Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Anatomy of an extensively drug-resistant Klebsiella pneumoniae outbreak in Tuscany, Italy.

A protracted outbreak of New Delhi metallo-ß-lactamase (NDM)-producing carbapenem-resistant Klebsiella pneumoniae started in Tuscany, Italy, in November 2018 and continued in 2020 and through 2021. To understand the regional emergence and transmission dynamics over time, we collected and sequenced the genomes of 117 extensively drug-resistant, NDM-producing K. pneumoniae isolates cultured over a 20-mo period from 76 patients at several healthcare facilities in southeast Tuscany. All isolates belonged to high-risk clone ST-147 and were typically nonsusceptible to all first-line antibiotics. Albeit sporadic, resistances to colistin, tigecycline, and fosfomycin were also observed as a result of repeated, independent mutations. Genomic analysis revealed that ST-147 isolates circulating in Tuscany were monophyletic and highly genetically related (including a network of 42 patients from the same hospital and sharing nearly identical isolates), and shared a recent ancestor with clinical isolates from the Middle East. While the blaNDM-1 gene was carried by an IncFIB-type plasmid, our investigations revealed that the ST-147 lineage from Italy also acquired a hybrid IncFIB/IncHIB-type plasmid carrying the 16S methyltransferase armA gene as well as key virulence biomarkers often found in hypervirulent isolates. This plasmid shared extensive homologies with mosaic plasmids circulating globally including from ST-11 and ST-307 convergent lineages. Phenotypically, the carriage of this hybrid plasmid resulted in increased siderophore production but did not confer virulence to the level of an archetypical, hypervirulent K. pneumoniae in a subcutaneous model of infection with immunocompetent CD1 mice. Our findings highlight the importance of performing genomic surveillance to identify emerging threats.

Emergency Preparedness in Tennessee Women with a Recent Live Birth.

OBJECTIVES: To assess emergency preparedness (EP) actions in women with a recent live birth. METHODS: Weighted survey procedures were used to evaluate EP actions taken by women with a recent live birth responding to an EP question assessing eight preparedness actions as part of the 2016 Tennessee Pregnancy Risk Assessment and Monitoring System (PRAMS) survey. Factor analysis was used to group preparedness actions. RESULTS: Overall, 82.7% [95% Confidence Interval (CI) 79.3%, 86.1%] of respondents reported any preparedness actions, with 51.8% (95% CI 47.2%, 56.4%) completing 1-4 actions. The most common actions were having supplies at home (63.0%; 95% CI 58.5%, 67.4%), an evacuation plan for children (48.5%; 95% CI 43.9%, 53.2%), supplies in another location (40.2%; 95% CI 35.6%, 44.7%), and a communication plan (39.7%; 95% CI 35.1%, 44.2%). Having personal evacuation plans (31.6%; 95% CI 27.3%, 36.0%) and copies of documents in alternate locations (29.3%; 95% CI 25.0%, 33.5%) were least common. Factor analysis yielded three factors: having plans, having copies of documents, and having supplies. Specific preparedness actions varied by education and income level. CONCLUSIONS FOR PRACTICE: Most Tennessee women (about 8 in 10 women) with a recent live birth reported at least one EP action. A three-part EP question may be sufficient for assessing preparedness in this population. These findings highlight opportunities to improve public health education efforts around EP.

Self-Directed Learning among Internal Medicine Residents in the Information Age.

OBJECTIVES: The revolution in information technology and a rapidly expanding evidence base are changing residency training. Understanding the habits and preferences of trainees' self-directed learning (SDL) has never been more important. Our goal was to provide a contemporary description of residents' SDL practices. METHODS: Internal medicine residents at four university-affiliated programs were surveyed in Spring 2017. Residents estimated the number of hours in their typical week spent in SDL on service and after hours when on inpatient and noninpatient rotations, how often they used specific educational resources for SDL, and the percentage of time that they used four different modes to access resources. RESULTS: Of 384 residents, a total of 254 (66%) responded. Residents spent more total hours in SDL on noninpatient services (median 11, interquartile range 8-17) than on inpatient services (median 7, interquartile range 4-10) and the same median number of hours in SDL on clinical duty as off hours for both inpatient (median 3 hours) and noninpatient (median 5 hours) rotations. Nearly all of the respondents (99%) reported using online point-of-care resources for SDL at least once per week. Most (77%) never used printed textbooks. Desktop/laptop was the most commonly used (47% of the time) medium to access resources. CONCLUSIONS: Although the resident learning environment and resource use are changing, residents engage in as much or more time in SDL as in previous studies, with a large proportion occurring during clinical service. Understanding residents' current SDL habits will better prepare educators to support and guide our trainees.

Change implementation: the association of adaptive reserve and burnout among inpatient medicine physicians and nurses.

Adaptive Reserve (AR) is positively associated with implementing change in ambulatory settings. Deficits in AR may lead to change fatigue or burnout. We studied the association of self-reported AR and burnout among providers to hospitalized medicine patients in an academic medical center. An electronic survey containing a 23-item Adaptive Reserve scale, burnout inventory, and demographic questions was sent to a convenience sample of nurses, house staff team members, and hospitalists. A total of 119 self-administered, online surveys collected from June 2014 to March 2015 were analyzed. Ordinal regression analyses were used to examine the association between AR and burnout. Eighty percent of participants reported either level 1 or 2 burnout. Additionally, 10.9% of participants responded level 0% and 7.6% of participants reported level 3. Participants reporting higher burnout were about three times more likely to report lower AR levels. AR is strongly associated with self-reported burnout by physicians and nurses providing inpatient care at this academic medical center. Growing evidence supports the positive association of AR to successful change implementation in ambulatory settings. Similar studies are needed to determine whether certain levels of AR can predict successful change in hospital settings.

Longitudinal dynamics of farmer and livestock nasal and faecal microbiomes and resistomes.

Globally, half a billion people are employed in animal agriculture and are directly exposed to the associated microorganisms. However, the extent to which such exposures affect resident human microbiomes is unclear. Here we conducted a longitudinal profiling of the nasal and faecal microbiomes of 66 dairy farmers and 166 dairy cows over a year-long period. We compare farmer microbiomes to those of 60 age-, sex- and ZIP code-matched people with no occupational exposures to farm animals (non-farmers). We show that farming is associated with microbiomes containing livestock-associated microbes; this is most apparent in the nasal bacterial community, with farmers harbouring a richer and more diverse nasal community than non-farmers. Similarly, in the gut microbial communities, we identify more shared microbial lineages between cows and farmers from the same farms. Additionally, we find that shared microbes are associated with antibiotic resistance genes. Overall, our study demonstrates the interconnectedness of human and animal microbiomes.

Medication management for complex patients in primary care: application of a remote, asynchronous clinical pharmacist model.

Purpose: Drug therapy problems impact about one-third of US adults, and these issues are likely to continue to worsen as the population of aging Americans increases. The objective of this study is to assess the feasibility of a remotely delivered Comprehensive Medication Management (CMM) for primary practice patients who are polypharmatic and at high risk for drug therapy problems.Methods: Using medical and prescription claims data, a list of Medicare Advantage beneficiaries at high risk for drug therapy problems was identified. Participants were enrolled in a 6-month CMM program from February - November 2020. In the program, their existing drug therapy was assessed by a pharmacist, Drug therapy problems were identified and resolved. A Collaborative Practice Agreement allowed the pharmacists to make prescription changes as needed.Results: Eighty-three percent (202) of contacted individuals agreed to participate in the study. All participants were on five medications or more, and 71% were on more than eight. A clinical pharmacist found that 86% of participants had a drug therapy problem according to classification criteria. Seventy-nine percent of all drug therapy problems identified were resolved upon completion of the study.Conclusion: The findings of this study suggest that engagement of a remote clinical pharmacist can contribute to efficient resolution of most drug therapy problems identified in a primary care population. A service model using remote pharmacist services may be an effective means of improving team-based primary care medication management for this population.

Pan-drug resistant Providencia rettgeri contributing to a fatal case of COVID-19.

Following prolonged hospitalization that included broad-spectrum antibiotic exposure, a strain of Providencia rettgeri was cultured from the blood of a patient undergoing extracorporeal membrane oxygenation treatment for hypoxic respiratory failure due to COVID-19. The strain was resistant to all antimicrobials tested including the novel siderophore cephalosporin, cefiderocol. Whole genome sequencing detected ten antimicrobial resistance genes, including the metallo-ß-lactamase bla NDM-1, the extended-spectrum ß-lactamase bla PER-1, and the rare 16S methyltransferase rmtB2.

A panel of diverse Pseudomonas aeruginosa clinical isolates for research and development.

OBJECTIVES: Pseudomonas aeruginosa is a leading cause of community- and hospital-acquired infections. Successful treatment is hampered by its remarkable ability to rapidly develop resistance to antimicrobial agents, primarily through mutation. In response, WHO listed carbapenem-resistant P. aeruginosa as a Priority 1 (Critical) pathogen for research and development of new treatments. A key resource in developing effective countermeasures is access to diverse and clinically relevant strains for testing. Herein we describe a panel of 100 diverse P. aeruginosa strains to support this endeavour. METHODS: WGS was performed on 3785 P. aeruginosa isolates in our repository. Isolates were cultured from clinical samples collected from healthcare facilities around the world between 2003 and 2017. Core-genome MLST and high-resolution SNP-based phylogenetic analyses were used to select a panel of 100 strains that captured the genetic diversity of this collection. Antibiotic susceptibility testing was also performed using 14 clinically relevant antibiotics. RESULTS: This 100-strain diversity panel contained representative strains from 91 different STs, including genetically distinct strains from major epidemic clones ST-111, ST-235, ST-244 and ST-253. Seventy-one distinct antibiotic susceptibility profiles were identified ranging from pan-susceptible to pan-resistant. Known resistance alleles as well as the most prevalent mutations underlying the antibiotic susceptibilities were characterized for all isolates. CONCLUSIONS: This panel provides a diverse and comprehensive set of P. aeruginosa strains for use in developing solutions to antibiotic resistance. The isolates and available metadata, including genome sequences, are available to industry, academia, federal and other laboratories at no additional cost.

Predicting the Future: Using Simulation Modeling to Forecast Patient Flow on General Medicine Units.

BACKGROUND: Hospitals are complex adaptive systems within which multiple components such as patients, practitioners, facilities, and technology interact. A careful approach to optimization of this complex system is needed because any change can result in unexpected deleterious effects. One such approach is discrete event simulation, in which what-if scenarios allow researchers to predict the impact of a proposed change on the system. However, studies illustrating the application of simulation in optimization of general internal medicine (GIM) team inpatient operations are lacking. METHODS: Administrative data about admissions and discharges, data from a time-motion study, and expert opinion on workflow were used to construct the simulation model. Then, the impact of four changes: aligning medical teams with nursing units, adding a hospitalist team, adding a nursing unit, and adding both a nursing unit and hospitalist team with higher admission volume were modeled on key hospital operational metrics. RESULTS: Aligning medical teams with nursing units improved team metrics for aligned teams but shifted patients to unaligned teams. Adding a hospitalist team had little benefit, but adding a nursing unit improved system metrics. Both adding a hospitalist team and a nursing unit would be required to maintain operational metrics with increased patient volume. CONCLUSION: Using simulation modeling, we provided data on the implications of four possible strategic changes on GIM inpatient units, providers, and patient throughput. Such analyses may be a worthwhile investment to study strategic decisions and make better choices with fewer unintended consequences.

Rpd3- and spt16-mediated nucleosome assembly and transcriptional regulation on yeast ribosomal DNA genes.

Ribosomal DNA (rDNA) genes in eukaryotes are organized into multicopy tandem arrays and transcribed by RNA polymerase I. During cell proliferation, ∼50% of these genes are active and have a relatively open chromatin structure characterized by elevated accessibility to psoralen cross-linking. In Saccharomyces cerevisiae, transcription of rDNA genes becomes repressed and chromatin structure closes when cells enter the diauxic shift and growth dramatically slows. In this study, we found that nucleosomes are massively depleted from the active rDNA genes during log phase and reassembled during the diauxic shift, largely accounting for the differences in psoralen accessibility between active and inactive genes. The Rpd3L histone deacetylase complex was required for diauxic shift-induced H4 and H2B deposition onto rDNA genes, suggesting involvement in assembly or stabilization of the entire nucleosome. The Spt16 subunit of FACT, however, was specifically required for H2B deposition, suggesting specificity for the H2A/H2B dimer. Miller chromatin spreads were used for electron microscopic visualization of rDNA genes in an spt16 mutant, which was found to be deficient in the assembly of normal nucleosomes on inactive genes and the disruption of nucleosomes on active genes, consistent with an inability to fully reactivate polymerase I (Pol I) transcription when cells exit stationary phase.