Fida, Madiha

Abstract Background Lyme arthritis is the most common late manifestation of disseminated Lyme disease in the United States. While most patients respond to antibiotic therapy, a subset develops postantibiotic Lyme arthritis (PALA), characterized by persistent noninfectious inflammatory arthritis. Data describing predictors of PALA and treatment patterns remain limited. Methods We conducted a retrospective observational cohort study of patients with polymerase chain reaction (PCR)−confirmed native joint Lyme arthritis treated at our institution from 2004 to 2025. Clinical, laboratory, imaging, treatment, and outcome data were abstracted from electronic health records. Continuous variables were compared using the Mann–Whitney U test, and categorical variables using Fisher's exact test. Results Seventy-seven patients with PCR-confirmed native joint Lyme arthritis were identified: 64 adults and 13 children. Children more frequently presented with fever and had significantly higher synovial fluid white blood cell counts compared with adults. Knee monoarthritis was the predominant presentation in both groups. Among adults, 41 (64%) achieved complete symptomatic resolution following antibiotic therapy, while 19 (29.7%) developed PALA. Adults who developed PALA had significantly lower synovial fluid white blood cell counts and more extensive joint involvement. The use of intravenous antibiotics and longer total antibiotic duration was more common among PALA patients without evidence of improved outcomes. Conclusions In this cohort of PCR-confirmed native joint Lyme arthritis, a substantial proportion of adults developed PALA. Failure to respond to initial antibiotic therapy and certain clinical features may identify patients at increased risk. These findings support judicious antibiotic use and early consideration of noninfectious mechanisms in persistent arthritis.

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 Background Adenovirus is a ubiquitous dsDNA virus with potential for end-organ disease. End-organ or disseminated adenoviral disease (EOD) occurs more frequently in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. We aim to characterize the clinical manifestations and outcome of adenovirus viremia in adults, including HSCT and SOT recipients. We describe severity of illness, organ-involvement, and graft and patient survival. Methods This retrospective, multi-site, study enrolled adults patients with positive adenovirus PCR in blood and other clinical specimens from January, 2010 through April, 2025. We excluded patients with insufficient medical records, follow up less than 30 days, and isolated conjunctivitis without viremia. EOD was defined by the presence of clinical signs or symptoms consistent with organ involvement, confirmed by a positive adenovirus PCR or by histopathology. Descriptive and comparative statistics were performed using R. Results Fifty patients with adenovirus viremia were included in this study. The most common immunocompromising conditions were corticosteroid use (84%, n = 42), HSCT (40%, n = 20) and SOT (34%, n = 17) (Table 1). Only 3 patients (6%) had no known immunocompromising condition. 20 patients (40%) had EOD while 30 patients (60%) had isolated viremia. Lungs were the most affected organ, followed by the gastrointestinal tract and liver (Figure 1). EOD was more prevalent in older patients (60 vs. 41 years, p =0.03) and in those with higher initial plasma viral load (673364 vs. 6593, p=0.005). The most common treatment was reduction in immunosuppression (Table 2). Cidofovir was more often used in patients with EOD. Adenovirus-related outcomes were worse in patients with EOD [higher rates of mortality (45% vs. 13.3%) and ICU admission (60% vs. 20%)] vs. without EOD (Table 3). Conclusion Adenovirus viremia is associated with high mortality in a cohort of mostly immunocompromised adults, particularly those with EOD. Older age and a higher initial plasma viral load are associated with EOD. Patients with EOD had worse clinical outcomes such as ICU admission and adenovirus-related mortality. Disclosures All Authors: No reported disclosures

Abstract Background Beta-lactam pharmacokinetics can be significantly altered in patients with malignancy. Therapeutic drug monitoring (TDM; i.e., drug level testing) may facilitate pharmacokinetic/pharmacodynamic (PK/PD) target attainment, but the data are limited. This study aimed to characterize PK/PD target attainment of anti-pseudomonal beta-lactams in hematology/oncology patients.Table 1:Case DescriptionGraph 1:Distribution of Beta-Lactam TDM Indications Methods We conducted a retrospective review of beta-lactam TDM performed between June 2022 and June 2024 in hospitalized adults with hematologic or solid organ malignancies. We included patients who underwent beta-lactam TDM during clinical care, typically for extracorporeal membrane oxygenation (ECMO), extremes of body weight, suspected augmented renal clearance, multidrug-resistant infection, or suspected dose-dependent beta-lactam toxicity. Primary outcomes were (1) the proportion achieving target beta-lactam concentrations and (2) the proportion undergoing antibiotic dose adjustment based on TDM results.Table 2:Institutional Dosing Guidelines Results There were 47 TDM episodes in 20 unique patients. Considering only the first TDM per patient, 10 (50%) patients achieved target concentrations, 2 (10%) were below target, and 6 (30%) were above target. Antibiotic dose adjustments were made in 8 (40%) patients in response to TDM results. The most common indication for beta-lactam TDM was concerns regarding accurate renal clearance, followed by extremes of weight. Conclusion Retrospective findings suggest that beta-lactam TDM facilitated individualization of therapy in 40% of patients with either hematological or solid organ malignancy, with dose adjustments often intended to improve antibiotic safety. Future studies should refine the criteria for beta-lactam TDM use in this population and determine the need for tailored PK/PD targets in patients with impaired host response to infection. Disclosures All Authors: No reported disclosures

Abstract Background Lyme arthritis is a manifestation of disseminated infection with Borrelia spp., typically presenting as knee monoarthritis weeks to months after infection. Most patients respond to antibiotics, but some develop antibiotic-refractory Lyme arthritis (ARLA), characterized by proliferative or autoimmune synovitis despite clearance of active infection, with proposed risk factors including treatment delay, host genetics, and intra-articular steroid use prior to antibiotics. Table 1 Characteristics of cohort. IQR = interquartile range, ESR = erythrocyte sedimentation rate, CRP = C-reactive protein, WBC = white blood cell. Table 2 Comparison of characteristics and outcomes between ARLA and non-ARLA patients Methods We performed a retrospective chart review of adult patients with Lyme PCR-positive synovial fluid at our center between 01/2004 and 02/2025. ARLA was defined as persistent inflammatory arthritis despite ≥8 weeks of antibiotics and/or negative repeat PCR after antibiotics. Statistical analysis was done on R and STATA. Figure 1 Type of antibiotics administered during the first course (A) and the second course (B) Figure 2 Box plot comparing the median time from symptom onset and treatment initiation in patients who had complete symptomatic resolution with any duration of antibiotic therapy, and those that did not have symptomatic resolution with antibiotic therapy. Results Table 1 summarizes the characteristics of the study cohort. Definitive Lyme arthritis was diagnosed in 67 patients. Of these, 35 patients (52%) achieved complete symptom resolution after one course of antibiotics, and 45 patients (67%) achieved resolution after up to two courses. Doxycycline was used as first-line therapy in 97% of cases (Figure 1). Antibiotic-refractory Lyme arthritis (ARLA) developed in 20 patients (30%); of these, 7 required disease-modifying antirheumatic drugs (DMARDs), and 3 underwent synovectomy. ARLA was associated with incomplete response to a single antibiotic course and persistent joint effusion on post-treatment radiography (Table 2). Intra-articular steroid use prior to antibiotic therapy was associated with a threefold increased odds of ARLA, although this did not reach statistical significance. Patients who responded to antibiotics had a shorter median time to treatment (19 days) compared to non-responders (42 days) (Figure 2). Conclusion In this cohort, 30% of patients were ultimately diagnosed with antibiotic-refractory Lyme arthritis (ARLA), a rate notably higher than the previously reported 10%. Despite advancements in Lyme disease diagnostics, we observed significant delays in diagnosis and initiation of appropriate antibiotic therapy, as well as the use of intra-articular steroids prior to antibiotics. These factors may contribute to the development of ARLA. Disclosures All Authors: No reported disclosures

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 .

Infective endocarditis (IE) remains a diagnostic challenge, particularly in cases where microbiological diagnosis is not established. Advances in molecular diagnostics have expanded the ability to identify causative pathogens beyond traditional culture-based methods. This review explores the role of molecular assays, including pathogen-specific PCR, multiplex PCR, broad-range PCR, and shotgun metagenomic sequencing, in diagnosing IE. These molecular techniques enhance pathogen detection, especially in patients with prior antibiotic exposure, and improve diagnostic accuracy in culture-negative IE. Broad-range PCR assays and metagenomic sequencing offer the untargeted detection of a wide spectrum of organisms. Despite their advantages, limitations such as availability, interpretation challenges, and a lack of antimicrobial susceptibility testing remain. A multimodal approach integrating molecular diagnostics with conventional methods is essential to optimize patient management. Further research is needed to refine diagnostic algorithms and improve cost-effectiveness in clinical practice.

Abstract Background There is a lack of comprehensive, large cohort studies investigating the predictors for severity and hospitalization in human granulocytic anaplasmosis (HGA). Methods We conducted a retrospective cohort study including all cases of HGA identified by positive blood Anaplasma polymerase chain reaction (PCR) at the Mayo Clinic Laboratory, Rochester between 2011 and 2021. Multivariable logistic regression was performed to evaluate risk factors associated with hospitalization. Results A total of 465 cases were identified. Of those, 67% (n = 312) were managed in the outpatient setting. Hospitalized patients (n = 153, 33%) were more likely to be older (median age of 71 vs 61; P ≤ .001) and immunocompromised (17% vs 7%; P ≤ .001). The triad of leukopenia, thrombocytopenia, and transaminitis was observed in 24% of the cases, but was associated with risk of hospitalization (odds ratio [OR] 1.78, 95% confidence interval [CI]: 1.05–3.03; P ≤ .033). The presence of a coinfection did not impact mortality or hospitalization. Conclusions The risk factors for hospitalization in patients with HGA include altered mental status, higher absolute neutrophil count (ANC), advanced age, comorbidities, and immunosuppression. The classic hematological and biochemical profile may be absent in the majority of cases. Co-testing may be of higher benefit in select cases.

Abstract Background The introduction of shotgun metagenomic sequencing (sMGS) methods that identify the presence of microbial cell-free DNA (mcfDNA) in peripheral blood have shown promising results in various populations of patients. There is a pressing need to evaluate its application for osteoarticular infections (OAIs) in real-world setting. Baseline characteristics of the patients with suspected osteo-articular infections, including demographics, clinical characteristics, diagnosis, and KT results. Methods We retrospectively collected data on 73 adult patients who presented to the Mayo Clinic with suspected OAIs between 2019 and 2023, and for whom mcfDNA sMGS (Karius®, KT) testing was part of their diagnostic workup. We collected data on comorbidities, diagnostics, microbiological workout and its concordance with the KT. The primary objective was to evaluate its clinical impact on OAI diagnoses and management distinguishing into four categories: (1) KT was able to confirm an established diagnosis, (2) KT supported non-ID diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information. Relevant microbiologic studies of patients with unsuspected diagnoses established by the KT (N=5) Results In our cohort KT was performed in 73 patients (Table 1). Among the infected individuals, KT yielded positive results in 22/43 (51.2%) cases. Out of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, while in five (22.7%) cases, the KT established an unsuspected diagnosis, improving the diagnostic power from 11/43 (25.6%) to 16/43 (37.2%) (Table 2). Moreover, yielded a negative result in 19/26 (73.1%) patients with non-infectious diagnosis (Figure 1). Native Vertebral Osteomyelitis (NVO) diagnosis (p < 0.001) or OAIs with concomitant presence of endocarditis or endovascular infection (p = 0.005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result (Table 3). Overall, KT influenced antibiotic therapy in six cases (8.2%). Table 3 Factors associated with diagnostic certainty categories Conclusion This is the first retrospective study aiming to assess the real-world usefulness of the KT on the clinical management of patients with OAIs, with a special focus on NVO. It underscores KT's real-world application in cases where traditional diagnostic methods fall short. In highly complex OAIs cases, KT added 11.6% to the diagnostic power by establishing unsuspected diagnosis in 5 of 43 infective patients. Patients with NVO or OAIs with concomitant endocarditis or endovascular infections particularly benefited from KT testing. Figure 1 Distribution of KT results and their respective outcome according to the final diagnosis of suspected OAIs cases. Disclosures All Authors: No reported disclosures

Abstract Background The underlying cause of fever of unknown origin (FUO) remains unidentified in up to 51% of cases despite systematic evaluation. Microbial cell-free DNA next-generation sequencing (mcfDNA-NGS) offers an agnostic, noninvasive approach to pathogen identification, but the utility and clinical impact of this assay in FUO remain unknown. Methods This retrospective cohort study evaluated adult patients referred for FUO evaluation at a tertiary medical center between November 2019 and November 2023. Patients underwent both standard microbiologic testing (ST) and mcfDNA-NGS. Diagnostic impact was assessed in 4 domains: new diagnoses, earlier time to diagnosis, avoidance of invasive procedures, and non-hypothesis-driven diagnoses. Logistic regression was used to identify predictors of positive mcfDNA-NGS testing. Results Among 176 patients, mcfDNA-NGS was positive in 44.3%, with 49% of these cases considered clinically significant. Infectious cause of FUO was identified in 39% of patients, noninfectious in 35%, and unknown in 26%. mcfDNA-NGS contributed to a positive diagnostic impact in 30% of cases, mainly by earlier diagnosis (16%) and potential for avoidance of invasive procedures (10%). Positive mcfDNA-NGS was significantly associated with higher Charlson comorbidity index score (odds ratio [OR], 1.22; P < .001) and white blood cell (WBC) count ≤4.5 × 109 cells/L (OR, 8.61; P < .001). Conversely, FUO without localization was associated with a decreased likelihood of positive mcfNDA testing (OR, 0.18; P < .001). Conclusions mcfDNA-NGS effectively complements ST in diagnosing FUO, providing earlier detection and minimizing invasive testing. Clinical predictors such as high comorbidity and low WBC count may guide the optimal use of mcfDNA-NGS in FUO. Prospective evaluation of optimal timing and use of mcfDNA-NGS and cost-benefit analysis in FUO is needed.