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OBJECTIVE To create antibiograms for commonly cultured organisms in a small animal tertiary care hospital following Clinical and Laboratory Standards Institute guidelines and to compare these local resistance patterns to published first-tier antimicrobial recommendations. SAMPLE Urine (n = 429), respiratory (41), and skin (75) isolates cultured from dogs between January 1, 2019, and December 31, 2020, at the Tufts University Foster Hospital for Small Animals. PROCEDURES MIC and susceptibility interpretations were recorded for multiple sites for 2 years. Sites with greater than 30 isolates for at least 1 organism were included. Urinary, respiratory, and skin antibiograms were created using Clinical and Laboratory Standards Institute breakpoints and guidelines. RESULTS Urinary Escherichia coli had a higher susceptibility percentage for amoxicillin–clavulanate (80% [221/275]) than amoxicillin alone (64% [175/275]). Respiratory E coli were greater than 80% susceptible to only 2 antimicrobials (imipenem, amikacin). Of skin Staphylococcus pseudintermedius isolates, 40% (30/75) were methicillin-resistant and frequently also displayed resistance to non-beta lactam antimicrobials. Susceptibility to recommended first-line antimicrobials varied and was greatest for gram-negative urinary isolates and lowest for methicillin-resistant S pseudintermedius skin isolates and respiratory E coli. CLINICAL RELEVANCE Local antibiogram creation identified frequent resistance that may preclude the use of guideline-recommended first-line therapy. High levels of resistance identified in methicillin-resistant S pseudintermedius isolates supports growing concern for methicillin-resistant staphylococci in veterinary patients. This project highlights the need for population-specific resistance profiles to be used in conjunction with national guidelines.

Background: Micafungin is increasingly used in the treatment and prevention of candidiasis in hospitalized patients. Limited data are available from which to assess the risk of drug-induced liver injury (DILI) with micafungin. No studies, to date, have applied a standardized causality assessment method to the study of micafungin-associated DILI. Objective: This study aimed to identify the frequency and clinical pattern of DILI in micafungin-treated patients as determined using 2 standardized causality assessment algorithms. Methods: A retrospective analysis was conducted of micafungin-treated patients at a single center between May 15, 2017, and May 15, 2018. DILI was defined on the basis of liver test elevations and the presence of associated signs and symptoms. The Roussel UClaf Causality Assessment Method (RUCAM) and the Naranjo algorithm were applied to each case. Results: A total of 99 patients were assessed; 52 were excluded, with a final sample of 47 evaluable patients. The definition of DILI was met in 9 (19%) patients, with a clinical pattern consistent with cholestatic injury in 7 of 9 (78%) patients. No cases were associated with jaundice. Agreement between the 2 causality assessment methods occurred in 4 of 9 (44%) cases. Application of the RUCAM algorithm led to the exclusion of 4 cases, resulting in a final reported prevalence of micafungin-associated DILI of 10.6%. Conclusion and Relevance: Asymptomatic DILI was identified in 10.6% of micafungin-treated patients. The choice of a causality assessment nomogram substantially influenced the determination of DILI prevalence. Compared with the Naranjo algorithm, the RUCAM algorithm is recommended as a more precise tool of assessing the relationship between drug exposure and DILI.

Antibiotic resistant bacterial infections are a growing global health crisis. Antibiograms, aggregate antimicrobial resistance reports, are critical for tracking antibiotic susceptibility and prescribing antibiotics. This research leverages fifteen years of the expansive Massachusetts statewide antibiogram dataset curated by the Massachusetts Department of Public Health. Given the lengthy annual antibiogram creation process, data are not timely. Our prior research involved forecasting the current antimicrobial susceptibility given historic antibiograms. The objective for this research is to expand upon this prior work by identifying which antibiotic-bacteria combinations have resistance trends that are not well forecasted. For that, our proposed Previous Year Anomalous Trend Identification (PYATI) strategy employs a cluster driven outlier detection solution to identify the trends to remove before forecasting. Employing PYATI to remove antibiotic-bacteria combinations with anomalous trends statistically significantly reduces the forecasting error for the remaining combinations. As antibiotic resistance is furthered by prescribing ineffective antibiotics, PYATI can be leveraged to improve antibiotic prescribing.

Antibiotic resistance is constantly evolving, requiring frequent reevaluation of resistance patterns to guide treatment of bacterial infections. Antibiograms, aggregate antimicrobial susceptibility reports, are critical for evaluating the likelihood of antibiotic effectiveness. However, these antibiograms provide outdated resistance knowledge. Thus, this research employs predictive modeling of historic antibiograms to forecast the current year’s resistance rates. Utilizing subsets of the expansive 15-year Massachusetts statewide antibiogram dataset, we demonstrate the effectiveness of using our model selector PYPER with regression-based models to forecast current antimicrobial susceptibility. A PYPER variant is effective since it leverages the fact that different antibiotic-bacteria-location combinations have different antimicrobial susceptibility trends over time. In addition, we discuss relative weighting of the regression-variant models, the impact of location granularity, and the ability to forecast multiple years into the future.

In the USA, two million people fall ill with antimicrobial-resistant infections every year; with at least 23,000 dying as a result. Global estimates reveal that more than 700,000 die worldwide yearly of antibiotic-resistant infections and an extra 10 million people across the world could die every year by 2050 due to antibiotic resistance if this is not addressed. Antimicrobial stewardship programs have been shown to be effective in both combating antibiotic resistance and health-care cost containment. This has recently led to US governmental and organizational mandates for antimicrobial stewardship targeting health-care institutions; but in our global community, these regulations will do little without international support. This article will review international antimicrobial stewardship legislation and point out gaps or areas still needing attention.

Background: The Tufts Medical Center Antimicrobial Stewardship (ASP) Team has partnered with the Massachusetts Department of Public Health (MDPH) to provide broad-based educational programs (BBEP) to long-term care facilities (LTCFs) in an effort to improve ASP and infection control practices. LTCFs have consistently expressed interest in individualized and hands-on involvement by ASP experts, yet they lack resources. The goal of this study was to determine whether “enhanced” individualized guidance provided by an ASP expert would lead to antibiotic start decreases in LTCFs participating in our pilot study. Methods: A pilot study was conducted to test the feasibility and efficacy of providing enhanced ASP and infection control practices to LTCFs. In total, 10 facilities already participating in MDPH BBEP and submitting monthly antibiotic start data were enrolled, were stratified by bed size and presence of dementia unit, and were randomized 1:1 to the “enhanced” group (defined as reviewing protocols and antibiotic start cases, providing lectures and feedback to staff and answering questions) versus the “nonenhanced” group. Antibiotic start data were validated and collected prospectively from January 2018 to July 2019, and the interventions began in April 2019. Due to staff turnover and lack of engagement, intervention was not possible in 2 of the 5 LTCFs randomized to the enhanced group, which were therefore analyzed as a nonenhanced group. An incidence rate ratios (IRRs) with 95% CIs were calculated comparing the antibiotic start rate per 1,000 resident days between periods in the pilot groups. Results: The average bed sizes for enhanced groups versus nonenhanced groups were 121 (±71.0) versus 108 (±32.8); the average resident days per facility per month were 3,415.7 (±2,131.2) versus 2,911.4 (±964.3). Comparatively, 3 facilities in the enhanced group had dementia unit versus 4 in the nonenhanced group. In the per protocol analysis, the antibiotic start rate in the enhanced group before versus after the intervention was 11.35 versus 9.41 starts per 1,000 resident days (IRR, 0.829; 95% CI, 0.794–0.865). The antibiotic start rate in the nonenhanced group before versus after the intervention was 7.90 versus 8.23 antibiotic starts per 1,000 resident days (IRR, 1.048; 95% CI, 1.007–1.089). Physician hours required for ASP for the enhanced group totaled 8.9 (±2.2) per facility per month. Conclusions: Although the number of hours required for intervention by an expert was not onerous, maintaining engagement proved difficult and in 2 facilities could not be achieved. A statistically significant 20% decrease in the antibiotic start rate was achieved in the enhanced group after interventions, potentially reflecting the benefit of enhanced ASP support by an expert.Funding: This study was funded by the Leadership in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) fellowship training grant award from the CDC.Disclosures: None

Background Screening for and treatment of asymptomatic bacteriuria (ASB) is controversial prior to surgical valve replacement (SVR). The theoretical concern that the bacteria can translocate to the surgical site, causing infective endocarditis (IE), has not been well-described. At our institution, screening for and treatment of ASB is routine prior to SVR. This study aims to identify whether an association exists between ASB and post-op infections in patients undergoing SVR. Methods A single-center retrospective study was conducted for patients who had SVR between 2016 and 2018. Pre-op urinalyses (UAs) and cultures, symptoms of UTI, and antibiotic therapy were collected during the 60-day pre-op period. Infections, antibiotic therapy, development of resistance, 30-day readmission rates, and 30- and 90-day mortality rates were collected up to 3 months post-op. Statistical analysis was performed using the Chi-square and Fisher exact tests. Results Of the 358 patients who underwent SVR, pre-op UAs were performed in 329 (92%) patients; of whom, 296 (91%) were asymptomatic. Amongst those asymptomatic, 14 (5%) cultures were positive and 11 (79%) positive cultures were treated. Patients with ASB had no difference in post-op infection (1/14 [7%] vs. 32/282 [11%]; P = 1), 30-day readmission rate (1/14 [7%] vs. 44/282 [16%]; P = 0.7), or 90-day mortality rate (0/14 [0%] vs. 4/282 [1%]; P = 1) compared with those with negative urine cultures. Patients who were treated for ASB also showed no difference in these same outcomes compared with those not treated. IE was a complication in 3 of 358 (1%) cases, and none of these patients had ASB or symptomatic UTI prior to surgery. Antibiotic treatment prior to surgery was associated with acquisition of a multi-drug-resistant organism (9/68 [13%] vs. 15/290 [5%]; P = 0.02). There was a trend toward increased 30-day readmission rate (15/68 [22%] vs. 43/290 [15%]; P = 0.15) and development of resistance (1/68 [1%] vs. 0/290 [0%]; P = 0.19) in patients who received pre-op antibiotics. Conclusion In this study, ASB prior to SVR was not related to post-op infection, and treatment of ASB did not prevent future infection. Antibiotic treatment prior to SVR was associated with the development of MDROs. Urine screening prior to SVR should be avoided. Disclosures All authors: No reported disclosures.

We created a 2013 combination antibiogram of healthcare-associated urinary tract infection. The 2013 antibiogram–determined regimen was evaluated in a 2014 cohort who had received empirical therapy. The regimen was statistically more likely to represent adequate treatment than actual prescriptions. A customized antibiogram may guide empirical therapy for specific patients.Infect Control Hosp Epidemiol 2016;37:1101–1104

OBJECTIVETo offer antimicrobial stewardship to a long-term acute care hospital using telemedicine.METHODSWe conducted an uninterrupted time-series analysis to measure the impact of antimicrobial stewardship on hospital-acquired Clostridium difficile infection (CDI) rates and antimicrobial use. Simple linear regression was used to analyze changes in antimicrobial use; Poisson regression was used to estimate the incidence rate ratio in CDI rates. The preimplementation period was April 1, 2010–March 31, 2011; the postimplementation period was April 1, 2011–March 31, 2014.RESULTSDuring the preimplementation period, total antimicrobial usage was 266 defined daily doses (DDD)/1,000 patient-days (PD); it rose 4.54 (95% CI, −0.19 to 9.28) per month then significantly decreased from preimplementation to postimplementation (−6.58 DDD/1,000 PD [95% CI, −11.48 to −1.67]; P=.01). The same trend was observed for antibiotics against methicillin-resistant Staphylococcus aureus (−2.97 DDD/1,000 PD per month [95% CI, −5.65 to −0.30]; P=.03). There was a decrease in usage of anti-CDI antibiotics by 50.4 DDD/1,000 PD per month (95% CI, −71.4 to −29.2; PPseudomonas antibiotics increased after implementation (30.6 DDD/1,000 PD per month [95% CI, 4.9–56.3]; P=.02) but with ongoing education this trend reversed. Intervention was associated with a decrease in hospital-acquired CDI (incidence rate ratio, 0.57 [95% CI, 0.35–0.92]; P=.02).CONCLUSIONAntimicrobial stewardship using an electronic medical record via remote access led to a significant decrease in antibacterial usage and a decrease in CDI rates.Infect. Control Hosp. Epidemiol. 2016;37(4):433–439

Background It has been shown that the use of antibiotics promotes resistance to that antibiotic, and that colonization with resistant pathogens can be transmitted from companion animals to their human owners. There is an evolving concern that use of medically important antibiotics in pets can confer colonization by resistant organisms in their human owners. Methods In dogs receiving amoxicillin/clavulanate for 14 days for a diagnosed infection, we screened stool both at the time of antibiotic initiation and at the end of the course for the dog taking antibiotics and their human owner. Owners had to meet a closeness score of 3 or 4, meaning living in same household with frequent contact, with or without oral contact, and have no recent antibiotic exposure. Stool samples were quantitatively cultured for enteric flora and incubated on selective media for ampicillin/sulbactam resistance (A/S-r), ciprofloxacin resistance (CIP-r), ESBL, MRSA, and VRE. Results We enrolled eight dog–human pairs. All had enteric flora present at the time of antibiotic initiation (Day 1), whereas two of the seven dog samples that could be analyzed had no detectable enteric flora by the end of antibiotics (Day 14). No humans or dogs acquired MRSA or VRE. One human lost colonization with CIP-r flora, whereas two dogs acquired CIP-r during antibiotic treatment that did not transmit to their owners. One dog and one unrelated human acquired ESBL colonization by day 14 that was not present at Day 1. There were three humans colonized with A/S-r on Day 1 which persisted through the treatment period. Of their three dogs, one had no A/S-r at either time point, one newly acquired high counts of A/S-r flora, and one did not provide enough stool at Day 14 for A/S-r testing. There was one other dog that acquired A/S-r flora and one dog that had increasing counts of A/S-r, both of which had human owners with no A/S-r on Day 1 or 14. Conclusion In this pilot study, we identified that use of amoxicillin-clavulanate, a common antibiotic prescribed to both humans and dogs, can lead to resistant colonization in the dog taking antibiotics, and may have some impact on their close human owners who may share or transmit colonization. Further study is under way to better understand this relationship. Disclosures L. A. McDermott, CutisPharma Inc.: Research Contractor, Contractual agreement with Tufts Medical Center.

Background Bloodstream infections are a major cause of morbidity and mortality worldwide, with favorable clinical outcomes associated with early optimal antibiotic selection. Rapid diagnostics have become a key part in achieving this. Biofire Filmarray® was introduced at our institution for rapid blood culture (BC) identification, coupled with antimicrobial stewardship (AS) interventions. We aimed to assess the impact of this test on time to adequate antimicrobial therapy in a setting with pre-existing effective AS interventions. Methods An observational retrospective chart review, pre and post study was performed. We reviewed adult positive BC before and after implementation of Biofire. Outcomes were: (1) time from BC result reported to health care provider to start of adequate antimicrobial therapy,(2) time to stopping antimicrobial therapy in BC thought to be contaminants, (3) time to any change in antimicrobial therapy and (4) a composite outcome of outcomes 1 and 2. A univariate Cox proportional hazards model was performed. Results 326 positive BC were analyzed, 173 before and 153 after Biofire implementation. At the time of healthcare provider notification, 77 were not on adequate antimicrobials, with median time to adequate therapy of 6.98 hours. (IQR 3.93–23.96) before and 6.1 hours. (IQR 1.84–20.95) after implementation, P = 0.48. There were 75 BC classified as contaminants and median time to stopping antimicrobials was 48.28 (IQR 18.56–89.36) vs. 45.25 hours. (IQR 15.12–100.60), P = 0.61. Time to any change in any antimicrobial therapy was similar with a median of 13.05 (IQR 4.00–36.77) vs. 10.90 hours. (IQR 2.97–31.10), P = 0.87. Analysis of the composite outcome revealed a median of 23.95 (6.29–58.50) vs. 14.82 (IQR 4.07–44.79) hours. (Hazard ratio 1.33, 95% confidence interval 0.96–1.84, P = 0.09). Conclusion Implementation of the Biofire Filmarray® did not have a statistically significant effect on our composite outcome of time to adequate therapy and time to discontinuation in the case of contaminants. Our findings suggests that when added to other effective AS surveillance and interventions, the magnitude of the clinical impact of rapid PCR diagnostics for BC identification is minimal. Disclosures D. R. Snydman, Merck: Scientific Advisor, Consulting fee; Shire: Scientific Advisor, Consulting fee