Citations

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.

Abstract Background Invasive listeriosis remains a leading cause of foodborne infection–related mortality in the United States and is associated with substantial case fatality despite appropriate antimicrobial therapy. Owing to the relative rarity of invasive disease, contemporary data evaluating clinical characteristics, optimal antimicrobial strategies, and predictors of mortality remain limited. Methods We conducted a retrospective cohort study of adults with laboratory-confirmed invasive Listeria monocytogenes infection at Mayo Clinic Health System sites from 1980 to 2024. Clinical syndromes were categorized into four mutually exclusive categories, namely bloodstream infection, central nervous system infection, pregnancy-associated infection, and other focal infections. The primary outcome was 1-year all-cause mortality. Secondary outcomes included 90-day mortality and residual neurological deficits among patients with neurolisteriosis. Results Fifty patients were included (median age, 72 years; 56% immunocompromised). The most common clinical presentations were bacteremia (44%) and neurolisteriosis (36%), followed by endovascular infection (12%) and peritonitis (6%). Most patients received a beta-lactam–based regimen, 46% aminopenicillin monotherapy, and 30% received combination therapy with gentamicin. Thirty-day, 90-day, and 1-year mortality were 10%, 12%, and 20%, respectively. Immunocompromised status and intensive care unit admission were associated with an increased risk of 1-year mortality, whereas adjunctive gentamicin therapy was not associated with improved survival. Conclusion Invasive listeriosis is associated with substantial morbidity and mortality, particularly among immunocompromised hosts. Host factors and severity of illness at presentation appear to be key drivers of unfavorable outcomes. Larger multicenter studies are needed to define optimal management strategies.

Background: Itraconazole is the preferred antifungal agent for mild to moderate histoplasmosis and step-down therapy following amphotericin B treatment. Although hydroxy-itraconazole, a major metabolite of itraconazole, displays antifungal activity comparable with that of the parent compound, its role in therapeutic drug monitoring targets for histoplasmosis remains uncertain. Methods: The objective was to compare clinical outcomes and adverse events using itraconazole parent-compound concentrations alone versus combined itraconazole and hydroxy-itraconazole concentrations in patients treated for histoplasmosis. This retrospective cohort study included adults with probable or proven histoplasmosis who received itraconazole and had at least 1 documented serum concentration. The primary outcome was clinical response across 3 groups: (1) parent (itraconazole parent-compound concentration >1.0 mcg/mL), (2) combined (parent-compound concentration <1.0 mcg/mL with combined itraconazole plus hydroxy-itraconazole >1.0 mcg/mL), and (3) subtherapeutic (failure to reach either threshold). Treatment response and adverse events were analyzed using the Fisher exact test. Results: Among 108 patients (parent, n = 40; combined, n = 40; subtherapeutic, n = 28), response rates differed across groups (parent (95%); combined (90%); subtherapeutic (67.9%); P = 0.006). There was no difference between the parent and combined groups. Adverse events did not differ, although drug discontinuation occurred more frequently in the subtherapeutic group (parent (5%); combined (20%); subtherapeutic (25%); P = 0.04). Conclusions: Patients who failed to achieve either an itraconazole concentration >1 mcg/mL or a combined itraconazole plus hydroxy-itraconazole concentration >1 mcg/mL had lower response rates. Similar outcomes among patients achieving the itraconazole target alone and those achieving the combined target suggest that hydroxy-itraconazole concentrations may contribute to therapeutic drug monitoring targets in histoplasmosis.

Background: Ceftriaxone and cefepime resistance among Enterobacterales continues to increase globally, partly due to the rising prevalence of extended-spectrum β-lactamase (ESBL) producing organisms. Surveillance of both resistance patterns and antimicrobial utilization is essential to inform empiric prescribing practices and stewardship strategies. Since carbapenems are frequently used to treat cephalosporin-nonsusceptible Enterobacterales infections, we evaluated trends in ceftriaxone and cefepime susceptibility among Escherichia coli and Klebsiella pneumoniae from 2012–2024 and institutional carbapenem utilization during overlapping years (2019–2025), following outcomes from the MERINO trial for management of ceftriaxone-resistant Enterobacterales infections. Methods: We conducted a retrospective review of annual cumulative inpatient antibiogram data for E. coli and K. pneumonia isolates for 2012-2024. Percent susceptibility to ceftriaxone and cefepime was assessed using Clinical and Laboratory Standards Institute (CLSI) breakpoints among a median of 1,532 E. coli isolates/year and 561 K. pneumoniae isolates/year. (Table 1). Institutional carbapenem utilization (combined meropenem and ertapenem use) was measured as days of therapy (DOT) per 1000 patient-days during 2019–2025 (not specifically representing treatment of E. coli or K. pneumoniae), following implementation of electronic medical record (EMR)–based antimicrobial utilization dashboards. Temporal trends were visualized using line plots. Pearson correlation coefficients (r) were calculated to assess percent susceptibility trends and carbapenem utilization during 2019–2024. Analyses are descriptive; no causal inference was made. Result: During 2012–2024, ceftriaxone susceptibility declined from 89% to 83% among E. coli and from 93% to 82% for K. pneumoniae, while cefepime susceptibility declined from 95% to 88% and 97% to 85% respectively (Figure 1). During the overlapping years 2019–2024, Pearson correlation showed modest downward susceptibility trends for ceftriaxone (E. coli r = −0.900, p = 0.014; K. pneumoniae r = −0.840, p = 0.036) and cefepime (E. coli r = −0.780, p = 0.067; K. pneumoniae r = −0.850, p = 0.033). Institutional carbapenem use increased from 15.2 to 19.3 DOT per 1,000 patient days between 2019 and 2025 (r = 0.79, p = 0.035) (Figure 2). Upon review, carbapenem use was substantially higher in hematology-oncology services (23.7–25.9 DOT/1000 patient-days, during 2022–2025) compared with overall institutional use (15.2–19.3 DOT/1000 patient-days). Conclusion: Ceftriaxone and cefepime susceptibility among Enterobacterales declined over the past decade, coinciding with a modest increase in institutional carbapenem use without a corresponding increase in carbapenem resistance during 2019-2024. Local susceptibility patterns and antimicrobial utilization data provide critical context for stewardship prioritization, especially in high-risk hematology-oncology populations.

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.

Abstract We describe early experience with beta-lactam therapeutic drug monitoring (TDM) in a high-volume outpatient parenteral antimicrobial therapy program. In selected patients, TDM informed dose optimization and toxicity mitigation. Illustrative cases highlight feasibility and emerging lessons supporting beta-lactam TDM in outpatient care.

Itraconazole is the recommended first-line antifungal agent in blastomycosis treatment. However, pharmacokinetic limitations and adverse drug events may necessitate the use of alternative antifungal agents. The primary objective of the study was to retrospectively describe a cohort of patients with blastomycosis who received voriconazole (as partial or complete therapy), for complete or partial treatment, compared to those who received itraconazole alone. Secondary objectives included rationale for voriconazole selection, treatment response, mortality, and adverse drug events. This retrospective multicenter cohort study included adult patients with proven/probable blastomycosis who received itraconazole or voriconazole. Treatment response was evaluated at one year or end of therapy, whichever came first. Mortality outcomes were assessed within 7 days of the last documented azole dose. Propensity score weighting and subgroup analysis were utilized to control confounding variables between cohorts. A total of 119 patients receiving itraconazole and 25 receiving voriconazole as complete or partial treatment were included. Voriconazole was often selected for CNS involvement or after intolerance to alternative azoles. After propensity score weighting, no significant difference in complete or partial treatment response was observed. Rates of all-cause mortality and blastomycosis-related mortality were numerically higher in the voriconazole cohort. Adverse drug event rates were similar between cohorts; however, discontinuation due to adverse events was more common in the voriconazole cohort. Voriconazole was most utilized for the treatment of blastomycosis in cases with CNS involvement or intolerance to other azoles. A statistically significant difference in response rate was not identified between voriconazole-containing or itraconazole-treated patients; however, given limited sample sizes, further data is needed to assess the equivalency of these agents in the treatment of blastomycosis.

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.