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Key Points Question Does COVID-19 convalescent plasma (CCP), compared with placebo, improve the clinical status of hospitalized patients with COVID-19 requiring noninvasive supplemental oxygen? Findings In this randomized clinical trial including 941 patients, based on the World Health Organization 11-point Ordinal Scale for Clinical Improvement, CCP did not benefit 468 participants randomized to CCP compared with 473 randomized to placebo from April 2020 to March 2021. However, in exploratory analyses, CCP appeared to benefit those enrolled from April to June 2020, the period when most participants received high-titer CCP and were not receiving remdesivir and corticosteroids at randomization. Meaning In this trial, CCP did not meet prespecified outcomes for efficacy, but high-titer CCP may have benefited hospitalized patients with COVID-19 early in the pandemic when other treatments were not in use, suggesting a heterogenous treatment effect over time., Importance There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR, This randomized clinical trial examines the use of convalescent plasma from patients with COVID-19 in hospitalized patients with COVID-19 who are not receiving invasive oxygenation treatment.

Background Therapeutic drug monitoring (TDM) for vancomycin (VAN) with Bayesian models is recommended by national guidelines. However, limited data incorporating the models may hurt the performance. Our aim is to develop a novel deep learning-based pharmacokinetic model for vancomycin (PK-RNN-V) using electronic medical records (EHRs) data to achieve more accurate and personalized predictions for VAN levels. Methods EHR data were retrospectively retrieved from Memorial Hermann Hospital System, comprising 14 hospitals in the greater Houston area. All patients who received VAN and had any VAN levels were eligible. Patients receiving hemodialysis and extracorporeal membrane oxygenation were excluded. Demographic data, vital signs, diagnostic codes, concomitant medications, VAN administration, and laboratory data were preprocessed as longitudinal data. VAN infusion, VAN level measurement, or each hospital day were the time steps for the models. The dataset was splited 70:15:15 for training, validation, and test sets. Our PK-RNN-V model predicted individual patient volume distribution (v) and VAN elimination (k) at each time step using an irregular timesteps GRU model. To compare, Bayesian models were developed from publicly available models, and tuned to feedback the first VAN level to update the v and k. (VTDM) Results A total of 12,258 patients with 195,140 encounters were identified from Aug, 2019 and March, 2020. After exclusion of 6,775 patients, 5,483 patients with 8,689 encounters were included. Table 1 summarized the characteristics of patients included in our study. 55,336 doses of VAN were administered with a median dosage of 1.0 gm. VAN levels were measured 18,588 times at various timings. The median VAN level was 14.7 mcg/mL Table 2 described the performance of our models and VTDM models. Our model exhibited better performance compared to VTDM model (RMSE: 5.64 vs. 6.57, respectively). Figure 1 shows example prediction curves of VAN levels from each model. Conclusion PK-RNN-V model is a novel approach to predict patient PK and VAN levels. Our results revealed promising performance of this model. Our model can take a wide range of real-world patient data into the model. Further studies are warranted for external validations and model optimizations. Disclosures All Authors: No reported disclosures

Background S. lugdunensis is a coagulase negative staphylococci (CoNS) demonstrating high level pathogenicity. In contrast to other CoNS, S. lugdunensis (SL) remains susceptible to most antibiotics. Prior to the implementation of Verigene®, SL was identified by provider request only. We sought to describe the susceptibility data of SL isolated from blood culture after the implementation of multiplex PCR, as well as to determine the correlation of the mecA gene provided by Verigene® and oxacillin resistance. Methods Retrospective review of all blood culture isolates positive for SL from two major hospital systems, Memorial Hermann Hospital System (14 hospitals) and HarrisHealth System (two acute care hospitals) identified on Verigene® PCR. Multiple isolates detected from the same patients were excluded from this analysis. Memorial Hermann utilized Microscan®, and HarrisHealth utilized BD Phoenix® for susceptibility testing. Results Between 2017 – 2021, 157 patients were identified with SL positive blood cultures. Of them, 141 isolates had susceptibility data collected, which is summarized in table 1. Resistance rates were highest amongst clindamycin 97/141 (68.8 %) susceptible, erythromycin 98/141 (69.5%) susceptible, and oxacillin 120/141 (85.1%) susceptible. 127/141 (90.1%) of isolates were tested for mecA on Verigene®. 13 of 21 oxacillin resistant isolates were from pure culture, of these isolates, none had mecA detected. Conclusion In our study, clindamycin and erythromycin demonstrated similar susceptibility compared to prior studies in the literature, however oxacillin susceptibility rate was lower than expected at 85.1%, compared to 95.3% in a prior large-scale United States based study in 2017. Absence of mecA gene detection on multiplex PCR did not correlate with oxacillin susceptibility suggesting that oxacillin susceptibility cannot be accurately predicted by the use of multiplex PCR systems, such as Verigene®, as demonstrated in Table 2. Our study also suggested that increased prevalence of oxacillin resistant SL isolates may be emerging. Disclosures All Authors: No reported disclosures

Background In 2017, Harris County had a total of 281 cases of newly diagnosed tuberculosis (Mtb), which was the highest incidence in Texas, United States. Lyndon B. Johnson (LBJ) hospital is one of the two HarrisHealth county hospitals which serve a wide population including immigrants and an indigent population. GeneXpert® MTB/RIF (GeneXpert) was implemented in our hospital since 4/2016. However, pulmonary Mtb cases with negative GeneXpert/AFB smears carry significant challenges in the initiation of therapy and hospital infection control. Our aim was to describe how Infectious diseases (ID) consultations helped to identify the cases of both GeneXpert and AFB smear-negative pulmonary Mtb cases without delaying therapy and unnecessary exposures. Methods The patients with newly diagnosed pulmonary Mtb in LBJ hospital were identified between January 2017 and December 2018. The patient’s characteristics, GeneXpert results, AFB smear results, and the presence of ID consultation were retrospectively collected. Delayed therapy is defined as the initiation of active four-drug Mtb therapy until the positive culture results. Results A total of 52 cases with newly diagnosed pulmonary Mtb confirmed by positive culture were identified, of which 44 cases who had GeneXpert on at least one sputum specimen were included in the final analysis. 7 out of 44 (20%) had negative GeneXpert on the first specimen and all three or more AFB smears were negative. The patients were the median age of 51 years and predominantly female (57%). 5 cases were Hispanic and 2 had HIV/AIDS. In 6 out of the 7 cases, ID consultation was made and anti-tuberculous therapy was empirically initiated without delay and all remained in the isolation. Only one case had delayed therapy despite ID consultation, three consecutive AFB sputum samples, and one GeneXpert was properly performed. The patient had newly diagnosed AIDS (CD4 of 2 cells/µL) and 3 weeks of chronic cough with normal lung parenchyma and minimal right pleural effusion on CT chest at his presentation. Conclusion We had 7 cases (20%) of GeneXpert and AFB smear-negative pulmonary Mtb. ID consultation properly identified 6 cases without delayed therapy. Early involvement of ID should be considered when pulmonary Mtb is suspected. Disclosures All authors: No reported disclosures.

Background Cytomegalovirus (CMV) is a rare cause of meningoencephalitis (ME) with clinical data limited to case reports. Methods Retrospective observational study of all viral central nervous system (CNS) infections identified in 17 hospitals in the Greater Houston area from 2000 to 2017. CMV, herpes simplex virus (HSV), varicella zoster virus (VZV), and enterovirus were all identified by a positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR) and all arboviruses were identified by serology. Results A total of 361 patients with viral CNS infections were identified: CMV (n = 33), enterovirus (n = 147), herpes simplex virus (n = 83), varicella zoster virus (n = 28), and arbovirus (n = 70). CMV ME occurred more frequently in immunosuppressed patients [e.g., Acquired Immune Deficiency Syndrome (AIDS)], had more hypoglycorrhachia (59%), and had worse clinical outcomes (61%) as compared with those with HSV, enterovirus, VZV and arboviruses. Furthermore, CMV ME had more altered mental status than enterovirus and HSV and had lower CSF pleocytosis compared with HSV. Additionally, CMV ME had higher CSF protein levels than enteroviral infections and had less CSF lymphocytosis than HSV and VZV. Conclusion CMV meningoencephalitis is seen more frequently in immunosuppressed patients (e.g., AIDS), is associated with more hypoglycorrhachia and have worse clinical outcomes compared with other viral CNS pathogens. Disclosures All authors: No reported disclosures.

Background Rapid identification of antimicrobial resistance markers has the potential to help targeting antimicrobial therapy and enhance efforts for antibiotic stewardship. However, limited data are available to correlate phenotypic and genotypic results for some of these platforms in positive blood cultures (BC). Here, we aimed to evaluate the ability of the Verigene® (VG) Blood Culture System to predict phenotypic susceptibility patterns with the detection of the genes encoding the CTX-M in Enterobacteriaceae and MecA in S. aureus (SA) in a large dataset. Methods Phenotypic susceptibility and VG results were retrospectively collected between August 2017 and December 2018 from 12 hospitals in Houston, TX. VG testing was performed on only the first isolate was considered in persistent positive BCs. The VG report of the presence of blaCTX-M or mecA was correlated with phenotypic susceptibility to ceftriaxone (CTO) (E. coli [EC] and Klebsiella spp.[KL]) or oxacillin (SA), respectively. Results We identified a total of 5,937 VG results. The final analysis was performed on 2,356 cases where EC, KL or SA was identified. Isolates detected KPC and NDM by VG were excluded. 30 EC/KL were missed by VG in polymicrobial bacteremia. 7 polymicrobial positive BCs with coagulase-negative staphyloccocci were mislabeled as MecA positive MSSA. Among isolated detected by VG, there were the high sensitivity and specificity of CTX-M to identify CTO resistance (97.2% and 99.7% in EC and 91.4% and 99.2% in KL). For SA, the sensitivity and specificity of mecA were 100% and 99.6% to identify oxacillin resistance. 2 isolates with mecA positive by VG were reported as oxacillin-suscpetible. Conclusion Our results revealed that there is a high correlation between VG and phenotype. For SA, discrepancies between genotype and phenotype seem to be influenced by the presence of other organisms in the sample. Genotypic information seems reliable and should guide targeted therapy in bloodstream infections. Disclosures All authors: No reported disclosures.