McHugh, Jack

Abstract Background The number of arthroplasty procedures and infection-related complications, including prosthetic joint infections (PJIs) and surgical site infections (SSIs), continues to rise. Although current guidelines recommend cefazolin or cefuroxime as the first-line perioperative prophylactic antibiotic, substitutions with non-cephalosporins remain common, especially among patients with reported β-lactam allergies. These substitutions may increase infection risk and healthcare costs. Evidence comparing outcomes across antibiotic classes remains variable. Methods We conducted a systematic review and meta-analysis of studies comparing single-agent cephalosporin versus single-agent non-cephalosporin prophylaxis in adults undergoing primary arthroplasty. Cochrane, Embase, Medline, Scopus, and Web of Science were searched from database inception through January 2025. Random-effect or fixed-effect models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses stratified results by cephalosporin type, study era, and risk of bias. Results Twenty-three studies (7 randomized controlled trials and 16 observational studies) were included, encompassing 191 527 arthroplasties in the cephalosporin arm and 20 058 in the non-cephalosporin arm. The odds of PJI were lower with cephalosporins (OR 0.59; 95% CI, .46–.75). No overall difference was observed for SSI (OR 0.70; 95% CI, .36–1.36), though post-2013 studies and the cefazolin subgroup demonstrated a significant protective effect. Randomized trial estimates were limited and heterogeneous and did not reach statistical significance. Certainty of evidence was graded as moderate. Conclusions Cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty. This quantitative synthesis reinforces their protective association against prosthetic joint infection and supports adherence to guideline-endorsed prophylaxis.

Abstract The practice patterns of fluorine 18–labeled fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG PET/CT) use in cardiac implantable electronic device infection remain undefined. Among 258 Emerging Infections Network respondents, 69% reported never or rarely using [18F] FDG PET/CT. Limited access and insurance barriers were the most common obstacles.

Abstract Background Chimeric antigen receptor T-cell therapy (CAR-T) has transformed care for relapsed or refractory B-cell malignancies. Cytokine-release syndrome (CRS) complicates most infusions, yet the ensuing infection risk is ill-defined.Table 1Profile of 230 patients undergoing with CRS following CAR-T therapyTable 2Cytokine Release Syndrome Severity, Management, and Early Outcomes by 90-Day Infection Status Methods CAR-T recipients who developed CRS at our institution from 1 Jan 2018 to 3 June 2024 were retrospectively reviewed. Variables were abstracted into REDCap. CRS was graded with American Society for Transplantation and Cellular Therapy (ASTCT) criteria. All infections occuring after CRS onset to day 90 were adjudicated. Continuous data are reported as medians with interquartile ranges (IQR); categorical data as counts and percentages. Table 2 comparisons used Mann-Whitney U for continuous and χ² or Fisher exact tests for categorical variables (two sided, P < 0.05). Multivariable logistic regression was used to identify independent predictors of infection.Table 3Infectious Syndromes, Pathogens, and Timing of First Infection Following CRS Onset Results Among 230 CRS cases, median age was 64 yr (IQR 57–70) and 59% were male. Non-Hodgkin lymphoma accounted for 62% and multiple myeloma for 38%. Median prior therapy lines were 3. CRS was grade 1–2 in 97%. CAR-HEMATOTOX was low in 156 (68%) (Table 1). Within 90 days, 51 patients (22%) developed infection; median onset was 15 days (IQR 5–26). Infected patients more often received anakinra (22% vs 8%, p = 0.02) and required ICU care (18% vs 7%, p = 0.05); grade ≥3 CRS trended higher (10% vs 3%, p = 0.06). In multivariable analysis adjusting for age, CAR-HEMATOTOX, ICU admission, and anakinra, both ICU admission (aOR 2.06; 95% CI 0.70–5.81; p = 0.18) and anakinra use (aOR 2.18; 95% CI 0.83–5.53; p = 0.10) were associated with higher infection odds, though not statistically significant. 90-day survival was 88% with infection versus 96% without (p = 0.09) (Table 2). 51 infectious episodes were documented: bacteremia 22; gastrointestinal 9; central line–associated bloodstream infection 7; other sites 22. Bacteria caused 59%, viruses 37% (15 CMV, 4 SARS-CoV-2), and fungi 4%. No infection-related deaths occurred (Table 3). Conclusion Infection was common after CRS, but did not alter early survival. Anakinra exposure and ICU admission were associated with a higher likelihood of infection, though not statistically significant. Targeted surveillance should focus on patients requiring intensified CRS management. Disclosures Yi Lin, M.D., BMS: Board Member|Caribou: Advisor/Consultant|Genentech: Board Member|Jassen: Board Member|Jassen: Steering Committee|Kite/Gilead: Steering Committee|Legend: Board Member|NexImmune: Advisor/Consultant|NexT Therapeutics: Board Member|Pfizer: Board Member|Regeneron: Board Member|Sanofi: Board Member|Tessera: Board Member Paschalis Vergidis, MD, MSc, Current Fungal Infection Reports: Honoraria|F2G: Grant/Research Support|Merck Manuals: Honoraria|Mundipharma: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support

Abstract Background Persistent candidemia (PC) occurs in a minority of Candida bloodstream infections (BSIs) but is associated with increased morbidity. Comparative data on patient profile, species distribution and outcomes are limited.Table 1Clinical profile and outcomes of patients with persistent candidemia in the primary study cohort. ANC = absolute neutrophil count. SD = standard deviation.Table 2Comparative analysis of persistent candidemia and non-persistent candidemia cases. Methods All candidemia episodes at three academic medical centers (2018-2025) were reviewed. Persistence was defined as ≥72 hours of positive blood cultures after appropriate antifungal initiation. Each PC case was matched 1:2 to non-PC controls who survived ≥72 hours. Demographics, Charlson Comorbidity Index (CCI), Candida species distribution, and outcomes were used for comparative analysis. Continuous variables were summarized as median (interquartile range [IQR]) and compared with Wilcoxon rank-sum, while categorical data (n%) were analyzed by Fisher’s exact test (species by χ²), yielding odds ratios (ORs) with 95% confidence intervals (CIs). Two-tailed p < 0.05 denoted significance. Results Each PC case (n = 46) was matched 1:2 to non-PC controls (n = 92). Clinical profiles and outcomes of PC cases are presented in Table 1. Most PC patients (54.3%) had an immunocompromising condition, and non-urinary intra-abdominal sources were the most frequently suspected infection source (21/46; 45.7%). All but one of 46 PC cases had antibiotic exposure within the preceding 90 days. Comparative demographics and outcomes for PC cases and non-PC controls are displayed in Table 2. PC patients were younger (median 62 yr, IQR 45–69 vs 68 yr, 57–76; p = 0.01), more often female (59% vs 30%; OR 3.3, 95% CI 1.5–7.1; p = 0.002), and had higher comorbidity (CCI 5, IQR 3–8 vs 3, 1–4; p < 0.001). Species distribution differed (χ² p = 0.04), driven by C. guilliermondii over-representation in PC cases (9% vs 0%) (Figures 1 and 2). Hospital stay was longer in PC cases (median 36 d, 24–54 vs 16 d, 8–28; p < 0.001) and time from admission to first culture greater (12 d, 3–26 vs 3 d, 1–10; p = 0.003). 90-day mortality was 54.3% (25/46) in PC cases versus 31.5% (29/92) in controls (OR 2.57, 95% CI 1.17–5.71; p = 0.016). Conclusion In this 7-year multicenter study, there were significant differences in demographics, microbiology, and clinical outcomes between PC and non-PC cases, including higher short-term mortality rates with PC in univariate analysis. Disclosures Paschalis Vergidis, MD, MSc, Current Fungal Infection Reports: Honoraria|F2G: Grant/Research Support|Merck Manuals: Honoraria|Mundipharma: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support

Abstract Background Native joint septic arthritis (NJSA) is a serious musculoskeletal infection requiring timely surgical intervention to prevent long-term morbidity. Although current guidelines recommend early surgical debridement, supporting data, particularly on long-term outcomes, remain scarce. Given this, we evaluated the association between surgical timing and 1-year clinical outcomes using the Desirability of Outcome Ranking (DOOR) framework, applied for the first time in NJSA.Table 1.Desirability of Outcome Ranking (DOOR) ordinal scaleTable 2.Baseline demographic, clinical characteristics, and treatment outcomes Methods We conducted a retrospective multicenter cohort study of adults (≥18 years) with NJSA who underwent surgery across Mayo Clinic campuses between 2012 and 2021. Clinical outcomes at one year were assessed using a 9-level DOOR scale, incorporating survival, treatment failure (relapse, reinfection, readmission, or significant surgical events), and joint recovery (full vs qualified) (Table 1). Time to surgery from hospital admission was analyzed both as a continuous variable and as categories: < 1, 1–2, or ≥3 days.Table 3.Associations between duration and outcomesFigure 1.Association Between Time to Surgery and DOOR Scores in Native Joint Septic Arthritis.A) Distribution of Modified DOOR Scores by Surgical Timing. B) Modeled Probability of DOOR Scores by Time to Surgery. Results Among 268 patients (median age 62 years, 61% male), 30% underwent surgery < 1 day from admission, 47% within 1–2 days, and 24% at ≥3 days. At 1 year, 57% achieved full recovery without unfavorable events (DOOR score 1), while treatment failure occurred in 34% (Table 2). In unadjusted analyses, longer surgical delay was significantly associated with higher DOOR scores (per IQR increase [from 0 to 2 days], OR: 1.5; 95% CI: 1.0–2.1; p = 0.026) and with increased 1-year mortality (HR: 1.7; 95% CI: 1.1–2.6; p = 0.019) and treatment failure (HR: 1.5; 95% CI: 1.1–2.0; p = 0.007). Similar results were obtained when delay was used as a categorical 3-level variable, with the highest risk observed in patients undergoing surgery after ≥3 days. After adjusting for age and Charlson index, only the association between surgical delay and treatment failure remained statistically significant (HR: 1.5; 95% CI, 1.1–2.0; p=0.016) (Table 3, Figure 1). Conclusion Delayed surgical intervention for management of NJSA was independently associated with higher risk of treatment failure at 1 year. These findings reinforce current guideline recommendations for timely operative management and further underscore the potential of the DOOR framework to capture clinically meaningful, multidimensional outcomes in NJSA. Disclosures All Authors: No reported disclosures

Abstract Background Although recent guidance recommends early surgical debridement for native joint septic arthritis (NJSA), supporting data, particularly on long-term outcomes, remains scarce. Methods We conducted a retrospective multicenter cohort study of adults (≥18 years) with NJSA who underwent surgery across Mayo Clinic campuses between 2012 and 2021. Clinical outcomes at 1 year were assessed using a 9-level Desirability of Outcome Ranking (DOOR) scale, incorporating survival, treatment failure (relapse, reinfection, readmission, or significant surgical events), and joint recovery. Time to surgery from hospital admission was analyzed both as a continuous variable and as categories: < 1, 1–2, or ≥3 days. Results Among 268 patients, 30% underwent surgery <1 day from admission, 47% in 1–2 days, and 24% in ≥3 days. At 1 year, 57% achieved full recovery without unfavorable events (DOOR score 1), while treatment failure occurred in 34%. In unadjusted analyses, longer surgical delay was significantly associated with higher (worse) DOOR scores (per IQR increase [from 0 to 2 days], OR: 1.5; 95% CI: 1.0–2.1; P = .026), increased 1-year mortality (HR: 1.7; 95% CI: 1.1–2.6; P = .019) and treatment failure (HR: 1.5; 95% CI: 1.1–2.0; P = .007). Even after adjusting for age and Charlson comorbidity index, the association between surgical delay and treatment failure remained significant (HR: 1.5; 95% CI, 1.1–2.0; P = .016). Conclusions The finding that delayed surgical intervention is associated with an increased risk of treatment failure reinforces current expert recommendations for timely surgical management in NJSA.

Abstract Background Recent clinical trial evidence supports broader use of partial oral therapy (POT) for infective endocarditis (IE), yet real-world uptake in the U.S. has not been investigated. Methods Adult infectious diseases (ID) physician members of the Infectious Diseases Society of America Emerging Infections Network were surveyed in April–May 2025. A 10-item instrument captured frequency of POT, organism-specific influence, decision factors, barriers, and facilitators. Results Among 1531 members, 516 (34%) responded; 452 (88%) of them managed IE. POT was uncommon: 16% never used, 53% used in ≤10% of cases, and only 10% used in >25% of patients. Frequent POT rose with caseload (23% in physicians treating >50 IE cases year vs ≤9% in lower-volume groups, P < .001) and with fewer years in clinical practice (13% in <5 yrs vs 5% in ≥25 yrs, P = .013). Comfort with POT depended on the pathogen: 66% were comfortable switching for Streptococcus spp., 52% for Gram-negative bacilli, 19% for methicillin-resistant Staphylococcus aureus. Three quarters of those who used POT finished with a single agent. In people who inject drugs, 34% of physicians often or always considered an oral regimen. Availability of an active oral agent (75%) and the pathogen involved (69%) were the leading decision drivers; principal barriers were fear of relapse (72%), adherence concerns (53%), and insufficient evidence (48%). Respondents most desired clearer guidelines (75%) and additional data (71%). Conclusions U.S. adult ID physicians adopt POT for IE sparingly. Updated IE treatment guidelines, additional clinical trial data, and broader access to complex outpatient antimicrobial therapy services may facilitate wider adoption.

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 Background We examined how the COVID-19 pandemic influenced influenza vaccination, healthcare engagement, and patient satisfaction. Methods We retrospectively analyzed influenza vaccination records and patient experience surveys of adult primary care patients in southeastern Minnesota during two 3-year phases: Prepandemic (1 January 2017–28 February 2020) and Pandemic-Plus (1 March 2020–31 December 2023). Vaccination status was defined as “always vaccinated” (AV), “never vaccinated” (NV), or “intermittently vaccinated” (IV) for seasonal influenza. Results During the Pandemic-Plus phase, 7.0% (n = 3556) of the Prepandemic AV and 48.7% (n = 16 710) of the Prepandemic IV patients never received another influenza vaccine. Compared to AV, IV and NV patients were more likely to reside in areas with greater socioeconomic deprivation (odds ratio [OR], 1.58 [95% confidence interval {CI}, 1.53–1.62] and 1.99 [1.94–2.05], respectively), have a high school education or less (2.86 [2.74–2.98] and 3.38 [3.23–3.53]), and report healthcare disengagement (1.59 [1.55–1.64] and 4.21 [4.09–4.33]). After adjusting for Area Deprivation Index and medical comorbidities, healthcare disengagement increased among the NV versus AV between phases (3.33 [3.24–3.41] and 4.23 [4.10–4.35]). In a subgroup analysis those with severe comorbidities were less likely AV (NV vs AV: 1.21 [1.14–1.27]) and more dissatisfied with care (NV vs AV: 1.25 [1.18–1.33]). Conclusions The COVID-19 pandemic altered vaccination behaviors and healthcare satisfaction, especially among those at high risk of developing influenza-related complications. Medical providers and public health officials should be aware of factors associated with vaccine refusal to better target interventions.