is the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the United States since the switch from the whole-cell pertussis vaccines (wP) to the acellular pertussis vaccines (aP; diphtheria-tetanus-acellular-pertussis vaccine/tetanus-diphtheria-pertussis vaccine). Adenylate cyclase toxin (ACT) is a major virulence factor of that is (i) required for establishment of infection, (ii) an effective immunogen, and (iii) a protective antigen. The C-terminal repeats-in-toxin domain (RTX) of ACT is sufficient to induce production of toxin-neutralizing antibodies. In this study, we characterized the effectiveness of vaccines containing the RTX antigen against experimental murine infection with RTX was not protective as a single-antigen vaccine against challenge, and adding RTX to 1/5 human dose of aP did not enhance protection. Since the doses of aP used in murine studies are not proportionate to mouse/human body masses, we titrated the aP from 1/20 to 1/160 of the human dose. Mice receiving 1/80 human aP dose had bacterial burden comparable to those of naive controls. Adding RTX antigen to the 1/80 aP base resulted in enhanced bacterial clearance. Inclusion of RTX induced production of antibodies recognizing RTX, enhanced production of anti-pertussis toxin, decreased secretion of proinflammatory cytokines, such as interleukin-6, and decreased recruitment of total macrophages in the lung. This study shows that adding RTX antigen to an appropriate dose of aP can enhance protection against challenge in mice.

We assessed the treatment of Serratia marcescens bacteremia and endocarditis in one of the largest single center studies. We could not identify an advantage with any particular antibiotic treatment regimen in this study. Induction of AmpC or selection of ESBL organisms was not displayed by any of the organisms.

Background Injection drug use is associated with infectious diseases such as endocarditis and osteomyelitis requiring prolonged intravenous (IV) antimicrobial therapy. Few programs offer simultaneous inpatient infectious disease and addiction treatment. WVU Medicine implemented a multidisciplinary Infusion Service (IS) to provide IV antimicrobial therapy while treating substance use disorder. From 2017 through 2019, IS cared for over 840 patients. The aim of this study was to evaluate IS by assessing patients’ perspectives of overall experience, interactions with healthcare providers, and preparation for continued recovery from substance use. Methods Adults ≥ 18 and < 90 years-old with substance use disorder on IS between November 2019 and May 2020 were eligible. Demographic, substance use, and infectious diseases data were obtained by chart review. Confidential surveys with questions about overall experience, interactions with healthcare providers, and preparation for continued recovery were administered during the first week after transfer to IS and again the week of discharge. Results Forty-two patients completed 39 initial and 12 follow up surveys. All used injection drugs, 85.7% (36/42) used opioids and 66.7% (28/42) used methamphetamine. Endocarditis was most common infection (61.9% (26/42)), with Staphylococcus aureus most often isolated (59.5% (25/42)). IS experience and care for infection were excellent or good in 97.4% (38/39) initial and 100% (12/12) follow up surveys. During IS, patients did not perceive being treated differently due to substance use in 94.9% (37/39) initial and 83.3% (10/12) follow up surveys. Before IS, patients perceived being treated differently in 84.6% (33/39) initial and 100% (12/12) follow up surveys. Patients felt IS would help with continued recovery in 84.6% (33/39) initial and 100% (12/12) follow up surveys. Conclusion According to patients’ perspectives, IS is effective in creating a positive overall healthcare experience, reducing stigma associated with substance use, and preparing patients for continued recovery after discharge. This study supports combining inpatient infectious disease and addiction therapy. Infectious diseases providers should be educated about this multidisciplinary approach. Disclosures All Authors: No reported disclosures

Similarly responsive neurons organize into submillimeter-sized clusters (domains) across many neocortical areas, notably in Areas V1 and V2 of primate visual cortex. While this clustered organization may arise from wiring minimization or from self-organizing development, it could potentially support important neural computation benefits. Here, we suggest that domain organization offers an efficient computational mechanism for intra-areal functional integration in certain cortical areas and hypothesize that domain proximity could support a higher-than-expected spatial correlation of their respective terminals yielding higher probabilities of integration of differing domain preferences. To investigate this hypothesis we devised a spatial model inspired by known parameters of V2 functional organization, where neighboring domains prefer either colored or oriented stimuli. Preference-selective joint probabilities were calculated for model terminal co-occurrence with configurations encompassing diverse domain proximity, shape, and projection. Compared to random distributions, paired neighboring domains (< or =1200 microm apart) yielded significantly enhanced coincidence of terminals converging from each domain. Using this reference data, a second larger-scale model indicated that V2 domain organization may accommodate relatively complete sets of intra-areal color/orientation integrations. Together, these data indicate that domain organization could support significant and efficient intra-areal integration of different preferences and suggest further experiments investigating prevalence and mechanisms of domain-mediated intra-areal integration.

Background Serratia Marcescens (SM) is often an opportunist that has been associated as a cause of healthcare-associated infection and in some people who inject drugs (PWID). Decisions about the treatment of SM infections are difficult given the small clinical studies available and concerns for multidrug resistance. SM has the ability to produce inducible AmpC b-lactamase and may acquire extended-spectrum b-lactamase (ESBL). Evidence-based guidance is lacking in terms of identifying preferred antimicrobial therapy of SM bacteremia and endocarditis. Compared to other reports, our hospital has one of the largest SM data sets to compare. Methods This observation study included adult patients admitted to our hospital (2016–2019) with SM bloodstream infections, including endocarditis. Patients were excluded from the analysis, if they had a concomitant infection with another gram-negative organism. Our evaluation was designed to: compare outcomes associated with different antibiotic regimens, evaluate how care differed in PWID patients versus others, and identify factors associated with obtaining infectious diseases expert consultations (ID Consult). Results Forty-three patients met study inclusion/exclusion. Twenty-eight patients (65.1%) had ID Consults. Twenty-four (55.8%) were PWID. Endocarditis was diagnosed in 30.2% of patients. The most common regimen was cefepime +/- aminoglycoside, followed by a carbapenem +/- aminoglycoside. Combination therapy was only recommended during ID Consult. Piperacillin-tazobactam was used in 11.6% of patients. No regimen displayed an efficacy or safety advantage over another. Most patients (90.7%) cleared their blood stream within 48 hours of antibiotic start. Phenotypic susceptibility testing did not identify either ESBL or AmpC production in any of the isolates, including recurrences. Multi-drug resistance was not appreciated. Significant factors associated with obtaining ID Consult were: PWID (p=0.004), endocarditis (p=0.0002), sepsis (p=0.022), surgical intervention (p=0.003). Conclusion We could not identify an advantage with any particular antibiotic treatment regimen in this study. Induction of AmpC or selection of ESBL organisms was not displayed by any of the organisms. Disclosures All Authors: No reported disclosures