Demonstrating the importance of local culture and susceptibility data: antibiograms from dogs at a veterinary tertiary care center.

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.

Impact of antimicrobial use in dogs on antimicrobial resistance and shared flora with human owners.

Transmission of bacteria between animals and humans in domestic households is increasingly recognized. We evaluated the presence of antimicrobial-resistant fecal bacteria in 8 dog-owner-dog pairs before and after the dog received amoxicillin-clavulanate. The study identified shared flora in the humans and dogs that were affected by antimicrobial administration.

Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19: A Phase 2 Randomized Clinical Trial.

Importance: Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective: To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants: This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions: In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures: Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase-polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results: Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 (P = .37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, -2.6 [95% CI, -7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P = .31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P = .82). Conclusions and Relevance: In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04399356.

Anomalous Antimicrobial Susceptibility Trend Identification.

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.

Drug-Induced Liver Injury (DILI) With Micafungin: The Importance of Causality Assessment.

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.

Evaluation of a Healthcare-Associated Urinary Tract Infection Combination Antibiogram.

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.

Antimicrobial Stewardship in a Long-Term Acute Care Hospital Using Offsite Electronic Medical Record Audit.

OBJECTIVE To offer antimicrobial stewardship to a long-term acute care hospital using telemedicine. METHODS We 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. RESULTS During 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; P<.001) at program implementation that was maintained afterwards. Anti-Pseudomonas 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). CONCLUSION Antimicrobial stewardship using an electronic medical record via remote access led to a significant decrease in antibacterial usage and a decrease in CDI rates.