia, Iran, and Japan . Candida spp. (93%) and Aspergillus spp. (75%) were considered the most relevant pathogens. Most institutions had access to microscopy (98%) or culture-based approaches (97%). Furthermore, 79% of them had access to antigen detection, 66% to molecular assays, and 63% to antibody tests. Access to antifungals varied between countries/territories. At least one triazole was available in 93% of the reporting sites (voriconazole [89%] was the most common mould-active azole), whereas 80% had at least one amphotericin B formulation, and 72% at least one echinocandin.Currently, based on the provided replies, the resources available for the IFI diagnosis and management vary in Asia/Pacific countries/territories. Economical or geographical factors may play a key role in the incidence and clinical handling of this disease burden. Regional cooperation may be a good strategy to overcome shortcomings.Martin Hoenigl, n/a, Astellas: Grant/Research Support|Euroimmun: Grant/Research Support|F2G: Grant/Research Support|Gilead: Grant/Research Support|Immy: Grant/Research Support|MSD: Grant/Research Support|Mundipharma: Grant/Research Support|Pfizer: Grant/Research Support|Pulmocide: Grant/Research Support|Scynexis: Grant/Research Support Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds


Nirmatrelvir with ritonavir (nirmatrelvir/r) is an oral antiviral treatment for COVID-19. EPIC-high risk (HR) was a Ph 2/3 double-blind, randomized, placebo (PBO)-controlled trial to evaluate nirmatrelvir/r in symptomatic, unvaccinated, nonhospitalized patients (pts) with ≥ 1 risk factor for progression to severe COVID-19. EPIC-standard risk (SR), a similarly designed trial enrolled pts with no risk factors, and fully vaccinated pts with ≥ 1 risk factor. An integrated analysis of treated pts with risk factors, including unvaccinated pts from EPIC-HR and vaccinated pts from EPIC-SR has been conducted.Eligible adults from EPIC-HR and EPIC-SR with confirmed SARS-CoV-2 were randomized 1:1 within 5 days (d) of symptom onset to receive nirmatrelvir/r 300 mg/100 mg or PBO every 12 hrs for 5 d. Efficacy of nirmatrelvir/r was compared with PBO for COVID-19-related hospitalization or death from any cause through day 28. Other endpoints, including number of medical visits/hospital days and quantification of SARS-CoV-2 viral RNA load in nasopharyngeal swabs, and TEAEs through day 35 were evaluated.Nirmatrelvir/r reduced COVID-19-related hospitalization or death due to any cause by 83%  compared to the PBO . The rate of hospitalization or death was lower among sero+ or vaccinated pts, however, nirmatrelvir/r treatment was associated with a substantial risk reduction among sero+ EPIC-HR pts (87.9% RRR), vaccinated EPIC-SR pts (57.6% RRR), or pts who were either vaccinated or sero+ (73.8% RRR) . These observations were regardless of age, gender, BMI, coexisting conditions, baseline serology status, viral RNA load and vaccination status . On average, pts treated with nirmatrelvir/r spent significantly fewer days in hospital and had significantly fewer medical visits compared with PBO. Nirmatrelvir/r treated pts had significantly greater reductions in viral RNA load from baseline to day 5 than PBO. Rates of all-causality TEAEs were similar between treatment groups and most were mild to moderate in severity.The efficacy and safety of nirmatrelvir/r was demonstrated in vaccinated and unvaccinated pts at high risk as well as in pts with serologic evidence of prior exposure to COVID-19.Heidi Leister-Tebbe, BSN, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Weihang Bao, PhD, Pfizer, Inc.: Employee of Pfizer|Pfizer, Inc.: Stocks/Bonds Robert Fountaine, PharmD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Mary Lynn Baniecki, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Victoria Hendrick, BSc, Pfizer: Employee|Pfizer: Stocks/Bonds Wayne Wisemandle, MA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jennifer Hammond, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds James Rusnak, MD, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds


C. difficile. In this study, we evaluated whether inclusion of microbiome characteristics improved a clinical prediction model for in-hospital mortality.Characteristics of the gut microbiome may be useful to predict resistance to colonization and expansion of pathogenic organisms such as Rectal or fecal swab samples were collected daily from medical intensive care unit (ICU) patients from three hospitals between 2017-2019 and underwent 16S rRNA gene sequencing of the V4 region. Patient admissions with ≥1 rectal swab collected < 48hrs from ICU admission were randomly selected 2:1 for calibration and validation analyses. Independent variables included Shannon Index, Microbiome Health Index, Community Type (CT) and relative abundance (RA) of specific bacterial taxa based on 3% sequence difference or class-level classification. The RA of each bacterial taxon was range-standardized (95%) and scaled to analyze a 10% relative difference within each taxon’s range. Logistic regression models identified microbiome characteristics at admission that were associated with in-hospital mortality. Fixed effects were included in all models to account for microbiome differences between facilities.Table), of which 134  died during hospitalization. Increase in Shannon Index by 1 , 10% relative increase in the RA of Bacilli  and 10% relative increase in the RA of Enterococcus  were associated with in-hospital mortality in calibration models after controlling for Charlson Comorbidity Index . Increase in Shannon Index by 1  had the same direction and similar odds in the validation cohort , supporting the findings of the calibration model.There were 1365 patient admissions  analyzed (In this secondary analysis of a large, multicenter, prospective medical ICU cohort, we found that higher alpha diversity of the gut microbiome was associated with decreased odds of in-hospital mortality.Michael Z. David, MD PhD, Covance: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support Vincent B. Young, MD/PhD, ASM: Senior Editor|Debiopharm: Advisor/Consultant|Vedanta Biosciences: Advisor/Consultant


The WHO estimated that in 2022 49% of people affected by Mpox were PLWH. Due to initial vaccine shortage in 2022, a 1/5 dose of vaccine given intradermally (ID) was FDA-authorized (8/9/22). The ID regimen had never been evaluated in PLWH. Here we describe the characteristics, and IgG responses of Mpox vaccination in PLWH and HIV-negative participants.We are conducting a longitudinal, observational study of adults with and without HIV who received the JYNNEOS vaccine or had Mpox infection in NYC. Clinical, demographic information, and Mpox H3L-specific serum IgG titers are assessed.145 participants are enrolled: 25% are PLWH (median CD4 685 cells/mm3), 14% had Mpox disease and 21% had prior smallpox vaccination. 71% with Mpox disease were PLWH. The cohort is racially/ethnically diverse, mostly men (81%) and LGBTQ+ (90%). A third of the participants were recruited from NYC DOHMH pop-up vaccination site (34%), followed by peer or professional referral (20% & 19%). Routes of vaccination were: SC-ID (49%), ID-ID (21%), SC-SC (20%), and ID-SC (10%). Redness (37%) & swelling (21%) at site of injection were common reactions. Prior smallpox vaccination was associated with higher and sustained IgG titers even after one vaccine dose. Excluding such participants, antibody titers start declining post-dose 2 . There was no difference in IgG titers at 3 months post-dose 2 between PLWH and HIV-negative for ID or any other route. Titers at 3 months post-dose 2 in PLWH correlated with CD4 counts. Longer interval between the two doses contributed to higher titers. Mpox infection yielded to significantly higher titers than vaccination post-dose 1, but no after 2 doses.Our study highlights the disproportionate burden of Mpox infection on PLWH. A diverse population representative of those most affected by 2022 Mpox was recruited. The vaccine, whether ID or SC, was well tolerated in PLWH and HIV-negative. More than two-thirds of participants with Mpox disease were PLWH. Individuals with prior smallpox vaccination maintain strong antibody levels post-dose 2, however, levels decline in individuals with no anterior prime. Our preliminary results show no negative impact of the ID dose regimen on antibody levels in PLWH.Ellie Carmody, MD, MPH, AstraZeneca: Stocks/Bonds|Merck: Stocks/Bonds Lalitha Parameswaran, MD, MPH, Pfizer: Grant/Research Support Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support


Microbial cell-free DNA (mcfDNA) sequencing is a promising potential tool in the detection of infectious pathogens when traditional methods fail to identify the causative agent. It may be particularly helpful in identifying pathogens that are present at low levels or that do not grow well in standard culture. The aim of this study was to determine whether plasma mcfDNA sequencing resulted in a change in therapeutic management.th, 2019, and January 4th, 2023, were included. Patient demographics, comorbid conditions, immunocompromised status, indication for testing, pre and post antimicrobial therapies from when the sample was collected, pathogen identified, ID consultation status, and ordering service at the time of testing were recorded. Each patient was analyzed by two independent reviewers for clinically significant microbial findings, treatment, and reviewer concordance with therapeutic management. If discordance between reviewers was present, a third reviewer analyzed the data.A retrospective cohort at UC Davis Medical Center was reviewed. All patients, both pediatric and adult, that underwent plasma mcfDNA (Karius) sequencing between December 11A total of 127 Karius tests were reviewed from 71 patients. Baseline characteristics included 62 (48%) pediatric and 65 (51%) adult tests. 25 (33%) tests were from female patients, and 37 tests (50%) were obtained from immunocompromised patients. The most frequent adult ordering services included the Medical Intensive Care Unit and Bone Marrow Transplant Unit. The most frequent pediatric ordering services included the Pediatric Intensive Care Unit followed by General Pediatrics. 69 (95%) of tests had a formal Infectious Diseases consultation associated with testing. 22 (30%) tests resulted in a change in antimicrobial therapy, and 35 (47%) of tests resulted in a clinically significant organism.In this retrospective cohort study conducted at a single center, Karius testing resulted in clinically significant pathogens in less than half of all tests conducted, and most test results did not lead to a change in therapeutic management. Testing in certain clinical scenarios or high-risk settings may be warranted, however further studies are needed.George R. Thompson, III, MD, Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mayne: Advisor/Consultant|Mayne: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support


In the 2022 Mpox outbreak, the US FDA issued an EUA for a low-dose intradermal (ID) vaccination regimen to increase vaccine supply by five-fold. The ID regimen had yet to be evaluated for immunogenicity or tolerability in persons with HIV or for general acceptability.We conducted a Knowledge, Attitudes and Practices survey to evaluate ID Mpox vaccine acceptability, comparing responses between participants with and without HIV and by route received.Of 119 ethnically and racially diverse respondents, 83% identified as male, 91% as LGBTQ+, median age was 38 years. 26% had HIV. 21% received ID/ID, 57% mixed subcutaneous (SC)/ID or ID/SC, and 18% SC/SC regimens. Vaccination route was similarly distributed across age, race, ethnicity, educational status, household income and HIV status. Knowledge of Mpox vaccines was moderate, with a mean of 4.36 of 7 responses correct. 62% were satisfied with Mpox vaccine rollout and 20% were neutral. 77% agreed that they trusted information received about the Mpox ID route by healthcare providers. Respondents with HIV were less likely to fully support the policy change to the ID route to stretch vaccine supply (Mann-Whitney p=0.039), but otherwise there were no significant differences between respondents with and without HIV in satisfaction with Mpox vaccine rollout, trust in vaccine-related information, confidence about ID regimen’s safety, efficacy, concern about cosmetic side effects, or overall acceptability. There were no significant differences between respondents by vaccination regimen in satisfaction with vaccine rollout, approval of the change toward ID formulation, concern about cosmetic side effects or overall acceptability. Compared to those who received mixed or ID/ID dosing regimens, SC/SC participants exhibited less confidence in efficacy of the ID formulation  and lower trust in information received by the US government about the ID formulation (p=0.01). Overall, 88% scored their Mpox vaccination experience as “excellent or very good,” and there was no difference between groups.Survey responses from this clinical study sample suggest high acceptability of the ID regimen for Mpox vaccination in all groups, including among people with HIV and those who had received this regimen.Ellie Carmody, MD, MPH, AstraZeneca: Stocks/Bonds|Merck: Stocks/Bonds Lalitha Parameswaran, MD, Pfizer: Grant/Research Support Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support


Due to a publishing error the article: “Stem cell-derived exosomes from human exfoliated deciduous teeth promote angiogenesis in hyperglycemic-induced human umbilical vein endothelial cells”, published at Journal of Applied Oral Science 31(e-20220427):1-13. doi: 10.1590/1678-7757-2022-0427 was printed with the following error:Where it reads:AcknowledgmentsThe authors thank Natthapatt Sooppapipatt, Pitchaporn Teacharushatakit, Wifada Powattanasuk, and Chareerut Phruksaniyom for their technical assistance. Moreover, the authors thank Enago (www) for the English language review.The sentence should read:AcknowledgmentsThe authors thank Natthapatt Sooppapipatt, Pitchaporn Teacharushatakit, Wifada Powattanasuk, and Chareerut Phruksaniyom for their technical assistance. Moreover, the authors thank Enago (www) for the English language review.This research work is supported by Mahidol University .


Respiratory viral infections (RVIs) are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon beta (IFN-β) is key in host defence against viruses but can be suppressed by virus or host factors locally at the site of infection. Inhalation of SNG001 (IFN-β-1a nebuliser solution) aims to restore lung IFN-β levels. SG015 (NCT03570359) was a randomized, placebo-controlled Phase 2 clinical study of inhaled SNG001 conducted in COPD patients. Here we describe lung antiviral biomarker and sputum viral clearance data from Part 2 of the study which was conducted in patients with a confirmed RVI.109 COPD patients with worsening symptoms and a positive respiratory viral test were randomized 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B . Sputum samples were collected on days 1, 4, 7, 10, 13, 17 and 28 for analysis of lung antiviral biomarker responses (interferon-stimulated genes (ISGs): Mx1, OAS1 and CXCL10) and lung viral load by RT-qPCR.post-hoc analysis was therefore conducted in the subgroup of patients who had detectable rhinovirus viral load in sputum. By Day 4 the proportion of patients receiving SNG001 who had detectable rhinovirus reduced to 40.0% , with a further reduction to 20.0% on Day 7 .Mx1 and OAS1 sputum cell gene expression were significantly upregulated on day 7, 10 and 13 (p< 0.05) overall and in Groups A and B with SNG001 treatment compared to placebo. CXCL10 sputum cell gene expression was significantly upregulated in the overall population with SNG001 treatment compared to placebo on days 7 and 10, in Group B on days 7, 10 and 13, and there was no significant difference in Group A. Patients had a broad range of RVIs, the most common being human rhinovirus. A Inhaled SNG001 upregulated lung antiviral defenses as assessed using sputum cell biomarker responses and accelerated viral clearance, supporting the proposed mechanism of action as an antiviral treatment for severe viral lung infections.Phillip D. Monk, PhD, Synairgen Research Plc: Employee of Synairgen Research Plc and has options on shares|Synairgen Research Plc: Stocks/Bonds Jody L. Brookes, BSc, Synairgen Research Ltd: Share options Victoria J. Tear, PhD, Synairgen Research Ltd.: Stocks/Bonds Marcin Mankowski, MD MFPM (Dis), Multiple companies: Advisor/Consultant|Synairgen: Advisor/Consultant Michael G. Crooks, MBChB (hons), MD, FRCP, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|Chiesi: Advisor/Consultant|Chiesi: Honoraria|Gilead: Honoraria|Synairgen: Advisor/Consultant Dave Singh, MD, AstraZeneca: Advisor/Consultant|Chiesi: Advisor/Consultant|gsk: Advisor/Consultant|Novartis: Advisor/Consultant|Orion: Advisor/Consultant|Pulmatrix: Advisor/Consultant|Sanofi: Advisor/Consultant|Synairgen: Advisor/Consultant|Synairgen: Grant/Research Support|Therevance: Advisor/Consultant Rekha Chaudhuri, MD, AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|Chiesi: Honoraria|GSK: Honoraria|Novartis: Honoraria|Sanofi: Honoraria|Teva: Honoraria Sarah Dudley, N/A, PhD, Synairgen Plc: Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc|Synairgen Plc: Stocks/Bonds Felicity Gabbay, MbChb, Synairgen: Board Member Stephen T. Holgate, FMedSci, MD, Synairgen Research Plc: Board Member|Synairgen Research Plc: Stocks/Bonds Ratko Djukanovic, MD, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Honoraria|KyMab: Advisor/Consultant|Sanofi: Advisor/Consultant|Synairgen: Advisor/Consultant|Synairgen: Stocks/Bonds Tom Wilkinson, PhD, PhD, Synairgen: Advisor/Consultant|Synairgen: Grant/Research Support|Synairgen: Honoraria


E. faecium) over a six-month period at a quaternary children’s hospital.Vancomycin-resistant enterococcus (VRE) colonization and infection is an increasing threat in pediatric oncology and bone marrow transplant (BMT) patients. We identified a cluster of 13 hospitalized patients who acquired VRE (An outbreak response was coordinated among Infection Prevention & Control (IP&C) and leadership of affected units. We defined a case as a hospitalized patient with new VRE colonization or infection beginning in April 2022. We reviewed electronic medical records of case patients and IP&C practice adherence on their service units, including biweekly VRE stool screening on BMT. Whole genome sequencing (WGS) was performed on all cluster isolates and pairwise single nucleotide polymorphisms (SNPs) were calculated. Three additional VRE isolates obtained at our institution within a 1-year period before the cluster were processed for comparison.From April 14 to October 21, 2022, 7 VRE healthcare-associated infections and 6 colonization events were identified on BMT and Oncology. Healthcare worker (HCW) hand hygiene (HH) adherence based on World Health Organization’s 5 moments was >95%, but supplemental observations during the outbreak period noted HH adherence of 70%. Personal protective equipment (PPE) adherence based on Centers for Disease Control and institutional requirements was 70-80% depending on the observed element. On BMT, VRE screening was completed on 33% of patients during admission; screening is not performed on Oncology. Although there was temporo-spatial overlap in some cases, no clear epidemiologic links were found. However, phylogenetic analysis revealed 11/13 (85%) isolates were closely-related . Improvement opportunities were shared with BMT and Oncology and no further VRE cases were identified.All VRE isolates sequenced and analyzed. Thirteen cluster isolates (VRE03 and VRE05-16) are starred (*). Three comparison isolates  are not starred. Abbreviations: Onc = Oncology, POA = present on arrival; HAC = hospital-acquired colonization; HAI = hospital-acquired infection.Phylogenetic analysis of 16 VRE isolates (13 cluster and 3 comparison) obtained in our institution (highlighted in red) compared with multiple reference VRE isolates. Eleven of thirteen cluster isolates (VRE03 and VRE07-VRE16) were revealed to be closely-related. Of note, VRE06 was so genetically dissimilar from the other cluster and comparison isolates, it was removed from this figure.We identified a likely nosocomial transmission of VRE among pediatric Oncology and BMT patients. Although no clear epidemiological links were found on extensive investigation, WGS revealed transmissions among patients occurred, reinforcing the importance of adherence to IP&C measures such as HH compliance, PPE utilization, and VRE screening for outbreak prevention in healthcare facilities.William R. Otto, MD, MSCE, Moderna: Grant/Research Support Lara A. Danziger-Isakov, MD, MPH, Aicuris: Contracted Clinical Research|Ansun Biopharma: Contracted Clinical Research|Astellas: Contracted Clinical Research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted Clinical Research|Pfizer: Contracted Clinical Research|Roche Diagnostics: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Contracted Clinical Research


Persons with respiratory viral infections (RVI) may shed detectable virus after symptom recovery. Duration of detection by molecular methods is not well described for non-SARS-CoV-2 respiratory viruses.School KIDS is a prospective respiratory viral surveillance program in a Missouri school district. Participating students and staff with RVI symptoms can receive respiratory viral testing using self-collected nasal swabs. Symptomatic participants with detectable virus(es) on primary swabs were scheduled to receive 2 convalescent swabs weekly after initial test during weekly school surveillance testing. All convalescent tests performed within 21 days of the primary specimen were included. Only participants providing ≥ 1 convalescent swab were included. Specimens were tested using Hologic® Panther Fusion® or QIAstat-Dx PCR assays that included adenovirus (AdV); seasonal coronaviruses (sCoV) 229E, HKU1, NL63, OC43; human metapneumovirus, influenza A and B (Flu), parainfluenza viruses 1-4, respiratory syncytial virus, rhinovirus/ enterovirus (RV/EV), and SARS-CoV-2. We used survival analysis to quantify median number of days until individuals tested negative for each virus.From November 3, 2022 – April 14, 2023, 344 symptomatic participants  submitted 586 primary specimens; 292 (50%) were positive for a virus. For positive primary specimens, median [IQR] time of symptom onset to specimen collection was 2  days. A total of 320 viruses were detected; most common were RV/EV (37%) and sCoVs (25%) (Table). An additional 370 convalescent specimens were collected . Median number of days [95% confidence interval] when repeat convalescent tests became negative varied by virus  .Students and staff continued to have detectable virus by nasal swabs 10-15 days after symptomatic positive specimen. Further data are needed to determine when participants are no longer infectious.Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support