Dumais, Mitchell

Abstract Background Chronic Q fever, caused by Coxiella burnetii, presents significant diagnostic and management challenges due to its variable presentation and high morbidity, especially among patients with underlying cardiac or vascular disease. In the United States, cases are rising, often without identifiable exposures, and diagnostic delays remain common. Methods We conducted a retrospective cohort study of chronic Q fever cases at the Mayo Clinic from 2007 to 2023. Patients with clinical evidence and a phase I IgG titer ≥1:1024 and/or positive PCR for C. burnetii were included. Data were abstracted from electronic health records, including demographics, exposures, clinical manifestations, diagnostics, treatments, and outcomes. Statistical analyses assessed factors influencing diagnostic delay and treatment response. Results We identified 33 patients with chronic Q fever (median age 56; 88% male). Median time to diagnosis was 99 days with 11.4 days between Infectious Diseases (ID) evaluation and diagnosis. Animal exposure was reported in 17 patients (52%), while eight (24%) had no identifiable exposure. Patients primarily presented with prosthetic valve endocarditis (n=14, 42%), or vascular graft infection (n=9, 27%). The majority were treated with doxycycline and hydroxychloroquine (n=25, 75%) and 14 patients (42%) required surgical intervention. Mortality attributable to chronic Q fever was 6% (n=2). Conclusions Chronic Q fever remains under-recognized, with substantial diagnostic delays prior to treatment. Cardiovascular infection predominates, and surgical intervention is often required despite prolonged antimicrobial therapy. Early specialist evaluation and standardized diagnostic pathways may improve outcomes.

Pasteurella species are facultatively anaerobic Gram-negative coccobacilli residing in the upper respiratory tract of mammals, fowl and domestic animals including cats and dogs. Localized infections with Pasteurella species are common but invasive infections are rare. There is a paucity of data available on risk factors, clinical presentations and outcomes with Pasteurella bloodstream infection. We conducted a retrospective review of patients with Pasteurella bacteremia presenting to our institution. There were 63 presentations (61 patients) with Pasteurella bacteremia. Immunosuppression, malignancy and alcohol misuse were common. Rates of admission to intensive care (n = 18, 29.5%) and death prior to hospital discharge (n = 7, 11.5%) were high.

ABSTRACT Achromobacter species are Gram-negative bacilli that predominantly affect individuals with cystic fibrosis or those with immunocompromising conditions. Clinical and microbiologic data on Achromobacter species are limited due to the rarity of these organisms and challenges with species-level identification. We conducted a 10-year retrospective analysis (1 January 2013 to 14 March 2023) of all bloodstream and non-bloodstream Achromobacter isolates identified at three tertiary-care Mayo Clinic locations (Minnesota, Arizona, and Florida). Additionally, we examined clinical characteristics of adult patients with Achromobacter bloodstream isolates. A total of 1,598 Achromobacter isolates, encompassing 1,545 non-bloodstream isolates and 53 bloodstream isolates, were identified. The most frequently identified species was Achromobacter xylosoxidans , though species-level identification was not possible for many isolates. Among adult patients with Achromobacter bloodstream infection, the mean age was 58.3 years (standard deviation ± 16.7), 73.1% had a central venous catheter, and 59.6% were immunocompromised. All-cause mortality was 10.2% at 30 days and 18.4% at 90 days. Bloodstream isolates exhibited greater than 90% susceptibility to meropenem, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole. The respiratory tract was the most common source of non-bloodstream isolates (57.5%). Non-bloodstream isolates showed high susceptibility to imipenem (94.6%), piperacillin-tazobactam (92.8%), trimethoprim-sulfamethoxazole (92.1%), and meropenem (87.5%) while demonstrating significant resistance to fluoroquinolones and aminoglycosides. Our findings support the use of piperacillin-tazobactam, carbapenems, or trimethoprim-sulfamethoxazole as initial therapy for Achromobacter infections. Further research is needed to better define the clinical and microbiologic characteristics of Achromobacter infections. IMPORTANCE Achromobacter is a rare but important genus of bacteria that tends to cause infection in those with cystic fibrosis, recurrent healthcare exposures, and/or an immunocompromising condition. There is limited data on the clinical profile of Achromobacter infections as well as optimal antibiotic selection for affected patients. We conducted a retrospective study to improve understanding of the microbiologic and clinical characteristics of Achromobacter . Our study consists of a 10-year survey of all Achromobacter isolates processed by three Mayo Clinic tertiary-care centers in Minnesota, Florida, and Arizona from 2013 to 2023. We report multiple findings, including the clinical characteristics of patients with Achromobacter bloodstream infection, the number of different Achromobacter species identified, and the sources of isolates not obtained from blood cultures. We additionally present antimicrobial susceptibility results for Achromobacter isolates. Our study provides guidance to clinicians treating Achromobacter infections and, it is hoped, will facilitate ongoing study of Achromobacter .

Abstract Objectives To compare the efficacy and safety of antibiotic lock therapy (ALT) versus catheter removal in managing central vascular catheter–associated bloodstream infection (CVC-BSI). Methods We conducted a single-centre, retrospective cohort study of adult patients treated with ALT or catheter removal for management of CVC-BSI between 2018 and 2022. The primary outcome was a composite of 90 day microbiological relapse or recurrent BSI. Secondary outcomes included 30 day mortality, CVC-associated complications and Clostridioides difficile infection (CDI). Logistic regression with propensity score-adjustment was used to evaluate differences in outcomes and identify predictors of relapse. Results During the study period, 106 participants received ALT and 181 underwent catheter removal. Patients treated with ALT received shorter courses of systemic antimicrobials (11 versus 14 days; P < 0.001) and had shorter hospital stays (4 versus 10 days; P < 0.001). Median duration of catheter salvage in patients receiving ALT was 28 days (IQR 7–80). Primary composite outcome was similar between both groups, but ALT was associated with a significantly higher risk of microbiological relapse within 90 days (20% versus 7%; adjusted odds ratio 3.93, 95% CI 1.64–9.40; P = 0.002). No significant difference in 30 day mortality, CVC-related complications or CDI was observed. CoNS BSI was an independent predictor of microbiological relapse in patients treated with ALT (OR 2.28; P = 0.05). Conclusions Although ALT offers a non-invasive catheter salvage strategy, its association with higher relapse rates, particularly in CoNS BSI, suggests catheter removal should remain the preferred approach when feasible. ALT could be considered a short-term catheter salvage strategy for pathogens with low virulence when used with close surveillance.

Abstract Background RSV is a common respiratory infection that causes significant morbidity in SOTR. However, risk factors for complications such as hypoxic respiratory failure, mechanical ventilation, and secondary infections have not been well described. Methods This retrospective, international, multicenter cohort study is actively recruiting SOTR hospitalized with RSV. Here, we analyzed data from Mayo Clinic (Rochester, Florida, Arizona), Miami Transplant Institute, Cleveland Clinic, and Royal Melbourne Hospital between 2016 and 2019. Secondary infection was defined as culture positive infection within 90 days of RSV diagnosis. Whenever appropriate, logistic and Cox regression analysis were conducted to identify risk factors. Survival functions were estimated using the Kaplan-Meier method.Figure 1:Forest plots of multivariable logistic regression models for risk factors for A) hypoxia, B) secondary infections, C) mechanical ventilation. Note: all variables included are the ones statistically significant on univariate analysis. Abbreviations: CI, confidence interval; OR, Odds ratio; LRTI: lower respiratory tract infection. Results 233 SOTRs (58.8% male; median, 61 years), including 77 (49.1%) kidney, 23 (9.9%) liver, 79 (33.9%) lung, and 38 (16.3%) heart transplants (Table). Hypoxic respiratory failure, mechanical ventilation, and secondary infection were seen in 98 (42.1%), 23 (9.9%), and 58 (24.9%) patients, respectively. After multivariate analysis, age >60 years, symptoms and imaging evidence of lower respiratory tract infection (LRTI) were associated with oxygen requirement (Figure 1A); similar results were observed in an analysis of the lung transplant cohort only. Risk factors on multivariate analysis for secondary infection include a history of rejection within six months and mechanical ventilation (Figure 1B). Risk factors for mechanical ventilation included age >60 years and LRTI on imaging (Figure 1C) after multivariate analysis. Seventeen (7.3%) patients died within 90 days of diagnosis. Cox univariate analysis identified age >60 years and LRTI on imaging, secondary infections, mechanical ventilation and hypoxia on admission were associated with higher mortality (Figure 2 and 3).Figure 2:Forest plot with Cox proportional hazards models. Note: only univariate results shown, multivariate not done due to low number of events. Conclusion This multicenter study of SOTR hospitalized with RSV identified older age ( >60 years old) as a risk factor for hypoxic respiratory failure, mechanical ventilation and death. Mechanical ventilation and a history if rejection within six months of RSV were associated with increased risk of secondary infections, identifying them as high-risk that needs close surveillance for this complication.Figure 3:Effects of A) Age older than 60 years old and B) mechanical ventilation on 90 day probability of survival after RSV infection Disclosures Michelle Yong, MBBS, FRACP, MPH, PhD, MSD: Grant/Research Support|MSD: Honoraria|Takeda: Advisor/Consultant Yoichiro Natori, MD, Eurofin/Viracor: Honoraria|Nobel Pharma: Advisor/Consultant

Abstract Background Catheter-related bloodstream infection (CRBSI) is an important complication of long-term central venous catheters (CVCs) and is associated with high morbidity and cost. While line removal is optimal, it is not always feasible and is not without complications. Antibiotic lock therapy (ALT) may be an alternative strategy for line salvage, but the efficacy of this approach particularly among immunocompromised hosts is unknown. Methods We retrospectively reviewed adult patients with CRBSI managed with ALT between 2018 and 2022 at our tertiary medical center. We reviewed patient comorbidities, type and indications for CVC use, microbiology of CRBSI, ALT, and use of systemic antibiotics. Outcomes included 30-day mortality, 90-day microbiologic relapse (with same bacteria as index case), 90-day recurrent BSI (with different bacteria from index case), and adverse events. Results 86 patients were reviewed, a majority of whom were immunocompromised (91%) due to hematopoietic stem cell transplantation (85%) and thrombocytopenic (platelet count 36; IQR 17-112). 78% had tunneled CVC for indications including peri-transplant therapy (72%), chemotherapy (15%), and TPN (6%) (Table 1). The median time to CRBSI following CVC insertion was 45 days (IQR 19-86). Infections were frequently monomicrobial (80%) due to Gram-positive organisms (n=75) including coagulase-negative staphylococci and Enterococcus spp. The minority of Gram-negative (n=17) infections were due to E coli and Enterobacter spp. 94% of patients received systemic antibiotics and all patients received ALT for a median of 11 days [IQR 6-15] and 11.5 days [IQR 6-14], respectively (Table 2). The 30-day attributable mortality rate was low at 1%. Rates of 90-day microbiologic relapse (20%) and recurrent BSI (16%) were high, occurring at a median of 42 days (IQR 12-55) and 35 days (IQR 25-50) following completion of ALT, respectively (Table 3). Conclusion Despite high rates of microbiologic relapse and recurrent BSI, ALT may be an effective line salvage strategy extending the use of CVC by up to 30 days with minimal impact on mortality even among immunocompromised patients. Disclosures John C. O'Horo, Sr., MD, MPH, Janssen Pharmaceuticals.: Grant/Research Support|nference: Grant/Research Support

Abstract Background As the acute phase of the COVID-19 pandemic subsides, an increasing number of individuals are recognized as having long COVID, affecting over 65 million people worldwide. Recent studies have suggested a potential link between long COVID and alterations in the gut microbiome. In this study, we examined the gut microbiome of a large outpatient cohort during acute phase of infection, with the ultimate goal of determining predictors of long-term COVID-19 health outcomes. Methods We conducted a study of 394 COVID-19 patients with positive SARS-CoV-2 testing from November 2020 to September 2021 at a multi-site healthcare system. Long COVID was defined as the persistence of symptoms for four weeks or more after illness onset. DNA extraction was performed using the MoBio PowerSoil Pro DNA isolation kit. Samples were sequenced using shotgun metagenomics. Stool SARS-CoV-2 RNA was tested using qRT-PCR of the E gene, and stool ELISA was performed for calprotectin levels. Standard biostatistical tools in R (v 4.2.3) were used for statistical analysis. Results Of the 394 COVID-19 patients, 84 (21%) had long COVID, with fatigue being the most common persistent symptom (Table 1). No significant differences were seen in age, BMI, and antibiotic use. Those with long COVID were more likely to be female, had higher Charlson's comorbidity scores, more severe index illnesses. However, the two groups had no difference in SARS-CoV-2 stool PCR positivity or stool calprotectin levels (Table 2). Principal coordinate analysis of Bray Curtis dissimilarities revealed that patients with long COVID had a distinct microbial composition compared with those without long COVID during the acute phase of infection (ANOSIM R2= 0.005, P= 0.01). Categorizing patients by number of long COVID symptoms showed significant differences among groups (ANOSIM R2=0.1, P=0.007), mainly between patients with >3 symptoms and those with 0-1 symptoms (Bonferroni, P= 0.018). Alpha diversity was lower in patients with > 3 symptoms, although this was not statistically significant (Shannon diversity, two-way-ANOVA, P=0.051). Figure 1 Conclusion Long COVID patients show distinct gut microbial composition during the acute phase of infection, suggesting a potential role in predicting long-term COVID health outcomes. Disclosures John C. O'Horo, Sr., MD, MPH, Janssen Pharmaceuticals.: Grant/Research Support|nference: Grant/Research Support Purna C. Kashyap, MD, Intrinsic Medicine: Advisor/Consultant|Novome Biotechnologies: Advisor/Consultant|Pendulum Therapeutics: Advisor/Consultant

Abstract Background Achromobacter spp. are important pathogens that are most frequently implicated in opportunistic infections, especially in patients with chronic lung disease, malignancy, and solid organ or hematopoietic stem cell transplantations. They commonly cause pneumonia, bacteremia, and device-associated infections. Intrinsic and acquired resistance mechanisms usually complicate treatment. Further characterization of the changing antibiotic susceptibilities and clinical manifestations of Achromobacter spp. are needed to improve clinical practice. Methods We performed a retrospective review of Achromobacter isolates from 2013 to 2023 in the Mayo Clinic Enterprise with available antimicrobial susceptibility testing (AST) data. Variables included sample source, collection date, and AST by agar dilution with susceptibility defined according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. Samples were categorized into quartiles based on collection date and grouped into source types (respiratory, genitourinary, etc.) and AST. Results A total of 1,506 patients were identified with a total of 1,546 unique Achromobacter spp. isolates from 2013 - 2023. The most common species was A. xylosoxidans, encompassing 40.1% of all isolates (Table 1). Respiratory samples (sputum, bronchoalveolar lavage) were the most common source (57.5%), followed by musculoskeletal and soft tissue (16.4%), genitourinary (12.2%), and oropharyngeal sources (10.3%). AST from 2013 to 2023 showed persistent high levels of resistance to aztreonam and tetracycline, with stable susceptibility to piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and carbapenems (Table 2). Over our 10-year analysis, there was increased resistance to aminoglycosides, fluoroquinolones, ceftazidime, and cefepime.Table 1.Achromobacter Species Identification and Isolate Percentage (%) Stratified by Year Table 1 lists the Achromobacter species identified stratified by the year each sample was collected. Each value represents the number of isolates that were identified as the listed Achromobacter species, with "Achromobacter sp." indicating an isolate without species identification. Percentages of species are listed in parentheses (%). Sample totals are listed in the right column.Table 2.Antibiotic Susceptibility of All Tested Achromobacter Isolates (Percentage of Susceptible Isolates) Table 2 lists antibiotics by class, stratified by year that Achromobacter isolates were tested. Each value is the total number of isolates tested for antimicrobial susceptibility, followed by the percentage of susceptible isolates in parentheses (%). Total isolates tested and overall susceptibility percentage is also listed over the 10-year period. Conclusion Achomobacter continues to be a clinically significant organism with a complex resistance profile. Our dataset shows a significant prevalence of non-respiratory and non-genitourinary samples, in addition to increasing resistance over many antibiotic classes. Our data suggests that piperacillin-tazobactam, imipenem, and minocycline are appropriate empiric regiments for Achromobacter. Disclosures All Authors: No reported disclosures