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Streptococcus iniae is a fish pathogen that can also infect mammals including dolphins and humans. Its prevalence in farmed fish, particularly tilapia, provides potential for zoonotic infections, as documented by multiple case reports. Systematic clinical data beyond cellulitis for S. iniae infection in humans, including antimicrobial susceptibility data, are unfortunately rare. Here, we present a case of cellulitis progressing to bacteremia caused by Streptococcus iniae in a functionally immunocompromised patient based on CDK4/CDK6 inhibitor and endocrine therapy, and we discuss risk factors, identification, and antimicrobial susceptibility of this rare pathogen.

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Background: Little is known about antimicrobial prescribing when patient care is transitioned to comfort measures only (CMO). We used a multidisciplinary survey and retrospective cohort study to gain insight into antimicrobial prescribing in this population at an academic medical center to inform future antimicrobial stewardship interventions. Methods: A survey focusing on antimicrobial prescribing during the transition to CMO was electronically distributed to providers in medical subspecialities and responses were compared across specialties. A retrospective chart review was performed of patients admitted to an academic medical center in 2020 who were on antimicrobials in the 48 hours prior to CMO. We investigated the percentage of patients who remained on antimicrobials after the transition to CMO and rationale for continuing antimicrobials. Results: We received 113 survey responses (35% response rate). Forty-one percent of respondents indicated that they "sometimes" or "often" continued antimicrobials during the transition to CMO. Patient/family preference and symptom palliation were the most common factors cited by respondents when deciding whether to continue antimicrobials in this population. Of the 546 patient charts reviewed, 140 (26%) patients were alive 48 hours after CMO order, and 19 (14%) of those patients remained on antimicrobials. Five of 19 (26%) patients had documentation that antimicrobials were continued due to patient/family preference and 5 of 19 (26%) patients had documentation that antimicrobials were continued for palliation of symptoms. Conclusions: Patient/family preference and symptom palliation are important factors in prescribing antimicrobials when patient care is transitioned to CMO. More evidence is needed regarding palliative benefits of antibiotics to inform provider discussions of benefits and harms of antimicrobial use in this setting.

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Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

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INTRODUCTION: Antimicrobial Stewardship programs promote appropriate antimicrobial use through different avenues, including education. Advanced Practice Providers (APPs) provide inpatient care in a wide-range of settings. Little is known about the educational needs of APPs at academic medical centers or the effect of educational interventions directed at inpatient APPs on clinical care. Our study looked at the effect of an educational intervention on antimicrobial prescribing by APPs for asymptomatic bacteriuria (ASB) and candiduria (ASC). We also conducted a needs assessment on the opportunities and barriers to continuing medical education. METHODS: The educational intervention consisted of in-person interactive learning accompanied by an online video. Pre-intervention and postintervention surveys included an educational needs assessment and knowledge acquisition assessment. A retrospective chart review of adult inpatients admitted to the APP services with bacteriuria or candiduria during the 3 months pre-intervention and postintervention was performed. RESULTS: Our needs assessment revealed several barriers to APP-focused education including no protected time for learning, and curricula predominantly directed at the Graduate Medical Education level. Engaged APPs had improved knowledge scores, but the proportion of treated ASB or ASC episodes did not differ between the pre-intervention and postintervention. DISCUSSION: Although our educational intervention did not change prescribing patterns, the intervention increased knowledge around ASB and ASC. The potential hierarchical structure of interprofessional care teams may be a barrier to changing antimicrobial prescribing. Our study identified the possibility of a hidden curriculum at academic medical centers that does not prioritize APP educational needs.

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