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Background Nosocomial acquisition of vancomycin-resistant Enterococcus (VRE) is one of the most challenging problems in healthcare. As Enterococcus isolates are increasingly resistant to vancomycin, clinicians now rely on alternative antimicrobial therapies including linezolid and daptomycin (DAP) to treat infections. For multidrug-resistant (MDR) VRE, combination therapy with beta-lactams and daptomycin has been shown to be effective. Methods Following initiation of empiric DAP and ceftaroline (CPT) for an MDR E. faecium bloodstream infection (VRE_001), we aimed to determine if there existed in vitro synergy between both agents that supported their clinical use. Combination synergy testing was performed using E-test strips and minimal inhibitory concentrations (MICs) were read at 24 hours. For whole genome sequence-based analysis (WGS), genomic DNA from VRE_001 was used for both short read (Illumina MiSeq) and long-read sequencing (MinION, Nanopore). The complete genome was assembled and the NCBI AMRFinderPlus program used to identify known resistance mechanisms. Results Original MICs of VRE_001 from the clinical microbiology laboratory at Northwestern Memorial revealed an MDR E. faecium (Table 1). Combination synergy testing in the experimental laboratory revealed only modest amounts of synergy between CPT and DAP (Table 2). Following WGS, VRE_001 was identified as an ST-584 E. faecium with a 3.2 Mbp genome, including a single chromosome and five plasmids. WGS analysis revealed several mechanisms of antimicrobial resistance (Table 3) genetically supporting the observed MDR-DLVRE phenotype. Conclusion Our investigational antimicrobial testing allowed for real-time in vitro analysis of synergistic MICs in a case of DLVRE bacteremia. Despite the fact that in vitro testing of CPT and DAP did not support the clinical usage of combination antimicrobial therapy, the patient cleared their blood cultures. WGS of VRE_001 revealed a plethora of antimicrobial resistance mechanisms including three mutations that explain high levels of DAP resistance. Synergy testing is not routinely available in most clinical laboratories, but rapid implementation of investigational MIC testing paired with genomic analysis may one day successfully support real-time clinical decision making. Disclosures All Authors: No reported disclosures

Background Coronavirus disease 2019 (COVID-19) has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking. Methods We conducted a retrospective case-control study across a single healthcare system of nonhospitalized patients, age 18 years or older, with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 polymerase chain reaction (PCR). Descriptive statistics, including χ 2 and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization. Results Between 30 November 2020 and 19 January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21–.64, P < .001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19 ,95% CI: 1.31–2.16, P < .001; OR 1.68, 95% CI: 2.12–8.30, P < .001, respectively). Conclusions Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization. Bamlanivimab’s role in preventing hospitalization associated with coronavirus disease 2019 (COVID-19) remains unclear. In a real-world, retrospective study of 403 high-risk, ambulatory patients with COVID-19, receipt of bamlanivimab compared to no monoclonal antibody therapy was associated with lower 30-day hospitalization.

Key points In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. Purpose There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. Methods We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19–targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). Results A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19–directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). Conclusion While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

Adults hospitalized with community-acquired pneumonia (CAP) typically receive antibiotics and thus are at increased risk of developing Clostridioides difficile infection (CDI), a disease of significant morbidity. We developed and validated a CAP-specific clinical decision algorithm to facilitate optimal diagnostic stewardship of C. difficile polymerase chain reaction (PCR) testing. The study was a single-center retrospective, case-control analysis of hospitalized adult patients empirically treated for CAP between January 1, 2014 and May 29, 2018. A series of predictive models and validity assessments were used to evaluate demographic and post-admission patient-specific risk factors as predictors of CDI case status among patients with CAP. Thirty-two PCR confirmed CDI cases were identified and 232 randomly selected controls were drawn from the total CAP population. After propensity score weighting, hospital-onset (HO) CDI was significantly associated with broad-spectrum Gram-negative antibiotic use (P=0.002) as was subsequent community-onset (CO) CDI (P=0.005). Modified-APACHE II > 8.5 (P=0.003) and broad-spectrum Gram-negative antibiotic use (P=0.002) were associated with healthcare-associated CDI and were robust in multiple validity analyses. Patients with m-APACHE II ≤ 8.5 who received broad-spectrum Gram-negative antibiotics were more likely (odds=1:2) to experience healthcare-associated CDI compared to those who did not receive these broad-spectrum agents (odds=1:125) and compared to those with m-APACHE II > 8.5 irrespective of treatment (odds=5:27). We conclude that broad-spectrum Gram-negative antibiotic use was the common factor in development of CDI in patients with CAP in all settings. Prospective studies are needed to confirm the reproducibility and clinical utility of our model when used for diagnostic test stewardship.

In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients.There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period.We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs).A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028).While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

Background Vancomycin-resistant enterococci (VRE) are nosocomial pathogens with extensive intrinsic and acquired antimicrobial resistance (AMR) mechanisms. We report a case in which intraabdominal (IA) and blood cultures grew linezolid and daptomycin resistant VRE (DLVRE). Methods We report a case of DLVRE bacteremia after prolonged treatment with linezolid and daptomycin. Results The patient was a 65-year-old female with a history of multiple abdominal surgeries who presented for elective incisional hernia repair. Her post-operative course was complicated by the development of loculated IA abscesses. A drain was placed into the largest abscess, and aspiration cultures were polymicrobial containing vancomycin-resistant E. faecium (Isolate 1). The patient was treated meropenem, fluconazole and linezolid for 6 weeks. Clinical and radiographic improvement was achieved. However, 4 days after competing antibiotics she developed recurrent abdominal pain and a leukocytosis. Daptomycin was chosen out of concern for long-term linezolid toxicity and IA cultures demonstrated new linezolid resistance (Isolate 2, LVRE). After an additional three weeks of therapy, she developed a catheter-associated bloodstream infection (CLABSI). Blood cultures revealed daptomycin-resistant LVRE bacteremia (Isolate 3, DLVRE). She was started empirically on a combination of ceftaroline and daptomycin, her PICC line removed, and her blood cultures cleared. Her antibiotic course is presented in Figure 1 and resistance patterns of the VRE in Table 1. Conclusion In this patient, an IA abscess known to harbor VRE developed resistance to both linezolid and daptomycin during prolonged treatment with both agents. Ultimately, the patient experienced an episode of CLABSI DLVRE. Limited data exists on appropriate antibiotic choice in such challenging situations. Based on prior clinical and experimental data, we elected to use daptomycin in conjunction with ceftaroline for synergy, and the patient achieved the desired clinical response, clearance of her blood cultures and diminishing size of her IA abscess. Further work is needed to elucidate the best course of treatment for patients with VRE requiring long-term antibiotic therapy and for those who have developed extensively drug-resistant E. faecium. Disclosures All Authors: No reported disclosures

Background Patients with community-acquired pneumonia (CAP) who are hospitalized and treated with antibiotics may carry an increased risk for developing Clostridioides difficile infection (CDI). Accurate risk estimation tools are needed to guide monitoring and CDI mitigation efforts. We aimed to identify patient-specific risk factors associated with CDI among hospitalized patients with CAP. Methods Design: retrospective case-control study of hospitalized patients who received CAP-directed antibiotic therapy between 1/1/2014 and 5/29/2018. Cases were hospitalized CAP patients who developed CDI post-admission. Control patients did not develop CDI and were selected at random from CAP patients hospitalized during this period. Variables: comorbidities, laboratory results, vital signs, severity of illness, prior hospitalization, and past antibiotic use. Propensity-score weights: identified via structural decomposition analysis of pre-treatment variables. Analysis: weighted classification tree models that predicted any CDI, hospital-onset CDI, and any healthcare-associated CDI according to CAP antibiotic treatment. Performance: percent accuracy in classification (PAC) and weighted positive (PPV) and negative predictive values (NPV). Modeling: completed using the ODA package (v1.0.1.3) for R (v3.5.1). Results A total of 32 cases and 232 controls were identified. Sixty pre-treatment variables were screened. Structural decomposition analysis, completed in two stages, identified prior hospitalization (OR 6.56, 95% CI: 3.01-14.31; PAC: 80.3%) and BUN greater than 29 mg/dL (OR 11.67, 95% CI: 2.41-56.5; PAC: 80.8%) as propensity-score weights. With respect to CDI, receipt of broad-spectrum anti-pseudomonal antibiotics was significantly (all P’s< 0.05) associated with any CDI (NPV: 90.29%, PPV: 27.94%), hospital-onset CDI (NPV: 97.53%, PPV: 26.86%), and healthcare-associated CDI (NPV: 92.89%, PPV: 27.94%). Conclusion We identified risk factors available at hospital admission and empiric use of broad-spectrum Gram-negative antibiotics as being associated with the development of CDI. Model PPVs were over two-fold greater than our sample base rate. Increased monitoring and avoidance of overly broad antibiotic use in high-risk patients appears warranted. Disclosures All Authors: No reported disclosures

Background Pseudomonas aeruginosa (PsA) is an infrequent pathogen associated with poor outcomes in community-acquired pneumonia (CAP). Identifying patients at high and low-risk for PsA in CAP is necessary to reduce inappropriate and overly broad-spectrum antibiotic use. We evaluated the distribution of risk-factors in hospitalized CAP patients with and without PsA infection. Methods Design: retrospective, single-center, case–control study. Inclusion: hospitalized CAP patients admitted to the general medicine wards between January 1, 2014 and May 29, 2018. Exclusion: cystic fibrosis, ≥ 3 admissions within 30 days, CAP requiring ICU admission, and death within 48 hours of admission. Case patients had PsA in respiratory or blood cultures during the index CAP admission. Controls were randomly selected targeting a 3:1 ratio. Comorbidities, pneumonia severity index, and m-APACHE II were assessed. Gram-negative risk factors defined by Shindo et al. 2013 (PMID: 23855620) and validated by Kobayashi et al. (2018; PMID: 30349327) were scored for each patient. Stepwise logistic regression was used to identify covariates that distinguished cases from controls at a P < 0.2; these were then used to generate propensity weights (i.e., inverse-probability conditioned on covariates). Unadjusted and adjusted odds ratios for case status were estimated using logistic regression according to: the total number of risk factors present and threshold values, respectively. All analyses were conducted using IC Stata (v.14.2). Results 54 cases and 152 controls were included. The distribution of the patient-specific sum of risk factors for PsA is shown in Figure 1. The univariate OR for case status was 4.29 (95% CI:1.55–11.9) at n = 3 risk factors, which was similar after propensity weight adjustment [aOR = 4.64 (95% CI: 1.32–16.3)]. The univariate OR of case status was 2.98 among patients with ≥ 3 risk factors (95% CI: 1.34–6.62), which was similar after propensity weight adjustment [aOR = 2.8 (95% CI: 1.02–7.72)], and correct classification was 73.8%. Conclusion At a threshold of ≥ 3 PsA risk factors, cases and controls were well classified, even after adjusting for propensity weights. The impact of patient-specific PsA risk-stratification on CAP outcomes and appropriate antibiotic use should be evaluated. Disclosures All authors: No reported disclosures.