Challener, Douglas W.

Abstract Cardiac implantable electronic device infection in the context of corynebacterial bloodstream infection (BSI) remains poorly understood. From 2012 to 2023 at Mayo Clinic, 4 of 12 patients with corynebacterial BSI had cardiac implantable electronic device infection: 1 patient was diagnosed during a relapsing BSI episode. Undefined source, persistent BSI, and the presence of a prosthetic cardiac valve were common characteristics.

Abstract Background Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration. Methods We retrieved records of adult Mayo Clinic patients (≥18 years) with positive Coxiella burnetii serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti–phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed. Results Thirty-one patients were included. Their median age was 58 years (IQR, 50–64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168–414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression. Conclusions Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.

Abstract Background Nocardia tends to cause infection in immunocompromised patients or those with chronic pulmonary disease. Nocardia is known to recur, prompting the practice of secondary prophylaxis in patients perceived at high risk. However, few data exist regarding the epidemiology of recurrent nocardiosis or the effectiveness of secondary prophylaxis. Methods We performed a multicenter, retrospective cohort study of adults diagnosed with nocardiosis from November 2011 to April 2022, including patients who completed primary treatment and had at least 30 days of posttreatment follow-up. Propensity score matching was used to analyze the effect of secondary prophylaxis on Nocardia recurrence. Results Fifteen of 303 (5.0%) patients developed recurrent nocardiosis after primary treatment. Most recurrences were diagnosed either within 60 days (N = 6/15, 40.0%) or between 2 to 3 years (N = 4/15, 26.7%). Patients with primary disseminated infection tended to recur within 1 year, whereas later recurrences were often nondisseminated pulmonary infection. Seventy-eight (25.7%) patients were prescribed secondary prophylaxis, mostly trimethoprim-sulfamethoxazole (N = 67/78). After propensity-matching, secondary prophylaxis was not associated with reduced risk of recurrence (hazard ratio, 0.96; 95% confidence interval, .24–3.83), including in multiple subgroups. Eight (53.3%) patients with recurrent nocardiosis required hospitalization and no patients died from recurrent infection. Conclusions Recurrent nocardiosis tends to occur either within months because of the same Nocardia species or after several years with a new species. Although we did not find evidence for the effectiveness of secondary prophylaxis, the confidence intervals were wide. However, outcomes of recurrent nocardiosis are generally favorable and may not justify long-term antibiotic prophylaxis for this indication alone.

Abstract Background Human granulocytic anaplasmosis (HGA) is an emerging tick-borne illness endemic to the northeastern and midwestern United States. Risk factors for the severity of infection, predictors for hospitalization, temporal trends, co-infections, and outcomes are poorly studied. Methods We conducted a retrospective review of HGA at Mayo Clinic, Rochester, between 2011-2021. Cases were identified by positive Anaplasma PCR at our reference laboratory. Variables included patients’ characteristics, symptoms, risk factors for tick-borne illness, laboratory parameters, co-infections, treatment, and clinical outcomes. Results We identified 471 cases with a positive Anaplasma PCR, and 146 cases were included in this interim analysis. Table 1 shows a summary of the baseline characteristics. An increasing annual trend in diagnosis of HGA was noted from 2014 to 2016 with lower rates observed during COVID-19 pandemic (2020 to 2022) (Figure 1). Of the 146 patients, 19 (13%) were immunocompromised secondary to hematologic malignancies, solid organ malignancies, and pharmacological immunosuppression. Frequently reported symptoms included fever (79.5%), malaise (68.5%), chills (51.4%), and myalgia (50%). Tick exposure was documented in 79.2 % of cases. Forty-seven (33%) patients were hospitalized; older patients were more likely to be hospitalized (Table 2). The most common complications among the hospitalized patients included respiratory failure (50%), encephalopathy (44.4%) and renal failure (37.5%). One patient required ICU admission. Twenty-five patients (17.5%) and one patient (0.7%) were co-infected with Lyme and Ehrlichiosis, respectively. Higher rates of leukopenia and thrombocytopenia were associated with mono-infection with Anaplasma (p < 0.001). Follow up data was available for 136 patients; all of them had favorable response to doxycycline.Table 1:Summary of baseline characteristics, labs and treatment.Table 2:Predictors of HospitalizationFigure 1:Annual Trends in Anaplasmosis from 2011-2021. Conclusion Our study demonstrated comprehensive clinical characteristics of patients with HGA. Interestingly, tick exposure history was common, yet most patients did not have other tick-borne co-infections. Furthermore, only a minority of patients developed severe diseases and required hospitalization. The recent decline in cases during the early part of the COVID-19 pandemic is worth further investigation. Disclosures All Authors: No reported disclosures

Abstract Background Urinary tract infections (UTIs) caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) have become increasingly challenging to manage due to the limited number of available effective oral agents. Minocycline, a second-generation tetracycline with a broad antimicrobial spectrum and reasonable urinary concentration, has recently gained attention as a potential treatment option for MDR-GNB UTIs. In this study, we aim to review the in vitro minocycline susceptibility against a wide spectrum of urinary GNB isolates performed at our reference lab. Methods We conducted a retrospective review of all minocycline susceptibility testing performed on urinary GNB isolates performed at the Mayo Clinic reference lab between 2013-2022. We stratified our results for different species based on phenotypic resistance profiles as well as known species-specific resistance association. Results During the study timeframe, we identified 28,388 GNB isolates that underwent minocycline susceptibility testing. Among the Escherichia coli (E.Coli) isolates resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibility was noted to be 78%, 46%, 76%, respectively (Fig 1). Among the Klebsiella pneumonia (KP) isolate resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibilities were 47%, 40%, and 53% respectively (Fig 1). Among the high risk Amp-C group Citrobacter freundii, Enterobacter Cloacae and Klebsiella aerogenes, minocycline susceptibility rate was noted to be 87%, 77%, and 89%, respectively (Fig 2). Finally, among the isolate group of non-fermenters including Achromobacter spp, Acinetobacter spp & Stenotrophomonas spp, susceptibility rates were noted to be 65%, 94%, and 100%, respectively (Fig 3). Conclusion Minocycline showed in vitro activity against many hard to treat GNB urinary isolates, including ceftriaxone and meropenem resistant E.coli & KP isolates. High-risk Amp-C producing GN species & some of the less common GN including Stenotrophomonas, Acinetobacter, and Achromobacter. Disclosures All Authors: No reported disclosures

Abstract Background Nocardia primarily infects patients who are immunocompromised or those with chronic lung disease. Although disseminated infection is widely recognized as an important prognostic factor, studies have been mixed on its impact on outcomes of nocardiosis. Methods We performed a retrospective cohort study of adults with culture-confirmed nocardiosis. Advanced infection was defined as disseminated infection, cavitary pulmonary infection, or pleural infection. The primary outcome was 1-year mortality, as analyzed by multivariable Cox regression. Results Of 511 patients with culture growth of Nocardia, 374 (73.2%) who had clinical infection were included. The most common infection sites were pulmonary (82.6%), skin (17.9%), and central nervous system (14.2%). In total, 117 (31.3%) patients had advanced infection, including 74 (19.8%) with disseminated infection, 50 (13.4%) with cavitary infection, and 18 (4.8%) with pleural infection. Fifty-nine (15.8%) patients died within 1 year. In multivariable models, disseminated infection was not associated with mortality (hazard ratio, 1.16; 95% CI, .62–2.16; P = .650) while advanced infection was (hazard ratio, 2.48; 95% CI, 1.37–4.49; P = .003). N. farcinica, higher Charlson Comorbidity Index, and culture-confirmed pleural infection were also associated with mortality. Immunocompromised status and combination therapy were not associated with mortality. Conclusions Advanced infection, rather than dissemination alone, predicted worse 1-year mortality after nocardiosis. N. farcinica was associated with mortality, even after adjusting for extent of infection. While patients who were immunocompromised had high rates of disseminated and advanced infection, immunocompromised status did not predict mortality after adjustment. Future studies should account for high-risk characteristics and specific infection sites rather than dissemination alone.

AbstractBackgroundSpecific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied.MethodsWe performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality.ResultsNine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart‐kidney (N = 1), liver‐kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152–283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim‐sulfamethoxazole (TMP‐SMX) and all patients received TMP‐SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow‐up of 1.96 (IQR 0.90–6.33) years. Two patients died during follow‐up, both without evidence of nocardiosis.ConclusionsThis study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP‐SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis. image

Abstract Background In contrast to bloodstream infection due to a variety of bacteria in patients with cardiovascular implantable electronic devices (CIED), there are limited data regarding candidemia and risk of CIED infection. Methods All patients with candidemia and a CIED at Mayo Clinic Rochester between 2012 and 2019 were reviewed. Cardiovascular implantable electronic device infection was defined by (1) clinical signs of pocket site infection or (2) echocardiographic evidence of lead vegetations. Results A total of 23 patients with candidemia had underlying CIED; 9 (39.1%) cases were community onset. None of the patients had pocket site infection. The duration between CIED placement and candidemia was prolonged (median 3.5 years; interquartile range, 2.0–6.5). Only 7 (30.4%) patients underwent transesophageal echocardiography and 2 of 7 (28.6%) had lead masses. Only the 2 patients with lead masses underwent CIED extraction, but device cultures were negative for Candida species. Two (33.3%) of 6 other patients who were managed as candidemia without device infection subsequently developed relapsing candidemia. Cardiovascular implantable electronic device removal was done in both patients and device cultures grew Candida species. Although 17.4% of patients were ultimately confirmed to have CIED infection, CIED infection status was undefined in 52.2%. Overall, 17 (73.9%) patients died within 90 days of diagnosis of candidemia. Conclusions Although current international guidelines recommend CIED removal in patients with candidemia, the optimal management strategy remains undefined. This is problematic because candidemia alone is associated with increased morbidity and mortality as seen in this cohort. Moreover, inappropriate device removal or retention can both result in increased patient morbidity and mortality.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.