Lessons Learned from a National Hospital Antibiotic Stewardship Implementation Project.

BACKGROUND: The goal of antibiotic stewardship programs (ASPs) is to ensure that patients receive effective therapy while minimizing adverse events. To overcome barriers commonly faced in implementing successful ASPs, the Agency for Healthcare Research and Quality (AHRQ) established a multifaceted, nationwide Safety Program for Improving Antibiotic Use in 2018. This report summarizes the lessons learned from the implementation of this initiative based on structured interviews of personnel from participating sites. METHODS: At the completion of the one-year initiative, semistructured exit interviews were conducted with site leaders at 151 of the 402 hospitals that participated. These interviews consisted of open-ended questions about the perceived effectiveness of components of the Safety Program. Qualitative analyses incorporated both deductive coding themes (based on existing literature) and an iteratively developed inductive coding framework (based on salient themes that emerged from a subset of interviews). RESULTS: Several components of the Safety Program were identified as effective in expanding local stewardship activities, including techniques and strategies to implement sustainable ASPs, access to Implementation Advisors to keep sites engaged, provision of local benchmarked antibiotic use data to compare to similar hospitals, and Safety Program materials such as the antibiotic time-out tool to integrate stewardship techniques into daily work flows. The biggest challenges to greater effectiveness were suboptimal frontline staff engagement and difficulty changing antibiotic prescribing culture. Some approaches used to overcome these barriers (peer-to-peer communication and education through team huddles, identifying physician champions, informal rounds to enhance collegiality and buy-in, and engagement of hospital leadership) were identified. CONCLUSION: Lessons learned from the Safety Program can be applied by other teams looking to promote an effective ASP at their hospital or system. The themes that emerged in this study likely also have relevance across a wide range of large-scale quality improvement initiatives.

Thoracic Outlet Syndrome in the Pediatric and Young Adult Population.

PURPOSE: This study aimed to assess both nonsurgical and operative treatment outcomes of pediatric and young adult patients with thoracic outlet syndrome (TOS) at a tertiary care pediatric hospital. METHODS: A retrospective chart review of patients diagnosed with TOS, who were seen between January 2010 and August 2022 at a tertiary care pediatric hospital, was conducted. Collected pre- and postoperative data included symptoms, provocative testing (ie, Roo's, Wright's, and Adson's tests), participation in sports or upper-extremity activities, additional operations, and surgical complications. Assessment of operative treatment efficacy was based on pre- and post-provocative testing, pain, venogram results, alleviation of symptoms, and return to previous activity level 6 months after surgery. RESULTS: Ninety-six patients, (70 females and 26 males) with an average age at onset of 15 ± 4 (4-25) years, met the inclusion criteria for TOS. Among them, 27 had neurogenic TOS, 29 had neurogenic and vasculogenic TOS, 20 had vasculogenic TOS, 19 had Paget-Schroetter Syndrome, and one was asymptomatic. Twenty-six patients were excluded because of less than 6 months of follow-up. Of the remaining 70, 6 (8.6%) patients (4 bilateral and 2 unilateral) underwent nonoperative management with activity modification and physical therapy only, and one was fully discharged because of complete relief of symptoms. Sixty-four (90.1%) patients (45 bilateral and 19 unilateral) underwent surgery. A total of 102 operations were performed. Substantial improvements were observed in provocative maneuvers after surgery. Before surgery, 79.7% were involved in sports or playing musical instruments with repetitive overhead activity, and after surgery, 86.2% of these patients returned to their previous activity level. CONCLUSIONS: Few patients were successfully managed with nonoperative activity modification and physical therapy. In those requiring surgical intervention, first or cervical rib resection with scalenectomy using a supraclavicular approach provided resolution of symptoms with 86.2% of patients being able to return to presymptom sport or activity level. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Investigation of a Mass Stranding Event Reveals a Novel Pattern of Cascading Comorbidities in Northern Fulmars (Fulmarus glacialis).

During 2018, a seabird mortality event occurred in central California, US, that affected Northern Fulmars (Fulmarus glacialis), Common Murres (Uria aalge), and Cassin's Auklets (Ptychoramphus aleuticus). An increase in beachcast birds were reported on standardized surveys in conjunction with an increased number of live-stranded birds admitted to rehabilitation centers. Neurologic symptoms were noted during intake examination for some birds. Coincident with the mortality event, increased levels of the harmful algal bloom toxins domoic acid and saxitoxin were recorded in Monterey Bay and Morro Bay. Birds that died in care and beachcast carcasses were submitted to the California Department of Fish and Wildlife-Marine Wildlife Veterinary Care and Research Center for postmortem examination (n=24). All examined birds were emaciated. Examined Common Murres and Cassin's Auklets had no gross evidence of preexisting disease; however, all examined Northern Fulmars exhibited severe pyogranulomatous inflammation of the urogenital system at gross postmortem exam. Tissues from nine Northern Fulmars were examined by histopathology, and samples from two Northern Fulmars were tested for the presence of domoic acid and saxitoxin. Histopathology revealed moderate to severe kidney infection by Eimeria sp. and gram-negative bacteria, intratubular urate stasis, ureter rupture, and emaciation. Additionally, domoic acid and saxitoxin were detected simultaneously in tissues of some tested birds. This communication highlights a novel pattern of cascading comorbidities in native seabirds from a mass stranding event.

Novel Presentation of Coccidioidomycosis with Myriad Free-Floating Proteinaceous Spheres in the Pericardial Sac of a Southern Sea Otter (Enhydra lutris nereis).

A southern sea otter (Enhydra lutris nereis) stranded dead in central California, USA, with a distended pericardial sac containing thousands of free-floating proteinaceous masses. Serology, fungal culture, PCR, and sequencing confirmed the etiology of this novel lesion as Coccidioides immitis. Range expansion of this zoonotic pathogen is predicted with climate change.

Pathology, microbiology, and genetic diversity associated with Erysipelothrix rhusiopathiae and novel Erysipelothrix spp. infections in southern sea otters (Enhydra lutris nereis).

Erysipelothrix spp., including E. rhusiopathiae, are zoonotic bacterial pathogens that can cause morbidity and mortality in mammals, fish, reptiles, birds, and humans. The southern sea otter (SSO; Enhydra lutris nereis) is a federally-listed threatened species for which infectious disease is a major cause of mortality. We estimated the frequency of detection of these opportunistic pathogens in dead SSOs, described pathology associated with Erysipelothrix infections in SSOs, characterized the genetic diversity and antimicrobial susceptibility of SSO isolates, and evaluated the virulence of two novel Erysipelothrix isolates from SSOs using an in vivo fish model. From 1998 to 2021 Erysipelothrix spp. were isolated from six of >500 necropsied SSOs. Erysipelothrix spp. were isolated in pure culture from three cases, while the other three were mixed cultures. Bacterial septicemia was a primary or contributing cause of death in five of the six cases. Other pathology observed included suppurative lymphadenopathy, fibrinosuppurative arteritis with thrombosis and infarction, bilateral uveitis and endophthalmitis, hypopyon, petechia and ecchymoses, mucosal infarction, and suppurative meningoencephalitis and ventriculitis. Short to long slender Gram-positive or Gram-variable bacterial rods were identified within lesions, alone or with other opportunistic bacteria. All six SSO isolates had the spaA genotype-four isolates clustered with spaA E. rhusiopathiae strains from various terrestrial and marine animal hosts. Two isolates did not cluster with any known Erysipelothrix spp.; whole genome sequencing revealed a novel Erysipelothrix species and a novel E. rhusiopathiae subspecies. We propose the names Erysipelothrix enhydrae sp. nov. and Erysipelothrix rhusiopathiae ohloneorum ssp. nov. respectively. The type strains are E. enhydrae UCD-4322-04 and E. rhusiopathiae ohloneorum UCD-4724-06, respectively. Experimental injection of tiger barbs (Puntigrus tetrazona) resulted in infection and mortality from the two novel Erysipelothrix spp. Antimicrobial susceptibility testing of Erysipelothrix isolates from SSOs shows similar susceptibility profiles to isolates from other terrestrial and aquatic animals. This is the first description of the pathology, microbial characteristics, and genetic diversity of Erysipelothrix isolates recovered from diseased SSOs. Methods presented here can facilitate case recognition, aid characterization of Erysipelothrix isolates, and illustrate assessment of virulence using fish models.

Divergent Serpentoviruses in Free-Ranging Invasive Pythons and Native Colubrids in Southern Florida, United States.

Burmese python (Python bivittatus) is an invasive snake that has significantly affected ecosystems in southern Florida, United States. Aside from direct predation and competition, invasive species can also introduce nonnative pathogens that can adversely affect native species. The subfamily Serpentovirinae (order Nidovirales) is composed of positive-sense RNA viruses primarily found in reptiles. Some serpentoviruses, such as shingleback nidovirus, are associated with mortalities in wild populations, while others, including ball python nidovirus and green tree python nidovirus can be a major cause of disease and mortality in captive animals. To determine if serpentoviruses were present in invasive Burmese pythons in southern Florida, oral swabs were collected from both free-ranging and long-term captive snakes. Swabs were screened for the presence of serpentovirus by reverse transcription PCR and sequenced. A total serpentovirus prevalence of 27.8% was detected in 318 python samples. Of the initial swabs from 172 free-ranging pythons, 42 (24.4%) were positive for multiple divergent viral sequences comprising four clades across the sampling range. Both sex and snout-vent length were statistically significant factors in virus prevalence, with larger male snakes having the highest prevalence. Sampling location was statistically significant in circulating virus sequence. Mild clinical signs and lesions consistent with serpentovirus infection were observed in a subset of sampled pythons. Testing of native snakes (n = 219, 18 species) in part of the python range found no evidence of python virus spillover; however, five individual native snakes (2.3%) representing three species were PCR positive for unique, divergent serpentoviruses. Calculated pairwise uncorrected distance analysis indicated the newly discovered virus sequences likely represent three novel genera in the subfamily Serpentovirinae. This study is the first to characterize serpentovirus in wild free-ranging pythons or in any free-ranging North America reptile. Though the risk these viruses pose to the invasive and native species is unknown, the potential for spillover to native herpetofauna warrants further investigation.

A framework for implementing antibiotic stewardship in ambulatory care: Lessons learned from the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use.

Antibiotic overuse is common in ambulatory care settings, underscoring the importance of outpatient antibiotic stewardship to ensure safe and effective antibiotic prescription. In response to this need, the Agency for Healthcare Research and Quality (AHRQ) developed the AHRQ Safety Program for Improving Antibiotic Use in Ambulatory Care. The Safety Program successfully assisted 389 outpatient practices across the United States to establish ambulatory antibiotic stewardship. Herein, we have used lessons learned from the AHRQ Safety Program to describe a step-by-step framework to assist practices with establishing antibiotic stewardship in the outpatient setting. Steps include obtaining support from practice leadership; establishing an antibiotic stewardship team; garnering support from practice members; determining how to access antibiotic prescribing data; building communication skills around antibiotic use in the practice; implementing educational content around an infectious syndrome; monitoring antibiotic prescription data; and implementing a sustainability plan.

Assessment of Changes in Visits and Antibiotic Prescribing During the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use and the COVID-19 Pandemic.

Importance: The Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use aimed to improve antibiotic prescribing in ambulatory care practices by engaging clinicians and staff to incorporate antibiotic stewardship into practice culture, communication, and decision-making. Little is known about implementation of antibiotic stewardship in ambulatory care practices. Objective: To examine changes in visits and antibiotic prescribing during the AHRQ Safety Program. Design, Setting, and Participants: This cohort study evaluated a quality improvement intervention in ambulatory care throughout the US in 389 ambulatory care practices from December 1, 2019, to November 30, 2020. Exposures: The AHRQ Safety Program used webinars, audio presentations, educational tools, and office hours to engage stewardship leaders and clinical staff to address attitudes and cultures that challenge judicious antibiotic prescribing and incorporate best practices for the management of common infections. Main Outcomes and Measures: The primary outcome of the Safety Program was antibiotic prescriptions per 100 acute respiratory infection (ARI) visits. Data on total visits and ARI visits were also collected. The number of visits and prescribing rates from baseline (September 1, 2019) to completion of the program (November 30, 2020) were compared. Results: Of 467 practices enrolled, 389 (83%) completed the Safety Program; of these, 292 (75%) submitted complete data with 6 590 485 visits to 5483 clinicians. Participants included 82 (28%) primary care practices, 103 (35%) urgent care practices, 34 (12%) federally supported practices, 39 (13%) pediatric urgent care practices, 21 (7%) pediatric-only practices, and 14 (5%) other practice types. Visits per practice per month decreased from a mean of 1624 (95% CI, 1317-1931) at baseline to a nadir of 906 (95% CI, 702-1111) early in the COVID-19 pandemic (April 2020), and were 1797 (95% CI, 1510-2084) at the end of the program. Total antibiotic prescribing decreased from 18.2% of visits at baseline to 9.5% at completion of the program (-8.7%; 95% CI, -9.9% to -7.6%). Acute respiratory infection visits per practice per month decreased from baseline (n = 321) to a nadir of 76 early in the pandemic (May 2020) and gradually increased through completion of the program (n = 239). Antibiotic prescribing for ARIs decreased from 39.2% at baseline to 24.7% at completion of the program (-14.5%; 95% CI, -16.8% to -12.2%). Conclusions and Relevance: In this study of US ambulatory practices that participated in the AHRQ Safety Program, significant reductions in the rates of overall and ARI-related antibiotic prescribing were noted, despite normalization of clinic visits by completion of the program. The forthcoming AHRQ Safety Program content may have utility in ambulatory practices across the US.

Implementation of an Antibiotic Stewardship Program in Long-term Care Facilities Across the US.

IMPORTANCE: Antibiotic overuse in long-term care (LTC) is common, prompting calls for antibiotic stewardship programs (ASPs) designed for specific use in these settings. The optimal approach to establish robust, sustainable ASPs in LTC facilities is unknown. OBJECTIVES: To determine if the Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use, an educational initiative to establish ASPs focusing on patient safety, is associated with reductions in antibiotic use in LTC settings. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study including 439 LTC facilities in the US assessed antibiotic therapy data following a pragmatic quality-improvement program, which was implemented to assist facilities in establishing ASPs and with antibiotic decision-making. Training was conducted between December 2018 and November 2019. Data were analyzed from January 2019 to December 2019. INTERVENTIONS: Fifteen webinars occurred over 12 months (December 2018 to November 2019), accompanied by additional tools, activities, posters, and pocket cards. All clinical staff were encouraged to participate. MAIN OUTCOMES AND MEASURES: The primary outcome was antibiotic starts per 1000 resident-days. Secondary outcomes included days of antibiotic therapy (DOT) per 1000 resident-days, the number of urine cultures per 1000 resident-days, and Clostridioides difficile laboratory-identified events per 10 000 resident-days. All outcomes compared data from the baseline (January-February 2019) to the completion of the program (November-December 2019). Generalized linear mixed models with random intercepts at the site level assessed changes over time. RESULTS: Of a total 523 eligible LTC facilities, 439 (83.9%) completed the safety program. The mean difference for antibiotic starts from baseline to study completion per 1000 resident-days was -0.41 (95% CI, -0.76 to -0.07; P = .02), with fluoroquinolones showing the greatest decrease at -0.21 starts per 1000 resident-days (95% CI, -0.35 to -0.08; P = .002). The mean difference for antibiotic DOT per 1000 resident-days was not significant (-3.05; 95% CI, -6.34 to 0.23; P = .07). Reductions in antibiotic starts and use were greater in facilities with greater program engagement (as measured by webinar attendance). While antibiotic starts and DOT in these facilities decreased by 1.12 per 1000 resident-days (95% CI, -1.75 to -0.49; P < .001) and 9.97 per 1000 resident-days (95% CI, -15.4 to -4.6; P < .001), respectively, no significant reductions occurred in low engagement facilities. Urine cultures per 1000 resident-days decreased by 0.38 (95% CI, -0.61 to -0.15; P = .001). There was no significant change in facility-onset C difficile laboratory-identified events. CONCLUSIONS AND RELEVANCE: Participation in the AHRQ safety program was associated with the development of ASPs that actively engaged clinical staff in the decision-making processes around antibiotic prescriptions in participating LTC facilities. The reduction in antibiotic DOT and starts, which was more pronounced in more engaged facilities, indicates that implementation of this multifaceted program may support successful ASPs in LTC settings.

Anatomy of the sense of touch in sea otters: Cutaneous mechanoreceptors and structural features of glabrous skin.

Sea otters (Enhydra lutris) demonstrate rapid, accurate tactile abilities using their paws and facial vibrissae. Anatomical investigations of neural organization in the vibrissal bed and somatosensory cortex coincide with measured sensitivity, but no studies describe sensory receptors in the paws or other regions of glabrous (i.e., hairless) skin. In this study, we use histology to assess the presence, density, and distribution of mechanoreceptors in the glabrous skin of sea otters: paws, rhinarium, lips, and flipper digits, and we use scanning electron microscopy to describe skin-surface texture and its potential effect on the transduction of mechanical stimuli. Our results confirm the presence of Merkel cells and Pacinian corpuscles, but not Meissner corpuscles, in all sea otter glabrous skin. The paws showed the highest density of Merkel cells and Pacinian corpuscles. Within the paw, relative densities of mechanoreceptor types were highest in the distal metacarpal pad and digits, which suggests that the distal paw is a tactile fovea for sea otters. In addition to the highest receptor density, the paw displayed the thickest epidermis. Rete ridges (epidermal projections into the dermis) and dermal papillae (dermal projections into the epidermis) were developed across all glabrous skin. These quantitative and qualitative descriptions of neural organization and physical features, combined with previous behavioral results, contribute to our understanding of how structure relates to function in the tactile modality. Our findings coincide with behavioral observations of sea otters, which use touch to maintain thermoregulatory integrity of their fur, explore objects, and capture visually cryptic prey.

INVESTIGATING ASSOCIATIONS AMONG RELATEDNESS, GENETIC DIVERSITY, AND CAUSES OF MORTALITY IN SOUTHERN SEA OTTERS (ENHYDRA LUTRIS NEREIS).

Southern sea otter (Enhydra lutris nereis) population recovery is influenced by a variety of factors, including predation, biotoxin exposure, infectious disease, oil spills, habitat degradation, and resource limitation. This population has also experienced a significant genetic bottleneck, resulting in low genetic diversity. We investigated how two metrics, familial relatedness and genetic diversity, are correlated with common causes of mortality in southern sea otters, including cardiomyopathy, acanthocephalan (Profilicollis spp.) peritonitis, systemic protozoal infection (Toxoplasma gondii and Sarcocystis neurona), domoic acid intoxication, end-lactation syndrome, and shark bite. Microsatellite genetic markers were used to examine this association in 356 southern sea otters necropsied from 1998 to 2012. Significant associations with genetic diversity or familial relatedness (P<0.05) were observed for cardiomyopathy, acanthocephalan peritonitis, and sarcocystosis, and these associations varied by sex. Adult male cardiomyopathy cases (n=86) were more related than the null expectation (P<0.049). Conversely, female acanthocephalan peritonitis controls (n=110) were more related than the null expectation (P<0.004). Including genetic diversity as a predictor for fatal acanthocephalan peritonitis in the multivariate logistic model significantly improved model fit; lower genetic diversity was associated with reduced odds of sea otter death due to acanthocephalan peritonitis. Finally, male sarcocystosis controls (n=158) were more related than the null expectation (P<0.011). Including genetic diversity in the multivariate logistic model for fatal S. neurona infection improved model fit; lower genetic diversity was associated with increased odds of sea otter death due to S. neurona. Our study suggests that genetic diversity and familial relatedness, in conjunction with other factors such as age and sex, may influence outcome (survival or death) in relation to several common southern sea otter diseases. Our findings can inform policy for conservation management, such as potential reintroduction efforts, as part of species recovery.

Exploration of serum cardiac troponin I as a biomarker of cardiomyopathy in southern sea otters (Enhydra lutris nereis).

OBJECTIVE: To compare serum cardiac troponin I (cTnI) concentrations between sea otters with and without cardiomyopathy and describe 2 cases of cardiomyopathy with different etiologies. ANIMALS: 25 free-ranging southern sea otters (Enhydra lutris nereis) with (n = 14; cases) and without (11; controls) cardiomyopathy and 17 healthy managed southern sea otters from aquariums or rehabilitation centers (controls). PROCEDURES: Serum cTnI concentration was measured in live sea otters. Histopathologic and gross necropsy findings were used to classify cardiomyopathy status in free-ranging otters; physical examination and echocardiography were used to assess health status of managed otters. Two otters received extensive medical evaluations under managed care, including diagnostic imaging, serial cTnI concentration measurement, and necropsy. RESULTS: A significant difference in cTnI concentrations was observed between cases and both control groups, with median values of 0.279 ng/mL for cases and < 0.006 ng/mL for free-ranging and managed controls. A cutoff value of ≥ 0.037 ng/mL yielded respective sensitivity and specificity estimates for detection of cardiomyopathy of 64.3% and 90.9% for free-ranging cases versus free-ranging controls and 64.3% and 94.1% for free-ranging cases versus managed controls. CONCLUSIONS AND CLINICAL RELEVANCE: Cardiomyopathy is a common cause of sea otter death that has been associated with domoic acid exposure and protozoal infection. Antemortem diagnostic tests are needed to identify cardiac damage. Results suggested that serum cTnI concentration has promise as a biomarker for detection of cardiomyopathy in sea otters. Serial cTnI concentration measurements and diagnostic imaging are recommended to improve heart disease diagnosis in managed care settings.

Demodectic mange in threatened southern sea otters (Enhydra lutris nereis).

BACKGROUND: Southern sea otters (Enhydra lutris nereis) rely on intact pelage for thermoregulation, and thus clinically significant demodicosis and associated alopecia can cause morbidity and death. HYPOTHESIS/OBJECTIVES: This study aimed to describe lesions associated with follicular Demodex sp. infestation, estimate the prevalence and intensity of infestation, describe mite distribution across key anatomical regions, and assess mite presence or absence in relation to lesions and host risk factors. ANIMALS: Twenty necropsied, wild southern sea otters that stranded along the central California coast from 2005 to 2018. METHODS AND MATERIALS: Grossly normal and abnormal integument from the head, perineum, genitals, mamillary papillae and limbs was assessed microscopically for mites and mite-associated pathological findings. RESULTS: Intrafollicular mites were observed in the integument of 55% of otters and 20% had clinical demodicosis. Demodicosis was considered to be contributory to death or euthanasia in two cases. Although Demodex sp. mites often were observed microscopically in grossly normal skin, the presence of multiple densely-packed intrafollicular mites generally was associated with pigmentary incontinence, ectatic follicles, lymphoplasmacytic perifolliculitis, and neutrophilic and lymphoplasmacytic, dermal inflammation. Other findings included epidermal hyperplasia, orthokeratotic hyperkeratosis of epidermis and follicular epithelium, concurrent pyoderma and cell necrosis. Perioral integument, especially of the chin, had the highest prevalence of mites and the highest mite density, suggesting facial contact as a means of mite transmission. CONCLUSIONS AND CLINICAL IMPORTANCE: Our research confirmed demodectic mange as a contributor to morbidity and mortality in sea otters, with important implications for clinical care, rehabilitation and conservation.

Argentine Black and White Tegu (Salvator merianae) can survive the winter under semi-natural conditions well beyond their current invasive range.

The Argentine Black and White Tegu (Salvator merianae, formerly Tupinambis merianae) is a large lizard from South America. Now established and invasive in southern Florida, and it poses threats to populations of many native species. Models suggest much of the southern United States may contain suitable temperature regimes for this species, yet there is considerable uncertainty regarding either the potential for range expansion northward out of tropical and subtropical zones or the potential for the species establishing elsewhere following additional independent introductions. We evaluated survival, body temperature, duration and timing of winter dormancy, and health of wild-caught tegus from southern Florida held in semi-natural enclosures for over a year in Auburn, Alabama (> 900 km northwest of capture location). Nine of twelve lizards emerged from winter dormancy and seven survived the greater-than-one-year duration of the study. Average length of dormancy (176 d) was greater than that reported in the native range or for invasive populations in southern Florida and females remained dormant longer than males. Tegus grew rapidly throughout the study and the presence of sperm in the testes of males and previtellogenic or early vitellogenic follicles in female ovaries at the end of our study suggest the animals would have been capable of reproduction the following spring. The survival and overall health of the majority of adult tegus in our study suggests weather and climate patterns are unlikely to prevent survival following introduction in many areas of the United States far from their current invasive range.

Association of a Safety Program for Improving Antibiotic Use With Antibiotic Use and Hospital-Onset Clostridioides difficile Infection Rates Among US Hospitals.

Importance: Regulatory agencies and professional organizations recommend antibiotic stewardship programs (ASPs) in US hospitals. The optimal approach to establish robust, sustainable ASPs across diverse hospitals is unknown. Objective: To assess whether the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use is associated with reductions in antibiotic use across US hospitals. Design, Setting, and Participants: A pragmatic quality improvement program was conducted and evaluated over a 1-year period in US hospitals. A total of 437 hospitals were enrolled. The study was conducted from December 1, 2017, to November 30, 2018. Data analysis was performed from March 1 to October 31, 2019. Interventions: The Safety Program assisted hospitals with establishing ASPs and worked with frontline clinicians to improve their antibiotic decision-making. All clinical staff (eg, clinicians, pharmacists, and nurses) were encouraged to participate. Seventeen webinars occurred over 12 months, accompanied by additional durable educational content. Topics focused on establishing ASPs, the science of safety, improving teamwork and communication, and best practices for the diagnosis and management of infectious processes. Main Outcomes and Measures: The primary outcome was overall antibiotic use (days of antibiotic therapy [DOT] per 1000 patient days [PD]) comparing the beginning (January-February 2018) and end (November-December 2018) of the Safety Program. Data analysis occurred using linear mixed models with random hospital unit effects. Antibiotic use from 614 hospitals in the Premier Healthcare Database from the same period was analyzed to evaluate contemporary US antibiotic trends. Quarterly hospital-onset Clostridioides difficile laboratory-identified events per 10 000 PD were a secondary outcome. Results: Of the 437 hospitals enrolled, 402 (92%) remained in the program until its completion, including 28 (7%) academic medical centers, 122 (30%) midlevel teaching hospitals, 167 (42%) community hospitals, and 85 (21%) critical access hospitals. Adherence to key components of ASPs (ie, interventions before and after prescription of antibiotics, availability of local antibiotic guidelines, ASP leads with dedicated salary support, and quarterly reporting of antibiotic use) improved from 8% to 74% over the 1-year period (P < .01). Antibiotic use decreased by 30.3 DOT per 1000 PD (95% CI, -52.6 to -8.0 DOT; P = .008). Similar changes in antibiotic use were not observed in the Premier Healthcare Database. The incidence rate of hospital-onset C difficile laboratory-identified events decreased by 19.5% (95% CI, -33.5% to -2.4%; P = .03). Conclusions and Relevance: The Agency for Healthcare Research and Quality Safety Program appeared to enable diverse hospitals to establish ASPs and teach frontline clinicians to self-steward their antibiotic use. Safety Program content is publicly available.

Exposure to domoic acid is an ecological driver of cardiac disease in southern sea otters✰.

Harmful algal blooms produce toxins that bioaccumulate in the food web and adversely affect humans, animals, and entire marine ecosystems. Blooms of the diatom Pseudo-nitzschia can produce domoic acid (DA), a toxin that most commonly causes neurological disease in endothermic animals, with cardiovascular effects that were first recognized in southern sea otters. Over the last 20 years, DA toxicosis has caused significant morbidity and mortality in marine mammals and seabirds along the west coast of the USA. Identifying DA exposure has been limited to toxin detection in biological fluids using biochemical assays, yet measurement of systemic toxin levels is an unreliable indicator of exposure dose or timing. Furthermore, there is little information regarding repeated DA exposure in marine wildlife. Here, the association between long-term environmental DA exposure and fatal cardiac disease was investigated in a longitudinal study of 186 free-ranging sea otters in California from 2001 - 2017, highlighting the chronic health effects of a marine toxin. A novel Bayesian spatiotemporal approach was used to characterize environmental DA exposure by combining several DA surveillance datasets and integrating this with life history data from radio-tagged otters in a time-dependent survival model. In this study, a sea otter with high DA exposure had a 1.7-fold increased hazard of fatal cardiomyopathy compared to an otter with low exposure. Otters that consumed a high proportion of crab and clam had a 2.5- and 1.2-times greater hazard of death due to cardiomyopathy than otters that consumed low proportions. Increasing age is a well-established predictor of cardiac disease, but this study is the first to identify that DA exposure affects the risk of cardiomyopathy more substantially in prime-age adults than aged adults. A 4-year-old otter with high DA exposure had 2.3 times greater risk of fatal cardiomyopathy than an otter with low exposure, while a 10-year old otter with high DA exposure had just 1.2 times greater risk. High Toxoplasma gondii titers also increased the hazard of death due to heart disease 2.4-fold. Domoic acid exposure was most detrimental for prime-age adults, whose survival and reproduction are vital for population growth, suggesting that persistent DA exposure will likely impact long-term viability of this threatened species. These results offer insight into the pervasiveness of DA in the food web and raise awareness of under-recognized chronic health effects of DA for wildlife at a time when toxic blooms are on the rise.

Spatial epidemiological patterns suggest mechanisms of land-sea transmission for Sarcocystis neurona in a coastal marine mammal.

Sarcocystis neurona was recognised as an important cause of mortality in southern sea otters (Enhydra lutris nereis) after an outbreak in April 2004 and has since been detected in many marine mammal species in the Northeast Pacific Ocean. Risk of S. neurona exposure in sea otters is associated with consumption of clams and soft-sediment prey and is temporally associated with runoff events. We examined the spatial distribution of S. neurona exposure risk based on serum antibody testing and assessed risk factors for exposure in animals from California, Washington, British Columbia and Alaska. Significant spatial clustering of seropositive animals was observed in California and Washington, compared with British Columbia and Alaska. Adult males were at greatest risk for exposure to S. neurona, and there were strong associations with terrestrial features (wetlands, cropland, high human housing-unit density). In California, habitats containing soft sediment exhibited greater risk than hard substrate or kelp beds. Consuming a diet rich in clams was also associated with increased exposure risk. These findings suggest a transmission pathway analogous to that described for Toxoplasma gondii, with infectious stages traveling in freshwater runoff and being concentrated in particular locations by marine habitat features, ocean physical processes, and invertebrate bioconcentration.

The inconvincible patient: how clinicians perceive demand for antibiotics in the outpatient setting.

BACKGROUND: Perceived patient demand for antibiotics drives unnecessary antibiotic prescribing in outpatient settings, but little is known about how clinicians experience this demand or how this perceived demand shapes their decision-making. OBJECTIVE: To identify how clinicians perceive patient demand for antibiotics and the way these perceptions stimulate unnecessary prescribing. METHODS: Qualitative study using semi-structured interviews with clinicians in outpatient settings who prescribe antibiotics. Interviews were analyzed using conventional and directed content analysis. RESULTS: Interviews were conducted with 25 clinicians from nine practices across three states. Patient demand was the most common reason respondents provided for why they prescribed non-indicated antibiotics. Three related factors motivated clinically unnecessary antibiotic use in the face of perceived patient demand: (i) clinicians want their patients to regard clinical visits as valuable and believe that an antibiotic prescription demonstrates value; (ii) clinicians want to avoid negative repercussions of denying antibiotics, including reduced income, damage to their reputation, emotional exhaustion, and degraded relationships with patients; (iii) clinicians believed that certain patients are impossible to satisfy without an antibiotic prescription and felt that efforts to refuse antibiotics to such patients wastes time and invites the aforementioned negative repercussions. Clinicians in urgent care settings were especially likely to describe being motivated by these factors. CONCLUSION: Interventions to improve antibiotic use in the outpatient setting must address clinicians' concerns about providing value for their patients, fear of negative repercussions from denying antibiotics, and the approach to inconvincible patients.