A subset of bacterial pathogens, including the zoonotic Brucella species, are highly resistant against polymyxin antibiotics. Bacterial polymyxin resistance has been attributed primarily to the ...modification of lipopolysaccharide; however, it is unknown what additional mechanisms mediate high-level resistance against this class of drugs. This work identified a role for the Brucella melitensis gene bveA (BMEII0681), encoding a predicted esterase, in the resistance of B. melitensis to polymyxin B. Characterization of the enzymatic activity of BveA demonstrated that it is a phospholipase A1 with specificity for phosphatidylethanolamine (PE). Further, lipidomic analysis of B. melitensis revealed an excess of PE lipids in the bacterial membranes isolated from the bveA mutant. These results suggest that by lowering the PE content of the cell envelope, BveA increases the resistance of B. melitensis to polymyxin B. BveA was required for survival and replication of B. melitensis in macrophages and for persistent infection in mice. BveA family esterases are encoded in the genomes of the alphaproteobacterial species that coexist with the polymyxin-producing bacteria in the rhizosphere, suggesting that maintenance of a low PE content in the bacterial cell envelope may be a shared persistence strategy for association with plant and mammalian hosts.
MRSA enterocolitis is under-recognized in the setting of PCR testing. In this case report, we describe risk factors, the importance of stool culture, and the third published case of MRSA ...enterocolitis in a patient with leukemia. In addition, we performed a retrospective analysis of all stool cultures at our institution that have grown Staphylococcus aureus, and we describe an additional five cases. We also report the diagnostic yield of organisms detected by culture, but not on the FilmArray panel. While rare, these cases demonstrate that MRSA in stool may indicate a severe and potentially life-threatening infection, particularly in immunocompromised persons.
Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of ...agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Brucella ovis is a major cause of reproductive failure in rams and it is one of the few well-described Brucella species that is not zoonotic. Previous work showed that a B. ovis mutant lacking a ...species-specific ABC transporter (ΔabcBA) was attenuated in mice and was unable to survive in macrophages. The aim of this study was to evaluate the role of this ABC transporter during intracellular survival of B. ovis. In HeLa cells, B. ovis WT was able to survive and replicate at later time point (48 hpi), whereas an ΔabcBA mutant was attenuated at 24 hpi. The reduced survival of the ΔabcBA mutant was associated with a decreased ability to exclude the lysosomal marker LAMP1 from its vacuolar membrane, suggesting a failure to establish a replicative niche. The ΔabcBA mutant showed a reduced abundance of the Type IV secretion system (T4SS) proteins VirB8 and VirB11 in both rich and acid media, when compared to WT B. ovis. However, mRNA levels of virB1, virB8, hutC, and vjbR were similar in both strains. These results support the notion that the ABC transporter encoded by abcEDCBA or its transported substrate acts at a post-transcriptional level to promote the optimal expression of the B. ovis T4SS within infected host cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The Veterans Affairs Central California Healthcare System (VACCHCS) antimicrobial stewardship program primarily utilizes prospective audit-feedback. Initially, antimicrobial ...recommendations were communicated to medicine and surgery teams exclusively through chart notes. Beginning September 2021, a new process was initiated whereby all antibiotic recommendations were communicated to care teams during daily face-to-face rounds. This pre-post cohort study is an assessment of the changes in antimicrobial use, inpatient mortality and 30-day readmissions that occurred with the intervention.
Methods
Both pre- and post- intervention, all admitted patients with active antibiotic orders were reviewed for antibiotic optimization by an ID team and a chart note was written to document recommendations. Post-intervention, recommendations were communicated via daily face-to-face rounds with medicine and surgery services. Total antibiotic use was collected from the National Healthcare Safety Network’s Antimicrobial Use and Resistance (NHSN-AUR) Module as antibiotic days-of-therapy per 1000 patient days (DOT/1000). Monthly in-hospital mortality and 30-day readmission data were collected from the VA’s Corporate Data Warehouse. Median monthly amounts of each measure were compared pre- and post-intervention. Antibiotic use was compared monthly for 2 years prior and 3 months post intervention, whereas mortality and readmission outcomes included 2 years prior and 6 months post-intervention.
Results
Pre and post-intervention median monthly antibiotic use was 728 and 741 DOT/1000, respectively. Median monthly mortality was seven deaths pre-intervention and six post-intervention. Median monthly 30-day readmissions were 48 pre-intervention and 36 post-intervention.
Conclusion
Total antibiotic use slightly increased after the intervention. Further post-intervention observation is needed in order to better characterize impact on antimicrobial use. Monthly in-hospital mortality and 30-day readmission data were decreasing prior to our intervention and continued to decrease post-intervention.
Disclosures
All Authors: No reported disclosures.
Abstract
Background
Washington State served as the initial epicenter of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in the United States. An understanding of the risk ...factors and clinical outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) may provide guidance for management.
Methods
All laboratory-confirmed COVID-19 cases in adults admitted to an academic medical center in Seattle, Washington, between 2 March and 26 March 2020 were included. We evaluated individuals with and without severe disease, defined as admission to the intensive care unit or death.
Results
One hundred five COVID-19 patients were hospitalized. Thirty-five percent were admitted from a senior home or skilled nursing facility. The median age was 69 years, and half were women. Three or more comorbidities were present in 55% of patients, with hypertension (59%), obesity (47%), cardiovascular disease (38%), and diabetes (33%) being the most prevalent. Most (63%) had symptoms for ≥5 days prior to admission. Only 39% had fever in the first 24 hours, whereas 41% had hypoxia at admission. Seventy-three percent of patients had lymphopenia. Of 50 samples available for additional testing, no viral coinfections were identified. Severe disease occurred in 49%. Eighteen percent of patients were placed on mechanical ventilation, and the overall mortality rate was 33%.
Conclusions
During the early days of the COVID-19 epidemic in Washington State, the disease had its greatest impact on elderly patients with medical comorbidities. We observed high rates of severe disease and mortality in our hospitalized patients.
In this case series of 105 consecutively hospitalized COVID-19 patients, the median age was 69 years, and 55% had 3 or more comorbidities. Severe disease occurred in 49% of patients, and overall mortality was 33%.
Abstract
Background
Vancomycin and piperacillin-tazobactam (VPT) combination therapy is associated with nephrotoxicity and provides broad-spectrum coverage that may be unnecessary. We conducted a ...pre-post implementation study to assess the impact of an audit and feedback program for VPT at our academic medical center.
Methods
Automated alerts were used to identify patients on VPT at the University of Washington Medical Center (UWMC)-Montlake (ML) and UWMC-Seattle Cancer Care Alliance (SCCA) hospitals. Baseline data was collected on patients from 1/20/20-6/2/20: electronic medical records were reviewed for antibiotic indication, duration, renal function, and presence of Infectious Disease (ID) consult. From 6/25/20-10/31/20, all patients on combination therapy without an ID consult were reviewed by the antimicrobial stewardship programs at ML and SCCA, respectively. If intervention was warranted, the ML steward discussed the case with the provider then documented the conversation. The SCCA steward, instead, discussed the case with the team pharmacist. The primary outcome was change in VPT duration post intervention. Secondary outcomes included nephrotoxicity rates and carbapenem escalation.
Results
Prior to the intervention, 66 ML and 33 SCCA patients were started on the combination compared to 110 ML and 50 SCCA patients post-intervention. Overall, 50% of ML and 14% of SCCA patients were on surgical primary services. Amongst ML patients, there was a decrease in patients on VPT for > 4 days (22 % to 8%), incidence of renal injury (30.3% to 10%), and percentage of ID consults (53.0% to 43.6%). Escalation to a carbapenem was stable (4.5% to 4.5%). In SCCA patients the percentage of patients on VPT for > 4 days decreased slightly (18.2% to 15.2%), incidence of renal injury was stable (18.2% to 18%), percentage of ID consults increased (45.5% to 50.0%), and escalation to a carbapenem was stable (12.1% vs 13.5%).
Conclusion
Prospective audit and feedback of VPT was associated with a decrease in duration and nephrotoxicity in ML but not SCCA patients. The difference in outcomes could be due to the patient populations, primary services, or intervention process. This study highlights the importance of tailoring interventions even within the same medical system.
Disclosures
All Authors: No reported disclosures
Abstract
Background
Patients labeled with penicillin allergies often receive alternative antibiotics, leading to increased cost, higher risk of adverse events, and decreased efficacy of procedural ...prophylaxis. However, most of those patients can tolerate a cephalosporin. University of Washington Medical Center – Montlake (UWMC-ML) Interventional Radiology (IR) frequently administer a pre-procedure prophylactic cephalosporin. We worked with the clinicians in IR to develop tools to allow them to better assess penicillin allergies, make the most appropriate antibiotic choice, and update the patient’s allergy documentation.
Methods
We identified all patients who underwent procedures in IR between 2017–2019. Chart review was done to determine the procedures performed, patient demographic information, allergies, allergy documentation, and prophylactic antibiotics received.
In May 2020 we implemented new Clinical Decision Support tools, including an online assessment app (https://tinyurl.com/IRPCNAllAssess) and handouts to guide antibiotic decision making to clinicians in IR.
Results
From 2017 to 2019, 381 patients underwent 958 procedures in IR. Of those, 379 patients underwent 496 procedures for which the recommended first line choice for antibiotic prophylaxis is a cephalosporin. Of patients who received pre-procedure prophylactic antibiotics for those procedures, 15.9% n=11 of patients with penicillin allergies received the first line antibiotic, compared to 89.9% n=319 of patients without a reported penicillin allergy. Since implementation, the online app has been used to evaluate 9 patients, of whom 8 had penicillin allergies. All 8 patients safely received the first line antibiotic (3 were delabeled, 4 reported a history of mild reactions, and 1 reported a history of an immediate IgE mediated response to penicillin but safely received cefazolin).
Conclusion
IR evaluates hundreds of patients who may receive prophylactic antibiotics each year. By providing tools to assess penicillin allergies, we were able to improve both their prescribing and de-label patients which will provide a much broader impact on their care than on just their current procedure. Our free tool can be accessed at the website above, and we will demonstrate in person.
Disclosures
All Authors: No reported disclosures
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