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INTRODUCTION: Severely ill patients with COVID-19 pneumonia have been found to have an extensive cytokine mediated inflammatory response This has been demonstrated by elevated pro-inflammatory markers, including interleukin 6 (IL-6) Tocilizumab is an IL-6 antagonist that has been hypothesized to benefit patients with COVID-19 by reducing cytokine release We set out to evaluate outcomes of patients who received tocilizumab at our health system We also assessed the impact that the timing of tocilizumab administration and the presence or absence of corticosteroids had on patient outcomes METHODS: A retrospective analysis was conducted of patients diagnosed with COVID-19 who received tocilizumab between March 20, 2020 and June 10, 2020 Data collected included patient age, weight, gender, timing of tocilizumab administration, dose, concomitant therapies including corticosteroids, respiratory status at the time of tocilizumab administration, patient disposition, change in C-reactive protein, change in lactate dehydrogenase, change in liver function tests, need for renal replacement therapy, and the incidence of secondary infections RESULTS: Two-hundred-twelve patients received tocilizumab during the specified period Overall, as of June 17, 2020, 165 patients (77 8%) had been discharged from the hospital, 14 patients (6 6%) were still hospitalized, 3 of those patients required mechanical ventilation, and 33 patients (15 6%) had died Among the subset of patients who received tocilizumab within 24 hours of admission and received corticosteroids (n=97), 82 patients (84 5%) had been discharged from the hospital, 5 patients (5 2%) were still hospitalized, one of whom required mechanical ventilation, and 10 patients (10 3%) had died Of the 212 total patients who received tocilizumab, 12 patients (5 7%) required initiation of renal replacement therapy, 4 patients (1 9%) had new onset seizure activity, and 23 patients (10 8%) developed a secondary infection as evidenced by at least one positive culture following administration CONCLUSIONS: The early use of tocilizumab in combination with corticosteroids may improve outcomes in patients with COVID-19 pneumonia Further evaluation of this treatment strategy is needed to fully assess clinical benefit

Background In June of 2016 at ChristianaCare a urinalysis with reflex to culture (UARC) order set was made available, which allows for urine cultures to be performed automatically if pre-defined criteria for a positive urinalysis are met. The objective of this study was to evaluate the utility of the UARC as it relates to identifying a symptomatic urinary tract infection (UTI), as well as to describe the impact of UARC on antibiotic utilization. Methods A retrospective cohort study was performed including patients aged 18 to 89 ordered a UARC. Patients were excluded if they were currently pregnant, had an absolute neutrophil count of < 100 cells/mm3, were undergoing a urological procedure, or receiving antibiotics for another indication. The primary outcome of this study was to determine the utility of the UARC in identifying a symptomatic UTI, as determined by the Youden index. Secondary outcomes evaluated included mean days antibiotics and length of stay, adherence to duration of treatment guidelines, 30 day post discharge readmissions, 30 day post discharge mortality, and new Clostridioides difficile infection within 30 days. Results A total of 123 patients were included in this study. A Youden index of 7.2% was calculated for the primary outcome. Patients with a positive UARC and UTI symptoms received an average of 7.54 days of antibiotics. Asymptomatic patients with a positive UARC received significantly more antibiotics than those with a negative UARC (3.05 vs 0 days, respectively,p=0.02). Adherence to duration of treatment guidelines was found to be 77.8%, 66.7%, and 50% for uncomplicated cystitis, complicated cystitis and pyelonephritis respectively. No difference was observed between groups for length of stay, 30 day post discharge readmissions, and 30 day post discharge mortality. No cases of new C. difficile infection were identified. Conclusion This study demonstrates that the UARC does not have utility as a diagnostic test for predicting a symptomatic UTI. The presence of a positive UARC in the absence of symptoms attributable to a UTI resulted in inappropriate prescribing of antibiotics. Further evaluation of how a UARC is ordered, perhaps requiring prescribers to document urinary symptoms, in addition to caregiver education is warranted Disclosures All Authors: No reported disclosures

Background Multidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections. Methods Data were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes. Results Two-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11–24) and median Charlson Comorbidity Indexes of 4 (IQR, 3–6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR], 5.55; 95% confidence interval [CI], 2.14–14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40–6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24–5.38). Conclusions Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.

PURPOSE To understand the ability of trigger tools to detect preventable adverse events (pAEs) in the primary care outpatient setting using the Institute for Healthcare Improvement's (IHI) Outpatient Adverse Event Trigger Tool (IHI Tool). METHODS The OVID MEDLINE and OVID MEDLINE In-process and non-Indexed citations databases were queried using controlled vocabulary and Medical Subject Headings related to the concepts "primary care" and "adverse events." Included articles were conducted in the outpatient setting, used at least 1 of the triggers identified in the IHI Tool, and identified pAEs of any type. Articles were selected for inclusion based first on assessment of titles then abstracts by 2 trained reviewers independently, followed by full text review by 2 authors. RESULTS Our search identified 6435 unique articles, and we included 15 in our review. The most common studied trigger was laboratory abnormalities. The most common pAEs were medication errors followed by unplanned hospitalizations. The effectiveness of triggers in identifying AEs varied widely. CONCLUSION There is insufficient data on the IHI Tool and its use to identify pAEs in the general real-world outpatient setting. Health care providers of the primary care setting may benefit from better trigger tools and other methods to help them detect pAEs. More research is needed to further evaluate the effectiveness of trigger tools to reduce barriers of cost and time and improve patient safety.

Background Complicated urinary tract infections (cUTI) including pyelonephritis may result in bacteremia, increasing the rate of morbidity and mortality. The Infectious Diseases Society of America recommends a fluoroquinolone as empiric therapy or trimethoprim/sulfamethoxazole as definitive therapy for acute pyelonephritis (AP). Oral β-lactams (BL) are considered sub-optimal based on historical efficacy data with aminopenicillins and variable bioavailability. Increasing resistance and toxicity with preferred agents, justifies further evaluation of oral BL for E. coli bacteremia secondary to urinary source. Methods This was a single-center, retrospective cohort study of patients with E. coli bacteremia secondary to AP or cUTI who received oral step-down therapy with a BL or non-BL. The primary outcome was the rate of clinical success defined by microbiological cure, clinical cure, and infection-related readmission. Secondary outcomes were time to oral step-down, total days of therapy, length of hospital stay, incidence of therapy escalation, 30-day readmissions, and antibiotic-associated adverse events. Results A total of 46 patients were included, with 23 patients in each group. The difference in clinical success between the BL and non-BL groups was not statistically significant (91.3% vs. 100%, P = 0.489). The most frequent oral step-down agents prescribed were cephalexin and ciprofloxacin. The median time to oral step-down was significantly lower in the non-BL group (4.39 vs. 3.41 days, P = 0.038), and the median duration of therapy in each group was 15 days. No patients required therapy escalation after oral step-down or had infection-related readmission within 30 days of discharge. Conclusion The observed clinical success rate of 91.3% remains consistent with previous studies evaluating oral BL as step-down therapy for Enterobacteriaceae bloodstream infections. The results of this study support the safety and efficacy of oral BL as step-down therapy for E. coli bacteremia due to cUTI, although larger studies may be beneficial. Disclosures All authors: No reported disclosures.

Background As antimicrobial exposure represents a major risk factor in the development of Clostridium difficile infection (CDI), optimization of antimicrobial selection is critical. While a number of antibiotics have been associated with increased risk of CDI, doxycycline may be considered protective. The combination of ceftriaxone and doxycycline (CTX-D) is supported by the Infectious Diseases Society of America (IDSA) for the management of community acquired pneumonia (CAP). The primary objective of this study was to evaluate if CTX-D is associated with a reduced incidence of CDI compared with ceftriaxone and azithromycin (CTX-A) among nonintensive care unit (ICU) patients with CAP at Christiana Care Health System. Methods A retrospective cohort study was conducted to evaluate patients who received CTX-D or CTX-A admitted to Christiana Care between June 1, 2015 and December 31, 2017. Non-ICU patients, aged 18 years or older, receiving at least one dose of CTX-D or CTX-A were included. The primary outcome of our study was the incidence of CDI within 30 days from initial dose of CTX-D or CTX-A. The secondary outcome was the time to onset of CDI from initial dose of CTX-D or CTX-A. Results One thousand sixty-four unique patients were included in this study. Overall, 778 patients received CTX-D and 286 received CTX-A. Among patients who received CTX-D, 2 patients developed CDI, compared with five patients who received CTX-A (relative risk, 0.15; 95% confidence interval, 0.03–0.75; P = 0.02). The mean time to onset of CDI from initiation of CTX-D was 22 days compared with 9.2 days from initiation of CTX-A. Conclusion In this cohort of non-ICU patients with CAP, CTX-D was associated with a reduced incidence of CDI. Further studies are necessary to confirm these preliminary findings to optimize clinical practice, while minimizing potential adverse outcomes associated with antimicrobial use. Disclosures All authors: No reported disclosures.