Purpose: Monotherapy with vancomycin or daptomycin remains guideline-based care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. Limited data support potential benefit of combination therapy with ceftaroline as initial therapy. We present an assessment of outcomes of patients initiated on early combination therapy for MRSA-B. Methods: This was a single-center, retrospective study of adult patients admitted with MRSA-B between July 1, 2017 and April 31, 2023. During this period, there was a change in institutional practice from routine administration of monotherapy to initial combination therapy for most patients with MRSA-B. Combination therapy included vancomycin or daptomycin plus ceftaroline within 72 hours of index blood culture and monotherapy was vancomycin or daptomycin alone. The primary outcome was a composite of persistent bacteremia, 30-day all-cause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were assessed. All outcomes were assessed using propensity score-weighted logistic regression. Results: Of 213 patients included, 118 received monotherapy (115 vancomycin, 3 daptomycin) and 95 received combination therapy with ceftaroline (76 vancomycin, 19 daptomycin). The mean time from MRSA-positive molecular diagnostic blood culture result to combination therapy was 12.1 hours. There was no difference between groups for the primary composite outcome (OR 1.58, 95% CI 0.60, 4.18). Time to microbiological cure was longer with combination therapy (mean difference 1.50 days, 95% CI 0.60, 2.41). Adverse event rates were similar in both groups. Conclusions: Early initiation of ceftaroline-based combination therapy did not improve outcomes for patients with MRSA-B in comparison to monotherapy therapy.

Journal Article Accepted manuscript The Value of Outpatient Parenteral Antimicrobial Therapy: Better Care in Twenty-Seven Minutes Get access Addison S Hicks, Addison S Hicks Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health, Charlottesville, Virginia, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Joshua C Eby Joshua C Eby Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health, Charlottesville, Virginia, USA Corresponding author: Joshua C. Eby, Division of Infectious Diseases and International Health, University of Virginia Health, P.O. Box 800419, Charlottesville, VA 22908. Phone: 434-243-3641. Email: jce4u@virginia.edu https://orcid.org/0000-0002-9683-1073 Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, ciae263, https://doi.org/10.1093/cid/ciae263 Published: 14 May 2024 Article history Received: 26 April 2024 Revision received: 06 May 2024 Accepted: 09 May 2024 Published: 14 May 2024

Quality is central to value-based care, and measurement is essential for assessing performance and understanding improvement over time. Both value-based care and methods for quality measurement are evolving. Infectious diseases (ID) has been less engaged than other specialties in quality measure development, and ID providers must seize the opportunity to engage with quality measure development and research. Antimicrobial stewardship programs are an ideal starting point for ID-related quality measure development; antimicrobial stewardship program interventions and best practices are ID specific, measurable, and effective, yet they are grossly undercompensated. Herein, we provide a scheme for prioritizing research focused on development of ID-specific quality measures. Maturation of quality measurement research in ID, beginning with an initial focus on stewardship-related conditions and then expanding to non-stewardship topics, will allow ID to take control of its future in value-based care and promote the growth of ID through greater recognition of its value.

Background: Directing COVID-19 diagnostic testing to healthcare workers (HCWs) who are likely to be infected has potential to reduce staffing shortages and decrease opportunity for in-hospital transmission; however, HCWs with COVID-19 may exhibit a range of symptoms. We assessed the burden of symptoms in relation to cycle threshold (Ct) values as a surrogate for viral shedding in vaccinated healthcare workers. Methods: We retrospectively reviewed employee health records of COVID-19–vaccinated employees who tested positive for SARS-CoV-2 between December 2020 and January 2022 at 2 academic hospital systems. We reviewed demographic data, reasons for testing including symptoms, exposure history, medical history, vaccination dates, Ct values, and genotypes when available. We compared mean Ct values between symptomatic and minimally symptomatic cases using independent sample t tests. Patients were defined as minimally symptomatic if they had no symptoms or a single symptom that is not cough, fever, or anosmia at the time of testing. Patients were defined as more symptomatic if they reported >1 symptom or cough, fever, or anosmia. Results: In total, 298 HCWs tested positive for COVID-19. Most positive cases were female (73%), white (78%), and had patient-facing roles (77%). Genotypic testing (n = 109) revealed that most genotypes belonged to the SARS-CoV-2 delta variant (AY lineages, B1.617.2). More cases were minimally symptomatic (62%) than were more symptomatic (38%). None required hospitalization during the study period. Mean Ct values (n = 141) showed no significant difference between more symptomatic and minimally symptomatic cases (19.8 vs 20.6; P = .40) (Fig. 1). Also, there was no significant difference in mean Ct value, comparing those with vaccination 90 days prior to positive (20.52 vs 19.88; P = .537). Conclusions: Our study shows no significant difference in cycle threshold values between minimally symptomatic and more symptomatic infections in vaccinated HCWs. In addition, HCWs exhibit high viral load even when infected within 90 days after vaccination. When considering whether to attend work, HCWs should be aware that mild symptoms and recent vaccination do not necessarily reflect low transmissibility and that they should follow CDC guidance regarding when to return to work. Disclosures: None

CR3 (CD11b/CD18; αmβ2 integrin) is a conserved phagocytic receptor. The active conformation of CR3 binds the iC3b fragment of complement C3 as well as many host and microbial ligands, leading to actin-dependent phagocytosis. There are conflicting reports about how CR3 engagement affects the fate of phagocytosed substrates. Using imaging flow cytometry, we confirmed that binding and internalization of iC3b-opsonized polystyrene beads by primary human neutrophils was CR3-dependent. iC3b-opsonized beads did not stimulate neutrophil reactive oxygen species, and most beads were found in primary granule-negative phagosomes. Similarly, Neisseria gonorrhoeae that does not express phase-variable Opa proteins suppresses neutrophil reactive oxygen species and delays phagolysosome formation. Here, binding and internalization of Opa-deleted (Δopa) N. gonorrhoeae by adherent human neutrophils was inhibited using blocking antibodies against CR3 and by adding neutrophil inhibitory factor, which targets the CD11b I-domain. No detectable C3 was deposited on N. gonorrhoeae in the presence of neutrophils alone. Conversely, overexpressing CD11b in HL-60 promyelocytes enhanced Δopa N. gonorrhoeae phagocytosis, which required the CD11b I-domain. Phagocytosis of N. gonorrhoeae was also inhibited in mouse neutrophils that were CD11b-deficient or treated with anti-CD11b. Phorbol ester treatment upregulated surface CR3 on neutrophils in suspension, enabling CR3-dependent phagocytosis of Δopa N. gonorrhoeae. Neutrophils exposed to Δopa N. gonorrhoeae had limited phosphorylation of Erk1/2, p38, and JNK. Neutrophil phagocytosis of unopsonized Mycobacterium smegmatis, which also resides in immature phagosomes, was CR3-dependent and did not elicit reactive oxygen species. We suggest that CR3-mediated phagocytosis is a silent mode of entry into neutrophils, which is appropriated by diverse pathogens to subvert phagocytic killing.

After receiving a monitored first-dose antimicrobial infusion at an infusion center, 6 of 93 (6%) patients enrolled in outpatient parenteral antimicrobial therapy services experienced an immediate reaction, none of which were consistent with immunoglobulin E-mediated reactions. These findings suggest it would be reasonable to forgo monitoring for most patients receiving first-dose intravenous antimicrobials outpatient.

Objective: Evaluate potential risk factors for severe coronavirus disease 2019 (COVID-19) among health care workers (HCWs) at the University of Virginia Medical Center in Charlottesville, Virginia. Methods: We conducted a retrospective manual chart review of data from HCWs who were diagnosed with COVID-19 from March 2020 to March 2021. Using data from patient medical histories, we ascertained risk factors for COVID-19-related emergency department encounter, hospitalization, or death. Results: We had 634 patients in total, and 9.8% had a severe COVID-19-related outcome. A history of deep vein thrombosis/pulmonary embolism/stroke (odds ratio, 19.6; 95% confidence interval, 5.11 to 94.7), as well as asthma, chronic lung disease, diabetes, or current immunocompromised status, was associated with increased adjusted odds of COVID-19-related emergency department encounter/hospitalization/death. Conclusions: A preexisting history of deep vein thrombosis/pulmonary embolism/stroke is a novel risk factor for poor COVID-19 outcomes among a cohort of HCWs.

Abstract Background The 2018 Infectious Diseases Society of America (IDSA) OPAT guidelines recommend that an outpatient-initiated first dose may be administered at home under the supervision of healthcare personnel who are trained to respond to IgE-mediated hypersensitivity reactions. This may involve a home health nurse, but if resources are limited, agencies may require a first-dose infusion to be completed in a monitored healthcare setting. The objective of this study is to assess the incidence of immediate reactions in UVA OPAT patients who received a supervised outpatient first-dose infusion as part of care for long term antimicrobial management. Methods This single center, retrospective case series evaluated adult patients enrolled in the UVA OPAT program who received a first-dose antimicrobial infusion for initiation of or change in IV antimicrobial therapy at a UVA-affiliated infusion center between January 2019 and October 2021. The primary endpoint is the percentage of UVA OPAT patients who experienced an immediate reaction, which includes IgE-mediated and infusion-related reactions, after receiving a supervised first-dose infusion outpatient. Secondary endpoints include the percentage of UVA OPAT patients who previously received the same antimicrobial and timing of receipt in patients who experienced an immediate reaction and in those who tolerated the first-dose antimicrobial infusion. Data were analyzed using descriptive statistics. Results There were 93 OPAT patients who received 115 first-dose infusions during the study timeframe. Daptomycin, ceftriaxone, and vancomycin accounted for 64% of first-dose infusions. Six patients (6%) experienced an immediate reaction, which included itching, erythema, and nausea. All patients received treatment for their reaction and were able to complete their infusion. Two patients who experienced an immediate reaction had received the same antimicrobial more than 12 months prior. Conclusion After receiving a first-dose antimicrobial infusion, few UVA OPAT patients experienced an immediate reaction, none of which were consistent with IgE-mediated reactions. These findings support the IDSA guidelines recommending a monitored first-dose infusion at home, particularly among those who recently tolerated the same agent. Disclosures All Authors: No reported disclosures.

BACKGROUND:Non-immunoglobulin E (IgE)-mediated hypersensitivity reactions (HSRs) to nafcillin are commonly reported, but scarce data are available to guide appropriate antibiotic change following these reactions. Although cefazolin is an attractive therapeutic alternative in methicillin-susceptible Staphylococcus aureus (MSSA) infections when patients experience an HSR to nafcillin, more data are needed to evaluate the tolerability of cefazolin after switching from nafcillin. The purpose of this study was to describe the tolerability of cefazolin in patients who develop a suspected non-IgE-mediated HSR to nafcillin.METHODS:This was a retrospective, descriptive case series of patients who received nafcillin for an MSSA infection, experienced a suspected non-IgE-mediated HSR, and were switched to cefazolin between October 2015 and November 2019 at a single academic medical center. The primary objective was to identify the percentage of patients who completed cefazolin after experiencing a suspected non-IgE-mediated HSR to nafcillin.RESULTS:There were 80 patients with 87 prespecified non-IgE-mediated HSRs during the study period. Seventy-one (89%) patients completed cefazolin, with 53 (75%) of these patients completing at least 2 weeks of therapy. One patient was ultimately switched from cefazolin to daptomycin due to concern for treatment failure. Eight patients (10%) did not tolerate cefazolin after switching from nafcillin. Of these, 3 patients experienced an unrelated HSR, whereas 5 patients experienced the same non-IgE-mediated HSR that was attributed to nafcillin and discontinued cefazolin within 7 days. The most common HSR cited was immune-mediated nephritis; however, the majority were clinically presumed but did not meet objective diagnostic criteria.CONCLUSIONS:Treatment with cefazolin after experiencing a suspected non-IgE-mediated HSR to nafcillin appears to be safe, even for patients requiring a prolonged duration of cefazolin.

Our results suggest that FFR fit during CPR is poor and that EMHRs provide superior fit, confirming previous research. 5 We chose to evaluate fit during CPR because it is highly aerosolizing, physically strenuous, and has been associated with occupational transmission.Strengths of our study include our real-world design and prospective data collection.Limitations include the lack of blinding or randomization and the use of participant-reported detection.The data suggest that the EMHR is more effective at preventing aerosol inhalation during strenuous clinical work and should be considered for preventing COVID-19 transmission.

Background:Although engagement of infectious disease physicians has been demonstrated to improve clinical outcomes in a variety of disease states, the extent of infectious disease (ID) physician engagement in quality improvement (QI) or their knowledge of QI has not been assessed.Methods:A 12-question, web-based survey was distributed to members of the Infectious Diseases Society of America (IDSA) between August and October 2019 to assess knowledge of and engagement in QI. The survey link was sent to IDSA members who self-identified patient care as their primary professional activity.Results:Responses were received from 200 individuals (5.4% response rate, which is just below the standard IDSA survey response rate of 6%), consisting of 175 adult infectious disease physicians (IDPs). Most respondents were employed in a hospital or clinic (41%), private or group practice (25%), or university/medical center (24%). Fifty-eight percent of respondents currently participate in QI projects, while 38% serve on QI oversight committees. Among respondents, 27% reported not being engaged in QI. Infection prevention/hospital epidemiology (77%), stewardship (72%), and antimicrobial resistance (56%) were the most commonly reported measure types. Respondents reported barriers that limited participation in QI, including cost (61%), lack of time (56%), lack of data collection resources (48%), and lack of an ID-specific registry (46%). IDPs report significant interest in additional training in QI and new quality measures.Conclusions:Although IDPs participate in QI, there are gaps in QI knowledge and measurement systems. The low response rate of our survey also suggests a lack of engagement in QI among IDPs. Closing these gaps will benefit ID in a value-driven health care economy.

Background A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value. Case presentation We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven Mycobacterium tuberculosis. Conclusions This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) programs have shown to reduce hospital readmissions; however, 20-25% of OPAT patients are readmitted. As 30-day readmissions is a healthcare quality measure, it is important to recognize predictors for readmissions in OPAT patients in an effort to minimize risk factors and optimize patient outcomes. The aim of this study was to identify modifiable and non-modifiable risk factors for 30-day unplanned readmission in patients discharged with OPAT. Methods This was a retrospective cohort study of patients admitted to University of Virginia (UVA) Health System between March 2019 and December 2019 who were discharged home with intravenous antimicrobials followed by the UVA OPAT program. Data collected included patient demographics, comorbidities, infection diagnosis, source control, and antimicrobial class. Variables were compared between patients with a 30-day unplanned readmission and those without a readmission. Mann-Whitney U, Pearson chi-squared, and Fisher’s exact tests were utilized, as appropriate. A multiple logistic regression analysis was performed to determine predictors of 30-day unplanned readmission. Results There were 334 OPAT patients who met inclusion criteria. Median age was 58 years, 58% were male, and the most common infection diagnoses were bone/joint (49%), bloodstream (22%), and endovascular (13%). There were 64 (19%) patients who had an unplanned 30-day readmission. The most common reasons for readmission included non-infection related (45%), worsening infection (28%), and antimicrobial-related complication (17%). Readmitted patients were more likely to have a higher Charlson Comorbidity Index (CCI); prior admissions; bloodstream, endovascular, or pulmonary infection; no source control; and an infection caused by a multi-drug resistant organism. CCI was found to be an independent predictor of readmission (OR 1.096, 95% CI 1.001-1.200). Conclusion Unplanned readmissions were common in patients discharged with OPAT. There should be an emphasis on interventions to prevent readmissions in OPAT patients, particularly those with high-risk clinical characteristics. Disclosures All Authors: No reported disclosures

Bordetella pertussis is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of B. pertussis growth and pathogenicity. While previous studies have provided insight into in vitro gene essentiality of this organism, very little is known about in vivo gene essentiality, a critical gap in knowledge, since B. pertussis has no previously identified environmental reservoir and is isolated from human respiratory tract samples. We hypothesize that the metabolic capabilities of B. pertussis are especially tailored to the respiratory tract and that many of the genes involved in B. pertussis metabolism would be required to establish infection in vivo In this study, we generated a diverse library of transposon mutants and then used it to probe gene essentiality in vivo in a murine model of infection. Using the CON-ARTIST pipeline, 117 genes were identified as conditionally essential at 1 day postinfection, and 169 genes were identified as conditionally essential at 3 days postinfection. Most of the identified genes were associated with metabolism, and we utilized two existing genome-scale metabolic network reconstructions to probe the effects of individual essential genes on biomass synthesis. This analysis suggested a critical role for glucose metabolism and lipooligosaccharide biosynthesis in vivo This is the first genome-wide evaluation of in vivo gene essentiality in B. pertussis and provides tools for future exploration.IMPORTANCE Our study describes the first in vivo transposon sequencing (Tn-seq) analysis of B. pertussis and identifies genes predicted to be essential for in vivo growth in a murine model of intranasal infection, generating key resources for future investigations into B. pertussis pathogenesis and vaccine design.

In vitro growth conditions for bacteria do not fully recapitulate the host environment. RNA sequencing transcriptome analysis allows for the characterization of the infection gene expression profiles of pathogens in complex environments. Isolation of the pathogen from infected tissues is critical because of the large amounts of host RNA present in crude lysates of infected organs. A filtration method was developed that enabled enrichment of the pathogen RNA for RNA-seq analysis. The resulting data describe the “infection transcriptome” of B. pertussis in the murine lung. This strategy can be utilized for pathogens in other hosts and, thus, expand our knowledge of what bacteria express during infection.

Abstract Background Patients discharged on parenteral antimicrobials often require in-person follow-up to determine antimicrobial discontinuation and coordination of central line (CL) removal at the end of therapy. Without close attention to timing of follow-up, antimicrobial courses may be extended beyond a planned end date until scheduled follow-up, leading to excess antimicrobial days of therapy (DOT) and CL retention. Excess DOT can result in increased cost of medication and CL supplies, antimicrobial exposure, and risk of CL-associated bloodstream infections or thrombosis. We sought to assess the impact of the University of Virginia (UVA) OPAT program on excess antimicrobial DOT and excess CL days. Methods This was a retrospective chart review of patients enrolled in the OPAT program at UVA between August 2018 and April 2019. The UVA OPAT program was started in August 2018. Quality improvement (QI) practice changes were implemented in February 2019 for improving follow-up and stopping antimicrobials at the projected end date. Patients were therefore divided into 2 cohorts – August through January 2018 and February through April 2019. Data collected included projected end date of therapy (EOT), actual EOT, actual removal date of CL, and follow-up date. Excess antimicrobial DOT and excess CL days were calculated by the difference in projected vs. actual dates. For continuous data, Student t-test was used. Results 248 patients enrolled in OPAT from August 2018 through April 2019. After implementation of QI efforts, mean time from projected EOT to follow-up appointment decreased from 10.0 days to 4.3 days for those with appointments after projected EOT. Mean excess antimicrobial DOT decreased from 2.8 ± 4.53 SD days to 1.6 ± 2.75 SD days (P = 0.026), and mean excess CL days decreased from 3.2 ± 4.63 SD days to 2.0 ± 2.89 SD days (P = 0.035). Conclusion The involvement of an OPAT program with close attention to outpatient follow-up and cessation of antimicrobials decreased the excess antimicrobial DOT and CL days and reduced variability in care. Reduction in antimicrobial overuse and CL overuse is expected to reduce cost and decrease the risk of medication- and CL-related collateral damage. Disclosures All authors: No reported disclosures.

Abstract Background The Occupational Safety and Health Administration (OSHA) of the Department of Labor requires that healthcare employers perform annual respiratory fit testing (RFT) for respiratory protection of employees with patient exposure. The annual cost of RFT in the United States is greater than $8 million and each fit test requires approximately 20 minutes. Due to the high resource expenditure for RFT, we sought to identify factors associated with changing respirators. Methods During annual RFT at the University of Virginia, employees complete a questionnaire about interval clinical changes since the last RFT. Questions are based on publications indicating that certain characteristics are associated with respirator change, including: have you had dental surgery, surgery on your face, or trauma; has your weight changed by >10%; have you been or are you currently pregnant; do you recall your mask type; do you want to change masks. Answers to these questions from May 2016 through March of 2018 were compiled and analyzed by Chi-square test using Excel and R. P-value of <0.05 was considered significant. Results A total of 4,278 employees completed questions at least once during the time period, with 29 requiring respirator change after RFT. Requesting a mask change, and 10% weight change were significantly associated with respirator change. Pregnancy and facial trauma were not significantly associated with respirator change. Of those who changed respirator, nine reported no change in weight, no facial trauma, and no pregnancy. Conclusion The infrequency of respirator change suggests that limiting RFT to those most likely to change their respirator may hold more value than screening all employees annually; however, questions included in this evaluation did not identify all employees who would require respirator change. We are continuing evaluation of predictors of respirator changes and association with tuberculin skin test conversion to improve efficiency of RFT. Disclosures All authors: No reported disclosures.

Mycobacterium immunogenum is a member of the rapidly growing non-tuberculous mycobacteria and is a relatively new species identified within this group. An 81-year-old immune-competent male was diagnosed with M. immunogenum infection of his peritoneal dialysis catheter exit site and surrounding soft tissue. To our knowledge, this is the first reported case of M. immunogenum infection of a peritoneal catheter. Treatment included catheter removal, local surgical debridement, and combination antimicrobial therapy. Herein, we review literature describing antibiotic management of M. immunogenum, an organism for which optimal therapy is not defined.