Implementation of indication-based antibiotic order sentences improves antibiotic use in emergency departments.

INTRODUCTION: Prior data have suggested that suboptimal antibiotic prescribing in the emergency department (ED) is common for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). The objective of this study was to measure the effect of indication-based antibiotic order sentences (AOS) on optimal antibiotic prescribing in the ED. METHODS: This was an IRB-approved quasi-experiment of adults prescribed antibiotics in EDs for uncomplicated LRTI, UTI, or ABSSSI from January to June 2019 (pre-implementation) and September to December 2021 (post-implementation). AOS implementation occurred in July 2021. AOS are lean process, electronic discharge prescriptions retrievable by name or indication within the discharge order field. The primary outcome was optimal prescribing, defined as correct antibiotic selection, dose, and duration per local and national guidelines. Descriptive and bivariate statistics were performed; multivariable logistic regression was used to determine variables associated with optimal prescribing. RESULTS: A total of 294 patients were included: 147 pre-group and 147 post-group. Overall optimal prescribing improved from 12 (8%) to 34 (23%) (P < 0.001). Individual components of optimal prescribing were optimal selection at 90 (61%) vs 117 (80%) (P < 0.001), optimal dose at 99 (67%) vs 115 (78%) (P = 0.036), and optimal duration at 38 (26%) vs 50 (34%) (P = 0.13) for pre- and post-group, respectively. AOS was independently associated with optimal prescribing after multivariable logistic regression analysis (adjOR, 3.6; 95%CI,1.7-7.2). A post-hoc analysis showed low uptake of AOS by ED prescribers. CONCLUSIONS: AOS are an efficient and promising strategy to enhance antimicrobial stewardship in the ED.

Phenol soluble modulin (PSM) variants of community-associated methicillin-resistant Staphylococcus aureus (MRSA) captured using mass spectrometry-based molecular networking.

Molecular genetic analysis indicates that the problematic human bacterial pathogen methicillin-resistant Staphylococcus aureus possesses more than 2000 open reading frames in its genome. This number of potential gene products, coupled with intrinsic mechanisms of posttranslational modification, endows methicillin-resistant Staphylococcus aureus with a highly complex biochemical repertoire. Recent proteomic and metabolomic advances have provided methodologies to better understand and characterize the biosynthetic factors released by microbial organisms. Here, the emerging tool of mass spectrometry-based molecular networking was used to visualize and map the repertoire of biosynthetic factors produced by a community-associated methicillin-resistant Staphylococcus aureus strain representative of the epidemic USA300 clone. In particular, the study focused on elucidating the complexity of the recently discovered phenol soluble modulin family of peptides when placed under various antibiotic treatment stresses. Novel PSM truncated variant peptides were captured, and the type of variants that were clustered by the molecular networks platform changed in response to the different antibiotic treatment conditions. After discovery, a group of the peptides were selected for functional analysis in vitro. The peptides displayed bioactive properties including the ability to induce proinflammatory responses in human THP-1 monocytes. Additionally, the tested peptides did not display antimicrobial activity as previously reported for other phenol soluble modulin truncated variants. Our findings reveal that the PSM family of peptides are quite structurally diverse, and suggest a single phenol soluble modulin parent peptide can functionally spawn differential bioactivities in response to various external stimuli.

Anthracimycin activity against contemporary methicillin-resistant Staphylococcus aureus.

Anthracimycin is a recently discovered novel marine-derived compound with activity against Bacillus anthracis. We tested anthracimycin against an expanded panel of Staphylococcus aureus strains in vitro and in vivo. All strains of S. aureus tested, including methicillin-susceptible, methicillin-resistant (MRSA) and vancomycin-resistant strains of S. aureus, were susceptible to anthracimycin at MIC values of ⩽0.25 mg l(-1). Although its postantibiotic effects were minimal, anthracimycin exhibited potent and rapid bactericidal activity, with a >4-log kill of USA300 MRSA within 3 h at five times its MIC. At concentrations significantly below the MIC, anthracimycin slowed MRSA growth and potentiated the bactericidal activity of the human cathelicidin, LL-37. The bactericidal activity of anthracimycin was somewhat mitigated in the presence of 20% human serum, and the compound was minimally toxic to human cells, with an IC50 (inhibitory concentration 50)=70 mg l(-1) against human carcinoma cells. At concentrations near the MIC, anthracimycin inhibited S. aureus nucleic acid synthesis as determined by optimized macromolecular synthesis methodology, with inhibition of DNA and RNA synthesis occurring in the absence of DNA intercalation. Anthracimycin at a single dose of 1 or 10 mg kg(-1) was able to protect mice from MRSA-induced mortality in a murine peritonitis model of infection. Anthracimycin provides an interesting new scaffold for future development of a novel MRSA antibiotic.