Abstract Background Traditional blood cultures for gram-negative bacteremia can take up to 72 hours or more to return results, prolonging the duration of empiric broad-spectrum intravenous antibiotics. The Accelerate Pheno system provides rapid identification and susceptibilities for blood cultures in gram-negative bacteremia. Current data on its clinical utility are mixed overall, so the system requires further research. Methods A multicenter, retrospective quasi-experimental study was conducted comparing the Accelerate Pheno rapid diagnostic system with antimicrobial stewardship intervention and traditional blood cultures alone. Results A total of 264 patients with blood cultures with gram-negative bacteria growth were included in the final analysis (102 pre-intervention, 162 post-intervention). The antimicrobial stewardship team made 364 recommendations in 152/162 (93.8%) patients in the post group. Duration of intravenous therapy was shorter (P < .001) for the post-intervention group (median, 4.0 days) compared with the pre-intervention group (median, 7.5 days). Hospital length of stay was also shorter (P < .001) for the post-intervention group (median, 5.1 days) compared with the pre-intervention group (median, 7.0 days). Readmission rates within 30 days were reduced (P = .042) post-intervention (13.0%) compared with pre-intervention (22.6%). In the post-intervention group, a larger proportion of patients were transitioned to oral therapy at any point (126/162, 77.8%) compared with pre-intervention (62/102, 60.8%; P < .001). Conclusions These results suggest that the Accelerate Pheno system, with active review and intervention by a multidisciplinary antimicrobial stewardship team, is a useful tool in improving both patient-centric and antimicrobial stewardship outcomes.
We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA. Functions of expansion segments in the ancestral ribosome are assigned by correspondence with their functions in the extant ribosome. The model explains the evolution of the large ribosomal subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. Two additional phases exclusive to eukaryotes led to tentacle-like rRNA expansions. In this model, ribosomal proteinization was a driving force for the broad adoption of proteins in other biological processes. The exit tunnel was clearly a central theme of all phases of ribosomal evolution and was continuously extended and rigidified. In the primitive noncoding ribosome, proto-mRNA and the small ribosomal subunit acted as cofactors, positioning the activated ends of tRNAs within the peptidyl transferase center. This association linked the evolution of the large and small ribosomal subunits, proto-mRNA, and tRNA.
We describe a case of relapsing babesiosis in an immunocompromised patient. A point mutation in the Babesia microti 23S rRNA gene predicted resistance to azithromycin and clindamycin, whereas an amino acid change in the parasite cytochrome b predicted resistance to atovaquone. Following initiation of tafenoquine, symptoms and parasitemia resolved.
As the point of entry into healthcare for many patients, the emergency department (ED) is an ideal setting in which to assess penicillin (PCN) allergies. An estimated 10% of the United States population has a reported PCN allergy; however, few studies have evaluated the prevalence and impact of PCN allergies on antibiotic selection within the ED. Patients with a documented PCN allergy are more likely to be exposed to costly alternative broad-spectrum antibiotics that have higher rates of adverse events, including C. difficile infections. We sought to determine the prevalence of PCN allergies within the UNC Medical Center ED. Key secondary outcomes included the percentage of patients with a documented PCN allergy who (1) received alternative antibiotics (carbapenems, aztreonam, fluoroquinolones, clindamycin, vancomycin), (2) received β-lactam antibiotics and experienced an allergic reaction during their ED visit, and/or (3) had received a β-lactam antibiotic during a past hospitalization or ED visit without their chart being appropriately updated. A retrospective evaluation included patients aged >18 years with a documented PCN allergy who were discharged from the ED between January 1, 2017, and December 31, 2019. Over the study period, there were 14,635 patient encounters with a documented PCN allergy that comprised 8,573 unique patients. The prevalence of PCN allergies was 14.3% for all ED encounters. PCN allergy–labeled patients received alternative antibiotics in 59.4% of ED encounters in which antibiotics were prescribed. Of the 454 β-lactam antibiotics (62 penicillins, 380 cephalosporins, 12 carbapenems) administered to PCN allergy-labeled patients within the ED, there were zero allergic reactions. Also, 18.6% of PCN allergy-labeled patients had received and tolerated a β-lactam antibiotic during prior hospitalizations or ED visits (1.7% penicillins, 14.4% cephalosporins, 2.6% carbapenems) without appropriate updated documentation to reflect β-lactam antibiotic tolerance. These findings confirm the utilization of non–β-lactam antibiotics in PCN allergy-labeled patients, highlighting the importance of accurate and updated allergy documentation in the electronic medical record. These findings also demonstrate the need for improved allergy documentation and protocols to proactively assess penicillin allergy labels while in the ED. Funding: No Disclosures: None
Significance Ribosomes exist in every cell and are responsible for translation from mRNA to protein. The structure of the ribosomal common core is highly conserved in all living species, while the outer regions of the ribosome are variable. Ribosomal RNA of eukaryotes contains expansion segments accreted onto the surface of the core, which is nearly identical in structure to that in prokaryotic ribosomes. Comparing eukaryotic and prokaryotic ribosomes allows us to identify 3D insertion fingerprints of the expansion segments. Similar fingerprints allow us to analyze the common core and detect ancestral expansion segments within it. We construct a molecular model of ribosomal evolution starting from primordial biological systems near the dawn of life, culminating with relatively recent changes specific to metazoans.
Penicillin (PCN) allergy is one of the most frequently reported medication allergies, with ~10% of the US population reporting a PCN allergy. However, studies have shown that only 1% of the US population have a true IgE-mediated reaction to PCN. Delabeling and appropriately updating patient allergy profiles could decrease the use of alternative broad-spectrum antibiotics, rates of infectious complications [ C. difficile , methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE)], antibiotic resistance, and overall healthcare cost. The emergency department (ED) is an important setting in which to assess PCN allergies and to delabel patients when appropriate because there are >130 million ED visits in the United States each year. We sought to determine the percentage of PCN allergy–labeled patients who could be delabeled through a PCN allergy assessment interview in an ED. Key secondary outcomes included the percentage of interviewed patients who could not be delabeled based on history alone but would be eligible for an amoxicillin oral challenge or a PCN skin test (PST). A prospective PCN allergy assessment pilot was performed for patients aged >18 years presenting to the UNC Medical Center ED between December 1 and December 17, 2020, with a documented PCN allergy. A pharmacist conducted penicillin allergy assessments on a convenience sample of patients presenting to the ED between 8 a.m. and 3 p.m. on weekdays. Based on patients’ reported and documented histories, charts were updated with the most accurate information and allergies were delabeled if appropriate. In total, 95 patients were assessed; 62 (65.3%) were interviewed and 15 (24.2%) were delabeled. In addition, 26 patients (41.9%) were deemed eligible for an oral amoxicillin challenge, 19 (30.6%) qualified for a PST, and 2 (3.2%) patients did not qualify for further assessment due to having a an IgE-mediated reaction in the past 5 years. Of the 15 patients who were delabeled, 6 (40.0%) received antibiotics during their admission: 4 (73.3%) of those patients received a penicillin and 2 (36.7%) received a cephalosporin, all without adverse reactions. Patient assessments took ~20 minutes to complete, including chart review, patient interview, and postinterview chart updating. The results from this pilot study demonstrate the impact of performing PCN allergy assessments in ED. Interdisciplinary opportunities should be explored to develop processes that will improve the efficiency and sustainability of PCN allergy assessments within the ED to allow this important stewardship intervention to continue. Funding: No Disclosures: None
Abstract Fungal infections are a recognized cause of increased morbidity and mortality in thermal burn patients. Adequate treatment regimens remain a challenge due to unpredictable pharmacokinetic/pharmacodynamic changes caused by a hypermetabolic state and individual patient factors. A retrospective evaluation of adult thermal burn patients from April 2014 to April 2020 was conducted to assess voriconazole and posaconazole antifungal dosing regimens. The primary outcome was the incidence of attaining a therapeutic steady-state trough level on the patient’s initial voriconazole or posaconazole regimen. Of the 33 patients analyzed, 26 (78.8%) patients achieved a therapeutic level during azole therapy. However, only 11 (33.3%) patients achieved a therapeutic level on their first azole regimen. The median time to therapeutic level was 8.0 + 21.8 days from the start of azole therapy. Optimal dosing strategies for azole therapy in patients with thermal burns remain undefined. Further assessment is needed to delineate patient-specific factors that can contribute to subtherapeutic azole levels in thermal burn patients and the overall clinical impact of population-specific dosing regimens.
